Basic & Clinical Pharmacology & Toxicology最新文献

Previous work in deprescribing interactions primarily involved surveys, interviews or reviews; there is a gap in utilizing real-time doctor–patient communication to understand what strategies physicians use to deprescribe and how patients respond. To move research methodology in this direction, our multidisciplinary team brought together professionals from biomedical, cognitive and social sciences to collaborate with a primary care practice and analyse nine quality-assurance recordings of doctor–patient visits. Eligible patients were 60 years or older and prescribed two or more medications. Through collaborative mixed-method analysis, we identified outcomes and themes of deprescribing conversations. An additional layer of analysis was conducted based on qualitative interviews with two deprescribing physicians for a conversation about physicians' decision-making process in initiating and responding to patient concerns in the interaction. Interplay between patient, physician and system factors was noted, highlighting the key role of health care team collaboration to support deprescribing. Our innovative research design enables a better understanding of deprescribing processes in a primary care setting and has implications for future research including patients, caregivers and community providers.

Respiratory syncytial virus (RSV) is a leading etiological agent of pneumonia, particularly affecting infants under 2 years and elderly populations, with characteristic clinical manifestations including fever, cough and wheezing. Although Feining mixture—a traditional Chinese medicine formulation based on the classical Maxing Shigan Decoction from the ‘Treatise on Febrile Diseases’—has shown clinical efficacy in ameliorating symptoms of viral pneumonias including RSV infection, its precise pharmacological mechanisms remain undefined. Through serum metabolomics and network pharmacology approaches, we systematically identified RSV-associated metabolic disturbances and characterised Feining mixture's regulatory effects on these pathological alterations. Our investigations revealed that Feining mixture significantly attenuated pulmonary inflammation, as evidenced by reduced pro-inflammatory cytokine levels in bronchoalveolar lavage fluid and improved histopathological features in RSV-infected mice. Metabolomic profiling identified 49 differentially expressed metabolites and 14 perturbed metabolic pathways. Network pharmacology and molecular docking analyses predicted the involvement of TP53, AKT1 and STAT3 as core targets, suggesting modulation of PI3K/AKT and TNF signalling pathways. These predictions were experimentally validated through qPCR and Wb analyses, which confirmed that Feining mixture's therapeutic effects are mediated through selective inhibition of the PI3K/AKT1 signalling cascade. These findings provide novel mechanistic insights into Feining mixture's anti-RSV activity, establishing its therapeutic potential through multi-target modulation of critical inflammatory and metabolic pathways.

Bleomycin (BLM), a chemotherapeutic agent commonly used in cancer treatment, is associated with oxidative stress and testicular toxicity, leading to impaired reproductive health. Hesperidin (HES), a citrus-derived flavonoid with strong antioxidant properties, has the potential to counteract these adverse effects. This study aimed to evaluate the protective effects of HES against the reproductive toxicity induced by BLM, focusing on oxidative stress, sperm characteristics and histological changes in the male reproductive system. Thirty-two rats were divided into four groups: Control, BLM, HES and BLM + HES. BLM was administered intraperitoneally at 10 mg/kg twice a week, while HES was given orally at 50 mg/kg/day for 30 days. The findings revealed that BLM induced significant oxidative stress by promoting lipid peroxidation and impairing antioxidant defence mechanisms in the testis. Additionally, BLM treatment caused a marked decline in sperm motility, an increase in abnormal sperm rates and severe histopathological damage in testicular tissue. However, co-administration of HES significantly mitigated these adverse effects by improving oxidative balance, restoring sperm quality and reducing histopathological injuries. In conclusion, HES demonstrated potential in alleviating BLM-induced reproductive toxicity, suggesting its therapeutic role in protecting against chemotherapy-induced male infertility.