Causal relationship between lipid-lowering drugs and ovarian cancer, cervical cancer: a drug target mendelian randomization study.

BACKGROUND: The causal impact of lipid-lowering drugs on ovarian cancer (OC) and cervical cancer (CC) has received considerable attention, but its causal relationship is still a subject of debate. Hence, the objective of this study is to evaluate the impact of lipid-lowering medications on the occurrence risk of OC and CC through Mendelian randomization (MR) analysis of drug targets. METHODS: This investigation concentrated on the primary targets of lipid-lowering medications, specifically, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and proprotein convertase kexin 9 (PCSK9). Genetic variations associated with HMGCR and PCSK9 were derived from published genome-wide association study (GWAS) findings to serve as substitutes for HMGCR and PCSK9 inhibitors. Employing a MR approach, an analysis was conducted to scrutinize the impact of inhibitors targeting HMGCR and PCSK9 on the occurrence of OC and CC. Coronary heart disease (CHD) risk was utilized as a positive control, and the primary outcomes encompassed OC and CC. RESULTS: The findings of the study suggest a notable elevation in the risk of OC among patients treated with HMGCR inhibitors (OR [95%CI] = 1.815 [1.316, 2.315], p = 0.019). In contrast, no significant correlation was observed between PCSK9 inhibitors and the occurrence of OC. Additionally, the analysis did not reveal any noteworthy connection between HMGCR inhibitors, PCSK9 inhibitors, and CC. CONCLUSION: HMGCR inhibitors significantly elevate the risk of OC in patients, but their mechanism needs further investigation, and no influence of PCSK9 inhibitors on OC has been observed. There is no significant relationship between HMGCR inhibitors, PCSK9 inhibitors, and CC.

COPD and T2DM: a Mendelian randomization study.

Introduction: Type 2 diabetes (T2DM) stands as a global chronic illness, exerting a profound impact on health due to its complications and generating a significant economic burden. Recently, observational studies have pointed toward a potential link between Chronic Obstructive Pulmonary Disease (COPD) and T2DM. To elucidate this causal connection, we employed the Mendelian randomization analysis. Method: Our study involved a two-sample Mendelian randomization (MR) analysis on COPD and T2DM. Additionally, tests for heterogeneity and horizontal pleiotropy were performed. Results: For the MR analysis, 26 independent single nucleotides polymorphisms (SNPs) with strong associations to COPD were chosen as instrumental variables. Our findings suggest a pronounced causal relationship between COPD and T2DM. Specifically, COPD emerges as a risk factor for T2DM, with an odds ratio (OR) of 1.06 and a 95% confidence interval ranging from 1.01 to 1.11 (P = 0.006). Notably, all results were devoid of any heterogeneity or pleiotropy. Conclusion: The MR analysis underscores a significant causal relationship between COPD and T2DM, highlighting COPD as a prominent risk factor for T2DM.

Scutellarin Alleviates Ovalbumin-Induced Airway Remodeling in Mice and TGF-ß-Induced Pro-fibrotic Phenotype in Human Bronchial Epithelial Cells via MAPK and Smad2/3 Signaling Pathways.

Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. Epithelial-mesenchymal transition (EMT) is an essential player in these alterations. Scutellarin is isolated from Erigeron breviscapus. Its vascular relaxative, myocardial protective, and anti-inflammatory effects have been well established. This study was designed to detect the biological roles of scutellarin in asthma and its related mechanisms. The asthma-like conditions were induced by ovalbumin challenges. The airway resistance and dynamic compliance were recorded as the results of AHR. Bronchoalveolar lavage fluid (BALF) was collected and processed for differential cell counting. Hematoxylin and eosin staining, periodic acid-Schiff staining, and Masson staining were conducted to examine histopathological changes. The levels of asthma-related cytokines were measured by enzyme-linked immunosorbent assay. For in vitro analysis, the 16HBE cells were stimulated with 10 ng/mL transforming growth beta-1 (TGF-ß1). Cell migration was estimated by Transwell assays and wound healing assays. E-cadherin, N-cadherin, and α-smooth muscle actin (α-SMA) were analyzed by western blotting, real-time quantitative polymerase chain reaction, immunofluorescence staining, and immunohistochemistry staining. The underlying mechanisms of the mitogen-activated protein kinase (MAPK) and Smad pathways were investigated by western blotting. In an ovalbumin-induced asthmatic mouse model, scutellarin suppressed inflammation and inflammatory cell infiltration into the lungs and attenuated AHR and airway remodeling. Additionally, scutellarin inhibited airway EMT (upregulated E-cadherin level and downregulated N-cadherin and α-SMA) in ovalbumin-challenged asthmatic mice. For in vitro analysis, scutellarin prevented the TGF-ß1-induced migration and EMT in 16HBE cells. Mechanistically, scutellarin inhibits the phosphorylation of Smad2, Smad3, ERK, JNK, and p38 in vitro and in vivo. In conclusion, scutellarin can inactivate the Smad/MAPK pathways to suppress the TGF-ß1-stimulated epithelial fibrosis and EMT and relieve airway inflammation and remodeling in asthma. This study provides a potential therapeutic strategy for asthma.

A large pericardial cyst mimicking a unilateral pleural effusion: A case report.

RATIONALE: Pericardial cysts are a rare benign disorder with a variable clinical presentation depending on their size and location. The diagnosis of pericardial cysts is usually based on imaging examinations. The definitive treatment is surgical resection. PATIENT CONCERN: A 36-year-old woman presented with progressive left-sided chest pain and exertional dyspnea, with symptoms resembling pleural effusion. DIAGNOSES: The patient was diagnosed with a pericardial cyst based on imaging and video-assisted thoracoscopic surgery (VATS). INTERVENTION: VATS was performed. OUTCOMES: The patient's symptoms improved after successful removal of the pericardial cyst. Follow-up chest computed tomography exhibited no evidence of recurrence. LESSONS: Clinicians should include pericardial cysts in the differential diagnosis of pseudopleural effusion. VATS is a feasible and safe method to treat symptomatic and large pericardial cysts.