Serum lipid levels, genetic risk, and lung cancer incidence: A large prospective cohort study.

BACKGROUND: Previous studies usually focused on the separate association of metabolism or genetic factors with lung cancer risk and have largely ignored their combined effect. We aimed to examine the associations between serum lipid levels, genetic risk, and lung cancer risk. METHODS: 426,524 participants of the UK Biobank were included. The Cox proportional hazards models and restricted cubic splines were performed to assess the association between serum lipid and lung cancer risk. Polygenic risk score (PRS) was constructed to assess its joint effect and interaction with serum lipid on lung cancer risk. RESULTS: Higher level of apolipoprotein A were significantly correlated with lower lung cancer risk. A inverse-J-shaped relationship between HDL and incident lung cancer was found. Individuals with low total cholesterol, HDL, LDL, apolipoprotein A, and apolipoprotein B, combined with high PRS, showed significantly elevated lung cancer risks. Compared to those with low PRS and low triglycerides, participants with high PRS and elevated triglyceride levels had a notably higher risk. The interaction effect of high PRS and low LDL (RERI:0.25, 95%CI: 0.04-0.46), as well as the interaction effect of high PRS and low apolipoprotein B (RERI:0.28, 95%CI: 0.07-0.48), were both greater than the sum of their individual effects on lung cancer risk. CONCLUSIONS: Serum lipids were associated with lung cancer risk. LDL or apolipoprotein B interacting with genetic risk may affect lung cancer risk. IMPACT: Our findings emphasize the need for individuals with heightened genetic risk should pay more attention to their lipid levels to reduce lung cancer risk.

The Role of microRNAs in Arsenic-Induced Human Diseases: A Review.

MicroRNAs (miRNAs) are noncoding RNAs with 20-22 nucleotides, which are encoded by endogenous genes and are capable of targeting the majority of human mRNAs. Arsenic is regarded as a human carcinogen, which can lead to many adverse health effects including diabetes, skin lesions, kidney disease, neurological impairment, male reproductive injury, and cardiovascular disease (CVD) such as cardiac arrhythmias, ischemic heart failure, and endothelial dysfunction. miRNAs can act as tumor suppressors and oncogenes via directly targeting oncogenes or tumor suppressors. Recently, miRNA dysregulation was considered to be an important mechanism of arsenic-induced human diseases and a potential biomarker to predict the diseases caused by arsenic exposure. Endogenic miRNAs such as miR-21, the miR-200 family, miR-155, and the let-7 family are involved in arsenic-induced human disease by inducing translational repression or RNA degradation and influencing multiple pathways, including mTOR/Arg 1, HIF-1α/VEGF, AKT, c-Myc, MAPK, Wnt, and PI3K pathways. Additionally, exogenous miRNAs derived from plants, such as miR-34a, miR-159, miR-2911, miR-159a, miR-156c, miR-168, etc., among others, can be transported from blood to specific tissue/organ systems in vivo. These exogenous miRNAs might be critical players in the treatment of human diseases by regulating host gene expression. This review summarizes the regulatory mechanisms of miRNAs in arsenic-induced human diseases, including cancers, CVD, and other human diseases. These special miRNAs could serve as potential biomarkers in the management and treatment of human diseases linked to arsenic exposure. Finally, the protective action of exogenous miRNAs, including antitumor, anti-inflammatory, anti-CVD, antioxidant stress, and antivirus are described.

Prevalence and associated outcomes of coinfection between SARS-CoV-2 and influenza: a systematic review and meta-analysis.

OBJECTIVES: To estimate the prevalence of influenza coinfection in COVID-19 patients and investigate its association with severe clinical outcomes. METHODS: We systematically searched the Web of Science, PubMed, Scopus, Embase, The Cochrane Library, and CNKI for studies published between January 01, 2020, and May 31, 2023. Meta-analysis was performed to estimate the pooled prevalence of coinfection and the impact on clinical outcomes. Systematic review registered in PROSPERO (CRD42023423113). RESULTS: A total of 95 studies involving 62,107 COVID-19 patients were included. The pooled prevalence of coinfection with influenza virus was 2.45% (95% confidence interval [CI]: 1.67-3.58%), with a high proportion of influenza A. Compared with mono-infected patients (COVID-19 only), the odds ratio (OR) for severe outcomes (including intensive care unit admission [OR = 2.20, 95% CI: 1.68-2.87, P < 0.001], mechanical ventilation support [OR = 2.73, 95% CI: 1.46-5.10, P = 0.002], and mortality [OR = 2.92, 95% CI: 1.16-7.30, P = 0.022]) was significantly higher among patients coinfected influenza A. CONCLUSION: Although the prevalence of coinfection is low, coinfected patients are at higher risk of severe outcomes. Enhanced identification of both viruses, as well as individualized treatment protocols for coinfection, are recommended to reduce the occurrence of serious disease outcomes in the future.

The challenges and applications of nanotechnology against bacterial resistance.

Bacterial resistance to the antibiotics develops rapidly and is increasingly serious health concern in the world. It is an insoluble topic due to the multiple resistant mechanisms. The overexpression of relative activities of the efflux pump has proven to be a frequent and important source of bacterial resistance. Efflux transporters in the membrane from the resistant bacteria could play a key role to inhibit the intracellular drug intake and impede the drug activities. However, nanoparticles (NPs), one of the most frequently used encapsulation materials, could increase the intracellular accumulation of the drug and inhibit the transporter activity effectively. The rational and successful application of nanotechnology is a key factor in overcoming bacterial resistance. Furthermore, nanoparticles such as metallic, carbon nanotubes and so on, may prevent the development of drug resistance and be associated with antibiotic agents, inhibiting biofilm formation or increasing the access into the target cell and exterminating the bacteria eventually. In the current study, the mechanisms of bacterial resistance are discussed and summarized. Additionally, the opportunities and challenges in the use of nanoparticles against bacterial resistance are also illuminated. At the same time, the use of nanoparticles to combat multidrug-resistant bacteria is also investigated by coupling natural antimicrobials or other alternatives. In short, we have provided a new perspective for the application of nanoparticles against multidrug-resistant bacteria.