CXCL1 is one of the most important chemokines, part of a group of chemotactic cytokines involved in the development of many inflammatory diseases. It activates CXCR2 and, at high levels, CXCR1. The expression of CXCL1 is elevated in inflammatory reactions and also has important functions in physiology, including the induction of angiogenesis and recruitment of neutrophils. Due to a lack of reviews that precisely describe the regulation of CXCL1 expression and function, in this paper, we present the mechanisms of CXCL1 expression regulation with a special focus on cancer. We concentrate on the regulation of CXCL1 expression through the regulation of CXCL1 transcription and mRNA stability, including the involvement of NF-κB, p53, the effect of miRNAs and cytokines such as IFN-γ, IL-1β, IL-17, TGF-β and TNF-α. We also describe the mechanisms regulating CXCL1 activity in the extracellular space, including proteolytic processing, CXCL1 dimerization and the influence of the ACKR1/DARC receptor on CXCL1 localization. Finally, we explain the role of CXCL1 in cancer and possible therapeutic approaches directed against this chemokine. N-terminal cysteine motif: CXC chemokines (α-chemokines), CC chemokines (β-chemokines), C chemokines (γ-chemokines) and CX3C chemokines (δ-chemokines) [Intercellular signaling is an essential part of the functioning of a multicellular organism, involving the flow of information between different cells through either direct contact or via factors secreted outside the cell: simple compounds such as lactate , or largCXCL1) belongs to the sub-family of CXC chemokines [CXCL1 is one of the four most studied CXC chemokines, with more than 5000 experimental papers available on PubMed , with more than 1000 of these on the role of CXCL1 in cancer. Although each year more than 400 new papers are published about this chemokine, there are no available review papers summarizing the current knowledge in this area. This paper is part of a greater project that aims to provide a comprehensive series of reviews on CXCL1; our focus is on the regulation of expression and activity of this chemokine in the intercellular space.CXC motif chemokine ligand 1  [CXCL1 is neutrophil-activating peptide-3 (NAP-3), a term associated with its ability to induce neutrophil chemotaxis [CXCL1 was shown to be a product of the growth-regulated gene (Gro) [CXCL1 has functioned under two names: MGSA and growth-regulated (or -related) oncogene (GRO) [CXCL2 and CXCL3 [CXCL1 [y (MGSA) . Anotheremotaxis . In subsne (Gro) ,8. Sincene (GRO) . In the ne (GRO) . They wend CXCL3 . GRO itsnd CXCL3 . With th3 [CXCL1 .CXCL1 has two important motifs in its sequence. One is the CXC motif (9–11 amino acids), which assigns this chemokine to CXC chemokines (or α-chemokines) [N-terminus, which makes CXCL1 one of the ELR+ CXC chemokines, currently also known as CXC motif chemokine receptor 2 (CXCR2) receptor agonists [mokines) . The secagonists ,14.CXCL1 gene is localized in the 4q12–q13 CXC chemokine gene cluster [CXCL2/GRO-β, CXCL3/GRO-γ, CXCL4/PF-4, CXC motif chemokine ligand 4 variant-1 (CXCL4L1), CXCL5/ENA-78, CXCL6/GCP-2, CXCL7/PPBP/NAP-2, and CXCL8/IL-8 [CXCL1P1) previously described as a growth-regulated oncogene δ-pseudogene (GRO-δ) [CXCL13 [CXCL1 gene amplification. The frequency of CXCL1 amplification increases with disease progression [CXCL1 gene is observed in 20% cases of breast cancer metastasis [The  cluster . This reCL8/IL-8 ,17. It a (GRO-δ) . Near th [CXCL13 . In breagression . The amptastasis .CXCL6 and CXCL8 , and CXCL1, CXCL2, CXCL3, CXCL5, and CXCL7  [The sequences of the chemokine genes in the 4q12–q13 CXC chemokine gene cluster are similar and located close to each other, which suggests that these genes originated as a result of duplication [e CXCR1) ,23,24,25e CXCR1) . For thiCXCL5 is to human CXCL6 (same species/genome) [CXCL1 in a given disease cannot be compared with rat cytokine-induced neutrophil chemoattractant-1 (CINC-1) [At this point, it should be noted that the ancestor of today’s mammals  had far fewer CXC chemokine genes. These genes were duplicated, and today, this gene cluster has seven CXC chemokine genes in mice and nine in humans . The opo/genome) . Therefo/genome) . For thi(CINC-1)  or mouse(CINC-1) ,31 withoCXCL1 gene does not correspond to the murine KC gene, but to the murine dendritic cell inflammatory protein-1 (DCIP-1) gene [KC gene corresponds to the human CXCL3, CXCL5 and CXCL7 genes, in many papers, CXCL1 and KC are used interchangeably. For this reason, in this review, we distinguish murine KC from human CXCL1.Importantly, given the arrangement of the genes on chromosomes, the human -1) gene . Even thCXCL1 gene consists of four exons and three introns. The exons and introns have a total length of 1845 bp [The  1845 bp . PrecediCXCL1 in inflammatory responses, the most important method for the induction of expression of this chemokine is the activation of NF-κB. At a locus −78 to −66 bp is the nuclear factor κB (NF-κB) binding site [CXCL1 expression [CXCL1 expression is increased by cytokines such as interleukin-1β (IL-1β) [CXCL1 expression is an increase in the stability of CXCL1 mRNA [CXCL1 expression [CXCL1 mRNA [CXCL1 can also increase its own expression via NF-κB activation, a mechanism that is important in cancer [CXCL1 expression is important because of inflammatory responses in malignant tumors. Depending on the type of cancer, there is an upregulation in pro-inflammatory cytokines, e.g., TNF-α [Due to the significance of ing site ,34,35,36pression . Therefo (IL-1β) ,38, tumo (IL-1β) ,38 and i (IL-1β) ,40,41. I (IL-1β) ,40. The CL1 mRNA ,43. In cCL1 mRNA . CXCL1 cn cancer ,45. The ., TNF-α  and IL-1., TNF-α ,48, whicCXCL1 expression. In hepatocytes, there is an important NF-κB p50/p50 homodimer that binds to the CXCL1 promoter to recruit the co-repressor histone deacetylase 1 (HDAC1) [CXCL1 expression, which is important for preventing chronic liver disease.In some cases, NF-κB can decrease  (HDAC1) . This reCXCL1 promoter [The NF-κB binding site also contains the AT motif (the exact locus is −74 bp and −73 bp), which can attach a high-mobility group, AT-hook 1 (HMGA1) (previous name: high-mobility group-I(Y) (HMGI(Y))) ,50. Thispromoter .CXCL1 expression by the exposure of cells to TNF-α, the formation of an NF-κB complex with cut-like homeobox 1 (CUX1) is important, and is much more intensely induced in the simultaneous exposure to IL-17 and TNF-α [CXCL1 gene promoter at the NF-κB binding site in the −94 bp to −84 bp region of the CXCL1 promoter, i.e., where the binding site for CUX1 is located, leading to an increase in CXCL1 expression. This process is significant in rheumatoid arthritis, which is marked by high concentrations of IL-17 and TNF-α at disease sites [In the induction of nd TNF-α . This cose sites .CXCL1 gene promoter also contains the immediate upstream region (IUR) at loci −93 bp to −78 bp  signal transducer, and the activator of transcription (STAT)1 can also inhibit CXCL1 expression. In particular, in peritoneal mesothelial cells, upon exposure of these cells to IFN-γ, STAT1 binds to the −154 bp region upstream of the transcription start site of the CXCL1 gene, which results in a decreased expression of CXCL1 [CXCL1 promoter. STAT1 may also increase the expression of CXCL1. However, its effect will depend on the selected cell model and the factor acting on these cells. In pancreatic ductal adenocarcinoma cells, there is an induction of CXCL1 expression by IL-35 [CXCL1 promoter.Locus −129 bp to −119 bp is the specificity protein 1 (Sp1) and specificity protein 3 (Sp3) binding site ,50, impond TNF-α ,57. Thisby IL-35 , which iCXCL1 expression [CXCL1 gene, is the TGF-β-inhibitory element (TIE), and at locus −560 bp is the SMAD-binding element (SBE) [CXCL1 expression is indirect, likely reducing the activity of either NF-κB or other signaling pathways [TGF-β reduces pression ,60. At lnt (SBE) . SMAD fapathways ,62.CXCL1, there is a different mechanism by which TGF-β regulates the expression of this chemokine. At loci −249 bp to −246 bp and −144 bp to −141 bp, upstream of the transcription start site of the KC gene, are SBEs, which can bind SMAD2/3, reducing KC expression [In contrast, in murine KC, a paralog for human pression .KC gene at loci −128 bp to −120 bp is the CCAAT/enhancer binding protein-β (C/EBP-β) binding motif. Upon activation of c-Met by the hepatocyte growth factor (HGF), C/EBP-β is activated and attaches to the C/EBP-β binding motif on the KC promoter, thus increasing the expression of this murine KC chemokine. Importantly, this mechanism only occurs in murine cells [https://www.ncbi.nlm.nih.gov/gene”; accessed date: 15 November 2021, we did not find any C/EBP-β binding motif according to the cited paper on mouse KC, i.e., 5′-TGGAGCAAG-3′ or any sequence complementary to it up to −2 kbp upstream of the human CXCL1 gene promoter. Therefore, theoretically, C/EBP-β does not directly affect the expression of human CXCL1. In addition, studies on human cells do not show that TGF-β and SMADs directly affect human CXCL1 expression [CXCL1 expression by HGF and C/EBP-β in humans are required.At the upstream transcription start site of the ne cells . Based opression . NeverthCXCL1 expression by TGF-β is an important mechanism observed in cancer [CXCL1 expression in the cancer cell [CXCL1 in these cells. As CXCL1 is a chemotactic factor for neutrophils [CXCL1 expression in colorectal cancer tumors results in the recruitment of tumor-associated neutrophils (TAN), cells with pro-cancer properties [CXCL1 causes tumor cell migration, and consequently, metastasis [The regulation of n cancer ,63. For cer cell . Notablycer cell . This detrophils , an incroperties ,66. Additastasis .TP53 gene are very common in cancer cells and lead to changes in the expression of various genes [TP53 mutations cause an increase in CXCL1 expression [CXCL1 with p53 is complicated, as CXCR2 activation reduces p53 expression, this action is associated with protein kinase B (PKB)/Akt activation, which in turn activates murine double minute 2 (Mdm2) [Gain-of-function and loss-of-function mutations of the us genes ,68. Losspression  due to rpression ,71. If ppression . In addi2 (Mdm2) .TP53 mutations cause mutated p53 proteins to directly bind to the CXCL1 promoter, which results in an increased CXCL1 expression in the tumor cell [CXCL1 expression depends on the type of p53 mutation. DNA-contact p53 mutants (for example R248Q and R273H) bind directly to the CXCL1 promoter [CXCL1 promoter. An example of this is the P72R SNP polymorphism of p53 (rs1042522) [CXCL1 promoter than the P72 p53 mutant. DNA-contact p53 mutants also increase NF-κB activation, which increases the expression of genes dependent on this transcription factor, including CXCL1 [The gain-of-function mor cell ,75. The ng CXCL1 .2+ region conformational p53 mutant. Examples of such p53 mutants are R175H and H179R, which attach directly to the CXCL1 promoter, and thus increase CXCL1 expression [CXCL1 expression by increasing H-Ras activity [CXCL1 expression by Zn2+ region conformational p53 mutants [Another type of mutation is the Znpression . It appeactivity . This ef mutants .CXCL1 expression, the effect is much smaller than when p53 expression is significantly reduced [The last type of mutation is the L3 loop conformational p53 mutant . An exam reduced . This isCXCL1 gene is p63, a transcription factor from the p53 transcription factor family [CXCL1 gene, thus increasing its expression [CXCL1 expression. The significance of p63 in CXCL1 expression was found in tumors, particularly in pancreatic ductal adenocarcinoma cells.Another protein that attaches near the r family ,77. BothCXCL1, contains five hypoxia response element (HRE) sequences at loci −1309 bp, −433 bp, −313 bp, −302 bp and −289 bp [CXCL1 expression may depend indirectly on HIF-1; for example, in human aortic endothelial cells and mouse aortic endothelial cells, HIF-1 increases miR-19a expression [CXCL1. Based on “https://www.ncbi.nlm.nih.gov/gene; accessed date: 15 November 2021”, we identified seven sequences thought to be an HRE, i.e., 5′-A/GCGTG-3′ and complementary ones in the region up to the −2 kbp upstream transcription start site of the human CXCL1 gene [CXCL1 expression—this was already shown by a study involving hepatocellular carcinoma cells [CXCL1 expression in lung adenocarcinoma cells [The promoter of murine KC, a paralog for human  −289 bp . The exp −289 bp  and muri −289 bp . HIF-1 a −289 bp . CXCL1 epression , which iCL1 gene ,83. HRE ma cells . Neverthma cells .CXCL1 expression of the aforementioned factor binding sites near the transcription start site, there are also regulatory sequences located at various distances from the CXCL1 gene.In addition to the effects on CXCL1 expression is increased in an AP-1-dependent manner, as shown by experiments using IL-17 [ng IL-17  and TNF-ng IL-17 ,87.CXCL1 expression by TNF-α also include early growth response gene 1 (Egr-1) [CXCL1 promoter at two loci: −367 bp and −134 bp. This process is significant in cancer, particularly in esophageal cancer, where Erg-1 is frequently overexpressed [The transcription factors responsible for the induction of  (Egr-1) , which bxpressed .CXCL1 expression [Studies on breast cancer cells showed that a breast cancer susceptibility gene 1 (BRCA1) complex with GATA-binding protein 3 (GATA3) reduced pression . NeverthCXCL1 promoter. In particular, the activation of transcription factor 2 (ATF2) and acute myeloid leukemia 1 (AML1) is responsible for the increase in CXCL1 transcription by IL-17, which attaches to the CXCL1 promoter [Other transcription factors also attach to the promoter .CXCL1 gene, a binding site for myeloid ecotropic viral integration site 1 (MEIS1) was identified [CXCL1, as the identified binding site of this transcription factor appears to be non-functional.At locus −277 bp, upstream of the transcription start site of the entified . MEIS1 iCXCL1 gene, a binding site for the microphthalmia-associated transcription factor (MITF) was identified [CXCL1 expression in melanoma depends partly on MITF.At −375 bp upstream of the transcription start site of the entified . This isThe −551 bp to −517 bp region upstream of the transcription start site region of the KC gene contains a binding site for Y-box protein-1 (YB-1) . KC exprCXCL1 gene, contains a binding site for Snail, a transcription factor crucial for epithelial–mesenchymal transition (EMT) [CXCL1 in this cell plays an important role in migration [The −984 bp to −301 bp region, upstream of the transcription start site of the on (EMT) ,94, a prigration  and metaigration ,96 by stCXCL1 gene at the locus −2 kbp, a Hey-like (HeyL) binding site is located [CXCL1 is an angiogenic chemokine [CXCL1 expression, and thus causes angiogenesis.Further from the transcription start site of the  located ,98. Thishemokine ,14, NotcCXCL1 can be bound very far from the CXCL1 gene. In particular, avian v-maf musculoaponeurotic fibrosarcoma oncogene homolog (MAF)F binds to three sites, precisely at the −15 kpb, −12.5 kpb and −7.5 kbp upstream of the transcription start site of CXCL1 gene [CXCL1 expression in human term myometrium [CXCL1 during labor is unknown. The mechanism of induction of CXCL1 expression in human term myometrium is not related to inflammatory factors, which means that CXCL1 expression is induced by a specific transcription factor independent of inflammatory responses [CXCL1 is not only a mediator of inflammatory responses but may also have its own physiological functions unrelated to inflammation.Some proteins regulating the expression of CL1 gene . MAFF inometrium ,100. Howesponses . This shCXCL1 expression. A −2.0 to −1.5 kbp fragment upstream of the transcription start site of the CXCL1 gene undergoes histone H3 Lys36 trimethylation (H3K36me3) by histone H3 lysine 36 methyltransferase SET-domain-containing 2 (SETD2) [CXCL1 expression. This process is important because, in cancers such as breast cancer [SETD2 gene is either mutated or there is a decreased expression of the product of this gene. However, in castration-resistant prostate cancer, SETD2 is an oncogene that supports tumor growth [CXCL1 expression by SETD2 is not known. As this enzyme modifies a fragment very far from the CXCL1 gene, it is possible that it alters the ability to bind some proteins that are important for the regulation of gene expression (Histone methylation is another important means of regulating  (SETD2) . This let cancer , glioblat cancer , hepatoct cancer  and lungt cancer  the SETDr growth . The prepression .CXCL1 gene is followed by transcription. RNA polymerase II (Pol II) begins to transcribe the CXCL1 mRNA fragment with a length of approximately 50 nucleotides [2 of Pol II by positive transcription elongation factor b (P-TEFb). Hairy and Enhancer of Split-1 (Hes1) prevent this phosphorylation, and therefore inhibit CXCL1 transcription [The induction of signaling pathways and attachment of all transcription factors to the promoter of the leotides . Then, tcription . This recription .CXCL1 expression, associated with changes in the stability of CXCL1 mRNA [CXCL1 mRNA is a transcript with a low half-life; if the cell is not influenced by any factors that increase its stability, then this transcript is degraded within 1 to 4 h [CXCL1 mRNA is estimated to be approximately 15 min [CXCL1 mRNA, an approximately 130-nucleotide fragment is removed [CXCL1 mRNA is transformed into a 0.9 kb transcript. However, there are many mechanisms, some of which increase and some of which decrease the half-life of CXCL1 mRNA. In particular, regions 6–23 and 632–651 on the 3′-UTR of CXCL1 mRNA are responsible for increasing the stability of the transcript. Region 562–581 on the 3′-UTR of CXCL1 mRNA is responsible for decreasing the stability of CXCL1 mRNA [CXCL1 mRNA [The production of a 1.1–1.2 kb-long transcript  is folloCL1 mRNA . CXCL1 m1 to 4 h ,110. They 15 min . After t removed ,110. CXCCL1 mRNA . The AUUCL1 mRNA .CXCL1 mRNA stability. This effect depends on the cell type and tissue selected as the research model, as these factors can also increase CXCL1 transcription, e.g., depending on NF-κB activation [CXCL1 expression [CXCL1 mRNA stability are miRNAs, which cause the decay of this transcript [CXCL1 mRNA. This alters the half-life of CXCL1 mRNA, and consequently, the number of these transcripts in the cytoplasm, at unchanged CXCL1 gene transcription levels.Various proteins that are activated by factors such as IL-1 ,109,110,tivation ,39,57. Npression . Additioanscript ,116,117.CXCL1 mRNA decay is IL-17-sensitive. In unstimulated cells, splicing factor 2 (SF2)/alternative splicing factor (ASF) attaches to the 3′-UTR of CXCL1 mRNA, which reduces the stability of this transcript [CXCL1 mRNA sites other than tristetraprolin (TTP). The activation of the receptor for IL-17 leads to activation of Act1, TRAF2 and TRAF5. Act1 causes the phosphorylation of SF2/ASF via the inhibitor of NF-κB kinase ε (IKKε) [CXCL1 mRNA, which increases the stability of this transcript. At the same time, Act1 causes K63-linked polyubiquitination of the human antigen R (HuR) [CXCL1 mRNA, causing its stabilization; HuR also promotes the translation of CXCL1.anscript . This faε (IKKε)  and formε (IKKε) ,119. In  R (HuR) . This prCXCL1 mRNA, and of other transcripts. On the 3′-UTR of CXCL1 mRNA, there is a fragment at locus 780–900 that forms a secondary structure with four stem loops. This is a “similar expression to fibroblast growth factor genes + IL-17R” (SEFIR)-binding element. Act1 binds directly to it, which increases the stability of the transcript in question by competing with SF2/ASF binding [Act1 can also cause the phosphorylation of decapping 1 (Dcp1) via TANK-binding kinase 1 (TBK1) . This in binding .CXCL1 mRNA stability, and thus CXCL1 expression. Nevertheless, IL-17 can also increase CXCL1 transcription, but this effect is not as significant as the change in CXCL1 mRNA stability and may also depend on the research model chosen [CXCL1 transcription is associated with NF-κB activation by the IL-17R receptor [CXCL1 expression, including AP1, ATF2, AML1 and SP1 [IL-17 increases l chosen . An incrreceptor ,40,41. A and SP1 .CXCL1 mRNA [In macrophages , keratinCL1 mRNA .CXCL1 expression. In particular, many of them have important roles in cancer due to the pro-tumorigenic properties of CXCL1 , i.e., it occurs in different locations than CXCL8 [CXCL1 allows for a rapid release of CXCL1 under the influence of pro-inflammatory factors. An example of this is TNF-α, which causes a p38 MAPK- and PI3K-dependent release of CXCL1 [CXCL1 into the same vesicles, and then a simultaneous secretion of both biomolecules [Following the production of vesicles . It was vesicles . CXCL1 ian CXCL8 . The locof CXCL1 . Additioolecules .CXCL1 binds to glycosaminoglycans (GAGs), in particular heparan sulfate, chondroitin sulfate, and dermatan sulfate [CXCL1, which inhibits an overly intense pro-inflammatory response [CXCL1 attached to GAG can be readily released by enzymes that degrade GAG. An example of such an enzyme is the matrix metalloproteinase (MMP)7/matrilysin during colon injury in mice [CXCL1 complexes. This complex is responsible for the neutrophil influx to pro-inflammatory response sites. In addition, GAGs are important for the full activation of CXCR2 receptor by CXCL1 [CXCL1 binds poorly to the aforementioned receptor.Following its secretion outside the cell,  sulfate . This meresponse ,143. CXC in mice ,145. Thiby CXCL1 . WithoutCXCL1 undergoes further proteolytic processing, which regulates the activity of this chemokine. From the N-terminus, three, four or five amino acids are removed, which produce CXCL1(4–73), CXCL1(5–73), and CXCL1(6–73), respectively [CXCL1 activity 30 times, as measured by its ability to induce the chemotaxis of treated cells. The process of amino acid removal may involve cathepsins, in particular cathepsin K, cathepsin L, and cathepsin S [N-terminus of CXCL1, resulting in the formation of CXCL1(5–73). Nevertheless, no proteases responsible for the formation of CXCL1(4–73) and CXCL1(6–73) have been identified so far. The identification of proteases responsible for processing CXCL1 would allow new pathways regulating the activity of this chemokine to be demonstrated. However, studies on metalloproteinases, MMP1 and MMP9, showed that they do not exhibit any activity against CXCL1 [CXCL1 could be sliced inside the ELR sequence by MMP12, which resulted in the formation of CXCL1(7–73) and the inactivation of CXCL1.After secretion, ectively . This inhepsin S . These pst CXCL1 . InsteadCXCL1 can be dimerized [CXCL1 molecules occur in the form of dimers. However, for mouse KC, which is the paralog of human CXCL1, this concentration can be higher: 36 μM [CXCL1 in normal- and cancer-tissue homogenates [CXCL1 proteins are dimerized during biochemical isolation [CXCL1 homodimers, for which it has a higher affinity than for the monomers of this chemokine [CXCL1 homodimers are bound to surface glycosaminoglycans, and the monomers are soluble forms of CXCL1. However, the arrangement of GAG-bound CXCL1 prevents the activation of CXCR2 [CXCL1. GAGs, particularly heparan sulfate proteoglycans, appear to play an important role in CXCR2 receptor activation by CXCL1 [imerized  and tendimerized ,151, espimerized  to 20 μMimerized , dependir: 36 μM . This coogenates ,156. At solation ,151. Thesolation . Importahemokine ,158. Thaby CXCL1 .CXCL1 monomers and homodimers have a similar ability to activate CXCR2 [CXCL1 monomers and homodimers is required for full CXCL1 activity [CXCL1 has a greater activity than stable CXCL1 homodimers and a greater activity than modified CXCL1 monomers, so that they do not dimerize [CXCL1 undergoes homodimerization.Both te CXCR2 ,159. It activity ,161. Thedimerize ,161. In CXCL1 is only a simplified model, as CXCL1 can also form heterodimers with other CXC chemokines. In particular with CXCL4 [CXCL7 [CXCL8 [CXCL1 homodimer [The mixture of monomers and homodimers of th CXCL4 , CXCL7 [4 [CXCL7  and CXCL7 [CXCL8 . Such a omodimer ,163. Howomodimer .CXCL1 heterodimers with other CXC chemokines has been poorly studied. Usually, the role of only a single selected chemokine is studied in a given process, even though the demonstration of interactions between different CXC chemokines may provide a better understanding of therapeutic methods against a selected chemokine, particularly in cancers, associated with the increased expressions of many various CXC chemokines, particularly in colorectal cancer [The formation of l cancer , head anl cancer  and skinl cancer .CXCL1 receptors have been discovered—CXCR1, CXCR2 and atypical chemokine receptor 1 (ACKR1) [CXCL1 binds with high affinity to just two of them—CXCR2 and ACKR1. ACKR1 binds CXCL1 with a dissociation constant (Kd) of 1.81 nM [CXCL1 to the CXCR2 receptor. Depending on the study, the half maximal effective concentration (EC50) for CXCR2 and 5.0 ± 1.7 nM [Kd of 3 nM [To date, three  (ACKR1) . Of thes 1.81 nM , similar± 1.7 nM  or 0.4 n± 1.7 nM , with Kd of 3 nM .CXCL1 can bind to and activate CXCR1, but the binding parameters to this receptor are 300 to 1000 times weaker than for CXCR2 [50 for CXCL1 to activate CXCR1 is 65 ± 13 nM [Kd is 300 nM [CXCL1 seem to mainly associate with CXCR2, especially in the light of its much higher affinity to CXCL1 than that observed for CXCR1, even though some papers show that CXCR1 in some models is important for the action of CXCL1 [or CXCR2 . The EC5 ± 13 nM  or 220 n ± 13 nM , while Ks 300 nM  or 450–8s 300 nM , dependiof CXCL1 ,171.Plasmodium vivax and Plasmodium knowlesi, to infect erythrocytes [ACKR1 was first described as a Duffy antigen, which forms the Duffy blood-group system, hence its original name: Duffy antigen receptor for chemokines (DARC) . With a hrocytes ,176,177.hrocytes .CXCL1 but also for CXCL8 and CC chemokines, CCL2 and CCL5, although not for CCL3 or CXCR3 receptor agonists [ACKR1 is not only a receptor for agonists ,178. Theagonists , a motifagonists ,181. Theagonists .CXCL1) from the blood, which leads to the maintenance of CXCL1 levels and regulation of the intensity of the inflammatory response [ACKR1 has an important role in chemokine action. On erythrocytes, it binds chemokines  [trophils . Additiotrophils . These ptrophils ,200 and trophils ,201,202 trophils . CXCL1 cs (Treg)  and MSCss (Treg)  into theCXCL1 is its ability to induce angiogenesis [CXCL1 is increased by the vascular endothelial growth factor (VEGF) [Another no-less-important property of ogenesis ,14. In pr (VEGF) ,207,208 CXCL1 are confirmed by clinical tumor studies, which showed that CXCL1 expression increased with cancer progression. This was also shown in studies of patients with cancers such as bladder cancer [All the pro-tumor properties of r cancer , colorecr cancer , gastricr cancer , hepatocr cancer , larynger cancer , prostatr cancer  and renar cancer .CXCL1 in tumorigenesis allows for the development of effective therapies targeting this chemokine. An example of this is HL2401—an anti-CXCL1 monoclonal antibody, which shows promising results against bladder cancer and prostate cancer in animal experiments [CXCL1 activity but also other CXCR2 agonists.The high importance of eriments . Additioeriments ,216,217.eriments , ladarixeriments , SCH-479eriments . They inCXCL1. For example, as T cells do not express CXCR2 [CXCL1. Therefore, such modified T cells could be recruited to solid tumors with an elevated concentration of CXCL1, which would result in the initiation of an anti-tumor immune response [Anti-cancer therapies do not just have to be associated with a reduction in the expression and effects of ss CXCR2 ,222, if response ,222. ThiCXCL1 expression and activity is very well researched. In particular, we already know much about the regulation of CXCL1 gene transcription and the role of miRNAs in CXCL1 mRNA stability. However, there are areas of knowledge that are poorly understood and should be further investigated in the near future. In particular, little is known about the following aspects of the regulation of CXCL1 expression and activity:-CXCL1 mRNA stability: The effect of IL-17 on this process is fairly well established, but the role of IL-1 and TNF-α requires further investigation. Additionally, the exact mechanism causing the low stability of CXCL1 mRNA in cells not stimulated by any cytokines are unknown;The regulation of -CXCL1 to vesicles and its release outside the cell: CXCL1 is an important component of cellular responses to dangerous agents. For this reason, intercellular signaling involving CXCL1 must sometimes be very rapid, and in some cases, the release of CXCL1 from the cell must be immediate. However, very little research is devoted to the regulation of CXCL1 levels outside cells;The mechanisms of sorting the -CXCL1 have been identified. The investigation of this mechanism could indicate new therapeutic avenues for diseases in which CXCL1 plays an important role;Proteolytic processing: Until now, not all proteases involved in proteolytic processing of -CXCL1 heterodimerization with other CXC chemokines and interactions between CXC chemokines: A characteristic feature of CXC subfamily chemokines is the eight different CXC chemokines that cause the same ability to activate CXCR2 at similar concentrations. Evolutionary pressures caused many duplications of the ancestral gene of all ELR+ CXC chemokines. However, it is not entirely clear why, perhaps due to the different regulation of expression for each chemokine in this group. This argument can be linked to the heterodimerization of ELR+ CXC chemokines. With 8 ELR+ CXC chemokines, we have 28 different heterodimers, 8 homodimers and 8 monomers—a total of 44 different molecules that can activate CXCR2 in slightly different ways. This is almost 5.5 times more than the number of chemokines. The interaction with GAG is also important in this model.The regulation of


Smelowskiasunhangii, from Qinghai and Tibet (China), is described and illustrated. Morphological and molecular data indicate that S.sunhangii is closely related to Smelowskiatibetica, from which it is easily distinguished by the densely hirsute (vs. glabrous or sparsely pubescent), elliptic to ovate-lanceolate  fruits with undulate (vs. straight) margins. A re-evaluation of the widely distributed S.tibetica and related taxa is also provided. Smelowskia C.A.Mey.  comprises 25 species distributed mainly in central and northeastern Asia, with fewer species in North America  Lipsky is the most widely distributed  and was recognized by these authors as most highly variable in fruit shape. Four new taxa were described by H.lata Xue L.He & C.H.An, H.rotundata C.H.An, H.taxkargannica G.L.Zhou & C.H.An, H.taxkargannicavar.hejigensis G.L.Zhou & C.H.An, but these were reduced by Smelowskiatibetica (Thomson) Lipsky based on the examination of all type collections of Smelowskia. The above Smelowskiatibetica complex is re-examined here in light of additional field and molecular studies.Nine species of to China , and theSmelowskia in Qinghai province, China , Kunming, China. Herbarium specimens of the S.tibetica complex and related taxa were examined from BNU, KUN, PE, WUK and XJA (acronyms follow http://www.cvh.ac.cn/index.php), and JSTOR Global Plants web portal (https://plants.jstor.org/). The voucher specimens for morphological observation were cited in the section of “Chinese specimens examined” of taxonomic treatment and Table Morphological data were recorded from field collections and herbarium specimens covering the full spectrum of geographical, plant type, and habitat variation in the Smelowskiatibetica complex, including the presumed new species. Leaf materials were collected from field works and dried herbarium specimens. Descurainiapinnata from tribe Descurainieae (sister to tribe Smelowskieae) and Shehbaziatibetica from tribe Chorisporeae were selected as outgroups based on previous molecular phylogenetic relationships  were amplified using the primers ITS1-18S described in ITS4 described in http://www.technelysium.com.au) and integrated into a single sequence. Sequences were then aligned with MEGA version 7.0 and gaps were treated as missing data  following the manufacturer’s protocol. The entire ITS region  and maximum likelihood (ML). The phylogenetic tree based on Bayesian inference was generated using MrBayes version 3.2.6 (AIC) was used in BI and ML analyses  and maximum likelihood bootstraps (ML) of the ITS sequences both showed that four accessions of Smelowskiasunhangii grouped together , however, an accession of previously determined Smelowskiatibetica (KX244397) was nested in it. After a critical examination of the voucher of this accession, Zh641 (KUN), we immediately concluded that it is S.sunhagii.A total of 15 taxa were included in this analysis Fig. . The resSmelowskiatibetica complex formed a monophyletic clade, sister to S.sunhangii with a strong support . In addition, the clade of Smelowskiatibetica complex formed a polytomy of three subclades, of which two belong to Smelowskiatibetica and the third is a polytomy of samples identifiable as members of the Hedinialata and H.rotundata as characterized morphologically above.All of the seven accessions of the Smelowskiatibeticasensu lato contains two, easily distinguished species, of which one is the new S.sunhangii and the other is S.tibetica including the taxa described by Hedinia. Although our data show some differentiation within S.tibetica, namely a polytomy of the Hedinia taxa forming another polytomy with the remaining samples of S.tibetica proper, such a current slight differentiation does not justify the recognition of more than two species. The principal reasons for not recognizing the Hedinia taxa are as follows.Our molecular and morphological analyses indicate that Smelowskiatibetica complex was critically studied by one of us (Al-Shehbaz) in plants from the entire range of this complex in Bhutan, India, China, Nepal, and Tajikistan both in herbaria worldwide and in the field in Xinjiang (China), Nepal, and Tajikistan. The conclusion of such observations was the acceptance of a single polymorphic species in the Himalayan region .China. Qinghai. Yushu Tibetan Autonomous Prefecture, Yushu City, Longbao Town, Smelowskiasunhangii is easily distinguished from its closest relative S.tibetica by having densely hirsute (vs. glabrous or sparsely pubescent), elliptic to ovate-lanceolate  fruits undulate (vs. straight) along margin.Herbs 5–15 cm tall, covered with simple trichomes, canescent. Stems procumbent or ascending, densely white hirsute. Basal leaves densely hirsute; petiole 0.5–1.5 cm long, often ciliate basally; leaf blade ovate or narrowly oblong in outline, 1-pinnatifid, 1–4 × 1–2.5 cm; cauline leaves similar to basal, reduced in size upwards. Racemes bracteate throughout, distal bracts subsessile. Sepals oblong, 1–2 × 0.5–0.8 mm, hirsute. Petals obovate, 2–3.2 × 0.9–1.4 mm, claw ca. 1.5 mm long. Fruit elliptic to ovate-lanceolate, densely white hirsute, 5–10 × 3–5 mm, undulate along margin, appressed to rachis. Seeds light to dark brown, oblong, 0.9–1.2 × 0.4–0.6 mm. Fl. Jul–Sep, fr. Aug–Oct.Smelowskiasunhangii is named after Prof. Sun Hang (1963–), director of the Kunming Institute of Botany (China) who conducted extensive research on plant taxonomy, biogeography, and evolutionary biology and made outstanding contributions towards understanding the plant diversity of China. Vernacular name: The Chinese name is given as “毛果藏荠” (máo guǒ zàng jì), referring to the densely hirsute fruit of the new species.China . Qinghai: Yushu Tibetan Autonomous Prefecture, Yushu City, 32°17'20.62"N, 95°50'15.29"E, 4,848 m, 23 July 2019, P.J. Liu & H.H. Shi deng7262 (KUN); Yushu Tibetan Autonomous Prefecture, Chindu City, 31 July 2019, T. Deng, X.H. Huang, Z.Y. Lv & L.J. Li DengT128-9 (KUN); Yushu Tibetan Autonomous Prefecture, T. Deng, X.H. Huang, Z.Y. Lv & L.J. Li DengT105-23 (KUN); Yushu Tibetan Autonomous Prefecture, Qumarlêb County, 2 September 2013, J.W. Zhang, B. Yang & H.L. Chen Zh641 (KUN).China. Taxon classificationPlantaeBrassicalesBrassicaceae(Thomson) Lipsky68E4D6FA-2E1C-5148-9CB6-C44E0E13BC06Hutchinsiatibetica Thomson, Hooker’s Icon. Pl. 9: t. 900. 1852. TYPE: WESTERN TIBET. Lanak Pass, 18–19,000 ft , Thomas Thomson s.n. (holotype: K!).  Basionym: Hediniatibetica (Thomson) Ostenf. in Hedin, S. Tibet 6: fig. 2. 1922.  Synonyms: HedinialataJ.X. Yang 2220 . Xue L.He & C.H.An, Acta Phytotax. Sin. 34(2): 205. 1996. TYPE: TIBET. Ando, alt. 4,750 m, on stony mountain slopes, 14 August 1963, HediniarotundataActa Bot. Boreali-Occid. Sinica 10: 325. 1990. TYPE: XINJIANG. The west of Altum Mountains, Qimantag, 2,700 m, 25 July 1984, Zhang Li-Yun 84-A-411 (holotype: XJA!) C.H.An, HediniataxkargannicaAn Zheng-xi N. 268 (holotype: XJA!) G.L.Zhou & C.H.An, Acta Bot. Boreal.-Occid. Sin. 10: 323. 1990. TYPE: XINJIANG. Tajik Autonomous County of Taxkargan Vaka, in alpina desert steppe zone, July 1986, Detailed descriptions of the species are found in the Flora of China , Nepal , and theChina ; Lhasa, Damxung County, Namtso, 25 July 2018, D.G. Zhang, Y. Wu & H. Ye ZDG18-9 (KUN); Nagqu, Sog County, 28 July 2018, D.G. Zhang, Y. Wu & H. Ye ZDG23-7 (KUN); Nagqu, Sog County, 28 July 2018, D.G. Zhang, Y. Wu & H. Ye ZDG24-24 (KUN); Nagqu, Shenza County, 3 August 1987, B.S. Li & D. Zheng 10888 (PE); Nagqu, Biru County, 3 September 1976, D.D. Tao 11181a (KUN); Nagqu, Anduo County, 10 September 2008, J.H. Chen, H.F. Zhuang & D.T. Liu Yangyp-Q-0258 (KUN); Nagqu, Baqing County, 26 June 2016, J.P. Yue, Z. Zhou & H.L. Chen YZC226 (KUN); Nagqu, Anduo County, 21 August 2009, J.H. Chen, H.F. Zhuang & P. Tashi YangYP-Q-2166 (KUN); Ngari, Rutog County, 29 July 1987, B.S. Li, D. Zheng 10848 (PE); Changdu, Jomda County, 1 August 2004, D.E. Boufford, J.H. Chen, S.L. Kelley, J.Li, R. H. Ree, H. Sun, J.P. Yue & Y.H. Zhang 31531 (KUN); Changdu, Riwoqê County, 11 August 2004, D.E. Boufford, J.H. Chen, S.L. Kelley, J. Li, R.H. Ree, H. Sun, J.P. Yue & Y.H. Zhang 32037 (KUN). Qinghai: Yushu Tibetan Autonomous Prefecture, Nangqên County, 24 July 1965, Y.C. Yang 1261 (KUN); Yushu Tibetan Autonomous Prefecture, Nangqên County, 24 July 2019, X. Zhang, J.T. Chen & T.H. Kuang HuangXH018-9 (KUN); Yushu Tibetan Autonomous Prefecture, Nangqên County, 23 July 2019, X. Zhang, J.T. Chen & T.H. Kuang HuangXH015-20 (KUN); Yushu Tibetan Autonomous Prefecture, Yushu City, 23 July 2019, P.J. Liu & H.H. Shi deng7261 (KUN); Yushu Tibetan Autonomous Prefecture, Zadoi County, 25 July 2019, P.J. Liu & H.H. Shi deng7359 (KUN); Haibei Tibetan Autonomous Prefecture, Menyuan Hui Autonomous County, 26 July 2008, Y.H. Wu LJQ-QLS-2008-0115 (KUN); Haibei Tibetan Autonomous Prefecture, Menyuan Hui Autonomous County, 18 June 2018, X.X. Zhu & Y.M. An ZXX18140 (KUN); Golog Tibetan Autonomous Prefecture, Madoi County, 31 July 2011, S.L. Chen, Q.B. Gao & F.Q. Zhang ChenSL1379 (KUN); Golog Tibetan Autonomous Prefecture, Baima County, 29 August 2013, J.W. Zhang, B. Yang & H.L. Cheng Zh537 (KUN); Golog Tibetan Autonomous Prefecture, Darlag County, 10 August 1993, H.B.G. 1033 (PE); Haixi Mongol and Tibetan Autonomous Prefecture, Golmud City, 11 September 2008, H.Y. Feng LiuJQ-08KLS-139 (KUN); Haixi Mongol and Tibetan Autonomous Prefecture, Golmud City, 19 August 2010, X.M. Tian, Z.Q. Wang & J.B. Zou LiuJQ-Txm10-097 (KUN); Haixi Mongol and Tibetan Autonomous Prefecture, Golmud City, Fenghuo mountain, 18 August 2010, X.M. Tian, Z.Q. Wang & J.B. Zou Liujq-Txm10-074 (KUN); Haixi Mongol and Tibetan Autonomous Prefecture, Golmud City, Ulan Moron, 22 August 1990, Yang Jingsheng 402 (KUN). Xinjiang: Bayin’gholin Mongol Autonomous Prefecture, Ruoqiang County, 10 August 1988, S.G. Wu, H. Ohba, Y.H. Wu & Y. Fei 2678 (KUN); Bayin’gholin Mongol Autonomous Prefecture, Hejing County, 16 August 1958, J.N. Zhu & A.R. Li 6543 (KUN); Kashgar Prefecture, Taxkorgan Tajik Autonomous County, 11 August 2008, J. Qiu & J.J. Feng LiuJQ0171 (KUN).China.


Journal of Intelligence. My predecessor, Paul De Boeck, has done an excellent job at the helm for the last eight years. And it has been my privilege to work with Paul as an Associate Editor here at the journal for the last three years. My primary goal as editor is to continue that success and to build upon the strong foundation that Paul and the editorial team have provided for the Journal of Intelligence.First, let me say that I am honored to take on the role of Editor in Chief at the Journal of Intelligence has now published 252 articles, and taken together, these 252 papers reflect the multi-faceted nature of the field. The journal has published papers on an extremely broad range of topics, from mitochondrial functioning to group problem solving.Intelligence is a complex psychological construct, and in turn, the science of intelligence is multi-faceted and interdisciplinary, including work from several broad fields, such as developmental psychology, cognitive psychology, psychometrics, behavioral genetics, and neuroscience. The In my view, the journal has already established a strong reputation in three areas: The application of cognitive models to the study of intelligence, psychometric network modeling, and the exploration of relatively novel concepts and constructs in the study of individual differences. I am enthusiastic about all of these areas of research, and I expect the journal to continue to build upon these strengths and be an outlet for more work along these lines.Journal of Intelligence as an outlet for their work. I would also like to see the journal publish more research at the intersection of cognitive neuroscience and psychometrics and therefore encourage research teams that bridge these two disciplines, as well as cognitive neuroscientists who do individual differences studies, to consider the Journal of Intelligence as an outlet for their work.At the same time, I believe there are some opportunities for broadening our scope. In particular, I would like to see the journal publish more developmental research, both theoretical and applied. I therefore encourage developmental, educational, and school psychologists to consider the https://doi.org/10.3390/jintelligence2020033), when the journal was just beginning, advances in psychometrics, cognitive psychology, and neuroscience set the stage for the development of stronger theories and more sophisticated models of intelligence. Having an open access journal as an outlet for this new research has been crucial. I am excited to see what new findings and ideas emerge in the coming years.As I said in 2014 (


The most common causes of technical failures in this cohort included abdominal hemorrhage (8.4%); graft pancreatitis (3.7%); fluid collections (2.6%); intestinal complications (6.6%); and vascular thrombosis (20.5%). Although IGL-1 solution provided lower surgical complication rates, no significant differences were found between studied groups. Nevertheless, HTK solution was associated with elevated pancreatitis rates. The best graft survival was achieved at 1 year using UW and IGL-1, and at 3 and 5 years using IGL-1 (p = 0.017). There were no significant differences in patient survival after a median follow-up of 118.4 months. In this setting therefore, IGL-1 solution appears promising for perfusion and organ preservation in clinical pancreas transplantation, compared to other commonly used solutions.Due to the high vulnerability of the pancreas to ischemia-reperfusion injury, choices regarding preservation solution markedly affect pancreas transplant success. A retrospective single-center analysis of 380 pancreas transplants (2000–2019) was performed to correlate current preservation solutions with transplant outcomes. Early graft failure requiring transplantectomy within 30 days post-transplant occurred in 7.5% for University of Wisconsin (UW) group ( For patients with diabetes mellitus (DM) type 1, pancreas transplantation (PTx) is the only therapeutic option capable of normalizing blood glucose and minimizing secondary complications of diabetes, resulting in an increase in the survival and an improved quality of life . In SpaiThe maintenance of organ viability from donation to transplantation is a decisive factor for the adequate function and survival of the graft, especially in organs such as the pancreas, which is highly susceptible to ischemic damage. Preservation has become a key challenge due to the increasing use of marginal donors, in whom the functionality of the organ is most affected ,7.In this scenario, four preservation solutions are currently in use for pancreas transplantation. University of Wisconsin (UW) solution has been considered for organ perfusion in abdominal organ transplantation since the late 80s . Its comAt present there is no universal consensus regarding the optimal preservation solution in the setting of PTx albeit UW solution continues to be recognized as the “gold standard” . ConsideIn recent years, the Pancreatic Transplant Unit at Hospital Clínic of Barcelona has routinely used IGL-1 as a preservation solution for PTx from its own donors. The aim of this study was to compare the effectiveness of the four currently in-use preservation solutions on the outcome of PTx regarding early pancreatic graft function as well as long-term patient and graft survival. Secondly, postoperative surgical complications were also evaluated, as well as their relation with ischemia-reperfusion injury.Five hundred ninety-one consecutive pancreas transplants were performed at the Hospital Clínic of Barcelona from 1983 through to the end of 2019. A prospectively assembled database of all pancreas transplants from January 2000 to March 2019 was reviewed, i.e. since surgical technique and immunosuppression strategies were standardized. The patient cohort included 380 patients who underwent PTx: 312 (82.1%) simultaneous pancreas-kidney (SPK); 27 (7.1%) pancreas after kidney (PAK) and 3 (0.8%) pancreas transplant alone (PTA). In addition, 38 (10%) patients received a pancreas retransplantation. Data from this cohort were stratified into four groups according to the organ preservation solution employed . UW and CS were used throughout the whole period of analysis, HTK from January to December 2013 while IGL-1 has been in use from 2014 to the present.This study protocol was approved by our institutional review board (HCB/2020/0499) and complied with the ethical standards of the Helsinki Declaration of 1975.Graft pancreas acceptance criteria was performed based on the consensus document of the National Transplant Organization described in 2005 and updated in 2018 . Donor aDuring organ procurement, both abdominal aorta and portal vein cannulation  were used to perfuse the organs (perfusion time 8–10 min). The perfusion volume differed depending on the surgeon criteria to obtain a clear effluent via vena cava. The standard, whole-pancreas graft included the entire pancreas and a duodenal segment.The indications for PTx were patients with DM who met the inclusion criteria according to the protocol established in our institution . Venous vintage), and type and duration of dialysis . In addition, surgical complications were defined according to the modified Clavien Dindo classification  and by clinical outcomes, including the need of transplantectomy within 30 days of transplantation.Routine immunosuppression in SPK and PAK consisted of different regimens administered following the institutional protocol, which varied according to the date of transplant including monoclonal antibody (OKT3), anti-interleukin-2 monoclonal antibody (basiliximab), rabbit anti-human lymphocytes polyclonal antibodies (thymoglobulin) among others, as standard induction therapy. Maintenance immunosuppression was based on triple therapy with calcineurin inhibitor (cyclosporine A until 2005 vs. tacrolimus introduced in the late 90s), mycophenolate and steroids.Our standard anticoagulation protocol included enoxaparin 20 mg every 12 h, starting 8-h post-surgery and maintained until patient discharge (in the absence of thrombotic/hemorrhagic complications), and aspirin 50 mg/d starting at 12-h post-surgery until discharge (100 mg/d).Vancomycin plus third-generation cephalosporin (from 2000 to 2014) or ertapenem (from 2015 to 2019) were used as antibiotic prophylaxis in the perioperative period. Fungal prophylaxis with fluconazole was universally used in all recipients. Cytomegalovirus prophylaxis was provided by ganciclovir or valganciclovir, depending on glomerular filtration rates.2 test. Mann-Whitney U test or the Kruskal Wallis in the case of nonparametric distribution were used for the analysis of continuous variables. Due to the limited number of cases for HTK group, and the resulting bias that may arise in subgroup analysis, we have deemed it appropriate to provide a detailed description of the immediate post-transplant complications instead of including it for comparison with other groups.Categorical variables are expressed as frequencies (%), percentages and continuous variables such as median and interquartile range (IQR). Categorical variables were analyzed by use of Fisher’s exact or χThe following variables have been included in the univariate and multivariate analysis as potential risk factors for early graft survival: donor demographics ; donor procurement factors ; era of transplant (before and after 2010); recipient demographics . Other factors related to surgical management and technique included were the type of arterial reconstruction in the backtable, the type of vascular  anastomosis and the intestinal anastomosis technique used in the recipient.p values of less than 0.05 were considered statistically significant. Significant covariates were subjected to multivariate cox regression analysis.Patient and graft survival were assessed using Kaplan–Meier curves and compared with the log-rank test (LR) and Breslow. Numeric covariates were dichotomized by their median. Patient survival was calculated from the time of transplant to death or the end of follow-up. Pancreas graft survival was calculated from the time of transplant until any of the following: the need for graft removal; the return to permanent insulin therapy dependency; retransplant or death/end of follow-up with a functioning graft. https://www.R-project.org/).Statistical calculations were made using SPSS for Windows software  and R statistical software (R Core Team (2017). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL A total 380 PTx’s were performed in our center with the use of four different preservation solutions, which differed in terms of their chemical composition . Some 26p < 0.05). IGL-1 and HTK exhibited shorter CIT (p < 0.05), with significantly larger volumes of perfusion solution as compared to CS and UW (p < 0.05). The preservation solutions did not differ regarding gender, cause of death, BMI, PPASS and the levels of lipase. Nevertheless, in relation to donor amylase levels, HTK group presented lower values compared to others.The four groups had similar characteristics regarding donors as shown in vintage, type of dialysis and type of transplant (p = 0.003) and had the lower proportion of patients with DM I compared to others. Thymoglobulin was the most frequently used drug as induction therapy for CS, HTK and IGL-1 groups.Recipient demographics showed no significant differences with respect to gender, BMI, dialysis ansplant . By contThere were, by far, more SPK compared to PAK and PTA in the UW, CS and IGL-1 group . PatientFor the vascular reconstruction of the pancreatic graft during backtable, arterial anastomosis between the splenic artery and the superior mesenteric artery was performed in the majority of cases for all analyzed groups. Regarding enteric exocrine drainage procedures, most UW, CS and HTK-preserved grafts were transplanted intraperitoneally (duodeno-jejunostomy), except for IGL-1, for which duodeno-duodenostomy technique was used in 69.6% of cases.On the immediate postoperative days (24h–48 h), serum amylase levels were the following: UW, 198 (IQR 127–341) IU/L; CS, 148 (IQR 100–295) IU/L; HTK, 206 (IQR 62–2821.5) IU/L and IGL-1, 193 (IQR 89–375) IU/L. Statistical differences were found between UW and CS . The serp < 0.001, HTK vs. others). Hemodialysis was required in 15 of them in the immediate postoperative period, with progressive normalization of renal function at the moment of discharge.Interestingly, a total of 30 patients presented kidney delayed graft function (DGF): UW (7.1%); CS (7.2%), HTK (57.1%); IGL-1 (4.3%), (Early graft failure requiring transplantectomy within 30 days post-transplant occurred in 31 (8.1%) patients , being mLate causes of graft failure requiring pancreas transplantectomy beyond 30-day post-transplant accounted for 2.4% of the cases .n = 142). The Clavien-Dindo grading system for the classification of surgical complications was as follow: grade I (5.3%), grade II (6%), grade IIIa (3.9%), grade IIIb (20.5%), grade IVa (1.6%).Technical failures in the total cohort amounted to 37.4% ; intra-abdominal hematoma (n = 3); and subcutaneous hemorrhage (n = 1). Graft pancreatitis was diagnosed in a total of 14 patients. There were numerical differences based on the preservation solution type (p < 0.001), with a significantly high rate for the HTK group , basiliximab (n = 1)). Regarding the whole series, some 8 cases required an immediate transplantectomy because of a severe graft necro-hemorrhagic pancreatitis after reperfusion (n = 4) at a median of 12 days (6.5–15) post-transplant and percutaneous abscess drainage (n = 1). Other intra-abdominal fluid collections were diagnosed in 10 patients, without impact on graft survival. A relaparotomy was needed in half of them, performed in most cases when the patient was readmitted after discharge because of fever and abdominal pain at a median of 28 days (18–43.5) after transplant. Intestinal complications (6.6%) included post-transplant duodenal-enteric leaks and those related to small-bowel obstruction. A total of 5 patients required early transplantectomy because of: anastomotic leak (n = 2); a leak of the duodenal stump site (n = 2), and ischemia of the duodenum (n = 1). The UW, CS and IGL-1 preservation solutions presented similar rates of vascular thrombosis (venous (77%), arterial (6.4%), both (16.6%). Note that, in a total of 25 out of 78 patients, surgery was applied as treatment. Other therapeutic options used for thrombosed pancreas grafts are also described in In most cases, a surgical reintervention was required due to: hemoperitoneum (erfusion . In thosp = 0.692).After a median follow-up of 118.4 months (IQR: 63.2–168.9), overall patient survival for the whole cohort at 1, 3, and 5 years was 98.4%, 96%, and 95%, respectively. Patient survival rates at 1, 3, and 5 years for the studied groups are depicted in p = 0.017).Overall death-censored pancreas graft survival for the whole cohort at 1, 3, and 5 years was 87.1%, 83.4%, and 79%, respectively. p = 0.035], HTK as preservation solution , pretransplant creatinine (>5.9 mg/dl) , type of transplant (other than SPK) , recipient gender  . Other variables with no statistical significance yet presented a tendency to influence graft survival were: donor BMI >27 kg/m2 (p = 0.057) and donor cause death other than trauma (p = 0.06). In a multivariate Cox regression model for graft survival, the variables associated with an increased risk for graft failure were: type of transplant (other than SPK)  and recipient gender  .Regarding pre-procedure variables related to donor and recipient, a significantly increased risk of graft loss on univariate analysis was associated with the following: CIT (>10 h), [hazard ratio (HR) 1.51, 95% CI 1.02–2.23; Of all solid organ transplant types, pancreas transplants are most susceptible to non-immunologic failure, with a reported graft loss rate of 5%–20% during the first year after transplantation -20. BecaHerein, we present the first retrospective single-center study comparing the effects of the four most commonly used preservation solutions in PTx, i.e. UW, CS, HTK, and IGL-1, on early pancreatic graft function as well as long-term patient and graft survival. By analyzing a large cohort of pancreas transplants in a 20–year period, this study shows that, although similar rates of graft survival were observed during the first year when comparing IGL-1, CS and UW, better results for IGL-1 were observed over the long term. Conversely, the HTK-preserved pancreas had the lowest graft survival in comparison to the other preservation solutions employed, supporting the findings of Hameed AM et al.  when comp < 0.001). These findings are in contrast to a larger series published by Fridell et al. ), the type of vascular reconstruction nor the intestinal anastomosis had an impact on the early graft functioning.In general, our findings are consistent with the scant published information in PTx using IGL-1. At the clinical level, one preliminary study suggests that IGL-1 is a safe preservation solution since it provides up to 17 h of cold ischemia. The five human pancreases preserved with IGL-1 acquired normal function immediately after reperfusion, without loss of the graft . SimilarTo the best of our knowledge, this is the only study exploring the effect of the four preservation solutions currently used for clinical PTx. We are aware that the suboptimal number of patients (mainly in the HTK group) limit the conclusions of the study, even though this factor is mitigated when evaluating the results from the point of view of “intention to treat”. A low number of HTK-flushed pancreases has arisen due to an unexpected increase in the rate of immediate transplantectomy due to acute pancreatitis following reperfusion, as the latter is also an independent risk factor for impaired graft survival. This fact limited HTK’s use in PTx and did not allow us to recruit an optimal number of cases for comparison with a suitable sample size. Furthermore, no hard conclusion could be obtained on the influence of induction therapy on technical failure as two out of the three cases with adverse effect were treated with thymoglobulin, which has potential broad anti-inflammatory properties that have been shown to reduce ischemia-reperfusion injury , 40. A lIn conclusion, the fruits of this study indicate a trend towards a better graft and patient survival among IGL-1 recipients. Besides, IGL-1 composition is similar to that of the UW solution, currently considered as the “gold standard” in the reduction ischemia-reperfusion injury of the pancreas. Hence, successful PTx can be safely performed using IGL-1 solution. Further multicenter studies are still required to identify the “holy grail” of preservation solutions, especially in the current scenario of using marginal donors, including donors following circulatory death, in which the graft is exposed to a warm ischemia insult before cold storage, raising susceptibility to graft dysfunction.


Objective: The aim of this systematic review was to summarize the literature regarding the clinical performance of zirconia crowns for primary teeth. Materials and Methods: Four electronic databases, Ovid, PubMed, Scopus, and Web of Science were searched. Clinical, observational, and laboratory studies were included. Studies that assessed the performance of zirconia crowns for primary teeth using outcomes such as gingival and periodontal health, parental satisfaction, color stability, crown retention, contour, fracture resistance, marginal integrity, surface roughness, and recurrent caries were included. Risk of bias was assessed using different assessment tools depending on the type of the assessed study. Results: Out of the 2400 retrieved records, 73 full-text records were assessed for eligibility. Thirty-six studies were included for qualitative analysis. The included studies reported that zirconia crowns for primary teeth were associated with better gingival and periodontal health, good retention, high fracture resistance, color stability, high parental acceptance, good marginal adaptation, smooth cosmetic surface, and no recurrent caries. Conclusion: Zirconia crowns are promising alternative to other restorative materials and crowns in the field of pediatric dentistry. They showed higher properties and performance in different clinical aspects and great parental satisfaction. Dental caries is considered the most common infectious disease globally ,2,3. IntThe most widely recognized full coverage restoration method used in pediatric dentistry is the use of stainless steel crowns ,11. StaiDespite the favorable qualities mentioned above, stainless steel crowns have some drawbacks, including their poor esthetic appearance. This led their rejection by most parents as they are becoming more engaged in the treatment planning for their children and more considerate of their esthetic appearance ,21,22,23Zirconia crowns were introduced in 2008 as an alternative restorative treatment. Zirconia has an extensive history of being an excellent biocompatible material . One of Zirconia as a material demonstrated excellent mechanical properties. Its flexural strength could reach up to 1200 MPa, and its toughness may reach up to 10 MPa ,34. WhenZirconia crowns are relatively a new topic in pediatric dentistry. In this review, we aimed to review the literature systematically and explore the performance of zirconia crowns for primary teeth in clinical or laboratory settings. Different outcomes measures were considered for a comprehensive review.Population: Primary teeth OR pediatric patients OR extracted teeth.Intervention: Pediatric zirconia crowns.Comparator: Other restorative materials OR crowns.Outcomes: Periodontal health, parental satisfaction, color stability, crown retention, contour, fracture resistance, marginal integrity, surface roughness, and recurrent caries.The review protocol was preset but not published. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews and meta-analysis were followed. The PICO question of this systematic review was:Four search strategies were built and applied for the following databases: PubMed, Web of Science, Scopus, and Ovid . The lasIn this systematic review, we included any relevant articles focused on prefabricated/ready-made zirconia crowns as permanent coverage crowns for primary teeth as interventions, with any other crown types or restorations as a comparison or no comparison. Clinical, observational, and laboratory in vitro studies were included with no restrictions used for language or the type of study. Clinical studies with special health care patients and studies on pediatric patients with permanent teeth only were excluded.The citations were then uploaded to the Covidence online platform for title and abstract screening. Two reviewers screened the titles and abstracts independently, and any conflict was resolved by a senior reviewer. The included citations were then screened as full texts.The data was extracted from the included studies by four reviewers. The extracted data included qualitative and quantitative data. The extracted data included publication date, sample size, size of each group, sex distribution, age, interventions, outcome parameters, and outcome findings.The risk of bias of the included studies was assessed by two independent reviewers. The assessment tools were adapted the Cochrane assessment tools for the included clinical and observational studies and from previously published scoping and systematic reviews for the laboratory studies ,36. Clin2 statistic at or below 50% was found with no significant methodological heterogeneity or an I2 statistic was found to be above 50% with no significant methodological heterogeneities, respectively. However, if significant statistical or methodological heterogeneity was found, a meta-analysis was not conducted.A qualitative summary of the included studies’ characteristics and findings was reported. We performed a quantitative meta-analysis using a fixed-effect model or a random-effect model if an IFrom the initial database searches, 2400 records were retrieved. Duplicates were removed, and 1877 records left for title and abstract screening. After title and abstract screening, full texts of 73 records were assessed for eligibility . Thirty-The characteristics of the included studies are presented in The quality assessments of the individual included studies are shown in Thirteen studies assessed gingival and periodontal health when placing different types of zirconia crowns. The assessment time varied between 1 week and 36 months after crown placement. Two studies ,53 showeEight studies evaluated the level of parental satisfaction of zirconia crowns. It was shown that zirconia crowns had a higher satisfaction rate than different control groups in all studies ,59,64,66Nine studies investigated the color stability and stain resistance when using zirconia crowns. The evaluation time was between 1 and 36 months after crown placement. All studies reported high color stability and stain resistance of zirconia crowns ,62,63,64Thirteen studies assessed the retention of zirconia crowns. The assessment time varied between 1 week and 36 months after crown placement. One randomized clinical trial showed that zirconia crowns had a statistically significant higher retention rate when using packable glass ionomer . Two ranEleven studies evaluated the fracture resistance of zirconia crowns. The evaluation time was between 1 week and 36 months. One randomized clinical trial showed high fracture resistance of zirconia crowns , and twoEight studies assessed the marginal integrity of zirconia crowns. The assessment time ranged from 3 to 33.8 months. One laboratory study showed that zirconia crowns cemented with resin cement had a statistically significant lower internal gap width than the control group . and fouFour studies investigated the presence of surface roughness among zirconia crowns. One randomized clinical trial showed that all zirconia crowns exhibited a smooth surface except two crowns that showed slight roughness but were clinically acceptable. However, the difference was not statistically significant when compared to the control group . A summaFour studies evaluated the presence of recurrent caries with different types of zirconia crowns. The follow-up time ranged from 3 to 24 months. It was shown that zirconia crowns did not cause recurrent caries in all included studies. One study showed a statistically significant difference between zirconia crowns and the control groups . SupplemTwo retrospective studies assessed the crown contour of zirconia crowns, and the majority were natural looking and cosmetic ,63. Suppp = 0.115; I2 = 53.8%) and 12  months, and for the recurrent caries at 6  and 12  months.Four meta-analyses were performed . Two anaZirconia crowns for primary teeth are in high demand from parents who seek more esthetically pleasant dental restorations for their children. Research has been undertaken to compare the properties of zirconia crowns for primary teeth with other similar restorations such as stainless steel crowns. This systematic review aimed to summarize the performance of zirconia crowns for primary teeth by reporting the findings in the literature of 3575 teeth that were included regarding their different clinical aspects and parental satisfaction. These clinical aspects include gingival and periodontal health, color stability, retention, fracture resistance, marginal integrity, restoration failure, surface roughness, recurrent caries, and crown contour.Zirconia crowns are indicated as the same as any other available type of crown in pediatric dentistry. However, there are some potential drawbacks of zirconia crowns such as the difficulty of adjustments to provide mechanical retention in contrast to stainless steel crown, the limitation of the shades available in the clinics, and the prolonged procedure time. The zirconia crowns require more tooth structure reduction to accomplish better adaptation. Pulpal exposure and postoperative complications also have been noted during the preparation for zirconia crowns . Even wiOne of the important parameters to assess in a crown is its effect on gingival and periodontal health. An ideal material for a crown would have no plaque accumulation on the surface. Different materials used for crowns may have different properties leading to different plaque accumulation amounts. Other factors such as types of cements also may affect periodontal health. In this review, we found that most of the included studies found that zirconia crowns had significantly lower levels of plaque accumulation, especially when compared to resin-coated crowns . This coIn this review, nearly all included studies showed greater parental acceptance of zirconia crowns compared to other treatment modalities, even when other esthetic restorations such as pre-veneered stainless steel crowns were offered or used. Zirconia crowns scored the highest satisfaction rates for the parents and their children ,21,37,40The review findings also showed that zirconia crowns have a high degree of color stability. This factor can be considered when offering zirconia as an esthetic solution to parents when compared to other crowns such as the resin-coated stainless steel crowns. Zirconia crowns exhibit a highly polished surface that prevents staining and color deterioration . With stThe color change of the latter can negate the original purpose of the resin as an esthetic solution as resin is prone to staining over time when exposed to agents such as coffee or dark soft drinks ,74.Although some studies have shown that the stainless steel crowns have a higher retention rate than the zirconia crown, the retention of the zirconia crown is acceptable. This is because the clinician is unable to crimp and counter the crown clinically to adapt it to the tooth and must rely upon the prefabricated form of the crown. This is also considering the relatively short period of time that the restoration will be in the patient mouth as the deciduous tooth will be exfoliated in a couple of years. Regardless, stainless steel crowns facilitate its retention through crimping and contouring while zirconia crowns require greater tooth reduction to create more surface area for cement anchorage ,32,39. FThe included studies in this review showed high fracture resistance of zirconia crowns for primary teeth. This may make them a good alternative to resin restorations in patients with grinding habits. Although some studies suggest that ceramic compounds can produce a degree of wear on the opposing teeth , a revieIn this review, meta-analyses were conducted on two parameters: the retention of zirconia crowns and the rate of recurrent caries. Both parameters were comparable to control treatments used in the included studies. However, more randomized clinical trials are recommended as only a few studies were included in these analyses as most of the clinical trials did not have control groups to compare the performance of zirconia crowns for primary teeth. The follow-up periods in the included studies in the meta-analyses were at 6 and 12 months. The total number of the included zirconia crowns assessed for retention were 83 crowns at 6-month follow-up and 78 crowns at the 12-month follow-up period with a total of 118 control crown/teeth at 6-month and 78 crowns/teeth at 12-month follow-up periods. For the recurrent caries assessment, intervention and control groups were almost similar in the number of included crowns/teeth which was around 100.It is important to point out the variation between the included studies in terms of age groups of the included patients. It was observed that participants’ ages ranged from three to nine years old. Additionally, the variation in the study types ranging from split-mouth design to observational design should be considered as this may affect the interpretation of the findings.This review was limited by several factors including the focus on only articles in English language and the lack of search in gray literature which may leave some evidence unavailable. However, this review included a larger number of studies than the previously published review . AdditioIn conclusion, zirconia crowns are a promising alternative to other restorative materials and crowns in the field of pediatric dentistry. They showed greater properties and performance in terms of different clinical aspects and great parental satisfaction. However, there is a need for more randomized clinical trials that assess the various clinical aspects of primary teeth zirconia crown performance in comparison to other types of crowns or restorations for primary teeth. Additionally, further clinical studies with longer follow-up periods are needed. When considering zirconia crowns as an alternative to other materials and crowns for primary teeth, length of procedure, expensive cost, and dentist skills should be considered, especially for primary teeth.


Canadian Journal of Pain, the official journal of the Canadian Pain Society. The Canadian Pain Society has been without a journal for approximately one year—and it would have been much longer—but thanks to the Board of Directors of the Canadian Pain Society, and in particular to Professor Jeffrey Mogil’s tireless efforts, we’re delighted to have found a home with Taylor & Francis for the new Journal. It’s especially pleasing for me to be the inaugural Editor-in-Chief because of Canada’s longstanding reputation as a leader in the field, having produced so many outstanding pain scientists and clinicians over the years.It’s an honor and a pleasure to have been selected as the inaugural Editor-in-Chief of the Canadian Journal of Pain is a peer-reviewed, Open Access journal that publishes original articles from all disciplines involved in the study of pain, including the clinical and basic sciences, epidemiology, and health policy and health systems. The Journal welcomes manuscripts presenting data from original experiments, studies, or clinical trials and will also publish scholarly review articles, meta-analyses, case series and reports, commentaries, editorials, and letters to the editor. The aims of the Journal are to advance the understanding and treatment of pain by providing clinicians, scientists and other health care professionals with an interdisciplinary forum in which to share cutting-edge information about new developments in the field of pain.The Journal to showcase the research of our many talented members. Of course we’re “open for business” to the international community as well and we welcome manuscripts from all over the world.The new Canadian Pain Society journal will give our members a high-quality outlet for their research and, at the same time, allow the Canadian Journal of Pain:Journal is fully Open Access so authors retain copyright of their own work and are permitted unrestricted use, distribution, and reproduction provided the original work is properly cited;The Taylor & Francis has waived publication fees for 2017 and has reduced the fees for 2018;Journal;The Editorial Board is a “who’s who” of pain, including world-renowned scientists and clinicians committed to upholding the high standards of the Experienced manuscript reviewers and receptive editorial staff who will work with authors to ensure as positive an experience as possible;An expeditious and streamlined review process overseen by highly experienced editorial staff to minimize time from manuscript submission to publication;Option to submit and publish a manuscript in French;Journal will have their abstracts translated into French at no cost to the authors;Articles published in the Canadian Journal of Pain providing the international community with free and open access to the meeting’s content, and presenters with a permanent record of their poster and podium presentation abstracts.Each year, the Canadian Pain Society will publish the abstracts of its annual meeting in the There are many advantages to publishing in the Canadian Journal of Pain is an attractive and reliable outlet for publishing pain-related content in today’s competitive market. Moreover with the recent demise of Beall’s list of “predatory” publishers and journals, authors seeking publication will have an increasingly difficult time discerning legitimate journals from those that exploit the world of publishing, making the Canadian Journal of Pain a logical and trustworthy choice.Taken together, the Canadian Journal of Pain will be a trusted and highly-respected outlet for innovative ideas and empirical research in the field of pain. We look forward to receiving your manuscripts and to working with you as we strive for a painless publishing experience.I am confident that within a few short years the


Full thickness skin grafts (FTSGs), although ideal for resurfacing large defects of the distal extremities in veterinary patients, have a high failure rate due to issues of adherence, infection and inadequate revascularisation because of its thickness and high nutritional demand. This study investigated the effect of Nigeria bee honey on FTSG take at the distal extremities of dogs. The study was conducted on 6 adult male Nigerian indigenous dogs using 3 of the 4 limbs of each dog randomly divided into 3 treatment groups: Nigerian bee honey (HON group), platelet-rich plasma (PRP group) and normal saline (CON group). Full‐thickness skin wounds (3 cm × 1.5 cm) were created on the lateral aspect of the radioulnar or metatarsal areas and dressed till adequate granulation tissues formed. Donor skins harvested from the lateral thorax of each dog were sutured to the recipient bed following application of the assigned treatment, and evaluated grossly and histologically on days 0, 4, 7, 10, 14, 17, and 21.p = 0.022) in percentage necrosis between the CON and HON/PRP groups on day 10, 14 and 17. The percentage open mesh area for the HON group was significantly lesser at day 4, 7 and 10 when compared with CON (p < 0.001) and at day 4 when compared with PRP (p = 0.001). At histology, graft neovascularisation score was highest in the HON group on days 4, 14 and 21.A higher percentage (4/6 representing 66.7%) of complete graft take was observed in the HON and PRP groups as compared to 3/6 (50%) in the CON group. The HON group had a greater percentage (5/6 representing 83.3%) of adhered grafts as compared to the PRP (4/6 representing 66.7%) and CON (3/6 representing 50%) groups at day 4. There was a significant decrease (Nigeria bee honey enhanced take of meshed full-thickness skin autografts by promoting adherence to the recipient bed, enhancing fibroblast proliferation and collagen laydown, and accelerating the rate of neovascularisation suggesting promising application as an alternative modality to enhance FTSG take.The online version contains supplementary material available at 10.1186/s12917-022-03192-w. Managing wounds of the extremities is relatively more challenging than other anatomical areas due to the limited amount of skin in the region , 2. MostFree skin grafts are classified into two main groups: full-thickness skin grafts (FTSGs) and partial/split-thickness skin grafts (STSGs), depending on the layers of skin harvested from the donor site –7. FTSGsA major challenge of FTSGs is the greater chance of graft failure attributed mostly to its thickness . Due to Due to the tendency of FTSGs to fail, techniques, as well as the use of natural products, for enhancing FTSG take are constantly being studied. The use of vasoendothelial growth factor (VEGF) , 17, fibHoney has been widely studied for its anti-inflammatory, tissue regeneration, angiogenic and epithelisation properties –26. HoneOut of the 18 wounds grafted at the distal extremities of the dogs, 11 (61.1%) had complete graft take, 5 (27.8%) had partial graft take while graft loss occurred in the remaining 2 (11.1%). The HON and PRP groups had higher percentages of complete graft take with 4 out of 6 (66.7%) each as compared to the CON group which had 3 out 6 (50%) complete graft take. Partial graft take was recorded in 2 out of 6 (33.3%) each for the CON and PRP groups, and 1 out of 6 (16.7%) in the HON group while graft loss was recorded in 1 out of 6 (16.7%) each in the CON and HON groups.Grafts were non-mobile (adhered to the recipient bed) in 3 (50%) and 4 (66.7%) out of 6 in the CON and PRP groups respectively and 5 out of 6 (83.3%) in the HON group on day 4. All 16 grafts with complete or partial graft take were non-mobile by day 7.Seroma was observed beneath the graft in 3 out of 6 for the CON group and 2 out of 6 for the PRP and HON groups. Seroma was present at both day 4 and 7 in 1 CON graft with all others present on day 4 only. Wound fluid across all the groups was minimal in quantity, pink or brown in colour and serosanguineous in nature on days 4 and 7 with the secondary layer appearing dry and clean by day 10, indicating cessation.The mean scores of graft colour at each day of dressing is presented in Table p = 0.022) between the CON and HON/PRP groups on day 10, 14 and 17  in open mesh area between the CON and HON groups on day 4, 7 and 10, and between the CON/PRP and HON groups on day 4 (p = 0.001). Re-epithelisation in the HON group was near complete by day 10. Re-epithelisation of grafts was more rapid in the HON and PRP groups between day 4 and 14 in comparison to the CON group which was gradual and complete by day 17  was marked in all the 3 groups on day 4, but progressively decreased from day 4 to 14. Full thickness epidermal architecture, including that of follicular epithelium was more well-structured by day 10 in the HON group in comparison to the PRP and CON groups Fig. . HoweverInflammatory cells, especially macrophages were observed from day 4 with a gradual decrease from day 4 to day 17. There was a gradual non-significant increase in fibroplasia and collagen laydown in all the groups from day 10 to 21 . The HON and CON groups had marked macrophage infiltration without collagen laydown on day 4 while the PRP group had mild collagen laydown and moderate macrophage infiltration Fig. . On day Graft neovascularisation score was higher in the HON group in comparison to the CON and PRP groups at all biopsy time points except on Day 10 when both HON and PRP had a mean score of 1.0 .The results of this study show that honey enhanced graft take of meshed FTSGs by promoting early graft adherence, accelerating the rate neovascularisation and epithelisation, and facilitating good hair regrowth after healing.In this study, graft take was classified as complete if there was full-thickness graft viability over more than three-quarters of the original (day 0) graft area on day 14 post-grafting  and partial where full-thickness graft viability was less than 3-quarters of the day 0 graft area and/or if there was epidermal sloughing . PreviouGraft adherence to the recipient bed is of utmost importance during the initial phases of graft healing before complete reattachment and revascularisation occurs. In this study, a higher percentage (83.3%) of non-mobile (adhered) grafts was observed in the HON group as compared with the PRP (57.1%) and CON 42.9%) groups at day 4. The first 48 to 72 h are very crucial to the survival of skin grafts, and the extent of adequate nutrition of the graft is solely dependent on how firmly adhered the graft is to the recipient bed , 40. Dur.9% groupThe presence of seroma or haematoma between the graft and recipient bed affects graft adherence and results in graft failure. The seroma creates a gap between the graft tissue and the recipient bed structures thus preventing plasmatic imbibition, capillary inosculation and revascularisation , 43. In Postoperative immobilisation is important to the graft healing process as it helps in reducing possible micro and macro movements that may disrupt the process of inosculation , 41. IncRevascularisation after skin grafting is reported to occur as early as 22 h post-grafting and depends on adequate undisrupted adherence, a healthy and well-vascularised recipient bed and rate of neoangiogenesis , 46, 50.p = 0.022) in percentage necrosis between the HON/PRP and CON groups on day 10, 14 and 17  present in honey [The rate of neovascularisation was assessed both qualitatively and quantitatively using graft colour and percent necrosis at each dressing change, respectively. Although there was no significant difference between groups for graft colour at all time points, clinically observable differences were notable at all dressing changes with the HON group returning more rapidly to a healthy pink colour Table , indicatin honey .p < 0.001) between the CON and HON groups on day 4, 7 and 10, and between the PRP/CON and HON groups on day 4 (p = 0.001) for percentage open mesh area. The increase in area of open mesh observed in the PRP and CON groups but not in the HON group on day 4 is worthy of note. Stanley et al. [The rate of re-epithelisation of meshed grafts is an indication of the rate of healing  There way et al.  observedy et al. . Nigeriay et al. , 33. HeaHistologically, there was no significant difference between the treatment groups for HAIS and HRS . However, it was observed that the PRP and HON groups had more fibroblast/fibrocytes proliferation in comparison to the CON group on day 10 Fig. . By day All grafts with complete or partial take were healed by day 21, assuming the original pigmentation of the donor skin . Grafts in the HON groups also had good hair regrowth, comparable to the PRP group. The extra cost involved with using PRP  and lack of constant electricity in most developing countries makes honey a better alternative for enhancing graft take.Nigeria bee honey enhances take of meshed full-thickness skin autografts, primarily within the first week of grafting, by promoting adherence of the graft to the recipient bed, neovascularisation, fibroblast proliferation and collagen laydown. Being readily available, honey can therefore be used as an alternative to more sophisticated and relatively more expensive modalities to enhance FTSG take.Ethical clearance (UI-ACUREC/19/0152) was obtained from the Animal Care and Use Research Ethics Committee (ACUREC) of the University of Ibadan, Nigeria. All methods were performed in accordance with the relevant guidelines and regulations stipulated in the ARRIVE guidelines.Six apparently healthy entire adult male Nigerian indigenous dogs weighing 8 ± 2 kg with body condition scores 4–5 out of 9 were purchased from previous owners and housed in well-aerated dog kennels for the whole duration of the study. The dogs were acclimatised for 2 weeks before the commencement of the study, during which they were properly dewormed, vaccinated for rabies, treated for ectoparasites and conditioned to their housing, feeding and social enrichment routines. The dogs were fed with a home-cooked diet  once daily, and water was provided ad libitum. Social enrichment consisted of petting and communal interactions with one another once daily. The dogs were adjudged to be healthy based on clinical evaluation  before the commencement of the study.n = 6)  of each dog were used. A total of 18 wounds were created, 1 wound per limb, and divided into 3 treatment groups (Preparation Of platelet-rich plasma (PRP).Platelet-rich plasma (PRP) was prepared according to a modified double centrifugation protocol described by Perazzi et al. . Eight mCrude Nigeria bee honey was purchased from a local apiary in Ibadan, Oyo Sate, Nigeria. The honey was sieved with a fine muslin cloth to remove all bee remnants and stored in a tightly sealed container for use.Each dog was premedicated with 5% Tramadol , 0.1% Atropine Sulphate  and 2% Xylazine HCl  at dosages of 5 mg/kg, 0.04 mg/kg and 2 mg/kg respectively via intramuscular (IM) injection. An intravenous (IV) line of Lactated Ringer’s solution  was set at 5 ml/kg/hr via the left lateral saphenous vein using a 20G catheter. Anaesthesia was achieved and maintained with 5% Ketamine  at a dose of 10 mg/kg IM injection. The hair on two forelimbs and right hindlimb were clipped, aseptically prepared  and draped for surgery, from just above the elbows/hock to the proximal phalanges.With the dogs on left lateral recumbency, 3 cm × 1.5 cm full-thickness skin wounds were created on the lateral aspects of the right fore- and hindlimbs with a size 21 scalpel blade, using a sterile template, and the underlying subcutaneous fascia were removed to simulate a degloving injury. Following adequate wound irrigation, the wounds were dressed by an assistant and the dogs were turned over unto right lateral recumbency to repeat the procedure on the left forelimb.The wounds were bandaged following creation. Bandaging consisted of a primary layer of sterile 5 cm x 3 cm gauze, a secondary layer of cotton padding and a tertiary layer of Crepe bandage held in place with circumferential strips of adhesive tape. Bandages were changed 24 h later and thereafter on alternate days for 5 to 6 days until adequate granulation tissues were formed after which the wounds were grafted.Following anaesthesia and patient positioning on lateral recumbency, the wound beds were prepared by creating fresh bleeding edges and undermining the skin around the wound through blunt-sharp dissection with Mayo scissors prior to harvesting of skin from the donor site. The wound was thoroughly irrigated with normal saline and covered with a saline-moistened sterile gauze while the donor skin was prepared and harvested.Donor skin harvesting consisted of using a sterile template to mark a 9 cm × 4.5 cm area of skin on the right lateral thorax while paying attention to hair direction and colour. Three sides of the demarcated area were incised using a scalpel blade. The resultant flap of skin was elevated by grasping the two vertices with Allis tissue forceps and separating the skin from the subcutaneous fascia via blunt-sharp dissection using scissors. The elevated skin flap was prepared for free skin grafting by meticulously removing all subcutaneous fascia and attached sub‐dermal remnants with scissors until the hair follicles were visible (cobblestone appearance) Fig. .Fig. 10IThe grafting procedure for each limb commenced with excising a 3 cm × 1.5 cm skin section from the elevated flap, and making 8 parallel stab incisions using a size 11 scalpel blade (meshing) as previously described . Each meFollowing sterilisation of the skin around each wound with povidone-iodine solution, treatments were applied to the assigned wounds by dropping the required volume  at the open mesh area with a 1 ml syringe and spreading it beneath the graft to form a thin layer between the donor skin and the recipient bed on day 0 of grafting prior to wound dressing. Wound dressing consisted of a single primary layer of non-adherent petrolatum-impregnated tulle gras and normal gauze, a secondary layer of cotton padding, and a tertiary layer of Crepe bandage taped with Pet Flex no chew veterinary adhesive bandage . The first dressing change was at day 4 after skin grafting and repeated on days 7, 10, 14, 17 and 21. Treatments were applied  on the surface of grafted area before wound dressing. Sutures for both the grafted wound and donor sites were removed on day 14 post-grafting.Amoxicillin  was administered at 15 mg/kg IM injection twice daily for 5 days. Pain was controlled with 5% Tramadol at a dosage of 5 mg/kg via IM injection once daily for 3 days.Qualitative  and quantitative (rate of wound epithelisation and neovascularisation) assessment protocols, including histopathological evaluation were used. Graft take was defined as complete (where there was full-thickness graft viability over more than three-quarters of the day 0 graft area on day 14 post-grafting), partial  and lost (where there was complete loss of the graft tissue).Graft adherence was assessed on Day 4 post-grafting as previously described  by applyA modified graft health evaluation form was used to record wound exudation, colour and nature, appearance of secondary dressing layer, graft oedema and hydration, and appearance of the skin around the wound at each dressing change. Seromas that developed under the grafts were treated by aspirating the fluid using a 30-gauge 1 ml syringe. Digital photographs were also taken at time of dressing, and qualitative assessments (scoring) of graft colour (Table http://www.digimizer.com) using the digital photographs taken at each dressing. The total area of graft (cm2), total area of graft necrosis (cm2) and total area of open mesh (cm2) were measured and used to determine the percentage necrosis and open mesh area using Eqs. Wound measurements were performed with downloadable software  for microscopic evaluation of inflammation and repair using a modified semi-quantitative scoring system , 61.To evaluate inflammation, inflammatory cell infiltration and degree of haemorrhage and necrosis were scored as follows: 0 = none, 1 = minimal, 2 = moderate, and 3 = marked. The individual scores were then summed to formulate a histologic acute inflammation score (HAIS) with range 0–9. For tissue repair, fibroblast proliferation, collagen density and neovascularisation were compared with the day 0 sample and scored as follows: 0 = absent, 1 = mild, 2 = moderate and 3 = marked. These were also summed to formulate a histologic repair score (HRS) with range 0–9.p < 0.05) were followed by post-hoc multiple comparison test.Numerical variables (percentage open mesh area and percentage necrosis) were expressed as mean ± standard error while the non-numerical variables were expressed as ordinal scores. Statistical significance between groups was assessed using 3 factor ANOVA with the fixed factors of group and time and the random factor of dog with SPSS v16 for windows. Statistically significant differences  and Histologic Repair Score (HRS).