A genome-wide cross-trait analysis identifies shared loci and causal relationships of obesity and lipidemic traits with psoriasis.

Background: Obesity and dyslipidemia, major global health concerns, have been linked to psoriasis, but previous studies faced methodological limitations and their shared genetic basis remains unclear. This study examines various obesity-related and lipidemic traits as potential contributors to psoriasis development, aiming to clarify their genetic associations and potential causal links. Methods: Summary statistics from genome-wide association studies (GWAS) conducted for obesity-related traits (body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for the body mass index (WHRadjBMI)) and lipidemic traits (high-density lipoprotein (HDL), LDL, triglyceride (TG), total Cholesterol (TC), apolipoprotein A1 (apoA1), apolipoprotein B (apoB), and apolipoprotein E (apoE)) and psoriasis, all in populations of European ancestry, were used. We quantified genetic correlations, identified shared loci and explored causal relationship across traits. Results: We found positive genetic correlation between BMI and psoriasis (rg=0.22, p=2.44×10-18), and between WHR and psoriasis (rg=0.19, p=1.41×10-12). We further found the positive genetic correlation between psoriasis and WHRadjBMI(rg=0.07, p=1.81×10-2) the genetic correlation, in while the effect of BMI was controlled for. We identified 14 shared loci underlying psoriasis and obesity-related traits and 43 shared loci between psoriasis and lipidemic traits via cross-trait meta-analysis. Mendelian randomization (MR) supported the causal roles of BMI (IVW OR=1.483, 95%CI=1.333-1.649), WHR (IVW OR=1.393, 95%CI=1.207-1.608) and WHRadjBMI (IVW OR=1.18, 95%CI=1.047-1.329) in psoriasis, but not observe any significant association between lipidemic traits and the risk of psoriasis. Genetic predisposition to psoriasis did not appear to affect the risk of obesity and lipidemic traits. Conclusions: An intrinsic link between obesity-related traits and psoriasis has been demonstrated. The genetic correlation and causal role of obesity-related traits in psoriasis highlight the significance of weight management in both the prevention and treatment of this condition.

Circadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity.

BACKGROUND: Circadian rhythm is crucial to the function of the immune system. Disorders of the circadian rhythm can contribute to inflammatory diseases such as Ulcerative colitis (UC). This Mendelian Randomization (MR) analysis applies genetic tools to represent the aggregated statistical results of exposure to circadian rhythm disorders and UC and its comorbidities, allowing for causal inferences. METHODS: Summary statistics of protein, DNA methylation and gene expression quantitative trait loci in individuals of European ancestry (pQTL, mQTL, and eQTL, respectively) were used. Genetic variants located within or near 152 circadian clock-related genes and closely related to circadian rhythm disorders were selected as instrumental variables. Causal relationships with UC and its comorbidities were then estimated through employed Summary data-based Mendelian Randomization (SMR) and Inverse-Variance-Weighted MR (IVW-MR). RESULTS: Through preliminary SMR analysis, we identified a potential causal relationship between circadian clock-related genes and UC along with its comorbidities, which was further confirmed by IVW-MR analysis. Our study identified strong evidence of positive correlation involving seven overlapping genes (CSNK1E, OPRL1, PIWIL2, RORC, MAX, PPP5C, and AANAT) through MWAS and TWAS in UC, four overlapping genes (OPRL1, CHRNB2, FBXL17, and SIRT1) in UC with PSC, and three overlapping genes (ARNTL, USP7, and KRAS) in UC with arthropathy. CONCLUSIONS: This SMR study demonstrates the causal effect of circadian rhythm disorders in UC and its comorbidities. Furthermore, our investigation pinpointed candidate genes that could potentially serve as drug targets.

Fuzhengjiedu formula exerts protective effect against LPS-induced acute lung injury via gut-lung axis.

BACKGROUND: Acute lung injury (ALI) is distinguished by rapid and severe respiratory distress and prolonged hypoxemia. A traditional Chinese medicine (TCM), known as the Fuzhengjiedu formula (FZJDF), has been shown to have anti-inflammatory benefits in both clinical and experimental studies. The precise underlying processes, nevertheless, are yet unclear. PURPOSE: This study sought to enlighten the protective mechanism of FZJDF in ALI through the standpoint of the gut-lung crosstalk. METHODS: The impact of FZJDF on lipopolysaccharide (LPS)-induced ALI murine model were investigated, and the lung injury score, serum interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) expression were measured to confirm its anti-inflammatory effects. Additionally, gut microbiota analysis and serum and fecal samples metabolomics were performed using metagenomic sequencing and high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry, respectively. RESULTS: FZJDF significantly induced histopathological changes caused by LPS-induced ALI as well as downregulated the serum concentration of IL-1ß and TNF-α. Furthermore, FZJDF had an effect in gut microbiota disturbances, and linear discriminant effect size analysis identified signal transduction, cell motility, and amino acid metabolism as the potential mechanisms of action in the FZJDF-treated group. Several metabolites in the LPS and FZJDF groups were distinguished by untargeted metabolomic analysis. Correlations were observed between the relative abundance of microbiota and metabolic products. Comprehensive network analysis revealed connections among lung damage, gut microbes, and metabolites. The expression of glycine, serine, glutamate, cysteine, and methionine in the lung and colon tissues was dysregulated in LPS-induced ALI, and FZJDF reversed these trends. CONCLUSION: This study revealed that FZJDF considerably protected against LPS-induced ALI in mice by regulating amino acid metabolism via the gut-microbiota-lung axis and offered thorough and in-depth knowledge of the multi-system linkages of systemic illnesses.

The clinical efficacy of type 2 monoclonal antibodies in eosinophil-associated chronic airway diseases: a meta-analysis.

Background: Anti-type 2 inflammation therapy has been proposed as a treatment strategy for eosinophil-associated chronic airway disorders that could reduce exacerbations and improve lung function. We performed a meta-analysis of randomized controlled trials to assess the effectiveness of type 2 monoclonal antibodies (anti-T2s) for eosinophil-associated chronic airway disorders. Methods: PubMed, Embase, Web of Science, and Cochrane Library were searched from their inception to 21 August 2022. Randomized clinical trials evaluating the effectiveness of anti-T2s versus placebo in the treatment of chronic airway diseases were selected. The outcomes were exacerbation rate and change in pre-bronchodilator forced expiratory volume in 1 s (FEV1) from baseline. The Cochrane Risk of Bias Assessment Tool 1.0 was used to evaluate the risk of bias, and the random-effects or fixed-effect model were used to pool the data. Results: Thirty-eight articles concerning forty-one randomized clinical trials with 17,115 patients were included. Compared with placebo, anti-T2s therapy yielded a significant reduction in exacerbation rate in COPD and asthma (Rate Ratio (RR)=0.89, 95%CI, 0.83-0.95, I2 = 29.4%; RR= 0.59, 95%CI, 0.52-0.68, I2 = 83.9%, respectively) and improvement in FEV1 in asthma (Standard Mean Difference (SMD)=0.09, 95%CI, 0.08-0.11, I2 = 42.6%). Anti-T2s therapy had no effect on FEV1 improvement in COPD (SMD=0.05, 95%CI, -0.01-0.10, I2 = 69.8%). Conclusion: Despite inconsistent findings across trials, anti-T2s had a positive overall impact on patients' exacerbation rate in asthma and COPD and FEV1 in asthma. Anti-T2s may be effective in treating chronic airway illnesses related to eosinophils. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022362280.

Efficacy of Chinese Herbal Formula Sini Zuojin Decoction in Treating Gastroesophageal Reflux Disease: Clinical Evidence and Potential Mechanisms.

BACKGROUND: Based on 122 cases reported in China, data mining indicated that Sini Powder (SNP) and the Zuojin Pill (ZJP) are both widely used as the basic recipe for treating Gastroesophageal Reflux Disease (GERD). OBJECTIVES: To evaluate the intervention effects of Sini Zuojin Decoction (SNZJD) in patients with GERD. METHODS: A comprehensive collection of randomized controlled trials (RCTs) using SNZJD in patients with GERD that were published in domestic and foreign journals was made by computer retrieval. RevMan 5.3 software was used for meta-analysis and bias risk assessment, Stata 14.0 software was used for sensitivity analysis, GRADE profiler 3.6 was used to evaluate the level of evidence, and trial sequential analysis (TSA), employed to control for random errors, was performed to assess the main outcomes. Network pharmacology analysis was applied to preliminarily study the mechanisms of action of SNZJD on GERD. RESULTS: Thirteen articles were eventually included, covering a total of 966 patients. Meta-analysis indicated that: ① the SNZJD plus traditional stomach medicines (SPTSM) group was more effective than the traditional stomach medicines (TSM) group (RR = 1.16, 95% CI [1.04, 1.29], P = 0.009); ② the experimental group with SNZJD was significantly better than TSM controls in improving heartburn, substernal chest pain, acid regurgitation, and food regurgitation symptoms (P < 0.0001); ③ SPTSM could significantly decrease total symptom scores with substantial effectiveness (P < 0.00001). The recurrence rate and adverse effects of SNZJD treatment were significantly reduced (P < 0.05). TSA showed that the effective rate of meta-analysis might be reliable, but the recurrence and safety results were still uncertain. According to the evaluation by the GRADE method, the quality of evidence was low. Besides, SNZJD might treat GERD by acting on related targets and pathways such as inflammation, hormone regulation, and so on. CONCLUSIONS: SNZJD might be useful in the treatment of GERD, but its long-term effects and specific clinical mechanisms are unclear. Due to the poor quality of the evidence, more samples and high-quality clinical studies should be tested and verified in the future.