Pharmacology最新文献

Introduction: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has a protective effect on acute coronary syndrome (ACS). However, most studies have shown that this protective effect is based on a decrease in low-density lipoprotein cholesterol, while other mechanisms remain limited. This study aimed to determine whether PCSK9i can improve the prognosis of ACS patients by protecting endothelial function.

Methods: A total of 113 ACS patients were enrolled and randomly assigned to PCSK9i group (PCSK9i combined with statins) and control group (statins only). Blood lipids and endothelial function indicators were measured and analyzed 6 weeks before and after treatment. The effect of PCSK9i on the expression and secretion of endothelial function indicators in vascular endothelial cells were studied by cell experiments.

Results: After 6 weeks of treatment, endothelial function indicators such as nitric oxide (NO), thrombomodulin, intercellular cell adhesion molecule-1, endothelin-1, and flow-mediated vasodilation were significantly improved in PCSK9i group compared with control group. Only the changes of NO and von Willebrand factor were associated with blood lipid levels, whereas the changes of other endothelial function indicators were not significantly associated with blood lipid levels. PCSK9i reduced the incidence of major adverse cardiovascular events in patients with ACS compared to those in the control group. In cell experiments, PCSK9i treatment significantly ameliorated LPS induced endothelial injury in HUVECs.

Conclusion: PCSK9i can protect vascular endothelial function partly independently of its lipid-lowering effect and ameliorate the prognosis of patients with ACS within 6 weeks. This mechanism may involve heat shock transcription factor 1/heat shock proteins -related signaling pathways. Early use of PCSK9i in patients with ACS should be strongly considered in clinical practice.

Introduction: Batryticatus bombyx (BB) (Beauveria bassiana Vuill.) is used as a herbal medicine and food additive. Although BB has neuroprotective and antiapoptotic effects, its impacts on atopic dermatitis (AD) are unknown. We evaluated the effects of BB in an NC/Nga mouse model of house dust mite (HDM)-induced AD, in TNF-α- and IFN-γ (TI)-stimulated HaCaT keratinocytes, and in a 3D human skin model.

Methods: NC/Nga mice were induced with HDM and treated with BB for 6 weeks. We assessed skin symptoms, serum levels of IgE, histamine, and IL-6, immune cell counts and performed histological analysis of dorsal skin tissue. Additionally, we induced inflammation in HaCaT cells and a 3D human skin model using TNF-α/IFN-γ. We measured inflammatory cytokine levels and skin hydration factors and delved into underlying mechanisms via ELISA, real-time PCR, and Western blot.

Results: BB improved skin lesions, reduced thickness, and inflammatory cell infiltration in HDM-induced mice. It alleviated scratching, improved moisture retention, and reduced IgE, histamine, and IL-6 levels. In HaCaT cells, BB inhibited thymic stromal lymphopoietin and increased hyaluronan content. It also upregulated aquaporin-3, hyaluronan synthase-1/3, filaggrin, involucrin, and occludin, enhancing skin hydration and tight junction stability. BB decreased STAT1, p38 MAPK, and NF-κB p65 levels in HaCaT cells and exhibited antioxidant effects by increasing HO-1/Nrf2 expression.

Conclusion: BB may serve as a therapeutic alternative for AD treatment by inhibiting skin inflammation.

Background: Doxorubicin is a first-line drug used in cancer chemotherapy, but its severe myocardial toxicity limits its widespread use. Indole derivatives, a large class of substances widely found in natural plants and metabolic products, exhibit a variety of biological effects.

Summary: Previous studies have shown that indole compounds can protect against doxorubicin-induced myocardial damage through multiple mechanisms, including antioxidant activity, mitochondrial protection, anti-inflammatory effects, ferroptosis inhibition, apoptosis suppression, and endoplasmic reticulum stress attenuation. Understanding the pathogenesis of doxorubicin-induced cardiomyopathy and the molecular mechanisms by which indole compounds protect the myocardium is crucial for the development of novel drug molecules based on indole compounds in the future.

Key messages: Focusing on the molecular characteristics of indole derivatives, investigating their pharmacodynamics and safety, and developing safe and effective antagonistic molecules to counteract doxorubicin toxicity, holds great potential, and significance.

Background: Cancer is a major cause of death worldwide. Although modern medicine has made strides in treatment, a complete cure for cancer remains elusive.

Summary: Utilization of medicinal plants in traditional medicine for the treatment of multiple diseases, including cancer, is a well-established practice. Sinomenine is an alkaloid extracted from a medicinal plant and has a diverse range of biological properties, including anti-oxidative, anti-inflammatory, and antibacterial effects. Sinomenine exhibits inhibitory effects on various types of tumor cells, including breast, lung, and liver cancers. The anticancer properties of sinomenine are believed to involve stimulation of apoptosis and autophagy as well as suppression of cell proliferation, invasion, and metastasis.

Key message: This review summarizes the current research on sinomenine's potential as an anticancer agent, which may contribute to the discovery of more effective cancer treatments.

Introduction: Proton pump inhibitors (PPIs) are known to decrease the risk of gastrointestinal (GI) bleeding. However, concerns have been raised regarding the potential pharmacodynamic interactions of PPIs and antiplatelet drugs with respect to cardiovascular risk. Patients with BCR::ABL1-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), and polycythemia vera (PV) often suffer from peptic ulcer disease (PUD) and frequently receive low-dose aspirin due to an intrinsically high thrombotic risk.

Method: This retrospective multicenter study from a community setting investigated whether continuous PPI use may affect thrombohemorrhagic risk in ET and PV patients treated with long-term aspirin.

Results: Ninety-four aspirin-treated MPN patients (ET = 36, PV = 58) were included; median age was 69.5 years (range 21-92) and 40 (42.6%) were males. Nineteen (20.2%) patients continuously received PPIs and pantoprazole (n = 15, 78.9%) was the most frequently received PPI. PV phenotype (p = 0.085), male sex (p = 0.011), and prior thrombosis (p = 0.005) were associated with PPI use, whereas no correlations were found with respect to age, disease risk, splenomegaly, mutational status, constitutional symptoms, cardiovascular risk factors, cytoreductive treatment, or any of the blood cell counts (p > 0.050 for all analyses). The median follow-up time was 55.5 months; 19 (20.2%) thrombotic and 13 (13.8%) bleeding events occurred during this time. The use of PPIs was not associated with an increased risk of thrombosis (p = 0.158) or overall bleeding (p = 0.229) and none of the patients treated with PPIs experienced GI bleeding.

Conclusions: Considering that Helicobacter pylori infection and PUD are quite frequent in ET and PV patients, these preliminary results may provide some reassurance to physicians regarding the absence of thrombohemorrhagic risk associated with prolonged PPI use in MPN patients treated with long-term aspirin. Our observations may be even more important in the light of recent evidence suggesting suboptimal platelet inhibition in ET with once-daily when compared to twice- or triple-daily aspirin which may also cause more abdominal discomfort. Limitations of this study are its retrospective design, limited number of patients included, and the lack of pharmacodynamic and pharmacokinetic assessments.

Introduction: The prevalence of potential drug-drug interactions (pDDIs) is becoming a major safety concern, as it has been previously linked to a significant number of adverse drug events and could have serious consequences for patients, including death. This is especially relevant for patients with chronic renal failure, as they are particularly vulnerable to drug-drug interactions. The aim of this study was to evaluate the prevalence and associated factors of pDDIs in patients receiving chronic peritoneal dialysis.

Methods: An observational, cross-sectional study was conducted on consecutive peritoneal dialysis patients attending four tertiary care hospitals for regular monthly examination. The primary outcome was the number of pDDIs identified using Lexicomp. Potential predictors were determined using multiple linear regression.

Results: Total number of patients included in the study was 140. The results showed that pDDIs were highly prevalent, especially in patients who use antiarrhythmics (p = 0.001), have diabetes mellitus (p = 0.001), recently started peritoneal dialysis (p = 0.003), or have higher number of prescribed drugs (p < 0.001). Number of prescribed drugs (p < 0.001) remained a significant predictor of high-risk pDDIs in addition to the female gender (p = 0.043).

Conclusion: Clinicians should be particularly cautious when prescribing multiple medications to high-risk patients, such as peritoneal dialysis patients, to mitigate the risk of drug-drug interactions and associated adverse health outcomes.

Introduction: Hyperuricemia may be involved in the phenotypic transformation of vascular smooth muscle cells, thus promoting the occurrence of atherosclerosis, and autophagy may be one of the important links, but little is known about the specific molecular mechanism.

Methods: We established a mouse model of hyperuricemia and studied the relationship between changes in autophagy levels and the phenotypic transformation of muscle cells.

Results: Our study found that high uric acid levels promote the phenotypic transformation of muscle cells by inhibiting autophagy, thus enhancing their proliferation and migration abilities. If autophagy is restored, phenotypic transformation can be reversed by reducing the levels of the transcription factor Kruppel-like factor 4.

Conclusion: Uric acid may induce the phenotypic transformation of muscle cells and promote the occurrence of atherosclerosis by disrupting normal autophagy.