Risk factors and lipid metabolism characteristics of early-onset male androgenetic alopecia: A pilot study.

BACKGROUND: Male androgenetic alopecia (MAA) is a multifactorial disease, with patients presenting at a younger age, which is a risk factor for many metabolic diseases. AIMS: To explore the risk factors associated with early-onset of MAA and its metabolic characteristics. METHODS: Forty patients with MAA and 45 healthy controls were collected. The serum levels of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total testosterone (TT), uric acid (UA), and 25-hydroxyvitamin D (25(OH)D) were measured. Meanwhile, lipid metabolites were detected by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). RESULTS: 37.50% MAA patients had metabolic syndrome, compared to 17.78% in control group (p < 0.05). The levels of HDL-C, UA, and 25(OH)D were decreased in patients with MAA compared to healthy controls (p < 0.05). However, there was no significant difference in the level of TT between the two groups. Additionally, there were no significant differences in the levels of HDL-C, UA, 25(OH)D, and TT among different grades of hair loss (p > 0.05). The lipid profile of early-onset MAA differed significantly from healthy controls. In early-onset MAA, the levels of ceramide (Cer) and sphingomyelin (SM) were significantly lower. Cer(d38:5) and TG(15:0/18:1/18:1) may be the biomarkers. CONCLUSION: Low HDL-C, UA, and 25(OH)D may be the independent risk factors for early-onset MAA. Abnormal lipid metabolism was observed in early-onset MAA, wherein Cer and SM may serve as protective factors.

The association of IL-33 and systemic sclerosis: a systematic review and meta-analysis.

A meta-analysis of the association between IL-33 and these diseases is lacking, and we aimed to perform a meta-analysis of the association between IL-33 and systemic sclerosis (SSc). We searched relevant papers through PubMed (via Medline), Embase (via Ovid), and the Cochrane Library through May 18th, 2022. Odds ratios (ORs) and weighted mean differences (WMDs) were estimated using a random effect model. A total of 8 papers were included in our meta-analysis. The pooled results showed that SSc patients had significantly higher serum IL-33 levels than healthy controls (HCs) (SMD = 0.64; 95% CI = 0.34, 0.93; P < 0.001); early SSc patients had significantly higher serum IL-33 levels than late SSc patients (SMD = 1.04; 95% CI = 0.28, 1.80; P = 0.007). However, no significant difference was observed between limited cutaneous SSc and diffuse cutaneous SSc (SMD = - 0.35; 95% CI = - 0.76, 0.06; P = 0.094). Our meta-analysis provided important evidence for the use of IL-33 in therapeutic strategies for fibrotic disorders.

RNF2 mediates pulmonary fibroblasts activation and proliferation by regulating mTOR and p16-CDK4-Rb1 signaling pathway.

BACKGROUND: Pulmonary fibrosis (PF) is a chronic, progressive interstitial lung disease with unknown etiology, associated with increasing morbidity and pessimistic prognosis. Pulmonary fibroblasts (PFbs) are the key effector cells of PF, in which abnormal activation and proliferation is an important pathogenesis of PF. Ring finger protein 2 (RNF2), is identified as the catalytic subunit of poly-comb repressive complex 1, which is closely related to occurrence and development of lung cancer, but its function in PF has not been revealed. In this paper, we sought to identify the regulatory role of RNF2 in lung fibrogenesis and its underlying mechanisms. METHODS: The expression of RNF2 in lung fibrosis tissue (human and Bleomycin-induced mouse) and cell model (TGF-ß1-induced HFL1 cells) was examined by immunoblotting analysis and immunofluorescence. Western blot, qRT-PCR were performed to evaluate the expression of pro-fibrogenic cytokines (including α-SMA, ECM and MMPs/ TIMPs) induced by TGF-ß1 in HFL1 cells. Cell proliferation, cycle progression and apoptosis were examined by fow cytometric. Molecular interactions were tested by Co-IP assays. RESULTS: RNF2 expression was elevated in PF tissues compared to normal adjacent tissues and in PFbs (HFL1) induced by TGF-ß1. Furthermore, knockdown of RNF2 could evidently inhibit the abnormal expression of pro-fibrogenic cytokines (including α-SMA, ECM and MMPs/TIMPs) induced by TGF-ß1 in HFL1 cells. Functionally, RNF2 silencing could significantly suppress TGF-ß1-induced anomalous proliferation, cell cycle progression, apoptosis and autophagy in HFL1 cells. Mechanistically, RNF2 deficiency could effectively inhibit the abnormal activation of mTOR signaling pathway in TGF-ß1-induced HFL1 cells, and mTOR pathway had feedback regulation on the expression of RNF2. Further studies RNF2 could regulate the phosphorylation level of RB1 through interacting with p16 to destroy the binding of p16 and CDK4 competitively. Simultaneously, overexpression of RNF2 could show the opposite results. CONCLUSIONS: These results indicated that RNF2 is a potent pro-fibrogenic molecule for PFbs activation and proliferation through mTOR and p16-CDK4-Rb signaling pathways, and RNF2 inhibition will be a potential therapeutic avenue for treating PF.

Therapeutic hexapeptide (PGPIPN) prevents and cures alcoholic fatty liver disease by affecting the expressions of genes related with lipid metabolism and oxidative stress.

PGPIPN is a therapeutic hexapeptide derived from bovine ß-casein. Here we investigated the role and mechanism of this peptide on alcoholic fatty liver disease (AFLD). We took human hepatic cell line LO2 and hepatocellular carcinoma cell line HepG2 to establish the models of steatosis hepatocyte induced by alcohol, taken PGPIPN as pharmacological intervention. And we also established the model of AFLD mice, taken PGPIPN as therapeutic drug and glutathione (GSH) as positive control. We assayed the biochemical materials related to liver injury, lipid metabolism and oxidation, and observed morphology change and fat accumulation of hepatocyte. The gene expressions and/or activities related to liver injury, lipid metabolism and oxidation, such as ACC, PPAR-γ, CHOP and Caspase-3, were assessed by real time PCR and western blot. Our results showed PGPIPN alleviated hepatic steatosis in both model cells and AFLD model mice. PGPIPN can effectively reduce the lipid accumulation and oxidative stress of hepatocyte in a dose-dependent manner. PGPIPN alleviated alcohol-induced cell steatosis and injuries by regulating the gene expressions and/or activities of ACC, PPAR-γ, CHOP and Caspase-3. Our results demonstrated PGPIPN had the protective and therapeutic effect on AFLD, which may serve as a potential therapeutic agent for AFLD.