Objective: To investigate the association between statin use and risk of gout in patients with hyperlipidemia.Methods: In this population-based retrospective cohort study, patients ≥20 years and diagnosed as having incident hyperlipidemia between 2001 and 2012 were identified from the 2000 Longitudinal Generation Tracking Database in Taiwan. Regular statin users (incident statin use, having 2 times and ≥90 days of prescription for the first year) and two active comparators [irregular statin use and other lipid-lowering agent (OLLA) use] were compared; the patients were followed up until the end of 2017. Propensity score matching was applied to balance potential confounders. Time-to-event outcomes of gout and dose- and duration-related associations were estimated using marginal Cox proportional hazard models.Results: Regular statin use non-significantly reduced gout risk compared with irregular statin use (aHR, 0.95; 95% CI, 0.90–1.01) and OLLA use (aHR, 0.94; 95% CI, 0.84–1.04). However, a protective effect was noted for a cumulative defined daily dose (cDDD) of >720 (aHR, 0.57; 95% CI, 0.47–0.69 compared with irregular statin use and aHR, 0.48; 95% CI, 0.34–0.67 compared with OLLA use) or a therapy duration of >3 years (aHR, 0.76; 95% CI, 0.64–0.90 compared with irregular statin use and aHR, 0.50; 95% CI, 0.37–0.68 compared with OLLA use). Dose- and duration-dependent associations were consistent in the 5-year sensitivity analyses.Conclusion: Although statin use was not associated with a reduction in gout risk, the protective benefit was observed in those receiving higher cumulative doses or with a longer therapy duration.

Red blood cells are the most abundant cells in the blood that deliver oxygen to the whole body. Erythropoietin (EPO), a positive regulator of erythropoiesis, is currently the major treatment for chronic anemia. Granulocyte colony-stimulating factor (G-CSF) is a multifunctional cytokine and a well-known regulator of hematopoietic stem cell proliferation, differentiation, and mobilization. The use of EPO in combination with G-CSF has been reported to synergistically improve erythroid responses in a group of patients with myelodysplastic syndromes who did not respond to EPO treatment alone; however, the mechanism remains unclear. C57BL/6 J mice injected with G-CSF or EPO were used to compare the erythropoiesis status and the efficiency of erythroid mobilization by flow cytometry. In this study, we found that G-CSF induced more orthochromatophilic erythroblast production than did EPO in the bone marrow and spleen. In addition, in contrast to EPO treatments, G-CSF treatments enhanced the efficiency of the mobilization of newly synthesized reticulocytes into peripheral blood. Our results demonstrated that the effects of G-CSF on erythropoiesis and erythrocytic mobilization were independent of EPO secretion and, in contrast to EPO, G-CSF promoted progression of erythropoiesis through transition of early stage R2 (basophilic erythroblasts) to late stage R4 (orthochromatophilic erythroblasts). We demonstrate for the first time that G-CSF treatments induce a faster erythropoiesis-enhancing response than that of EPO. These findings suggest an alternative approach to treating acute anemia, especially when patients are experiencing a clinical emergency in remote areas without proper blood bank supplies.

Bladder cancer (BCa) is a significant health issue and poses a healthcare burden on patients, highlighting the importance of an effective detection method. Here, we developed a urine DNA methylation diagnostic panel for distinguishing between BCa and non-BCa. In the discovery stage, an analysis of the TCGA database was conducted to identify BCa-specific DNA hypermethylation markers. In the validation phase, DNA methylation levels of urine samples were measured with real-time quantitative methylation-specific PCR (qMSP). Comparative analysis of the methylation levels between BCa and non-BCa, along with the receiver operating characteristic (ROC) analyses with machine learning algorithms (logistic regression and decision tree methods) were conducted to develop practical diagnostic panels. The performance evaluation of the panel shows that the individual biomarkers of ZNF671, OTX1, and IRF8 achieved AUCs of 0.86, 0.82, and 0.81, respectively, while the combined yielded an AUC of 0.91. The diagnostic panel using the decision tree algorithm attained an accuracy, sensitivity, and specificity of 82.6%, 75.0%, and 90.9%, respectively. Our results show that the urine-based DNA methylation diagnostic panel provides a sensitive and specific method for detecting and stratifying BCa, showing promise as a standard test that could enhance the diagnosis and prognosis of BCa in clinical settings.

Lethal toxin (LT) is the critical virulence factor of Bacillus anthracis, the causative agent of anthrax. One common symptom observed in patients with anthrax is thrombocytopenia, which has also been observed in mice injected with LT. Our previous study demonstrated that LT induces thrombocytopenia by suppressing megakaryopoiesis, but the precise molecular mechanisms behind this phenomenon remain unknown. In this study, we utilized 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced megakaryocytic differentiation in human erythroleukemia (HEL) cells to identify genes involved in LT-induced megakaryocytic suppression. Through cDNA microarray analysis, we identified Dachshund homolog 1 (DACH1) as a gene that was upregulated upon TPA treatment but downregulated in the presence of TPA and LT, purified from the culture supernatants of B. anthracis. To investigate the function of DACH1 in megakaryocytic differentiation, we employed short hairpin RNA technology to knock down DACH1 expression in HEL cells and assessed its effect on differentiation. Our data revealed that the knockdown of DACH1 expression suppressed megakaryocytic differentiation, particularly in polyploidization. We demonstrated that one mechanism by which B. anthracis LT induces suppression of polyploidization in HEL cells is through the cleavage of MEK1/2. This cleavage results in the downregulation of the ERK signaling pathway, thereby suppressing DACH1 gene expression and inhibiting polyploidization. Additionally, we found that known megakaryopoiesis-related genes, such as FOSB, ZFP36L1, RUNX1, FLI1, AHR, and GFI1B genes may be positively regulated by DACH1. Furthermore, we observed an upregulation of DACH1 during in vitro differentiation of CD34–megakaryocytes and downregulation of DACH1 in patients with thrombocytopenia. In summary, our findings shed light on one of the molecular mechanisms behind LT-induced thrombocytopenia and unveil a previously unknown role for DACH1 in megakaryopoiesis.

Cancer immunotherapy using monoclonal antibodies targeting immune checkpoint proteins, such as PD-L1 or PD-1 (i

Titanium dioxide nanoparticles (TiO₂-NPs) are widely produced and persist in aquatic ecosystems, yet their indirect effects on host–microbe interactions remain poorly defined. By using zebrafish (Danio rerio) as a sentinel species, this study investigated the effects of subchronic 5 mg/L TiO₂-NP exposure. Dynamic light scattering was utilized to characterize the bimodal aggregates (peaks at 917 and 46,841 nm; surface charge: +22.08 mV) that define the environmental state of TiO₂-NPs. Parallel 16S rRNA metagenomic profiling on Day 6, prior to mortality, revealed profound gut dysbiosis. A marked increase in Chao1 richness (p < 0.01), alongside a catastrophic 333-fold reduction in beneficial Cetobacterium and an 856-fold enrichment of pathogenic Mycobacterium, was observed. Beta-diversity and hierarchical clustering analyses revealed a striking convergence between gut and gill microbial signatures, supporting a gut-to-gill translocation model. These results suggest that TiO₂-NPs exposure induces intestinal dysbiosis, facilitating opportunistic bacterial migration via internal (gut–blood–gill) or external (fecal–water–gill) pathways. This study identifies dysbiosis-driven secondary infection as a novel, overlooked mechanism of nanoparticle toxicity, necessitating a shift in ecological risk assessments toward host–microbe interactions.