Archives of Physiology and Biochemistry最新文献

Introduction: Obesity is a complex disorder characterised by inflammatory and metabolic response system disorders. There is increasing evidence that the gut microbiota influences host physiology by producing bioactive metabolites. The metabolic byproducts of probiotic fermentation, such as branched-chain amino acids and short-chain fatty acids, affect immune regulation. However, we do not know how these metabolites systemically act in host inflammatory signalling. Methods: A meta-analysis was performed to characterise interactions between microbial metabolites and host inflammatory markers related to obesity. The Human Metabolome Database (HMDB) was used to retrieve metabolites, and the STRING database was used to identify host protein targets. Analysis using KEGG and Reactome revealed important involvement in sphingolipid metabolism, antimicrobial peptide activity, and BCAA degradation. Results: With network analysis, cytokine signalling, insulin regulation, and adipocytokine pathways were disturbed. Conclusion: This revealed the immunometabolic importance of the gut microbiota and suggested that probiotic metabolites could be potential therapeutic targets for obesity-induced inflammation.

Atoms emit energy in the form of ionising radiation, which can be transmitted as particles (alpha, beta, or neutrons) or electromagnetic waves (gamma or X-rays). Ionising radiation has been shown in cellular and animal models to be a potential toxicity risk factor. The purpose of this research was to examine the probable protective effect of cinnamaldehyde nano-emulsion against gamma-irradiation-induced nephrotoxicity in albino rats. Forty-eight rats were separated into eight groups (6 rats/group) as follow; the control group I, the first treated group II (rats were received 40 mg/kg B.W. cinnamaldehyde), second treated group III (rats were received 40 mg/kg B.W cinnamaldehyde nano-emulsion), irradiated group IV (rats were exposed to 8 Gy single dose gamma-radiation), first treated irradiated group V (rats were received 40 mg/kg B.W. cinnamaldehyde for 7 days, and at day 7, they were exposed to 8 Gy single dose gamma-radiation), the other treated irradiated groups VI, VII, and VIII (rats were received 40, 20, and 10 mg/kg B.W. cinnamaldehyde nano-emulsion respectively, for 7 days and on day 7, they were exposed to 8 Gy single dose gamma-radiation). The results demonstrated that the cinnamaldehyde and cinnamaldehyde nano-emulsion administration to animals before irradiation significantly amended the alterations that happened in the renal functions compared with irradiated group. Similarly, the alterations in renal tissue malondialdehyde, total antioxidant capacity, tumour necrosis factor-α, interleukin-1β levels, and nuclear factor erythroid 2-related factor 2, and haem oxygenase-1 relative genes expressions were markedly ameliorated compared with the irradiated group. The irradiation group's histological results displayed characteristic renal lesions, but the other irradiated treated groups' renal tissues had relatively well-preserved architecture. Cinnamaldehyde and cinnamaldehyde nano-emulsion act as a potent free radicals' scavenger in the kidney to prevent or improve the toxic consequences of gamma-irradiation as revealed by biochemical and histopathological variations, and may provide considerable protection against radiation-induced inflammatory damage, particularly in the nano-emulsion form.

Type 2 diabetes mellitus (T2DM) affects over 415 million individuals globally, with excessive hepatic glucose production representing a primary contributor to hyperglycaemia. Fructose-1,6-bisphosphatase (FBP1), a rate-limiting gluconeogenic enzyme, has emerged as a promising therapeutic target. This review examines FBP1's molecular mechanisms, including its tetrameric structure and allosteric regulation by AMP. FBP1 dysregulation in diabetes involves transcriptional control by FOXO1, CREB, PGC-1α, and epigenetic modifications. Drug discovery efforts have yielded diverse inhibitor classes, including AMP-competitive inhibitors, covalent modulators targeting cysteines C128/C179, and natural products. Leading compounds demonstrate exceptional potency (IC₅₀ 0.029 μM) with favourable bioavailability and efficacy in preclinical models. Structure-based design and AI-driven approaches have accelerated optimisation. Clinical translation of FBP1 inhibitors represents a paradigm-shifting opportunity, potentially providing the first medication class specifically targeting hepatic gluconeogenesis for T2DM treatment.

Aim: The objective of this study was to assess the protective effects of melatonin (Mel) and selenium nanoparticles (SeNPs) against cisplatin (Cis)-induced nephrotoxicity in rats.

Methods: Sixty male rats were categorised into five groups: Control, Cis, Cis + Mel, Cis + SeNPs, and Cis + Mel + SeNPs. Kidney injury was evaluated at 5 and 11 days using biochemical markers, oxidative stress indicators, gene expression analysis as well as histopathological and immunohistochemical assessments.

Results: The combined treatment of Mel + SeNPs significantly improved kidney function biomarkers, reduced MDA levels, increased the activities of SOD, CAT, and GSH, decreased the expression of Bax and IL-6, and increased the expression of Bcl-2, Nrf2, and HO-1 compared to Cis group (p < 0.05). The histological structure and protein expression profiles indicated the most significant enhancement in the combined therapy group, especially on day 11.

Conclusion: The co-administration of Mel and SeNPs demonstrated a significant synergistic effect in protecting the kidneys from Cis-induced nephrotoxicity.

Blood glucose metabolism is a key process for maintaining normal physiological functions of the human body. The maintenance of its homeostasis relies on complex hormone regulation and the synergistic effect of tissues and organs. However, when insulin resistance occurs in skeletal muscles, insulin signalling is impaired, and glucose uptake decreases, leading to elevated blood sugar levels. This study investigates the SARS-CoV-2 spike protein's effect on insulin resistance in type 2 diabetes (T2DM) skeletal muscle in a specific demographic. In the cell experiment, we used human C2C12 skeletal muscle cells and co-cultured them with the spike protein to observe the effects of the spike protein on the proliferation, apoptosis, and glucose uptake. The research results show that the spike protein may reduce the expression and transport of GLUT4 by inhibiting the PI3K/AKT/mTOR signalling pathway, thereby decreasing glucose uptake, intensifying insulin resistance in skeletal muscle, and affecting blood glucose metabolism.

Context: Paraoxonase 1 (PON1) is a crucial antioxidant enzyme involved in the hydrolysis of organophosphates and the prevention of oxidative damage to lipoproteins. Objective: This study aimed to purify PON1 using a newly synthesised hydrophobic interaction chromatography gel and to investigate the inhibitory effects of selected emergency cardiac drugs on PON1 activity through in vitro and in silico approaches. Materials and methods: PON1 was purified using a Sepharose-4B-L-tyrosine-6-aminochrysene hydrophobic interaction chromatography gel. The inhibitory effects of deslanoside, digitoxin, esmolol, and adenosine were evaluated via kinetic inhibition assays, molecular docking, molecular dynamics simulations, and MMPBSA calculations. Results: Among the tested compounds, esmolol exhibited the strongest inhibition of PON1 activity (IC₅₀ = 0.131 ± 0.071 μM, K_i = 0.044 ± 0.009 μM) via a competitive mechanism. Molecular docking revealed strong binding affinity of esmolol to the PON1 active site, which was further supported by molecular dynamics simulations over 150 ns. Discussion and conclusion: The findings indicate a potential interaction between commonly used emergency cardiac drugs and PON1, highlighting the importance of evaluating off-target effects on critical metabolic enzymes in cardiovascular therapy.

Background: Diabetes mellitus (DM) is a chronic metabolic disorder that requires effective treatment strategies with minimal side effects.

Methods: DM was induced by intraperitoneal injection of nicotinamide (NA) at dose 60 mg/kg 15 minutes before streptozotocin (STZ) intraperitoneal injection (60 mg/kg) to 16 hours-fasted Wistar rats. The diabetic rats were treated with xanthine-based dipeptidyl peptidase-4 inhibitor (linagliptin) (1 mg/kg), and diosmin (10 mg/kg) either singly or in combination every other day for 4 weeks via oral gavage in NA/STZ-induced diabetic rats.

Results: Both linagliptin and diosmin potentially lowered the fasting and postprandial blood glucose levels, and fructosamine concentrations, indicating improved glycemic control. The combined treatment effects were the most potent. The treatments also improved serum lipid profile, and cardiac function markers, including AST and CK-MB, suggesting protective effects on the heart. Histopathological analysis demonstrated enhanced adipose tissue integrity and structural improvements. Additionally, inflammatory markers, including TNF-α and IL-1β, were significantly reduced, highlighting the anti-inflammatory properties of linagliptin and diosmin.

Conclusion: the findings suggest that linagliptin and diosmin exert strong anti-hyperglycemic, anti-hyperlipidemic, cardioprotective, and anti-inflammatory effects in diabetic rats; the combined treatment effect was the most potent.

Hepatotoxicity is a pathological condition characterised by disrupted biochemical parameters. This study aims to evaluate the hepatoprotective effects of Eriobotrya japonica fruit extract (EJFE) by assessing biochemical endpoints in a rat model of carbon tetrachloride (CCl₄)-induced liver injury. The study was carried out with five experimental groups of Wistar rats (n = 6): I- Control, II- Negative Control, III- EJFE (200 mg/kg b.w.), IV- EJFE (400 mg/kg b.w.), and V- Standard (Silymarin-treated). CCl₄ exposure resulted in a marked reduction in antioxidant potential (p < 0.05) and increases in oxidative stress (p < 0.05), accompanied by detrimental alterations in the lipid, liver-specific enzymes, and biomolecules. Significant (p < 0.05) elevated levels of protein carbonyl (PCO), malondialdehyde (MDA), and low-density lipoprotein (LDL) oxidation susceptibility, along with reduced paraoxonase-1 (PON-1) activity and reduced glutathione (GSH) level, reflect compromised liver function. Treatment with EJFE significantly ameliorated these effects via enhancing PON-1 activity and reducing susceptibility of LDL to oxidation, further supporting the extracts antioxidative and hepatoprotective potential.

Context: Polycystin-2 (PC2), a calcium-permeable ion channel, is localised to the endoplasmic reticulum, plasma membrane, and primary cilium. Mutations in PC2 are linked diseases, such as autosomal dominant polycystic kidney disease (ADPKD), cardiovascular disorders, and cancer.

Objective: This review highlights the structural features, distribution, and regulatory mechanisms of PC2, emphasising its involvement in renal and extra-renal diseases.

Methods: Through a systematic review and analysis of existing literature, we evaluated evidence on the molecular function of PC2 and its pathophysiological involvement in disease processes.

Discussion and conclusion: Despite advances in understanding PC2's role, further research is needed to elucidate its full functional spectrum and therapeutic potential.