Hickssullivan8817

In vivo application of siRNA formulation to SKH-1E hairless mice significantly suppressed Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression with no clinical evidence of toxicity. This strategy suggests a simple, personalized, and scalable platform for effective topical delivery of RNAi for treating genetic skin diseases. V.Cannabis is the most commonly used illicit drug among adolescents and young adults, including pregnant women. There is substantial evidence for a significant association between prenatal cannabis exposure and lower birth weight in offspring, and mixed results regarding later behavioural outcomes in the offspring. Adolescent cannabis use, especially heavy use, has been associated with altered executive function, depression, psychosis and use of other drugs later in life. Human studies have limitations due to several confounding factors and have provided scarce information about sex differences. In general, animal studies support behavioural alterations reported in humans and have revealed diverse sex differences and potential underlying mechanisms (altered mesolimbic dopaminergic and hippocampal glutamatergic systems and interference with prefrontal cortex maturation). More studies are needed that analyse sex and gender influences on cannabis-induced effects with great clinical relevance such as psychosis, cannabis use disorder and associated comorbidities, to achieve more personalized and accurate treatments. The analysis of viral kinetics models is mostly achieved by numerical methods. We present an approach via a Magnus expansion that allows us to give an approximate solution to the interferon-dependent viral infection model of influenza which is compared with numerical results. The time of peak viral load is calculated from the approximation and stays within 10% in the studied range of interferon (IFN) efficacy ϵ ∈ [0, 1000]. We utilize our solution to interpret the effect of varying IFN efficacy, suggesting a competition between virions and interferon that can cause an additional peak in the usually exponential increase in the viral load. Adverse effects of drugs on male reproductive system can be categorized as pre-testicular, testicular, and post-testicular. Pre-testicular adverse effects disrupt the hypothalamic-pituitary-gonadal (HPG) axis, generally by interfering with endocrine function. It is known that the HPG axis has roles in the maintenance of spermatogenesis and sexual function. The hypothalamus secretes gonadotropin-releasing hormone (GnRH) which enters the hypophyseal portal system to stimulate the anterior pituitary. The anterior pituitary secretes gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) which are vital for spermatogenesis, into the blood. The FSH stimulates the Sertoli cells for the production of regulatory molecules and nutrients needed for the maintenance of spermatogenesis, while the LH stimulates the Leydig cells to produce and secrete testosterone. Many neurotransmitters influence the hypothalamic-pituitary regulation, consequently the HPG axis, and can consequently affect spermatogenesis and sexual function. Psychotropic drugs including antipsychotics, antidepressants, and mood stabilizers that all commonly modulate dopamine, serotonin, and GABA, can affect male spermatogenesis and sexual function by impairment of the hypothalamic-pituitary regulation, act like endocrine-disrupting chemicals. Otherwise, studies have shown the relationship between decreased sperm quality and psychotropic drugs treatment. Therefore, it is important to investigate the adverse reproductive effects of psychotropic drugs which are frequently used during reproductive ages in males and to determine the role of the hypothalamic-pituitary regulation axis on possible pathologies. Metformin, a US Food and Drug Administration-approved "star" drug used for diabetes mellitus type 2, has become a topic of increasing interest to researchers due to its anti-neoplastic effects. Growing evidence has demonstrated that metformin may be a promising chemotherapeutic agent, and several clinical trials of metformin use in cancer treatment are ongoing. However, the anti-neoplastic effects of metformin and its underlying mechanisms have not been fully elucidated. In this review, we present the newest findings on the anticancer activities of metformin, and highlight its diverse anticancer mechanisms. Several clinical trials, as well as the limitations of the current evidence are also demonstrated. This review explores the crucial roles of metformin and provides supporting evidence for the repurposing of metformin as a treatment of cancer. Knowing the damage that PM can lead to skin is important to a tight control of air pollutants release and to prevent more serious diseases. This study investigates if such alterations are present in a Reconstructed Human Epidermis (RHE) exposed to PM10. Following exposure of RHE to increasing concentrations (2.2, 8.9 and 17.9 μg/cm2) of a standard Urban Particulate Matter over time, led to decreased cell viability at 48 hours. The barrier function was shown to be compromised by 24 hours of exposure to high doses (17.9 μg/cm2). Morphological alterations included cytoplasm vacuolization and partial loss of epidermal stratification. Cytokeratin 10, involucrin, loricrin and filaggrin protein levels were significantly decreased. We confirmed an inflammatory process by IL-1α release and found a significant increase in Aquaporin-3 (AQP3) expression. GDC-0077 datasheet We also demonstrated changes in NOTCH1 and AhR expression of epidermis treated with PM10. The use of hydrogen peroxide altered AQP3 and NOTCH1 expression, and the use of N-acetyl-L-cysteine (NAC) altered NOTCH1 expression, evidencing this is a redox-dependent process. These results demonstrate coarse PM10 induces dose-dependent inflammatory response and alterations in proteins markers of differentiation and water transport in the epidermis that could ultimately compromise the structural integrity of the skin, promoting or exacerbating various skin diseases. Hidradenitis Suppurativa (HS) is a chronic inflammatory disease of the skin associated with specific lesional dysbiotic features. We studied the microbiome of clinically unaffected typical HS sites (armpits, inguinal folds and gluteal clefts) in 60 HS patients and 17 healthy controls.192 samples obtained by swabbing were analyzed by bacterial cultures. 116 randomly selected samples were studied by 16S rRNA gene amplicon sequencing. Patients and controls showed similar characteristics, except for smoking (87% vs 6%, respectively). HS skinfolds were characterized by an increased abundance of anaerobes, predominantly Prevotella, but also Actinomyces, Campylobacter ureolyticus and Mobiluncus, contrasting with a lower abundance of skin commensals such as Staphylococcus epidermidis, a major component of the skin microbiome, Kocuria and Micrococcus luteus. Three independent factors were associated with high anaerobes abundance by multivariate analysis samples originating from HS patients (p= 2.1 x 10-4), body mass index (p= 5 x 10-5) and the sampling site, the gluteal cleft being the most anaerobic area, followed by inguinal folds and axilla (p= 3 x 10-6). The microbiome of clinically unaffected HS skinfolds is reminiscent, albeit to a minor extent, of the microbiome of chronic suppurative HS lesions and may fuel inflammation at a preclinical stage of the disease. CC chemokine receptor 6 (CCR6) is important for the trafficking of IL-17A-producing γδ T cells and required for the development of psoriasiform dermatitis (PsD) in an IL-23 intradermal injection model. The role of CCR6, however, in IL-23-mediated joint inflammation is unclear. We herein hydrodynamically delivered IL-23 minicircle DNA into wild-type (WT) and CCR6-deficient (CCR6-KO) mice to induce overexpression of IL-23 systemically. After IL-23 gene transfer, WT mice exhibited concurrent skin and joint changes that recapitulate some features found in human psoriatic skin and joints. CCR6-KO mice were resistant to IL-23-induced skin inflammation but exhibited no changes in joint inflammation compared to WT mice. Depletion of neutrophils protected WT mice from skin and joint disease without suppressing Th17 cytokine expression. In contrast, mice lacking γδ T cells showed a partial reduction in neutrophilic recruitment and a significant decrease in IL-17A expression in skin and paw tissue. Thus, in an IL-23-mediated model that allows concurrent assessment of both skin and joint disease, we showed that CCR6 is critical for inflammation in the skin but not in the joint. Furthermore, our data suggest that neutrophils and γδ T cells are key effector cells in IL-23 mediated skin and joint inflammation in mice. Failure of dermal protection or repair mechanisms might lead to visibly aged skin. The study aimed to identify genetic associations with perceived age. A genome-wide association study was undertaken in 423,992 adult participants of UK Biobank, using questionnaire data on perceived age and genetic data imputed to the Haplotype Reference Consortium imputation panel. Seventy-four to our knowledge previously unreported and independent associated genetic loci were identified (P less then 5x10-8), which were enriched for cell signaling pathways including the NEK6 and SMAD2 subnetworks. Common genetic variation was estimated to account for 14% of variation in perceived age and the heritability of perceived age was partially shared with that of 75 other traits including multiple traits representing adiposity, suggesting that perceived age may be a useful proxy trait in genetic association studies. The pathogenesis of an emerging virus disease is a difficult task due to lack of scientific data about the emerging virus during outbreak threats. Several biological aspects should be studied faster, such as virus replication and dissemination, immune responses to this emerging virus on susceptible host and specially the virus pathogenesis. Integrative in silico transcriptome analysis is a promising approach for understanding biological events in complex diseases. In this study, we propose an in silico protocol for identifying key genes and pathways useful to understand emerging virus disease pathogenesis. To validate our protocol, the emerging arbovirus Zika virus (ZIKV) was chosen as a target micro-organism. First, an integrative transcriptome data from neural cells infected with ZIKV was used to identify shared differentially expressed genes (DEGs). The DEGs were used to identify the potential candidate genes and pathways in ZIKV pathogenesis through gene enrichment analysis and protein‑protein interaction network construction. Thirty DEGs (24 upregulated and 6 downregulated) were identified in all ZIKV-infected cells, primarily associated with endoplasmic reticulum stress and DNA replication pathways. Some of these genes and pathways had biological functions linked to neurogenesis and/or apoptosis, confirming the potential of this protocol to find key genes and pathways involved on disease pathogenesis. Moreover, the proposed in silico protocol performed anintegrated analysis that is able to predict and identify putative biomarkers from different transcriptome data. These biomarkers could be useful to understand virus disease pathogenesis and also help the identification of candidate antiviral drugs.