Archives of Physiology and Biochemistry最新文献

This study assessed the cardioprotective effects of <1 kDa peptide fractions from neem seed protein hydrolysates (NSPHs) in cardiac tissues ex vivo. Oxidative injury was induced in cardiac tissues from male Wister rats by incubating with 0.1 mM FeSO₄ (pro-oxidant) for 30 minutes. Untreated tissues lacked peptide fractions, while normal control tissues lacked peptide and pro-oxidant. Treatment with the peptides increased the activities/levels of catalase, superoxide dismutase, ENTPDase, 5'NTPDase, glutathione, and HDL-cholesterol. Conversely, the levels/activities of malondialdehyde, nitric oxide, cholesterol, LDL-cholesterol, ACE, acetylcholinesterase, ATPase decreased following treatment with NSPH peptide fractions. Furthermore, the peptides depleted oxidative metabolites, while concomitantly inactivating plasmalogen synthesis and beta-oxidation of long-chain saturated fatty acids. These findings suggest that <1 kDa peptide fractions from neem seed protein hydrolysates have cardioprotective properties, potentially offering a natural therapeutic option for managing oxidative cardiac dysfunction through the regulation of oxidative stress, cholinesterase and purinergic activities, and lipid metabolism.

Purpose: Bariatric surgery can effectively alleviate obesity and diabetes by regulation of the gut microbiota. This study aimed to investigate the change in the gut microbiota metabolite TMAO and to explore its effect on glucose metabolism after sleeve gastrectomy (SG).

Materials and methods: Diet-induced obesity mouse models were established, and the mice were randomly divided into four groups: an SG group, a sham-operated group pair-fed with the SG group (PF), a sham-operated group fed ad libitum (AL), and a lean control group (C). At 10 weeks post-surgery, the changes in glycogen content of liver, gut microbiota and the level of FMO3 in the liver were evaluated, and their correlation with TMAO production was analysed. The expression levels of the TMAO/PERK/FOXO1 pathway and the gluconeogenic genes G6PC and PCK1 were measured.

Results: At 10 weeks post-surgery, hepatocyte glycogen levels were restored, and serum TMA and TMAO levels were significantly increased. Faecal metagenomic sequencing results showed that the abundances of Ruminococcaceae and Lachnospiraceae, which were positively correlated with TMAO production, were significantly increased after surgery. While the changes in FMO3, the key enzyme producing TMAO in the liver was found decreased significantly after SG. The expression levels of the TMAO/PERK/FOXO1 pathway and the gluconeogenic genes G6PC and PCK1 were measured. Inconsistent with the changing trend of TMAO, the expression of PERK, FOXO1, PCK, and G6PC significantly decreased after SG.

Conclusions: SG can significantly reduce obesity and restore glucose metabolism. After surgery, TMAO metabolites increased in a microbiota-dependent manner.

Objective: This study explores the mechanism of methyltransferase like 3 (METTL3) on sepsis-associated encephalopathy (SAE)-induced hippocampal neuronal injury.

Methods: A murine model of SAE was established by caecal ligation and puncture. Hippocampal cells were induced by lipopolysaccharide (LPS). The mouse survival was observed and behavioural tests evaluated cognitive function. METTL3 and glutamic-oxaloacetic transaminase 1 (GOT1) expressions were detected via RT-qPCR and Western blot. Immunofluorescence staining examined the co-localization of NeuN and METTL3. The m6A enrichment on GOT1 was determined by MeRIP.

Results: METTL3 and GOT1 were highly expressed in SAE mice and LPS-stimulated hippocampal cells. SAE mice exhibited cognitive function impairment, reduced survival rate, and decreased neuronal cells. LPS induction increased hippocampal cell apoptosis and enhanced inflammation. Silence of METTL3 reduced hippocampal neuronal injury in SAE mice and LPS-induced hippocampal cell injury.

Conclusion: METTL3-mediated m6A modification on GOT1 mRNA elevates GOT1 expression, thereby aggravating SAE-induced hippocampal neuronal injury.

Gestational diabetes mellitus (GDM) is one of the most prevalent metabolic diseases in pregnant women. In this study, we investigated the effects of Salusin-α in rodent models of GDM. We observed decreased levels of Salusin-α in the placental tissue of GDM mice. Salusin-α alleviated GDM symptoms by reducing blood glucose and increasing serum insulin levels. Further analysis revealed that Salusin-α improved lipid profiles and foetal outcomes in GDM mice. Additionally, Salusin-α mitigated oxidative and nitrosative stress in the placental tissue of GDM mice by enhancing the levels of Vitamin E, Vitamin C, and reduced GSH, while decreasing levels of TBARS and nitric oxide metabolites (nitrite + nitrate = NOx). Salusin-α also reduced the levels of MCP-1 and IL-8. Mechanically, Salusin-α inhibited the activation of p38/NF-κB by reducing phosphorylated p38 and phosphorylated NF-κB p65. In conclusion, our findings support the potential clinical application of Salusin-α as a novel peptide for molecular intervention in GDM.

Objective: Androgenic steroids abuse among young athletes has long-term health consequences, causing profound damage to vital organs such as the heart, blood vessels, brain, liver, gonads, kidneys, and skin.

Results: In the vessels, steroids cause plaque formation, vascular calcification, thrombosis, and coronary artery disease, and in the heart, they lead to pathological fibrosis, dilated cardiomyopathy, heart failure, fatal ventricular arrhythmias, acute myocardial infarction, and reduced ejection fraction. The brain also suffers from cognitive decline, memory impairment, and a constellation of neurotransmitter abnormalities that lead to depression. In the liver, the consequences are severe and manifest as increased oxidative stress, liver dysfunction, hepatotoxicity, cholestatic jaundice, liver tumours, cell death, and elevations in liver enzymes, bilirubin, and cholesterol. Male athletes experience testicular atrophy, temporary suppression of spermatogenesis, hypogonadism, reduced fertility, infertility, and hormonal imbalance. In contrast, women experience ovarian dysfunction and menstrual irregularities. In the kidney, steroids lead to increased inflammatory cytokines, fibrosis, renal tubular hypertrophy, glomerular changes, and structural damage, and show higher levels of serum creatinine, urinary protein, and cystatin C. In athletes, steroids can lead to various skin problems such as acne, gynecomastia, prostatitis, and alopecia.

The neem plant (Azadirachta indica) has popular ethnomedicinal applications. The anti-diabetic potential and mechanism of neem seed oil (NSO) in a rodent model of type 2 diabetes mellitus was evaluated in the present study. Experimentally-induced diabetic animals were administered NSO (200 and 400 mg/kg) or metformin (150 mg/kg) orally for 30 days, with some animals serving as positive and negative controls. NSO significantly (p < .05) reversed diabetes-induced impaired glucose metabolism, dyslipidaemia, and oxido-inflammatory imbalances typified by changes in the NADH/NAD+ ratio (p < .001) and increases in the mRNA or protein levels of C-reactive protein, 4-hydroxynonenal, and pro-inflammatory cytokines (TNF-α and Il-1β) among others in the hepatic or pancreatic tissues of diabetic animals. The histological evaluation of the pancreatic tissue corroborated the protective effect of NSO. The findings showed that the antidiabetic effect of NSO proceeded through its hypolipidemic effect and modulation of redox and inflammatory signalling events in the tissues of animals.

Diabetic nephropathy (DN) is the main cause of end-stage kidney disease and has become a global public health problem. Currently, treatment of DN is limited to alleviating disease progression rather than curing diseases or restoring renal function, thus more effective therapeutic strategies against DN are urgently needed. Mesenchymal stem cells (MSCs) have been widely applied in the prevention and treatment of DN. Preclinical studies have proved that MSCs exhibited favourable therapeutic effects on DN by regulation of hyperglycaemia, reduction of urinary albumin, and protecting renal function. Hence this review provides an overview of the biological properties of MSCs, summarises the regulatory mechanisms of MSC-based therapy for DN, presents ongoing or completed clinical trials, as well as discusses the potential challenges and new strategies of MSCs in the treatment of DN, with the aim of providing a balanced and unbiased view of MSC transplantation as promising therapeutic strategies for DN.

Sustained adrenergic overload in the heart causes maladaptive cardiac remodelling, which involves oxidative stress. Boldine (BOL) has antioxidant activity and represents a novel therapeutic approach. This study explored the cardioprotective role of BOL in adverse left ventricular remodelling induced by isoproterenol. The rats were divided into four groups: control; BOL (25 mg/kg daily); isoproterenol (ISO) (5 mg/kg daily), and ISO + BOL. Morphometric, echocardiographic, and oxidative stress parameters were evaluated. BOL attenuated both cardiac hypertrophy and increased diastolic volume caused by adrenergic overstimulation (P < 0.05). BOL treatment reduced lipid peroxidation induced by ISO (ISO vs. ISO + BOL; P < 0.05), and this effect was associated with increased superoxide dismutase (SOD) (ISO vs. ISO + BOL; P < 0.05) and glutathione-S-transferase levels (GST) (ISO vs. ISO + BOL; P < 0.05). This data suggest that BOL may improve cardiac oxidative stress and attenuate some parameters of adverse cardiac remodelling.

Introduction: This study aimed to assess the expression changes of BTG1, PGI, and PGII in tissues and serum of patients with gastric cancer, atrophic gastritis, and healthy individuals.

Methods: QRT-PCR was used to measure BTG1, PGI, and PGII expression in 30 cancers, 30 atrophic gastritis, and 30 healthy tissue samples. Serum levels of PGI and PGII were measured using ELISA. Statistical tests included the Mann-Whitney U and independent T-test. Covariates like tumour stage and H. pylori status were considered.

Results: BTG1 expression was significantly lower in cancer and gastritis tissues. Serum PGI and PGII levels were significantly reduced in cancer patients (P ≤ 0.001).

Discussion: The PGI/PGII ratio in serum emerged as a strong non-invasive biomarker for distinguishing cancer from healthy individuals. While BTG1 provides insights into gastric carcinogenesis, its clinical utility is limited due to the need for tissue samples. The serum-based PGI/PGII ratio shows greater promise as a non-invasive screening tool for GC.