Electroacupuncture preconditioning protects against myocardial ischemia-reperfusion injury by modulating dynamic inflammatory response.

Background: The protective effects of electroacupuncture (EA) preconditioning against myocardial ischemia-reperfusion injury (MIRI) have been reported. However, the underlying mechanism remains unclear. Recent research has indicated that the dynamic inflammatory response following MIRI plays an essential role in the progression of myocardial injury. This study aimed to investigate the myocardial protective effects of EA preconditioning on MIRI in rats and to explore the relevant mechanism from the perspective of dynamic inflammatory response. Methods: A MIRI model was employed, and the rats were subjected to EA on Neiguan for four days prior to modeling. The myocardial protective effect of EA preconditioning was evaluated by echocardiography, Evans blue and triphenyltetrazolium chloride staining. Real-time polymerase chain reaction, Western blot, hematoxylin & eosin staining, and immunohistochemistry were utilized to detect the content of mitochondrial DNA, NOD receptor family protein 3 (NLRP3) inflammasome activation, neutrophil recruitment and macrophage infiltration in blood samples and myocardium below the ligation. Results: We found that EA preconditioning could accelerate the recovery of left ventricle function after MIRI and reduce the myocardial infarction area, thereby protecting the myocardium against MIRI. Furthermore, EA preconditioning was observed to ameliorate mitochondrial impairment, reduce the level of plasma mitochondrial DNA, modulate NLRP3 inflammasome activation, attenuate neutrophil infiltration, and promote the polarization of M1 macrophages towards M2 macrophages in the myocardium after MIRI. Conclusion: EA preconditioning could reduce plasma mtDNA, suppress overactivation of the NLRP3 inflammasome, facilitate the transition from the acute pro-inflammatory phase to the anti-inflammatory reparative phase after MIRI, and ultimately confer cardioprotective benefits.

Pre-clinical pharmacological profile of QF-036, a potent HIV-1 maturation inhibitor.

QF-036 is an HIV-1 maturation inhibitor in pre-clinical development, and its antiviral activity against a laboratory HIV-1 strain and two drug-resistant strains was determined in the C8166 line. QF-036 was also subjected to absorption, distribution and metabolism (ADM) assessment in vitro, and pharmacokinetic profiles were evaluated in rats and monkeys. The 50% effective concentrations (EC50 ) of QF-036 against the three strains were 20.36 nM, 0.39 µM and 2.11 nM, respectively, demonstrating better antiviral potential than the first-generation antiviral maturation inhibitor bevirimat. QF-036 demonstrated moderate cell permeability, high plasma protein binding ability and good metabolic stability in vitro. After oral QF-036 administration to rats and monkeys, both species exhibited moderate bioavailability, and the plasma drug exposure increased in an approximately dose-proportional manner. When administered orally (30 mg/kg) to monkeys, the QF-036 plasma concentration (Cmax ) peaked at 3671 ng/mL (4.82 µM), 12 to 2410 times higher than the EC50 of laboratory or resistant HIV-1 strains. Moreover, the plasma concentration of QF-036 at 12 hours after administration was 263 ng/mL (0.35 µM), which approximately matched the highest EC50 value of the three test strains. The favourable viral inhibitory activity and pharmacokinetic properties provide critical support for QF-036 as a promising anti-HIV therapeutic candidate.

Relationships between Chronic Diseases and Depression among Middle-aged and Elderly People in China: A Prospective Study from CHARLS.

Given the rapid increase in the prevalence of chronic diseases in aging populations, this prospective study including 17 707 adults aged ≥45 years from China Health and Retirement Longitudinal Study was used to estimate the associations between chronic disease, multimorbidity, and depression among middle-aged and elderly adults in China, and explore the mediating factors. Depressive symptoms were assessed using the 10-item Centre for Epidemiological Studies Depression Scale (CES-D-10) questionnaire. Twelve chronic physical conditions, including hypertension, diabetes, dyslipidemia, cancer, chronic lung disease, liver disease, heart failure, stroke, kidney disease, arthritis or rheumatism, asthma, digestive disease were assessed. The prevalence rates for physical multimorbidity and depression (CES-D-10 ≥10) were 43.23% and 36.62%, respectively. Through multivariable logistic models and generalized estimating equation (GEE) models, we found all 12 chronic physical conditions, and multimorbidity were significantly associated with depression. Both mobility problems and chronic pain explained more than 30% of the association for all chronic conditions, with particularly high percentages for stroke (51.56%) and cancer (51.06%) in mobility problems and cancer (53.35%) in chronic pain. Limited activities of daily living (ADL) explained 34.60% of the stroke-cancer relationship, while sleep problems explained between 10.15% (stroke) and 14.89% (chronic lung disease) of the association. Individuals with chronic diseases or multimorbidity are significantly more likely to be depressed. Functional symptoms involving limitations of ADL and mobility difficulties mediated much of the association between chronic diseases and incident depression. These symptoms could be targeted for interventions to ameliorate the incidence of depression among individuals with chronic conditions.

Single- and repeated-dose toxicity studies on the novel HIV maturation inhibitor QF-036 in Sprague-Dawley rats.

QF-036 is a novel human immunodeficiency virus (HIV) maturation inhibitor that is a lupine triterpenoid derivative. The objective of this study was to evaluate the safety of QF-036. A single oral toxicity and a 4-week repeated oral toxicity were investigated in Sprague-Dawley (SD) rats. The single oral toxicity study of QF-036 in SD rats showed that no mortality or visible pathological changes were noted at doses of 100, 300, and 1000 mg/kg. QF-036 exhibited a non-linear toxicokinetic profile over the dose range of 100-1000 mg/kg in the single dose study, and a saturation trend appeared at doses of 100 and 300 mg/kg. In the 4-week oral toxicity and toxicokinetic study, SD rats were given 0, 50, 100, and 200 mg/kg QF-036 once daily for 4 weeks, followed by a 4-week recovery period. No mortality or significant effects on food consumption, body weight, or behavior were observed. In addition, there were no test article-related changes in hematology, clinical biochemistry and histopathology. The no observed adverse effect level (NOAEL) was 200 mg/kg. The toxicokinetic study demonstrated a dose-dependent increase in the systemic exposure to QF-036 after 4 weeks of oral administration. There were no marked sex differences or drug accumulation observed for repeated doses of QF-036.

[Safety of animal traditional Chinese medicine (TCM) injections].

Animal medicine injection is an important part of traditional Chinese medicine (TCM) injections. All or part of animals with a significant curative effect and little side reactions as raw materials as well as modern technology are used to produce traditional Chinese medicine injections with a reliable and rapid drug efficacy and high bioavailability. Due to the complex composition of traditional Chinese medicine injections, imperfect quality standards, and unreasonable clinical use, the incidence of adverse reactions of traditional Chinese medicine injections has been significantly higher than that of traditional Chinese medicine for oral use. Animal medicine injections contain rich protein and fat, and heteroproteins are the main sensitization source in animal medicine injections. At present, the adverse reactions of animal medicine injections are mainly manifested in the anaphylaxis-like reactions at skin, mucous membranes and organ systems. The adverse reactions that occur during the first medication are more common. Specific causes for allergic-like adverse reactions in animal injections and related substances in traditional Chinese medicine injections made of animals that induce allergies or anaphylactoid reactions are currently not specifically reported. This article reviews the current adverse reactions of animal TCM injections, allergies and pseudoallergic reactions of animal TCM injections, the pharmacokinetics of animal TCM injections, and the combined use of drugs, in order to improve the quality standards of Chinese medicine injections for animals and provide reference for further safety related research.

[Pharmacokinetic characteristics of fourteen main components of Gegen Qinlian Decoction in rats].

Animal traditional Chinese medicine has a long history of application in China, and its clinical application is very extensive. Due to the complex chemical composition in animal traditional Chinese medicine, the basis of chemical research is relatively weak, which leads to the unclear composition and toxic components of many animal Chinese medicines. The relationship between the medicinal and toxic components of animal Chinese medicine has not yet been elucidated. The non-clinical safety evaluation of animal traditional Chinese medicine mainly includes acute toxicity, long-term toxicity, safety pharmacology, reproductive toxicity, genotoxicity experiments, and experimental studies such as carcinogenicity are needed when necessary. The current preclinical safety research on animal traditional Chinese medicine is mainly based on the study for toxic animal traditional Chinese medicines. Most animal Chinese medicines have not carried out systematic preclinical and clinical safety studies. The research method is mainly focused on acute toxicity test. It is necessary to carry out systematic preclinical safety studies on animal traditional Chinese medicines, to clarify the possible side effects and its characteristics, its toxic target organs, toxic doses and poisoning mechanisms induced by different animal traditional Chinese medicines. Finally, this paper suggests that in the preclinical safety study of animal traditional Chinese medicine, in-depth research and comparison should be carried out in combination with chemical substance foundation, origin, and collection season, and the safety of "non-toxic" animal traditional Chinese medicine should be carried out when necessary. In addition, it is necessary to rationally use the cutting-edge technologies and methods of toxicology research to fully clarify the preclinical safety information of animal Chinese medicines.