β-catenin and transforming growth factor β have distinct roles regulating fibroblast cell motility and the induction of collagen lattice contraction

<p>Abstract</p> <p>Background</p> <p>β-catenin and transforming growth factor β signaling are activated in fibroblasts during wound healing. Both signaling pathways positively regulate fibroblast proliferation during this reparative process, and the effect of transforming growth factor β is partially mediated by β-catenin. Other cellular processes, such as cell motility and the induction of extracellular matrix contraction, also play important roles during wound repair. We examined the function of β-catenin and its interaction with transforming growth factor β in cell motility and the induction of collagen lattice contraction.</p> <p>Results</p> <p>Floating three dimensional collagen lattices seeded with cells expressing conditional null and stabilized β-catenin alleles, showed a modest negative relationship between β-catenin level and the degree of lattice contraction. Transforming growth factor β had a more dramatic effect, positively regulating lattice contraction. In contrast to the situation in the regulation of cell proliferation, this effect of transforming growth factor β was not mediated by β-catenin. Treating wild-type cells or primary human fibroblasts with dickkopf-1, which inhibits β-catenin, or lithium, which stimulates β-catenin produced similar results. Scratch wound assays and Boyden chamber motility studies using these same cells found that β-catenin positively regulated cell motility, while transforming growth factor β had little effect.</p> <p>Conclusion</p> <p>This data demonstrates the complexity of the interaction of various signaling pathways in the regulation of cell behavior during wound repair. Cell motility and the induction of collagen lattice contraction are not always coupled, and are likely regulated by different intracellular mechanisms. There is unlikely to be a single signaling pathway that acts as master regulator of fibroblast behavior in wound repair. β-catenin plays dominant role regulating cell motility, while transforming growth factor β plays a dominant role regulating the induction of collagen lattice contraction.</p

Gene Polymormisms and Prostate Cancer: A Systematic Review

Introduction: The prostate is a gland that surrounds men's urethra and helps to produce semen. In developed countries, prostate cancer (PCa.) is the second most common and lethal disease in men. Hereditary history of PCa. is a major contributor to this cancer? While a number of genetic and molecular changes have been reported in PCa, the general picture of the genetic aberrations is needed in Iranian population.Methods: In this study, a literature search from Jan. 2000 to June 2018 was performed through the PubMed, Google Scholar, Scopus, Web of Science, IranMedex, MEDLIB, IranDoc and Scientific Information databases using the keywords “genetic polymorphisms”, “prostate cancer”, “Iranian, and compare with regional and international population”.Results: The results revealed that several genome-wide association studies (such as rs2070744 and rs1799983 in the eNOS, rs243865 in the MMP2, rs1902023 in the UGT2B15, rs266882 in the PSA, rs10625775443 in the GNB3, rs 1800682 in the FAS, rs12052398 and rs13393577 in the ERBB4, rs181133 in the MTHFR, rs 1805087 in the MTR, rs1805355 in the MSH3, (rs60271534 in the CYP19, rs2234693 and rs9340799 in the ER-a, rs4986938 and rs1256049 in the ER-b) and single-nucleotide polymorphisms in important pathways (such as angiogenesis, androgen receptor binding site, cell signaling, folate metabolism, DNA repair, hormone synthesis and metabolism polymorphisms ) involved in prostate cancer occurrence and mechanism could serve as candidate biomarkers for the detection of PCa. The most important results of the all studied articles is summarized in Table 1 and 2.Conclusion: Several studies have been conducted on the family history of PCa. The main reason for this gathering is to inherit the involved genes. Additional studies are required to decipher precisely the gene combinations and personalize the management of prostate cancer. This article is the first comprehensive overview of genetic investigations of gene polymorphisms on PCa. in Iran.

5-HT1A Receptor Function Makes Wound Healing a Happier Process

Skin wound healing is a multistage phenomenon that is regulated by cell–cell interplay and various factors. Endogenous serotonin is an important neurotransmitter and cytokine. Its interaction with the serotonin 1A receptor (5-HTR1A) delivers downstream cellular effects. The role of serotonin (5-hydroxytryptamine, 5-HT) and the 5-HT1A receptor has been established in the regeneration of tissues such as the liver and spinal motor neurons, prompting the investigation of the role of 5-HT1A receptor in skin healing. This study assessed the role of 5-HT1A receptor in excisional wound healing by employing an excisional punch biopsy model on 5-Ht1a receptor knockout mice. Post-harvest analysis revealed 5-Ht1a receptor knockout mice showed impaired skin healing, accompanied by a greater number of F4/80 macrophages, which prolongs the inflammatory phase of wound healing. To further unravel this phenomenon, we employed the 5-HT1A receptor agonist [(R)-(+)-8-Hydroxy-DPAT hydrobromide] as a topical cream treatment in an excisional punch biopsy model. The 5-HT1A receptor agonist treated group showed a smaller wound area, scar size, and improved neovascularization, which contributed to improve healing outcomes as compared to the control. Collectively, these findings revealed that serotonin and 5-HT1A receptor play an important role during the healing process. These findings may open new lines of investigation for the potential treatment alternatives to improve skin healing with minimal scarring

Ultrafast Mid-IR Laser Scalpel: Protein Signals of the Fundamental Limits to Minimally Invasive Surgery

Lasers have in principle the capability to cut at the level of a single cell, the fundamental limit to minimally invasive procedures and restructuring biological tissues. To date, this limit has not been achieved due to collateral damage on the macroscale that arises from thermal and shock wave induced collateral damage of surrounding tissue. Here, we report on a novel concept using a specifically designed Picosecond IR Laser (PIRL) that selectively energizes water molecules in the tissue to drive ablation or cutting process faster than thermal exchange of energy and shock wave propagation, without plasma formation or ionizing radiation effects. The targeted laser process imparts the least amount of energy in the remaining tissue without any of the deleterious photochemical or photothermal effects that accompanies other laser wavelengths and pulse parameters. Full thickness incisional and excisional wounds were generated in CD1 mice using the Picosecond IR Laser, a conventional surgical laser (DELight Er:YAG) or mechanical surgical tools. Transmission and scanning electron microscopy showed that the PIRL laser produced minimal tissue ablation with less damage of surrounding tissues than wounds formed using the other modalities. The width of scars formed by wounds made by the PIRL laser were half that of the scars produced using either a conventional surgical laser or a scalpel. Aniline blue staining showed higher levels of collagen in the early stage of the wounds produced using the PIRL laser, suggesting that these wounds mature faster. There were more viable cells extracted from skin using the PIRL laser, suggesting less cellular damage. β-catenin and TGF-β signalling, which are activated during the proliferative phase of wound healing, and whose level of activation correlates with the size of wounds was lower in wounds generated by the PIRL system. Wounds created with the PIRL systsem also showed a lower rate of cell proliferation. Direct comparison of wound healing responses to a conventional surgical laser, and standard mechanical instruments shows far less damage and near absence of scar formation by using PIRL laser. This new laser source appears to have achieved the long held promise of lasers in minimally invasive surgery

Familial Adenomatous Polyposis-Associated Desmoids Display Significantly More Genetic Changes than Sporadic Desmoids

Desmoid tumours (also called deep or aggressive fibromatoses) are potentially life-threatening fibromatous lesions. Hereditary desmoid tumours arise in individuals affected by either familial adenomatous polyposis (FAP) or hereditary desmoid disease (HDD) carrying germline mutations in APC. Most sporadic desmoids carry somatic mutations in CTNNB1. Previous studies identified losses on 5q and 6q, and gains on 8q and 20q as recurrent genetic changes in desmoids. However, virtually all genetic changes were derived from sporadic tumours. To investigate the somatic alterations in FAP-associated desmoids and to compare them with changes occurring in sporadic tumours, we analysed 17 FAP-associated and 38 sporadic desmoids by array comparative genomic hybridisation and multiple ligation-dependent probe amplification. Overall, the desmoids displayed only a limited number of genetic changes, occurring in 44% of cases. Recurrent gains at 8q (7%) and 20q (5%) were almost exclusively found in sporadic tumours. Recurrent losses were observed for a 700 kb region at 5q22.2, comprising the APC gene (11%), a 2 Mb region at 6p21.2-p21.1 (15%), and a relatively large region at 6q15-q23.3 (20%). The FAP-associated desmoids displayed a significantly higher frequency of copy number abnormalities (59%) than the sporadic tumours (37%). As predicted by the APC germline mutations among these patients, a high percentage (29%) of FAP-associated desmoids showed loss of the APC region at 5q22.2, which was infrequently (3%) seen among sporadic tumours. Our data suggest that loss of region 6q15-q16.2 is an important event in FAP-associated as well as sporadic desmoids, most likely of relevance for desmoid tumour progression

Advances in Liver Regeneration: Revisiting Hepatic Stem/Progenitor Cells and Their Origin

The liver has evolved to become a highly plastic organ with extraordinary regenerative capabilities. What drives liver regeneration is still being debated. Adult liver stem/progenitor cells have been characterized and used to produce functional hepatocytes and biliary cells in vitro. However, in vivo, numerous studies have questioned whether hepatic progenitor cells have a significant role in liver regeneration. Mature hepatocytes have recently been shown to be more plastic than previously believed and give rise to new hepatocytes after acute and chronic injury. In this review, we discuss current knowledge in the field of liver regeneration and the importance of the serotonin pathway as a clinical target for patients with liver dysfunction.Peer Reviewe