FoxG1/BNIP3 axis promotes mitophagy and blunts cisplatin resistance in osteosarcoma.

Cisplatin (CDDP) is a commonly used chemotherapeutic for osteosarcoma (OS) patients, and drug resistance remains as a major hurdle to undermine the treatment outcome. Here, we investigated the potential involvement of FoxG1 and BNIP3 in CDDP resistance of OS cells. FoxG1 and BNIP3 expression levels were detected in the CDDP-sensitive and CDDP-resistant OS tumors and cell lines. Mitophagy was observed through transmission electron microscope analysis. The sensitivity to CDDP in OS cells upon FoxG1 overexpression was examined in cell and animal models. We found that FoxG1 and BNIP3 showed significant downregulation in the CDDP-resistant OS tumor samples and cell lines. CDDP-resistant OS tumor specimens and cells displayed impaired mitophagy. FoxG1 overexpression promoted BNIP3 expression, enhanced mitophagy in CDDP-resistant OS cells, and resensitized the resistant cells to CDDP treatment in vitro and in vivo. Our data highlighted the role of the FoxG1/BNIP3 axis in regulating mitophagy and dictating CDDP resistance in OS cells, suggesting targeting FoxG1/BNIP3-dependent mitophagy as a potential strategy to overcome CDDP resistance in OS.

Role of the RIP3-PGAM5-Drp1 pathway in aluminum-induced PC12 cells necroptosis.

Epidemiological studies from diverse global regions suggest a correlation between the accumulation of aluminum in the brain and the onset of various neurodegenerative diseases, including Alzheimer's disease, of which, neuronal cells death happen. Our previous research has found the potential of aluminum to induce neuronal cell death. A comprehensive exploration of the regulatory pathways influenced by aluminum in neuronal cell death could contribute to the development of strategies aimed at preventing the detrimental impact of aluminum on neuronal cells. This study is dedicated to exploring the impact of aluminum on mitochondrial homeostasis through the RIP3-PGAM5-Drp1 pathway, with a specific focus on its potential role in necroptosis. We observed that the inhibition of RIP3 function and the reduction in PGAM5 protein expression both mitigate aluminum-induced necroptosis in PC12 cells and enhance mitochondrial function. However, the inhibition of PGAM5 protein expression does not exert an impact on the expression of RIP3 and MLKL proteins. In summary, our study posits that aluminum can induce necroptosis in PC12 cells through the RIP3-PGAM5-Drp1 pathway.

Association Between Serum Magnesium Levels and Glycemic Control in Type 2 Diabetes.

Introduction: Serum magnesium is a crucial mineral within the human body. It is imperative for diabetic patients to maintain optimal serum magnesium levels. We focus on the relationship between glycemic control and serum magnesium in type 2 diabetes mellitus (T2DM). Methods: The retrospective, observational, cross-sectional study comprised 1694 patients recruited from the People's Hospital of Yuxi. Fasting blood samples were collected for analysis, accompanied by the recording of participants' demographic characteristics. Patients were categorized into two groups based on whether their glycosylated hemoglobin (HbA1c) levels < 7%. A t-test was employed to identify significant differences between the two groups. Correlation coefficients were calculated using Pearson's method. A Logistic regression analysis was conducted to assess the association between variables and glycemic control. A linear regression analysis was performed to assess the relationship between serum magnesium levels and HbA1c. Results: Patients with poor glycemic control exhibited elevated age, low-density lipoprotein (LDL-C), fasting plasma glucose (FPG), and homeostasis model assessment (HOMA-IR) compared to those with good glycemic control (P < 0.001). Additionally, total cholesterol (TC) levels were significantly higher in patients with poor glycemic control. Conversely, high-density lipoprotein (HDL-C) and serum magnesium levels were lower in patients with poor glycemic control. Serum magnesium levels exhibited negative correlations with HOMA-IR (r = -0.05, P < 0.05), HbA1c (r = -0.29, P < 0.05), and FPG (r = -0.20, P < 0.05). Moreover, serum magnesium was significantly associated with reduced odds of glycemic control (OR = 0.0005, 95% CI 0.0001-0.0027, P < 0.001). Conclusion: The serum magnesium level in patients with T2DM is closely associated with glycemic control.

A Bayesian network for estimating hypertension risk due to occupational aluminum exposure.

Background: The correlation between metals and hypertension, such as sodium, zinc, potassium, and magnesium, has been confirmed, while the relationship between aluminum and hypertension is not very clear. This study aimed to evaluate the correlation between plasma aluminum and hypertension in electrolytic aluminum workers by the Bayesian networks (BN). Methods: In 2019, 476 male workers in an aluminum factory were investigated. The plasma aluminum concentration of workers was measured by inductively coupled plasma mass spectrometry. The influencing factors on the prevalence of hypertension were analyzed by the BN. Results: The prevalence of hypertension was 23.9% in 476 male workers. The risk of hypertension from plasma aluminum in the Q2, Q3, and Q4 groups was 5.20 (1.90-14.25), 6.92 (2.51-19.08), and 7.33 (2.69-20.01), respectively, compared with that in the Q1 group. The risk of hypertension from the duration of exposure to aluminum of >10 years was 2.23 (1.09-4.57), compared without aluminum exposure. Area under the curve was 0.80 of plasma aluminum and the duration of exposure to aluminum was based on covariates, indicating that aluminum exposure had important predictive value in the prevalence of hypertension in the occupational population. The results of the study using the BN model showed that if the plasma aluminum of all participants was higher than Q4 (≥47.86 µg/L) and the participants were drinking, smoking, diabetes, central obesity, dyslipidemia, and aged >50 years, the proportion of hypertension was 71.2%. Conclusions: The prevalence of hypertension increased significantly with the increase of plasma aluminum level.