Macrophage-Mediated Inflammation in Skin Wound Healing.

Macrophages are key immune cells that respond to infections, and modulate pathophysiological conditions such as wound healing. By possessing phagocytic activities and through the secretion of cytokines and growth factors, macrophages are pivotal orchestrators of inflammation, fibrosis, and wound repair. Macrophages orchestrate the process of wound healing through the transitioning from predominantly pro-inflammatory (M1-like phenotypes), which present early post-injury, to anti-inflammatory (M2-like phenotypes), which appear later to modulate skin repair and wound closure. In this review, different cellular and molecular aspects of macrophage-mediated skin wound healing are discussed, alongside important aspects such as macrophage subtypes, metabolism, plasticity, and epigenetics. We also highlight previous studies demonstrating interactions between macrophages and these factors for optimal wound healing. Understanding and harnessing the activity and capability of macrophages may help to advance new approaches for improving healing of the skin.

Whole exome sequencing in 17 consanguineous Iranian pedigrees expands the mutational spectrum of inherited retinal dystrophies.

Inherited retinal dystrophies (IRDs) constitute one of the most heterogeneous groups of Mendelian human disorders. Using autozygome-guided next-generation sequencing methods in 17 consanguineous pedigrees of Iranian descent with isolated or syndromic IRD, we identified 17 distinct genomic variants in 11 previously-reported disease genes. Consistent with a recessive inheritance pattern, as suggested by pedigrees, variants discovered in our study were exclusively bi-allelic and mostly in a homozygous state (in 15 families out of 17, or 88%). Out of the 17 variants identified, 5 (29%) were never reported before. Interestingly, two mutations (GUCY2D:c.564dup, p.Ala189ArgfsTer130 and TULP1:c.1199G > A, p.Arg400Gln) were also identified in four separate pedigrees (two pedigrees each). In addition to expanding the mutational spectrum of IRDs, our findings confirm that the traditional practice of endogamy in the Iranian population is a prime cause for the appearance of IRDs.

Pooled Prevalence of NS5A Resistance-Associated Substitutions in Chronic HCV Genotype 3 Infection: A Study Based on Deposited Sequences in GenBank.

Using direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection results in a high treatment response rate. However, several factors can significantly alter this outcome such as resistance-associated substitutions (RASs) in HCV NS5A gene. This study aimed to evaluate the prevalence of naturally occurring RASs of NS5A in HCV genotype 3 (HCV-3) sequences isolated from individuals with chronic HCV-3 infection. All the registered sequences in the GenBank under "NS5A" AND "Hepacivirus C" query were evaluated and screened, those which followed our inclusion criteria were enrolled in our pooled analysis. The retrieved sequences of included studies were evaluated for substitutions, RASs, and RASs conferring >100 resistance fold change (RASs >100 × ) in NS5A amino acid positions 24, 28, 30, 31, 62, 92, and 93. From 7 enrolled studies, a total of 370 HCV-3a isolates were retrieved and investigated. Forty-eight (13.0%, 95% CI = 9.9-16.8%) isolates harbored NS5A RASs. Moreover, Y93H was the only NS5A RAS >100 × observed in 13 (3.5%, 95% CI = 2.0-5.9%) retrieved sequences. The low frequency of naturally occurring NS5A RASs, especially those with clinical relevance (RASs >100 × ), among individuals with HCV-3 infection and the high rate of treatment response to DAAs suggest not to investigate every individual with HCV-3 infection for NS5A RASs before treatment.

Adipose-derived stem cells for wound healing.

Wound healing is a complex but a fine-tuned biological process in which human skin has the ability to regenerate itself following damage. However, in particular conditions such as deep burn or diabetes the process of wound healing is compromised. Despite investigations on the potency of a wide variety of stem cells for wound healing, adipose-derived stem cells (ASCs) seem to possess the least limitations for clinical applications, and literature showed that ASCs can improve the process of wound healing very likely by promoting angiogenesis and/or vascularisation, modulating immune response, and inducing epithelialization in the wound. In the present review, advantages and disadvantages of various stem cells which can be used for promoting wound healing are discussed. In addition, potential mechanisms of action by which ASCs may accelerate wound healing are summarised. Finally, clinical studies applying ASCs for wound healing and the associated limitations are reviewed.

Association of PNPLA3 rs738409 polymorphism with liver steatosis but not with cirrhosis in patients with HBV infection: Systematic review with meta-analysis.

BACKGROUND: Hepatitis B virus (HBV) infection is a worldwide health issue and is well known for being the main cause of developing secondary liver complications such as cirrhosis and hepatocellular carcinoma (HCC). The PNPLA3 rs738409 polymorphism has been investigated conclusively with occurrence risk of steatosis and cirrhosis. Therefore, performing a meta-analysis of the available studies with the aim of clarifying the association between rs738409 and occurrence risk of steatosis and cirrhosis among HBV-infected patients would be helpful. METHODS: Chronic HBV infection was defined as the persistence of HBsAg for more than 6 months. To gather sufficient data for this meta-analysis, reliable databases were conclusively searched using appropriate keywords. Only studies that satisfied the inclusion criteria were enrolled in the present study. RESULTS: This meta-analysis pooled four studies with 1135 cases of chronic hepatitis B (CHB) to evaluate the impact of PNPLA3 SNP on liver steatosis and also pooled five studies with 3713 cases of CHB to evaluate the impact of PNPLA3 SNP on cirrhosis. The association of rs738409 with each complication was investigated. The rs738409 was found to be associated with steatosis in recessive [p = 4.57 × 10-6 , odds ratio (OR) = 2.85], dominant (p = 4.35 × 10-6 , OR = 1.84), co-dominant (p = 6.18 × 10-8 ; OR = 3.74) and allelic (p = 9.79 × 10-9 ; OR = 1.78) models. No association was found between rs738409 and cirrhosis development in recessive (p = 0.99, OR = 1.00), dominant (p = 0.30, OR = 0.92), co-dominant (p = 0.74; OR = 0.96) and allelic (p = 0.45; OR = 0.96) models. CONCLUSIONS: Although the PNPLA3 rs738409 G allele has been associated with the risk of steatosis in CHB patients, no association between this polymorphism and the risk of cirrhosis was seen.