Latest ArticlesTo explore the effects of psoralen and clopidogrel on metabolism of ciprofol in human liver microsomes.
A high performance liquid chromatography-tandem mass spectrometry method for the detection of ciprofol concentrations in human liver microsomes was established, and the specificity, linearity and lower limit of quantitation, precision, recovery rate, matrix effect and stability of this method were investigated. A series of remaining concentrations of ciprofol after co-incubation of with human liver microsomes were detected, and the results were substituted into GraphPad Prism 8 software to calculate the kinetic parameters of the enzymatic reaction of ciprofol in human liver microsomes. Afterwards, psoralen and clopidogrel were co-incubated with ciprofol, respectively, and the median inhibitory concentrations (IC50) were calculated to investigate the effects of the two cytochrome P450 2B6 (CYP2B6) inactivators on ciprofol metabolism.
Ciprofol was linear in the range of 1.00-100.00 μg·mL-1. The standard curve equation was y=0.15x-0.11 (r=0.999 2); the lower limit of quantification was 1.00 μg·mL-1. The relative standard deviation (RSD) values for intra-day and inter-day precision were less than 7%, with relative error not exceeding ±5%. The extraction recoveries and matrix effects were 92.69%-99.62% and 94.77%-101.84%, respectively. In addition, the samples exhibited satisfactory stabilities incubated in a water bath at 37 ℃ for 2 h, stored at room temperature for 8 h or processed and placed in the autosampler for 24 h. The Michaelis constant (Km), maximum reaction rate (Vmax) and intrinsic clearance (CLint) of ciprofol were 37.81 μg·mL-1, 41.54 ng·min-1·mg protein-1 and 0.91 mL·min-1·mg-1, respectively. Psoralen and clopidogrel inhibited the metabolism of ciprofol in human liver microsomes in a dose-dependent manner with IC50 values of 30.25 and 2.09 μmol·L-1, showing mild and moderate inhibition of the metabolism of ciprofol, respectively.
Psoralen and clopidogrel can reduce the metabolism of ciprofol in human liver microsomes.
Atherosclerosis (AS), a multifactorial inflammatory disease characterized by complex interactions among biomolecules and signaling pathways, poses significant cardiovascular risks. Emerging evidence highlights phosphatidylethanolamine (PE), a key phospholipid component of cellular membranes, as playing pivotal regulatory roles in both the initiation and progression of AS. While existing studies have elucidated PE’s fundamental biological functions, its precise molecular mechanisms governing inflammatory responses, lipid homeostasis, and signal transduction remain incompletely characterized. This comprehensive review systematically examines PE’s involvement in atherogenesis, explores its underlying pathophysiological mechanisms, and critically evaluates current research limitations alongside promising therapeutic avenues. Through this synthesis, we aim to advance mechanistic understanding of PE’s pleiotropic functions and inform novel intervention strategies for atherosclerotic cardiovascular diseases.
Hepatocellular carcinoma (HCC) is the most common type of primary hepatocellular carcinoma, and advanced HCC is severe, difficult to treat, and has a poor prognosis. Since most patients have already lost the chance of surgery at the time of diagnosis, systemic drug therapy has become the main therapeutic tool. Currently, targeted therapeutic agents for advanced HCC are mainly divided into two categories: Tyrosine kinase inhibitors and vascular endothelial growth factor inhibitors. Approved tyrosine kinase inhibitors include sorafenib, lenvatinib, donafenib, regorafenib, cabozantinib and apatinib, etc. Vascular endothelial growth factor inhibitors include ramucirumab and bevacizumab. In recent years, the combination of targeted therapeutics and immune checkpoint inhibitors has effectively prolonged the overall survival of patients in several clinical trials, and this treatment model has become an important breakthrough in the current systemic treatment of advanced HCC. This article provides a brief introduction to the clinical application of targeted therapeutics for HCC.
Ovarian cancer (OC) exhibits the highest mortality rate among gynecological tumors, with platinum-based chemotherapy resistance representing a pervasive therapeutic challenge. MicroRNAs (miRNAs) critically influence platinum drug response through multifaceted mechanisms: modulating DNA damage repair pathways such as nucleotide excision repair, homologous recombination repair, non-homologous end joining, and mismatch repair; regulating apoptotic processes via the inhibitor of apoptosis proteins (IAPs) family and B-cell lymphoma-2 (Bcl-2) family proteins; and controlling intracellular platinum levels through copper transporters, adenosine triphosphate-binding cassette (ABC) transporters, and metallothioneins. This review synthesizes current evidence on miRNA-mediated platinum resistance in OC, providing mechanistic insights to inform future research and potential clinical applications for overcoming chemoresistance.
Postmenopausal osteoporosis (PMOP) is a systemic metabolic bone disease characterised by significant bone loss and deterioration of the bone microstructure. Although traditional anti-osteoporosis drugs have been shown to be effective in preventing and treating PMOP, they can also cause various side effects. Traditional Chinese medicine has been used to treat various diseases for many years and is widely used to treat PMOP due to its high tolerability, low toxicity, good efficacy and minimal adverse reactions. This review summarises the mechanisms of action of PMOP and the current state of research on the mechanisms of action of commonly used Chinese medicinal compounds and combinations for treating PMOP. The aim is to provide ideas for the future clinical treatment of PMOP and related basic research.
Osteoarthritis (OA) is a prevalent chronic degenerative condition in clinical settings, marked by a prolonged disease course and unfavorable prognosis. It imposes a substantial burden on both society and affected families. Chondrocyte apoptosis is a typical pathological manifestation of OA cartilage degeneration, and autophagy is a biological process in which cells are induced by various stressors to activate the lysosomal degradation pathway, selectively degrade and remove the organelles and protein aggregates damaged by internal aging, so as to maintain their own homeostasis. The mammalian target of rapamycin (mTOR)-related signaling pathway is an important regulatory pathway for autophagy. The mTOR signaling pathway is involved in the physiological and pathological processes such as apoptosis and autophagy of OA chondrocytes, and is one of the important targets for the study of OA at home and abroad. Based on the relevant literature in recent years, this paper summarizes the specific role of mTOR in the development of OA and the mechanism of action of traditional Chinese medicine in regulating the mTOR signaling pathway in the prevention and treatment of OA.
G protein-coupled estrogen receptor (GPER) is expressed in a variety of tissues and cells, mainly in the inner cell membrane (endoplasmic reticulum and Golgi apparatus), and also localized in the nucleus. Studies have shown that the GPER signaling pathway is involved in regulating the development of metabolic syndrome (MS), and the lack of GPER expression significantly induces MS features such as obesity, disorders of glucose-lipid metabolism, and hypertension in mice, whereas GPER agonists can improve glucose-lipid metabolism. In this paper, the correlation between GPER and various features of MS is reviewed, with the aim to providing research ideas for the development of anti-MS drugs based on GPER.
Recent advancements in Janus kinase (JAK) inhibitors have highlighted their therapeutic potential in autoimmune diseases, yet safety concerns persist. Chinese pharmaceutical companies are advancing selective JAK inhibitor research and development, focusing on trials for rheumatoid arthritis (RA) patients failing biologic disease-modifying antirheumatic drugs (bDMARDs) and exploring superiority/non-inferiority against tumor necrosis factor (TNF) inhibitors. In the future, JAK inhibitors need to be combined with long-term real-world data to expand the applicable population. This article provides important evidence for new drug research and development, regulatory decisions, and rational clinical medication, with the aim of promoting the safer and more effective use of JAK inhibitors in the treatment of autoimmune diseases.
To observe the clinical efficacy and safety of sivelestat sodium for injection combined with atomized ambroxol hydrochloride injection in the treatment of acute respiratory distress syndrome patients.
The patients with acute respiratory distress syndrome were divided into treatment group and control group by block randomization method. All patients received high-flow nasal cannula oxygen therapy. The control group was given ambroxol hydrochloride injection 15 mg on this basis. The treatment group was treated with sivelestat sodium for injection 4.80 mg·kg-1 on the basis of control group. Both groups were treated for 7 days. Clinical score, respiratory function, pulmonary microvascular resistance index and 28-day mortality were compared between the two groups, and the safety was evaluated.
Treatment group was enrolled 47 cases, 1 case dropped out, and 46 cases were finally included in the analysis; control group was enrolled 48 cases, 2 cases dropped out, and 46 cases were finally included in the analysis. After treatment, the total effective rate of the treatment group and the control group was 89.86% (40 cases / 46 cases) and 67.39% (31 cases / 46 cases), respectively, and the difference was statistically significant (P<0.05). After treatment, the scores of acute physiology and chronic health evaluation Ⅱ in the treatment group and control group were (12.38±2.54) and (14.16±2.79) points, respectively; the Murray lung injury scores were (0.93±0.22) and (1.06±0.27) points, respectively; the scores of sequential organ failure assessment were 5.43±1.22 and 6.14±1.59, respectively; partial pressure of carbon dioxide values were (37.43±3.62) and (39.51±4.11) mmHg, respectively; respiratory rates were (22.43±2.72) and (23.96±3.24) time·min-1, respectively; extra vascular lung water indexes were (8.54±1.62) and (9.37±1.85) mL·kg-1, respectively; pulmonary vascular permeability indexes were (2.58±0.52)% and (2.86±0.54)%, respectively; the fatality rates at 28 days were 10.87% (5 cases/46 cases) and 28.26% (13cases /46 cases), respectively. In comparison to the control group, the aforementioned indicators in the treatment group demonstrated notable statistical differences (all P<0.05). Abnormal liver function, indigestion and stomach burn were the main adverse reactions in treatment group and control group. The total incidence of adverse drug reactions in treatment group and control group were 8.70% (4 cases/46 cases) and 10.87% (5 cases/46 cases), respectively, with no statistical significance (P>0.05).
The use of sivelestat sodium for injection combined with atomized ambroxol hydrochloride injection in treating acute respiratory distress syndrome patients yields favorable clinical outcomes, alleviates patient symptoms, enhances respiratory function, lowers 28-day mortality rates, and is considered safe.
To observe clinical effect and safety of dapagliflozin tablets combined with metformin tablets in the treatment of patients with diabetic kidney disease (DKD).
According to cohort method, DKD patients were divided into control group and treatment group. The control group was given oral metformin tablets (0.5 g per time, twice a day), while treatment group was given oral dapagliflozin tablets (10 mg per time, once a day) on basis of control group. All patients were treated for 12 weeks. The clinical curative effect, glucose metabolism indexes [glycated hemoglobin (HbA1c), fasting blood glucose (FPG), 2 h postprandial blood glucose (2 h PG)], renal function [urine albumin/creatinine (UACR), serum creatinine (SCr), estimated glomerular filtration rate (eGFR)], renal vascular function [resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), end-diastolic velocity (EDV)], urine α-smooth muscle actin (SMA), membrane protein, transforming growth factor (TGF)-β1 and inflammatory factors [interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α] in the two groups were compared, and the safety was evaluated.
There were 40 cases in control group and 40 cases in treatment group. After treatment, difference in total response rate between treatment group and control group was statistically significant [92.50% (37 cases/40 cases) vs 72.50% (29 cases/40 cases), P<0.05]. After treatment, HbA1c levels in treatment group and control group were (6.52±0.76)% and (7.44±0.98)%; FPG levels were (7.11±1.05) and (8.05±1.21)mmol·L-1; 2 h PG levels were (9.32±1.08) and (10.57±1.35) mmol·L-1; UACR levels were (104.76±13.85) and (138.41±16.07)mg·g-1; SCr levels were (82.27±10.38) and (101.68±13.54) μmol·L-1; eGFR levels were (88.06±8.37) and (80.52±7.64) mL·min-1·1.73 m-2; RI levels were 0.51±0.10 and 0.65±0.13; PI were 1.15±0.24 and 1.49±0.31; PSV were (38.30±5.29) and (34.59±4.71) cm·s-1; EDV were (15.73±2.49) and (13.41±2.02) cm·s-1; levels of urine SMA were (26.31±2.39) and (30.47±2.86)kU·L-1; levels of urine membrane protein were (528.41±50.78) and (581.65±57.22) μg·L-1; levels of urine TGF-β1 were (85.01±9.82) and (102.94±13.57) μg·L-1; levels of serum IL-1β were (26.93±3.36) and (40.14±4.57)ng·L-1; levels of serum IL-6 were (14.36±1.59) and (17.94±2.01) ng·L-1; levels of serum TNF-α were (30.22±3.37) and (43.81±4.06) ng·L-1, and differences of all the above indexes between the two groups were statistically significant (all P<0.05). The adverse drug reactions were mainly on loss of appetite, diarrhea, fatigue and nausea in treatment group, while which were mainly on loss of appetite, headache and nausea in control group. There was no significant difference in total incidence of adverse drug reactions between treatment group and control group [12.50% (5 cases/40 cases) vs 7.50% (3 cases/40 cases), P>0.05].
Dapagliflozin combined with metformin can improve glucose metabolism, promote recovery of renal function and renal vascular function, regulate levels of SMA, membrane protein and TGF-β1, relieve inflammatory response and improve clinical curative effect in DKD patients.
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