Clinical and Experimental Pharmacology and Physiology最新文献

This article investigates the intricate associations between apolipoprotein E (APOE) gene alleles variation, insulin resistance (IR) and amyloid-β aggregation in cardiovascular disease (CVD) patients. A cohort of 250 patients exhibiting the symptoms of CVD and 50 control subjects participated in this study. After applying the stringent inclusion and exclusion criteria, the diseased group was further stratified into three categories: CVD+ (Alzheimer's disease) AD, CVD + (diabetes mellitus) DM and CVD + DM + AD. Blood samples were collected from all recruited participants for the biochemical analyses of lipid profile, glycaemic status, liver function enzymes, inflammatory and oxidative stress biomarkers. Tetra amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) was employed for APOE gene analysis. Biochemical evaluations revealed the significant elevations in the serum levels of glucose, liver enzymes, interleukin-6 (IL-6), cholesterol, low-density lipoproteins (LDL), triglycerides (TG) and malondialdehyde (MDA) in CVD + DM + AD group. Conversely, the serum levels of insulin, HDL and hexokinase decreased in CVD + DM + AD group compared to the controls and other CVD groups. Tetra ARMS-PCR results indicated a higher percentage of the risk allele in CVD + DM + AD group when compared with the other groups. Our study elucidates the multifaceted cardiovascular risk factors contributing to IR and AD in CVD patients. Age-related risk factors, prevalence of APOE risk alleles and the impact of statin use on AD incidences were identified. These findings underscore the need for tailored preventive measures, particularly in APOEε4 and ε3/ε4 carriers with CVD. Further studies should delve into the knowledge-based protocols to comprehend the underlying mechanisms. Focusing on the therapeutic targets to prevent or delay DM and AD progression in CVDs, especially in APOEε4 carriers, is essential.

RETRACTION: G. Mo, Y. He, X. Zhang, X. Lei and Q. Luo, “ Diosmetin Exerts Cardioprotective Effect on Myocardial Ischaemia Injury in Neonatal Rats by Decreasing Oxidative Stress and Myocardial Apoptosis,” Clinical and Experimental Pharmacology and Physiology 47, no. 10 (2020): 1713–1722, https://doi.org/10.1111/1440-1681.13309.

The above article, published online on 27 March 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Yang Yang; and John Wiley & Sons Australia, Ltd. Following publication, the authors notified the journal of significant issues affecting the validity and integrity of their findings. They acknowledged that several data points for oxidative stress markers and myocardial apoptosis levels were inconsistent with the original laboratory records. Following our own analysis, further concerns were identified. Specifically, the actin bands shown in the western blot in Figure 1D and the P65, p-P65, and p-AKT bands in Figure 5A were found to be duplicated in other articles. The authors did not respond to our requests for comments on these additional issues. The editors have deemed the results and conclusions of this article invalid.

This study investigated the disability status of middle-aged and older adults in Anhui Province, China, with a primary focus on physical disability, and constructed a nomogram to predict disability risk. Data was collected through a province-wide questionnaire survey conducted in 16 cities and counties from January to December 2021, involving 3386 participants aged 60 years and above. The abilities of daily living (ADL) scale assessed participants' comprehensive ability. Risk factors for disability were identified using least absolute shrinkage and selection operator and logistic regression, highlighting six independent factors: age, poor sleep quality, depression, malnutrition, stroke, and the number of comorbid chronic diseases. A nomogram prediction model was then established and validated internally and externally. The model demonstrated good fit according to the Hosmer–Lemeshow test and provided significant benefits across various thresholds, as shown by decision curve analysis. This nomogram accurately and quickly identifies high-risk groups, aiding in early intervention.

Ulcerative colitis (UC) is a condition characterized by inflammation and ulcer formation in the colon and rectum due to genetic and environmental factors. It is a common condition, with a global prevalence rate exceeding 0.3%. Current treatments have limited efficacy and can cause unwanted side effects, leading to a high recurrence rate and reduced quality of life for patients. This study suggests that Bacillus clausii has a beneficial role in reducing intestinal inflammation and relieving colitis symptoms in mice. The study aimed to examine B. clausii's potential to reduce the progression and pathogenesis of dextran sulphate sodium (DSS)–induced UC. Bacillus clausii was administered to mice as a pre-treatment, post-treatment and adjunct treatment with sulfasalazine for 14 days. The study found that B. clausii effectively reduced the severity of colitis in mice when used preventatively. Administering B. clausii after the onset of colitis also effectively alleviated symptoms. Combining B. clausii with standard sulfasalazine as adjunct therapy was more effective in reducing intestinal inflammation than using a single therapy alone. B. clausii has shown the potential to prevent colon damage and decrease the likelihood and severity of the disease. Immunohistochemistry results revealed a decrease in the expression of pro-inflammatory cytokines such as IL-1β, TNF-α and NFkB in colon tissue. Additionally, mice that received B. clausii showed a significant increase in anti-oxidant levels and improved haematological markers. In conclusion, it must be emphasized that B. clausii possesses the potential to alleviate the symptoms of UC.

Evodiamine is a biologically active alkaloid extracted from the fruit of the traditional Chinese medicine Evodia rutaecarpa (Juss.) Benth. (Fructus Evodiae, Wuzhuyu). However, due to its lipophilic chemical structure, low water solubility results in poor bio-availability, which limits its broader application. 3-Amino-10-hydroxyl-evodiamine (E2) was a water-soluble derivative of evodiamine with good anti-tumour bioactivity previously developed by our team; however, its anti-osteoporosis activity remains unclear. This study demonstrates that E2 inhibits the maturation of osteoclasts and bone resorption promoted by receptor activator of nuclear factor-κB ligand (RANKL). Mechanistically, E2 reduced RANKL-induced activation of nuclear factor kappa B (NF-κB) as well as mitogen-activated protein kinase (MAPK) pathways, causing the suppression of the expression of genes associated with osteoclasts in vitro. These genes included nuclear factor of activated T cells c1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), cathepsin k (CTSK) and dendritic cell–specific transmembrane protein (DC-STAMP). Treatment with E2 in vitro resulted in the attenuation of p-ERK, p-JNK, p-p38 and NFATc1 levels. Furthermore, ovariectomized (OVX) mice treated with E2 showed a decrease in osteoclast formation as well as preservation of bone mass. This study concludes with evidence that E2 decreases osteoclast maturation and bone resorption through the regulation of multiple signalling pathways, thereby exhibiting an osteoprotective role in OVX mice. Consequently, E2 exhibits significant potential as a prospective drug candidate for treating osteoporosis.

Senescence impairs liver physiology, mitochondrial function and circadian regulation, resulting in systemic metabolic dysregulation. Given the limited research on the effects of combined exercise on an ageing liver, this study aimed to evaluate its impact on liver metabolism, circadian rhythms and mitochondrial function in senescence-accelerated mouse-prone 8 (SAMP8) and senescence-accelerated mouse-resistant 1 (SAMR1) mice. Histological, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunoblotting analyses were conducted, supplemented by transcriptomic data sets and AML12 hepatocyte studies. Sedentary SAMP8 mice exhibited decreased muscle strength, reduced mitochondrial complex I levels and increased lipid droplet accumulation. In contrast, combined exercise mitigated muscle strength loss, upregulated proteins involved in mitochondrial complexes (CIII, CIV, CV) and increased Bmal1 messenger RNA (mRNA) expression in the liver. These molecular adaptations are associated with healthier liver phenotypes and may influence metabolic function and cellular longevity. Notably, elevated lipid content in aged mice was reduced post-exercise, indicating liver benefits even after a relatively short intervention. The combined exercise regimen did not improve aerobic capacity, likely due to the low volume and brief duration of running. Moreover, no significant effects were observed in SAMR1 mice, possibly because the training intensity was insufficient for younger, healthier animals. These findings underscore the potential of combined strength and endurance exercise to attenuate age-related liver dysfunction, particularly in ageing populations.

Diabetic nephropathy (DN) is a severe renal disorder that arises as a complication of diabetes. Liraglutide, an analogue of a glucagon-like peptide 1 (GLP-1) receptor agonist, has been shown to decrease diabetes-caused renal damage. Nevertheless, the complete understanding of the roles and mechanism remains unclear. In our study, diabetic rat models were created through a single intraperitoneal injection of streptozotocin (STZ). The level of fasting blood glucose, 24-h urine protein, serum creatinine (Scr) and blood urea nitrogen (BUN) were assessed. Periodic acid-Schiff (PAS) staining was applied to examine the pathological changes in renal tissues. Reactive oxygen species (ROS) formation was measured via dichloro-dihydro-fluorescein diacetate (DCFH-DA) probes. Western blot was conducted to examine the levels of oxidative stress-related and extracellular matrix (ECM)-associated proteins. The nuclear translocation of NRF2 was investigated through immunofluorescence and Western blot assays. We demonstrated that liraglutide attenuated DN-induced oxidative stress and ECM deposition in vitro and in vivo. Liraglutide exerted a reno-protective effect by promoting nuclear translocation of NRF2 in mesangial cells. ML385, an NRF2 inhibitor, counteracted the beneficial impact of liraglutide.

Myocardial fibrosis is a critical concern in clinical medicine. This study explores the potential of odoratin as a treatment for myocardial fibrosis and investigates its underlying mechanisms. In vitro experiments involved stimulating primary mouse cardiomyocytes with TGF-β1, followed by odoratin treatment, to assess levels of reactive oxygen species (ROS) and nitric oxide (NO). In vivo, a mouse model of myocardial fibrosis was established using abdominal aortic constriction (AAC) and treated with odoratin. ROS and NO levels in myocardial tissue were then evaluated. Immunofluorescence and Western blotting analysis showed that odoratin reduced excess ROS, enhanced NO production and decreased fibrosis-related protein expression in vitro. In vivo, odoratin significantly improved cardiac function, reduced ROS, increased NO levels and mitigated fibrosis in AAC-induced mice. Both in vitro and in vivo, odoratin inhibited the expression of NADPH oxidase 4 and EZH2, while promoting the expression of phosphorylated endothelial nitric oxide synthase (p-eNOS) and PPARγ. The anti-fibrotic effects of odoratin were reversed by PPARγ antagonism, and EZH2 overexpression diminished PPARγ activation by odoratin. These findings suggest that odoratin may combat myocardial fibrosis by balancing ROS and NO through PPARγ activation, with EZH2 inhibition likely playing a key regulatory role.