Biochemistry Research International最新文献

Background: Crohn's disease (CD) is a chronic, complex inflammatory condition that can affect the entire digestive tract, most commonly the terminal ileum. The exact cause of CD remains unknown. Bioinformatics was used in this study to identify the differentially expressed genes (DEGs) and microRNAs (miRNAs) that show potential as diagnostic and therapeutic agents in treating CD.

Materials and methods: Datasets were downloaded from the Gene Expression Omnibus database and filtered. DEGs between CD samples and healthy control samples were identified using the GEO2R tool (including GEOquery and Linear Models for Microarray Analysis), and Kyoto Encyclopedia of Genes and Genomes/Gene Ontology enrichment analyses were conducted as part of the study to gain deeper insights into the data. A network depicting protein-protein interactions was established and visualized using the STRING database and Cytoscape software, and hub genes were identified and extracted utilizing the cytoHubba program. Cytoscape and miRTarBase were used to construct the miRNA-hub gene regulatory network and predict the potential miRNAs associated with the DEGs. The hub genes were analyzed further using ROC curves and combined ROC curve analyses of the GSE179285, GSE186582, and GSE112366 datasets. A regularized LASSO regression model was constructed to reduce the risk of overfitting.

Results: Three datasets (GSE179285, GSE186582, and GSE112366) were selected. A comprehensive analysis of the three datasets revealed 60 DEGs that showed significantly altered expression levels, including 44 upregulated genes and 16 downregulated genes. Ten different algorithms were randomly used, and three hub genes (CXCL1, CXCL2, and CXCR2) were identified. Based on the miRNA-hub gene regulatory network, hsa-miR-1-3p and hsa-miR-335-5p were recognized as potentially vital miRNAs.

Conclusion: Three hub genes (CXCL1, CXCL2, and CXCR2) and two miRNAs (hsa-miR-1-3p and hsa-miR-335-5p) are postulated to play a role in the initiation and progression of CD, thereby offering potential as biomarkers for this condition.

Introduction: Compensated cirrhosis carries a significant risk of progression to decompensation, which substantially worsens prognosis. Accurate prediction of decompensation events is critical for guiding surveillance, optimizing intervention timing, and improving patient outcomes. Although many prognostic biomarkers have been studied, findings remain heterogeneous. This umbrella review synthesizes evidence from systematic reviews and meta-analyses to identify and appraise biomarkers predicting decompensation in alcoholic and nonalcoholic compensated cirrhosis.

Methods: PubMed, Scopus, and Web of Science were searched to August 15, 2025, for English-language systematic reviews and meta-analyses. From the included meta-analyses, prognostic performance, heterogeneity, and publication bias were recorded.

Results: Four systematic reviews were included, two with meta-analyses. Strong predictors across reviews were serum albumin, INR, bilirubin, platelet count, and liver stiffness measurement. HVPG remained a robust invasive predictor, while emerging biomarkers-interleukin-6, keratin-18, and extracellular vesicles-were associated with an increased risk of decompensation, although the certainty of evidence was limited by heterogeneity and methodological constraints. Composite scores enhanced predictive accuracy. AMSTAR 2 ratings ranged from high to low, with common reporting limitations. Overlap analysis indicated moderate redundancy among primary studies.

Conclusions: Both established and emerging biomarkers predict decompensation in compensated cirrhosis. Integrated multidomain models combining clinical, biochemical, and imaging-derived measures may provide the greatest predictive value for guiding clinical decision-making.

Whey, a by-product of the cheese manufacturing industry, represents one of the most abundant and polluting effluents in the global food industry. Despite traditionally being underutilized and often discarded, its rich nutrient profile, particularly protein and lactose, has increasingly sparked an interest in its value within biotechnological processes. This review analyses the potential of whey as a sustainable substrate for the microbial production of value-added bioproducts, focussing on L-threonine production as a strategic case study, while addressing the environmental impact of inadequate disposal and current utilization strategies. A comparative analysis with other agroindustrial waste demonstrates whey's competitive advantages in terms of composition, cost-effectiveness and sustainability metrics. Furthermore, L-threonine biological and industrial importance, and the most relevant advances in metabolic engineering, optimized fermentation and emerging tools such as optogenetics and machine learning are discussed, as they facilitate enhanced L-threonine yields through the creation of robust, high-producing strains. Technoeconomic analysis at pilot scale (33.8 tons/year) indicates that whey-based production offers a comparative cost advantage of 7.4% over glucose-based processes (20.55 USD/kg vs. 22.20 USD/kg). While absolute costs at pilot scale exceed current industrial market prices (1.31-1.66 USD/kg)-reflecting typical scale effects-the demonstrated comparative advantage and substantial environmental benefits (waste valorization, elimination of disposal costs and circular economy alignment) position whey-based L-threonine production as a strategic biorefinery opportunity with significant potential for industrial-scale implementation. This cost benefit is primarily driven by the lower market price of whey compared to commercial glucose substrates, which compensates for the slightly higher downstream processing costs (5.90 vs. 5.40 USD/kg) required for complex matrices. Downstream processing considerations, including recovery, purity requirements and economic viability, are comprehensively addressed. This review concludes that whey, far from being merely a pollutant, has the characteristics required to become an asset for biotechnology. Utilizing whey as a culture medium for L-threonine production by E. coli in bioreactors not only offers a solution to mitigate a significant environmental issue but also opens a path for the cost-effective, sustainable production of a globally high-demand amino acid. Whey represents a strategic biorefinery platform with potential for industrial-scale implementation. Continued research and development in this area are fundamental to fully realizing this potential.

Chronic kidney disease (CKD) is a major health issue associated with oxidative stress and inflammation that leads to progressive renal damage. Natural antioxidants, gallic acid (GA) and alpha-tocopherol (AT), have gained attention for their strong free radical-scavenging, inflammation-reducing, and tissue-repairing properties, and their individual or combined administration may offer therapeutic potential in CKD management. This experiment was designed to explore the potential ameliorative effects of GA and AT against CKD induced by adenine in male rats. Adult rats weighing 180-220 g (n = 48) were distributed among eight experimental groups. Except for Group I (control), all groups received a standard rat diet supplemented with 0.75% (w/w) adenine for 4 weeks to induce CKD. During the same period, the experimental groups received oral treatments of GA and AT at doses of 100 and 400 mg/kg body weight, respectively, as well as their combinations (GA-AT) at the same doses. The treatments were administered simultaneously for 4 weeks to evaluate their effects on adenine-induced CKD. The results indicated that both GA and the combination of GA-AT were significantly more effective than AT alone in improving renal function markers such as uric acid, creatinine, albumin, and urea. Additionally, these treatments led to better outcomes for serum concentrations of these markers and oxidative stress biomarkers. Histopathological analysis confirmed the beneficial effects on kidney tissue compared to the diseased group. Moreover, both GA and the GA-AT combination treatments showed superior results in the relative expression of mRNA markers related to kidney function, including Igfbp7, Vcam1, and Timp2. Molecular docking studies demonstrated notable binding affinities and interactions between key kidney markers and selected GA and AT compounds. These findings suggest that GA, particularly in combination with AT, effectively restores kidney function in adenine-induced CKD, supporting further research to optimize their clinical applications in CKD management.

Background: The leaves of Dimocarpus longan Lour. are used unilaterally as Chinese herbal medicines to treat diabetes in Chongzuo and Hezhou, Guangxi, but the mechanism of its treatment of diabetes is not yet clear, and further research is needed.

Methods: This study examined the effects of leaf ethanol extract of D.s longan Lour. on metabolic pathways and gut microbiota in rats with type 2 diabetes mellitus (T2DM). The rats were randomly divided into four groups: HG + HFD (T2DM model, fed with high-sugar and high-fat diet), control (regular diet), MET (positive metformin), and LYY (leaf ethanol extract of D. longan Lour). Metabolite profiles and gut microbiota composition were analyzed using liquid chromatography_mass spectrometry and 16S rDNA sequencing.

Results: Metabolomics analysis revealed 61 distinct metabolites in the LYY group, such as Leu-Pro and taurolithocholic acid 3-sulfate, which influence valine, leucine, and isoleucine metabolism, unsaturated fatty acid biosynthesis, fatty acid metabolism, bile secretion, and pyruvate and propanoate metabolism. Additionally, 16S rDNA sequencing showed that LYY significantly altered the abundance of gut microbiota such as Ligilactobacillus and Desulfobacterota (vs. HG + HFD group, p < 0.05).

Conclusion: LYY improved T2DM in rats may be associated with modulating metabolite levels and indirectly regulating glucose metabolism balance through changes in gut microbiota abundance. The efficacy of LYY in treating T2DM in rats may be related to the regulation of six metabolic pathways; it increased the abundance of Ligilactobacillus and Christensenellaceae _ R-7 _ group and decreased the abundance of Desulfobacterota, Colidextribacter, and Oscillibacter, thereby promoting impaired glucose tolerance and indirectly regulating the balance of glucose metabolism.

Polycystic ovary syndrome (PCOS) accelerates ovarian follicular depletion through atresia. This study investigated the therapeutic potential of aqueous (AE) and hydroethanolic (HEE) extracts of Cymbopogon citratus in mitigating PCOS-induced ovarian damage (specifically ferroptosis, apoptosis, and oxidative stress) in a rat model of PCOS. PCOS was induced by oral administration of letrozole (1 mg/kg/day for 21 days), followed by treatment with AE or HEE (100, 200, or 400 mg/kg/day for 20 days) with metformin (200 mg/kg) as a positive control. The results showed that HEE contains 5 times more alkaloids than AE. In experimental animals, C. citratus corrected ovarian damage caused by PCOS, compared to the disease control treated with distilled water. Indeed, C. citratus decreased serum testosterone levels [maximum decrease rate of 37.10% (p < 0.0001) obtained with HEE100] and increased estradiol levels [maximum increase rate of 56.15% (p < 0.0001) obtained with AE200]. An increase in serum ghrelin levels [maximum increase rate of 129.38% (p < 0.0001) obtained with AE400] and a decrease in leptin levels [maximum decrease rate of 43.85% (p < 0.0001) obtained with AE400] were observed. In the ovaries, C. citratus decreased Fe²⁺ [maximum decrease rate of 31.57% (p < 0.01) obtained with HEE200], caspase 3 [maximum decrease rate of 24.47% (p < 0.05) obtained with HEE400], oxidative stress markers [MDA: up to 23.28% decrease (p < 0.05) induced by AE100], and increased antioxidants [catalase: up to 29.99% increase (p < 0.05) induced by HEE100 and GSH: up to 42.37% increase (p < 0.01) induced by HEE200]. C. citratus also decreased cystic and atretic follicles and promoted follicle growth and ovulation. In conclusion, C. citratus extracts are capable of protecting the ovaries from the adverse effects of PCOS, primarily ferroptosis, and apoptosis of follicular cells. Of the two extracts, AE seems ideal due to its low alkaloid content.

Glioblastoma is one of the most aggressive and widely recognized types of brain tumors, characterized by significant cellular and molecular diversity and an inherently aggressive nature. The treatment remains highly challenging, with limited effectiveness and persistently low survival rates. For this reason, researchers are continuously expanding the chemical space of anticancer agents by exploring complex sources such as animal venoms and incorporating in silico tools to accelerate discovery. Indeed, venoms serve as libraries of proteins and peptides, providing a rich source of novel chemical structures for glioblastoma therapy. Some review articles have examined the mechanisms by which venom-derived peptides target glioblastoma cell lines; nevertheless, key structural insights and computational analyses remain underexplored. In this era of artificial intelligence (AI) and advancements in in silico approaches, our review documented the antiglioblastoma properties of venom peptides and underscores the value of computational methods in peptide-based drug development. To this end, a comprehensive search was conducted in PubMed, Elsevier, Springer, Lilacs, Google Scholar, and SciELO databases. Furthermore, in silico analyses were conducted to evaluate the anticancer potential, hemolytic activity, toxicity, and blood-brain barrier (BBB) penetrating properties of venom-derived peptides. In total, 26 unique sequences were identified, with their structural properties and mechanisms of cell death comprehensively characterized. The development of peptide-based anticancer drugs remains in its early stages, with minimal advancement toward preclinical evaluation using in vivo models. The advancement of AI models offers opportunities to accelerate peptide discovery. However, our case study revealed divergences among AI-based predictions, as well as discrepancies between computational and experimental findings, underscoring the need for further model refinement and validation through experimental data integration. In summary, venoms remain promising peptide libraries that offer valuable natural molecular templates. These peptides require chemical optimization to enhance their stability and BBB permeability. Such advances could enable selective targeting within the glioblastoma niche and support the development of more effective therapies.

This study investigated the effects of swimming training (ST) on hippocampal structure, specifically glial fibrillary acidic protein (GFAP), dark neurons, and the thickness of the CA1 region and dentate gyrus (DG), as well as spatial memory performance in young male rats subjected to chronic stress (CS). Adult male Wistar rats were randomly assigned to five groups: swimming training (ST), chronic mild stress (CMS), chronic mild stress followed by swimming training (CS + ST), chronic mild stress followed by a recovery period (CS + recovery), and a control group with no exercise or stress intervention. Spatial memory was assessed using the Morris water maze (MWM). The findings revealed that the ST group exhibited the lowest levels of GFAP and dark neurons, as well as the highest thickness of the CA1 and DG regions and the best spatial memory performance. In the CS + ST group, ST reduced GFAP and dark neurons, increased the thickness of the CA1 and DG, and improved memory performance compared to the control and CS + recovery groups. The CS group had the highest levels of GFAP and dark neurons, alongside the thinnest CA1 and DG regions. Meanwhile, in the CS + recovery group, GFAP and the number of dark neurons were lower than in the CS group. In summary, ST reduced GFAP and the number of dark neurons in both stressed and nonstressed rats, with a more pronounced effect observed in nonstressed rats. Overall, ST improved stress-induced spatial memory performance and hippocampal morphology in young male rats.

Background and aims: The more severe forms of sickle cell disease (SCD) are highly inflammatory genetic disorders that cause significant oxidative stress. To fight against the free radicals produced, the body has an antioxidant system. In addition, haptoglobin has been reported in several studies as possessing oxidant and inflammatory properties depending on the nature of the genotype. This study hypothesizes that the HP2 allele of haptoglobin may exacerbate oxidative stress in sickle cell patients with inflammation.

Methods: An analytical cross-sectional study was conducted for 6 months. The patients recruited were those with severe forms of sickle cell anemia, regularly followed at the hematology department of the Yaoundé Central Hospital and the Bafoussam Regional Hospital. The Public Health Research Biotechnology Laboratory (LAPHER-Biotech) in Yaoundé provided a framework for genotyping haptoglobin by allele-specific PCR. Next, iron, oxidative stress, and inflammatory parameters were assessed by standard methods, and the statistical software R Version 4.1.1. allowed for the data analysis.

Results: Samples from 149 participants were analyzed. Patients with Hp phenotypes 2-2 had a considerable elevation of reduced glutathione (14.3 μmol/L) compared to those of phenotype Hp 2-1 (11.2 μmol/L) and genotype Hp 1-1 (11.8 μmol/L) (p = 0.075). Malondialdehyde was significantly higher in patients with Hp phenotypes 2-2 compared to those with Hp phenotype 2-1 and Hp phenotype 1-1 (p = 0.008). The oxidative stress index (OSI) was higher in patients with the Hp 2-2 phenotype than those with the Hp 2-1 and Hp 1-1 phenotypes (p = 0.008) suggesting that they are more affected by oxidative stress.

Conclusion: This study supports the hypothesis that the Hp 2-2 phenotype of haptoglobin is associated with an imbalance in the oxidative balance in favor of oxidants, suggesting that the latter is a major contributor to the worsening pathophysiology of SCD.

Melanin plays significant roles in biophysical, biochemical, light-filtering, and cosmetic functions of the skin. The melanin content in pigmented cells, such as melanoma cells, can be accurately measured. This study focused on evaluating the effects of tetrahydrocurcumin (THC), a hydrogenated derivative of curcuminoids, on melanogenesis in melanoma cells. We specifically investigated how THC influences melanin production and tyrosinase activity, a key enzyme in the melanogenesis pathway, in A375 melanoma cells. Our results provide experimental evidence supporting THC's potential as an inhibitor of melanin synthesis and tyrosinase activity. This suggests that THC could be an effective component in skin-whitening products. By demonstrating THC's ability to suppress melanin content and tyrosinase activity, our study highlights its potential for use as a dermatological agent in skincare formulations aimed at reducing pigmentation.