Background: Astragalus polysaccharides (APS) are active constituents of Astragalus membranaceus. They have been widely studied, especially with respect to their immunopotentiating properties, their ability to counteract the side effects of chemotherapeutic drugs, and their anticancer properties. However, the mechanism by which APS inhibit cancer and the issue of whether that mechanism involves the reversal of multidrug resistance (MDR) is not completely clear. The present paper describes an investigation of the effects of APS on P-glycoprotein function and expression in H22 hepatoma cell lines resistant to Adriamycin (H22/ADM). Methods: H22/ADM cell lines were treated with different concentrations of APS and/or the most common chemotherapy drugs, such as Cyclophosphamid, Adriamycin, 5-Fluorouracil, Cisplatin, Etoposide, and Vincristine. Chemotherapeutic drug sensitivity, P-glycoprotein function and expression, and MDR1 mRNA expression were detected using MTT assay, flow cytometry, Western blotting, and quantitative RT-PCR. Results: When used alone, APS had no anti-tumor activity in H22/ADM cells in vitro. However, it can increase the cytotoxicity of certain chemotherapy drugs, such as Cyclophosphamid, Adriamycin, 5-Fluorouracil, Cisplatin, Etoposide, and Vincristine, in H22/ADM cells. It acts in a dose-dependent manner. Compared to a blank control group, APS increased intracellular Rhodamine-123 retention and decreased P-glycoprotein efflux function in a dose-dependent manner. These factors were assessed 24 h, 48 h, and 72 h after administration. APS down regulated P-glycoprotein and MDR1 mRNA expression in a concentration-dependent manner within a final range of 0.8–500 mg/L and in a time-dependent manner from 24–72 h. Conclusion: APS can enhance the chemosensitivity of H22/ADM cells. This may involve the downregulation of MDR1 mRNA expression, inhibition of P-GP efflux pump function, or both, which would decrease the expression of the MDR1 protein.

Chronic stress is strongly associated with the occurrence and development of depression and cardiovascular disease. Stress can induce altered mitochondrial function and activation of apoptosis in the cardio-cerebral system. However, it is unknown whether the protein kinase C ε (PKCε)-aldehyde dehydrogenase 2 (ALDH2) pathway is altered under chronic stress, and this study sought to address this question. A rat model of depression was established using a chronic unpredictable mild stress (CUMS) protocol. After experiencing CUMS for 4 weeks, the sucrose preference test and the forced swim test verified depressive-like behaviors. Enzyme linked immunosorbent assays showed that ALDH2 activity was decreased in the rat hippocampus and prefrontal cortex, but was not altered in the myocardium. Western blot assays demonstrated reduced levels of ALDH2 and PKCε, but increased levels of 4-hydroxy-2-nonenal (4HNE) adducts. Caspase-3 expression did not obviously alter, but active forms of caspase-3 were increased in the hippocampus and prefrontal cortex. In the myocardium, expression of ALDH2, PKCε and 4HNE adducts did not remarkably alter; while caspase-3 expression was reduced and the active forms of caspase-3 were upregulated. Pearson’s correlation test demonstrated that expression of 4HNE adducts was positively correlated with levels of the active forms of caspase-3 in the hippocampus and prefrontal cortex, but not in the myocardium. In conclusion, chronic stress can damage the PKCε-ALDH2 signaling pathway in the hippocampus and prefrontal cortex, but not in the myocardium. Moreover, 4HNE is associated with active forms of caspase-3 in the hippocampus and prefrontal cortex.

An essential medicine (EM) system has been implemented in China to reduce patients’ financial burden and to make the use of drugs more rational. This study aims to evaluate the current state of the EM system in Guangdong Province. We conducted surveys in 21 cities in 2012, covering 98 medical institutions, 1,509 doctors, 17 medicine manufacturers, and 17 distribution companies. We also reviewed outpatient prescriptions (n = 9,941) for treating hypertension, diabetes, bacterial infections and gout to measure the rational use of drugs in secondary and tertiary (upper-level) hospitals. The percentage of non-priority EM use ranged from 8.1% to 10.7% in upper-level hospitals, and this non-priority use significantly increased prescription drug costs. Other types of inappropriate medicine use were found more frequently in treating bacterial infections (7.4%) than in treating hypertension (1.6%), diabetes (1.3%) and gout (1.7%). Tertiary hospitals prescribed fewer EMs than secondary hospitals; moreover, tertiary hospitals had higher prescription drug costs. The zero mark-up policy decreased prescription drug costs in secondary hospitals. The survey revealed that forced full-prescription EM use might lead to fewer patient visits to primary hospitals. Manufacturers had halted the production of four (1, 23) types of EMs at the time of the survey. Encouraging the priority use of EMs and implementation of the zero mark-up policy were effective in curtailing prescription medicine costs in upper-level hospitals. Further work should focus on the following: creating guidelines to enhance rational prescription behavior, establishing policies to support EM use in upper-level hospitals and improving the bidding system to ensure a steady supply of the lowest-priced generic drugs.

Acute myocarditis, characterized by inflammatory myocardial injury, significantly risks heart failure and sudden death. Despite its severity, specific biomarkers are lacking. This study applied metabolomic analysis to urine samples from 21 acute myocarditis patients and 21 controls using UPLC-MS/MS, revealing 728 increased and 820 decreased metabolites in patients. The affected pathways were predominantly related to the amino acid metabolism, lipid metabolism, carbohydrate metabolism, nucleotide metabolism, and others. We have validated 19 metabolites with an area under the receiver operating characteristic curve (AUC-ROC) greater than 0.7 and a high level of identification confidence. Potential biomarkers upregulated in acute myocarditis patients included phytosphingosine, N-acetylneuraminic acid, indolelactic acid, L-glutamic acid, 4-pyridoxic acid, N1-methyl-2-pyridone-5-carboxamide, palmitic acid, hydroxyphenyllactic acid, riboflavin, nicotinic acid, choline, N-formylkynurenine, guanine, and hypoxanthine. Conversely, sebacic acid, 4-vinylphenol sulfate, capryloylglycine, 4-ethylphenylsulfate, and azelaic acid were found to be decreased. Collectively, the metabolomic profiling has uncovered distinct metabolic signatures in patients with acute myocarditis. The amino acid metabolism appears to play a pivotal role in the pathogenesis of acute myocarditis, offering potential avenues for diagnostic and therapeutic development.

Background: Acute myocarditis is one of the common causes of sudden cardiac death among young adults. While melatonin has been recognized for its cardioprotective properties, the specific relationship between melatonin and acute myocarditis in humans is not well established. Methods: We collected morning urine samples from 21 patients diagnosed with acute myocarditis and 21 healthy controls to measure the levels of 6-sulfatoxymelatonin (aMT6s), a biomarker of nocturnal melatonin secretion, using an ELISA assay. Results: The mean age of the control group was 31.05 ± 9.75 years, and the acute myocarditis group had a mean age of 30.71 ± 10.11 years. Both groups were evenly divided by gender, with 15 males and 6 females in each. Acute myocarditis patients exhibited significantly lower aMT6s levels (50.57 ± 36.39 ng/mL) compared with healthy volunteers (80.36 ± 48.92 ng/mL; P = 0.031). Similarly, the aMT6s-to-creatinine ratio was reduced in patients (106.95 ± 73.45 ng/mg cr) vs. controls (159.73 ± 92.96 ng/mg cr; P = 0.048). Conclusion: Lower melatonin levels, measured via urinary aMT6s concentrations in acute myocarditis patients, suggest a link to the disease process.