Berberine increases the killing effect of pirarubicin on HCC cells by inhibiting ATG4B-autophagy pathway.

Pirarubicin (THP) is a new generation of cell cycle non-specific anthracycline-based anticancer drug. In the clinic, THP and THP combination therapies have been shown to be effective in hepatocellular carcinoma (HCC) patients with transcatheter arterial chemoembolization (TACE) without serious side effects. However, drug resistance limits its therapeutic efficacy. Berberine (BBR), an isoquinoline alkaloid, has been shown to possess antitumour properties against various malignancies. However, the synergistic effect of BBR and THP in the treatment of HCC is unknown. In the present study, we demonstrated for the first time that BBR sensitized HCC cells to THP, including enhancing THP-induced growth inhibition and apoptosis of HCC cells. Moreover, we found that BBR sensitized THP by reducing the expression of autophagy-related 4B (ATG4B). Mechanistically, the inhibition of HIF1α-mediated ATG4B transcription by BBR ultimately led to attenuation of THP-induced cytoprotective autophagy, accompanied by enhanced growth inhibition and apoptosis in THP-treated HCC cells. Tumor-bearing experiments in nude mice showed that the combination treatment with BBR and THP significantly suppressed the growth of HCC xenografts. These results reveal that BBR is able to strengthen the killing effect of THP on HCC cells by repressing the ATG4B-autophagy pathway, which may provide novel insights into the improvement of chemotherapeutic efficacy of THP, and may be conducive to the further clinical application of THP in HCC treatment.

Dexmedetomidine affects the NOX4/Nrf2 pathway to improve renal antioxidant capacity.

OBJECTIVES: The study aimed to investigate the protective effects of dexmedetomidine (DEX) on renal injury caused by acute stress in rats and explore the protective pathways of DEX on rat kidneys in terms of oxidative stress. METHODS: An acute restraint stress model was utilized, where rats were restrained for 3 hours after a 15-minute swim. Biochemical tests and histopathological sections were conducted to evaluate renal function, along with the measurement of oxidative stress and related pathway proteins. KEY FINDINGS: The open-field experiments validated the successful establishment of the acute stress model. Acute stress-induced renal injury led to increased NADPH oxidase 4 (NOX4) protein expression and decreased expression levels of nuclear transcription factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1). Following DEX treatment, there was a significant reduction in renal NOX4 expression. The DEX-treated group exhibited normalized renal biochemical results and less damage observed in pathological sections compared to the acute stress group. CONCLUSIONS: The findings suggest that DEX treatment during acute stress can impact the NOX4/Nrf2/HO-1/NQO1 signaling pathway and inhibit oxidative stress, thereby preventing acute stress-induced kidney injury. Additionally, DEX shows promise for clinical applications in stress syndromes.

Glufosinate-ammonium causes liver injury in zebrafish by blocking the Nrf2 pathway.

Glufosinate-ammonium (GLA) is a widely used herbicide, but less research has been done on its harmful effects on non-target organisms, especially aquatic organisms. In this study, 600 adult zebrafish were exposed to different concentration of GLA (0, 1.25, 2.5, 5, 10, and 20 mg/L) for 7 days, and the livers were dissected on the eighth day to examine the changes in liver structure, function, oxidative stress, inflammation, apoptosis, and Nrf2 pathway, and finally to clarify the mechanism of GLA induced liver injury in zebrafish. The levels of alanine aminotransferase, aspartate aminotransferase, reactive oxygen species, malondialdehyde, inflammatory factors (IL-6 and TNF-α), and caspase-3 gradually increased, while the levels of superoxide dismutase, catalase, glutathione, and glutathione peroxidase gradually decreased with the increase of GLA concentration. The Nrf2 pathway was activated at low concentrations (1.25-5 mg/L) and significantly inhibited at high concentrations (10 and 20 mg/L). These results suggested that GLA could cause oxidative stress, inflammation, and apoptosis in zebrafish liver. Therefore, GLA can cause liver injury in zebrafish, and at high concentrations, the inhibition of Nrf2 pathway is one of the important causes of liver injury.

Evaluation of left and right ventricular myocardial function after lung resection using speckle tracking echocardiography.

The impact of major lung resections on myocardial function has not been well-investigated. We aimed to identify this impact through the use of speckle tracking echocardiography (STE) to evaluate the right and left ventricular myocardial function in patients who underwent lung resections.Thirty patients who had lung resections were recruited for this study. Ten patients who underwent pneumonectomies were matched by age and sex, with 20 patients who underwent lobectomies. STE was performed on both right and left ventricle (RV and LV). Strain values of pre and postlung resections were compared in both the pneumonectomy group and the lobectomy group. Comparison between the pneumonectomy group and the lobectomy group was also studied.Left ventricular ejection fraction remained normal (>55%), but significantly decreased after lung resection in both the pneumonectomy group and the lobectomy group. An accelerated heart rate was observed in both groups after lung resection, with the pneumonectomy group demonstrating extra rapid heart rate (P < 0.05). Strain values in the RV and LV decreased in both groups after lung resection, with the pneumonectomy group exhibiting a further decrease in longitudinal strain in LV and RV when compared with the lobectomy group (P < 0.05).Right and left ventricular dysfunction can occur after lung resection regardless of pneumonectomy or lobectomy, and lobectomy may have a less significant impact on myocardial functions. This study demonstrated that STE is able to detect acute cardiac dysfunction after lung resection.

Analysis for hypertension and related risk factors of physical examination population.

BACKGROUND AND OBJECTIVES: Essential hypertension is the most common chronic disease. To provide a basis for developing the prevention and control strategies of hypertension by epidemiological investigation on factors related to hypertension in health examination population. METHODS: Data of health examination population from Jilin municipal enterprise and public institutions during January 2011 and July 2012 were randomly selected, and statistical analysis was performed for the age, gender, body mass index, blood lipids, blood uric acid, serum creatinine, blood glucose and hypertension classification indexes. RESULTS: 1859 patients were diagnosed as hypertension. The detection rate of hypertension, awareness rate, new discovery rate, treatment rate, control rate and rate of the patients with family history of hypertension were 21.0%, 27.5%, 72.5%, 19.1%, 6.0% and 26.7%, respectively. A statistically significant difference was found in serum creatinine, blood glucose, serum cholesterol, L-DLC, coronary disease, stroke and diabetes mellitus by the comparison among the different blood pressure grades. There was a difference in blood pressure, blood uric acid, blood creatinine, glucose, total cholesterol, triglycerides, H-DLC, L-DLC and other indexes between female and male. No difference was found in the family history of hypertension, renal damage, blood uric acid, triglycerides and H-DLC among the different blood pressure levels. CONCLUSIONS: The hypertension in health examination population has the features of high new discovery rate, low awareness rate and low treatment rate. The factors of age, gender, body mass index, serum creatinine, blood glucose, blood cholesterol, L-DLC, coronary heart disease, stroke and diabetes are associated closely with hypertension.