OTUD1 enhances gastric cancer aggressiveness by deubiquitinating EBV-encoded protein BALF1 to stabilize the apoptosis inhibitor Bcl-2.

The Epstein-Barr virus (EBV) is implicated in several cancers, including EBV-associated gastric cancer (EBVaGC). This study focuses on EBV-encoded BALF1 (BamH1 A fragment leftward reading frame 1), a key apoptosis regulator in EBV-related cancers, whose specific impact on EBVaGC was previously unknown. Our findings indicate that BALF1 overexpression in gastric cancer cells significantly enhances their proliferation, migration, and resistance to chemotherapy-induced apoptosis, confirming BALF1's oncogenic potential. A novel discovery is that BALF1 undergoes degradation via the ubiquitin-proteasome pathway. Through analysis of 69 deubiquitinating enzymes (DUBs), ovarian tumor protease (OTU) domain-containing protein 1 (OTUD1) emerged as a vital regulator for maintaining BALF1 protein stability. Furthermore, BALF1 was found to play a role in regulating the stability of the B-cell lymphoma-2 (Bcl-2) protein, increasing its levels through deubiquitination. This mechanism reveals BALF1's multifaceted oncogenic role in gastric cancer, as it contributes both directly and indirectly to cancer progression, particularly by stabilizing Bcl-2, known for its anti-apoptotic characteristics. These insights significantly deepen our understanding of EBV's involvement in the pathogenesis of gastric cancer. The elucidation of OTUD1's role in BALF1 regulation and its influence on Bcl-2 stabilization provide new avenues for therapeutic intervention in EBVaGC, bridging the gap between viral oncogenesis and cellular protein regulation and offering a more holistic view of gastric cancer development under the influence of EBV.

Association between monocyte to high-density lipoprotein-cholesterol ratio and osteoporosis: An analysis of the National Health and Nutrition Examination Survey 2013-2014.

The monocyte to high-density lipoprotein-cholesterol (HDL-C) ratio (monocyte-to-HDL-C ratio) was proposed as a marker of atherosclerosis. Osteoporosis and atherosclerosis share common risk factors and pathophysiological mechanisms. This study aimed to assess the relationship between monocyte-to-HDL-C ratio and osteoporosis. Participants aged ≥50 years with complete bone mineral density (BMD), monocyte, and HDL-C examination data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 were included. Descriptive analysis was performed separately according to males and females. Weight linear regression and weight logistic regression analyses were used to analyze the association between the monocyte-to-HDL-C ratio and BMD and osteopenia and osteoporosis and vertebral fracture. A total of 1804 participants were included. Among the participants with osteopenia, 398 (48.31%) were males and 466 (51.91%) were females. Among those with osteoporosis, 38 (2.77%) were males and 95 (9.50%) were females. In females, monocyte-to-HDL-C ratio was negatively associated with femoral neck BMD (regression coefficient (ß) = -0.18; 95% confidence interval (CI): (-0.29, -0.07)) and high monocyte-to-HDL-C ratio was associated with higher odds of osteopenia (odds ratio (OR) = 1.22; 95% CI: (1.01, 1.47)) and osteoporosis (OR = 1.68; 95% CI: (1.13, 2.49)) after adjusting for confounders. In males, only monocyte-to-HDL-C ratio >0.35 was observed to be associated with higher odds of osteoporosis (OR = 1.96; 95% CI: (1.02, 3.79)). Stratified analyses showed that similar results were also found in different populations. This study showed that the monocyte-to-HDL-C ratio was negatively associated with BMD and the risk of osteopenia and osteoporosis in females. The monocyte-to-HDL-C ratio may be a new marker of osteoporosis or osteopenia.

Exposure to echimidine impairs the heart development and function of zebrafish larvae.

Pyrrolizidine alkaloids (PAs) are a class of phytotoxins that are widely distributed and can be consumed by humans through their daily diets. Echimidine is one of the most abundant PAs, but its safety, particularly its effects on development, is not fully understood. In this study, we used a zebrafish model to assess the developmental toxicity of echimidine. Zebrafish embryos were exposed to echimidine at concentrations of 0.02, 0.2, and 2 mg/L for 96 h. Our study revealed that embryonic exposure to echimidine led to developmental toxicity, characterized by delayed hatching and reduced body length. Additionally, echimidine exposure had a notable impact on heart development in larvae, causing tachycardia and reducing stroke volume (SV)and cardiac output (CO). Upon exposing the transgenic zebrafish strain Tg(cmlc2:EGFP) to echimidine, we observed atrial dilation and thinning of the atrial wall in developing embryos. Moreover, our findings indicated abnormal expression of genes associated with cardiac development (including gata4, tbx5, nkx2.5 and myh6) and genes involved in calcium signaling pathways (such as cacna1aa, cacna1sa, ryr2a, ryr2b, atp2a2a, atp2a2b, slc8a1, slc8a3 and slc8a4a). In summary, our findings demonstrate that echimidine may impair cardiac development and function in zebrafish larvae by disrupting calcium transport, leading to developmental toxicity. These findings provide insights regarding the safety of products containing PAs in food and medicine.