Pigment epithelium-derived factor (PEDF) represses the glucose transporter 1 (GLUT1) mRNA expression and may be a potential therapeutic agent in psoriasis: a case-control and experimental study.

We investigated the whole blood GLUT1 mRNA expression and serum pigment epithelium-derived factor (PEDF), interleukin-6 (IL-6), fetuin-A, and pentraxin-3 (PTX3) levels in psoriatic patients and tested their correlations with the severity of psoriasis using the psoriasis area and severity index (PASI) score. Also, we tested the GLUT1 mRNA expression after an in vitro treatment of human skin fibroblast (HSF) cell lines with PEDF. The case-control part of the study recruited 74 participants (44 psoriatic patients and 30 healthy volunteers). Whole blood GLUT1 mRNA fold changes were estimated by RT-PCR, and serum PEDF, IL-6, fetuin-A, and PTX3 levels were measured by ELISA kits. In the experimental part, the HSF cell lines were treated with different concentrations of PEDF for different times to test its effect on the GLUT1 mRNA expression. The whole blood GLUT 1 expression significantly increased in psoriatic patients and correlated positively with serum IL-6, fetuin-A, PTX3 levels and with the severity of psoriasis while negatively with serum PEDF levels. The PEDF-treated HSF cell lines showed a time- and dose-dependent decline in the GLUT 1 mRNA expression. The whole blood GLUT 1 mRNA is a non-invasive biomarker that is associated with the severity of psoriasis. PEDF represses GLUT 1 expression and may be a potential therapeutic agent in psoriasis.Trial registration: ClinicalTrials.gov Identifier: NCT04242082.

Semaglutide for the treatment of type 2 Diabetes Mellitus: A systematic review and network meta-analysis of safety and efficacy outcomes.

BACKGROUND AND AIMS: To assess the safety and efficacy of semaglutide compared with placebo and other anti-hyperglycaemic agents in type 2 diabetes (T2DM). METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane library for relevant randomized controlled trials (RCTs). A network meta-analysis was conducted to compare different doses, durations, and interventions in T2DM. We presented results as mean difference (MD) or relative risk (RR) and 95% confidence interval (CI). RESULTS: Twenty-six included RCTs studied different doses of subcutaneous (SC) and oral semaglutide, tirzepatide, liraglutide, sitagliptin, canagliflozin, and empagliflozin compared with placebo. Tirzepatide showed the highest efficacy, however, it was comparable to semaglutide. SC semaglutide 1 mg once-weekly showed higher reduction in HbA1c (MD = -1.72, 95% CI [-2.32; -1.12]), and fasting blood glucose (MD = -1.93, 95% CI [-2.81; -1.04]) versus placebo at 30 weeks and other timepoints. Adverse events (ADs) were comparable to placebo with oral and SC semaglutide, oral sitagliptin, SC liraglutide, and oral empagliflozin at most timepoints. However, SC semaglutide 0.8 mg and tirzepatide 10 mg groups had the highest gastrointestinal adverse events. CONCLUSION: Tirzepatide, oral and SC semaglutide has a favourable efficacy in treating T2DM. The adverse events were comparable to placebo; however, gastrointestinal adverse events were highly recorded in tirzepatide, oral and SC semaglutide groups.

Efficacy and Safety of Pectoral Nerve Block (Pecs) Compared With Control, Paravertebral Block, Erector Spinae Plane Block, and Local Anesthesia in Patients Undergoing Breast Cancer Surgeries: A Systematic Review and Meta-analysis.

OBJECTIVE: We aimed to compare the safety and efficacy of pectoral nerve block (Pecs) I and II with control or other techniques used during breast cancer surgeries such as local anesthesia, paravertebral block, and erector spinae plane block (ESPB). METHODS: We searched 4 search engines (PubMed, Cochrane Library, Scopus, and Web of Science) for relevant trials, then extracted the data and combined them under random-effect model using Review Manager Software. RESULTS: We found 47 studies, 37 of them were included in our meta-analysis. Regarding intraoperative opioid consumption, compared with control, a significant reduction was detected in Pecs II (standardized mean difference [SMD]=-1.75, 95% confidence interval [CI] [-2.66, -0.85], P=0.0001) and Pecs I combined with serratus plane block (SMD=-0.90, 95% CI [-1.37, -0.44], P=0.0002). Postoperative opioid consumption was significantly lowered in Pecs II (SMD=-2.28, 95% CI [-3.10, -1.46], P<0.00001) compared with control and Pecs II compared with ESPB (SMD=-1.75, 95% CI [-2.53, -0.98], P<0.00001). Furthermore, addition of dexmedetomidine to Pecs II significantly reduced postoperative opioid consumption compared with Pecs II alone (SMD=-1.33, 95% CI [-2.28, -0.38], P=0.006). CONCLUSION: Pecs block is a safe and effective analgesic procedure during breast cancer surgeries. It shows lower intra and postoperative opioid consumption than ESPB, and reduces pain compared with control, paravertebral block, and local anesthesia, with better effect when combined with dexmedetomidine.

Cutaneous JAK Expression in Vitiligo.

BACKGROUND: The Janus kinase-signal transducer and activator of transcription signaling pathway has been suggested as a promising therapeutic target in vitiligo. However, limited data is available on the cutaneous expression of JAK in vitiligo. AIM: This study is designed to analyze the cutaneous expression patterns of JAK1, 2, and 3 in vitiligo and investigate their relation to the disease clinical parameters. METHODS: This case-control study recruited 24 patients having active vitiligo and 20 age, sex, and skin type-matched healthy volunteers. Skin biopsies were obtained from patients (lesional, perilesional and nonlesional) and controls for assessment of JAK1, 2, and 3 expression using RT-PCR. RESULTS: JAK1 and JAK3 were overexpressed in patients' skin compared to control skin and showed a stepwise pattern of upregulation from control to nonlesional, perilesional and lesional skin. However, JAK3 showed much stronger expression. In contrast JAK2 expression showed no significant difference in any of lesional, perilesional or nonlesional skin compared to control skin. JAK1 and JAK3 expression levels showed no correlation with neither the disease activity nor severity. CONCLUSION: JAK1 and more prominently JAK3 are upregulated in vitiliginous skin and possibly contribute to the pathogenesis of the disease. Accordingly, selective JAK3/1 inhibition may provide a favorable therapeutic opportunity for vitiligo patients.This study is registered on the ClinicalTrials.gov Identifier: NCT03185312.