Archives of Physiology and Biochemistry最新文献

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.

Background: We investigated whether the probiotic yeast Saccharomyces boulardii confers cardiometabolic protection and prevents diabetic cardiomyopathy by modulating inflammation, cardiac remodelling, cardiovascular function, and autonomic regulation.

Methods: Male C57BL/6 mice were allocated into four groups: Control (C), Diabetes (DM), Control+Saccharomyces boulardii (CSb), and Diabetes+Saccharomyces boulardii (DMSb). Diabetes was induced with intraperitoneal streptozotocin (STZ), and treatments (sterile water or Saccharomyces boulardii) were administered orally for 8 weeks. Blood glucose, cytokines, and nitric oxide levels were measured, along with cardiac function via echocardiography and direct blood pressure recordings.

Results: Saccharomyces boulardii reduced blood glucose and increased cardiac IL-10 in diabetic mice, restoring nitric oxide levels. These effects were associated to reduced collagen deposition, preventing vascular damage and ventricular fibrosis, and were accompanied by improved systolic/diastolic function and autonomic control.

Conclusion: Saccharomyces boulardii improved cardiac structure, function, and autonomic control in diabetic mice, supporting its potential as adjunct therapy for diabetic cardiomyopathy.

This study explored the neuroprotective effects of honokiol against oxidative stress, neuroinflammation and transforming growth factor-beta1 (TGF-β1) pathways in kainic acid (KA)-induced neurodegeneration in rats. The animals were divided into: control [Honokiol solvent (dimethyl sulphoxide), intraperitoneal for 7 days]; sham [single-dose KA solvent (saline, intracerebroventricular)]; KA (0,5 μg/μl, single-dose, intracerebroventricular); Honokiol [5 mg/kg-intraperitoneal) for 7 days]; and KA+Honokiol [KA single dose and Honokiol (for 7 days)]. Cerebral cortex and hippocampus tissues of the right hemispheres of rat brains were removed and examined biochemically and histopathologically. KA administration caused an increase in malondialdehyde levels and a decrease in reduced glutathione (GSH) and superoxide dismutase (SOD) levels. In addition, interleukin-1β levels and TGF-β1 expression were increased. Honokiol treatment decreased malondialdehyde levels, increased SOD and GSH levels, increased interleukin-1β levels and improved TGF-β1 expression in rats. Our data showed Honokiol has a protective potential against kainic acid-induced neurodegeneration by suppressing oxidative stress, inflammation and TGF-β1 expression.

Context: Physical exercise is one of many environmental variables that may affect an organism through epigenetic mechanisms, and thus, it may be passed on to the offspring.

Objective: We assessed the effect of resistance training by the parents on mice offspring.

Materials and methods: Training protocol lasted eight weeks, being males and females paired for mating. After birth, the litters were adjusted to eight pups, organised into four groups: sedentary parents (SS), trained parents (TT), sedentary fathers and trained mothers (ST), and trained fathers and sedentary mothers (TS). Male and female pups were analysed separately at the age of 21 days. One-way ANOVA or Kruskal-Wallis was applied when appropriate at the significance level of p < 0.05.

Results: Resistance training improved the strength of both male and female parents. HOMA-IR index of the female offspring of groups ST and TS was improved, as well as that of the male offspring of groups TT and ST. In addition, there was a discrete reduction of adiposity in the offspring when at least one of the parents was trained.

Conclusion: Therefore, parental resistance training improved insulin sensitivity and adiposity of male and female offspring suggesting resistance training as a beneficial preconception health strategy for better metabolic outcomes in future generations.

Background: Chemotherapeutics target cancerous cells, but they also have unavoidable toxicities in healthy tissues.

Aim: In this study, the effects of the commonly used chemotherapeutic 5-fluorouracil (5FU) on lung tissue were investigated, along with the possible protective benefits of apigenin (API), hesperidin (HES), and their combination.

Methodology: The study consisted of control, 5FU, API + 5FU, HES + 5FU, and API+HES + 5FU groups. API 50 mg/kg and HES 200 mg/kg were administered for 7 days. On the 8th day, 5FU was administered a dose of 100 mg/kg.

Results: Analyses showed that API and HES were effective in preventing oxidative stress induced by 5FU in lung tissue, attenuating inflammation and apoptosis by suppressing MAPK/NFκB and Caspase-3/Bax/Bcl-2 pathways, suppressing autophagy by decreasing LC3B expression, and regulating Sigmar1 expression.

Conclusion: These results suggest that the two flavonoids, when administered separately or in combination, may be useful in reducing side effects that often occur during the use of chemotherapeutics.

The present study examined the effects of Tartrazine, a common industrial food colourant, on the pancreas and the protective role of Thymoquinone. Thirty-two Wistar albino male rats were randomly divided into four equal groups: Control, Tartrazine, Thymoquinone, and Tartrazine + Thymoquinone. The rats received Tartrazine and Thymoquinone treatments for 21 days. At the end of this period, pancreatic tissues and blood samples were collected for analysis. Tartrazine administration elevated malondialdehyde (MDA), total oxidant status (TOS), and oxidative stress index (OSI) levels, while decreasing glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and total antioxidant status (TAS) in pancreatic tissue. It increased glucose, total cholesterol, triglycerides, and LDL levels, while decreasing insulin and HDL levels in blood samples. Tartrazine administration aggravated pancreatic histopathology and enhanced Caspase-3 positive immunoreactivity. Thymoquinone administration reduced the harmful effects of Tartrazine on biochemical and histopathological parameters. Tartrazine administration negatively impacted pancreatic tissue and blood samples. The increased oxidant capacity and oxidative stress led to these harmful effects. Conversely, Thymoquinone alleviated oxidative stress by increasing antioxidant capacity and could act as a protective agent.

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.