3 Biotech最新文献

The microbiota-gut-brain axis is a pivotal medium of crosstalk between the central nervous system (CNS) and the gastrointestinal tract. It is an intricate network of synergistic molecular pathways that exert their effects far beyond their local vicinity and even affect the systemic functioning of the body. The current review explores the involvement of the gut-brain axis (GBA) in the functioning of the nervous system, with a special emphasis on the neurodegeneration, cognitive decline, and neuroinflammation that occur in Alzheimer's disease (AD) and Parkinson's disease (PD). Gut-derived microbial metabolites play an important role in facilitating this interaction. We also highlighted the complex interaction between gut-derived metabolites and CNS processes, demonstrating how microbial dysbiosis might result in clinical disorders. Short-chain fatty acids have neuroprotective properties, whereas branched-chain amino acids, trimethylamine-N-oxide (TMAO), and tryptophan derivatives such as indole have negative effects at high concentrations. Furthermore, we cover pharmaceutical and nonpharmacological approaches for restoring the gut microbial balance and promoting neurological health. We further expanded on nutritional therapies and lifestyle changes, such as the Mediterranean diet and exercise. Next, we focused on food-controlling habits such as caloric restriction and intermittent fasting. Moreover, interventional techniques such as prebiotics, probiotics, and pharmacological medications have also been utilized to modify the GBA. Historical microbiome research from early discoveries to recent studies linking gut health to cognitive and emotional well-being has increased our understanding of the GBA.

Diabetes mellitus (DM) is a metabolic disease marked by an excessive rise in blood sugar (glucose) levels caused by a partial or total absence of insulin production, combined with alterations in the metabolism of proteins, lipids, and carbohydrates. The International Diabetes Federation estimates that 425 million individuals globally had diabetes in 2017 which will be 629 million by 2045. Several medications are used to treat DM, but they have limitations and side effects including weight gain, nausea, vomiting, and damage to blood vessels and kidneys. Therefore, it is essential to identify anti-diabetic drugs that have less or no side effects. Hence, the current study employed in silico approaches to discover new DPP-IV inhibitors that might be associated with diabetes. Thirty-four (34) co-crystalized DPP-IV enzymes were found from the protein data bank and the co-crystal ligands were docked into the active-site 6B1E protein to find out the hit compounds. From the docking results, we found two hit compounds (5T4E and 4J3J) which were used to find out the analogs from the experimental drug database using the DrugRep software. According to the results, twenty (20) analogs were found from the experimental drug database with the similarity score of ≥ 0.790 and docked once again into the active site of the DPP-IV (PDB ID: 6B1E) enzyme. Interestingly, DB02226 showed the best binding affinity (-10.3 kcal/mol) and prime MM/GBSA (-68.73 kcal/mol) compared to the reference drug (co-crystal ligand; -7.4 kcal/mol and -47.49 kcal/mol, respectively). Additionally, DB02226 has shown excellent reactivity, efficacy, and structural stability in the binding region of target proteins in studies using MD simulation, MM/GBSA, DFT, and MESP analysis. These findings can be utilized to support further in vitro, in vivo, pre-clinical and clinical research rather than definitively confirming anti-diabetic effectiveness.

Wheat (Triticum aestivum L.), a vital cereal crop, provides over 20% of the total calories and protein in the human diet. However, Fusarium graminearum, the pathogen responsible for Fusarium head blight (FHB), poses a significant threat to wheat production by contaminating grains with harmful mycotoxins. Although Fusarium head blight is currently a minor disease in India, it has the potential to cause substantial yield and quality losses, especially if rain occurs during mid-anthesis. Epigenetic mechanisms, including DNA methylation and sRNA accumulation, are crucial in regulating gene expression and enabling plants to adapt to environmental stresses. Previous studies investigating wheat's response to F. graminearum through transcriptome analysis of lines differing in 2DL FHB resistance QTLs did not fully explore the role of methylation-related genes. To address this gap, we re-analyzed RNA-Seq data to uncover the response of methylation-related genes to pathogen infection. Our analysis revealed that 16 methylation-related genes were down-regulated in the susceptible line 2-2890, with Gene Ontology (GO) analysis linking these genes to L-methionine salvage from methylthioadenosine (GO:0019509), S-adenosylmethionine metabolism (GO:0033353), and steroid biosynthesis (GO:0006694) (p-value = 0.001). Co-expression analysis identified a negative correlation (-0.82) between methionine S-methyl-transferase (MSM; TraesCS1A02G013800) and 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR; TraesCS5A02G269300). HMGCR also showed negative correlations (-1.00) with genes encoding pathogenesis-related, detoxification proteins, and xylanase inhibitors, with GO associating these genes with methionine S-methyl transferase activity (p-value = 0.001). In pathogen-inoculated samples, the elevated expression of HMGCR (Log2 3.25-4.00) and the suppression of MSM (Log2 1.25-3.25) suggest a dual role in stress response and susceptibility, potentially linked to disrupted DNA methylation and isoprenoid biosynthesis pathways. Furthermore, 43 genes down-regulated by miR9678 were associated with biotic stimulus responses and glucan endo-1,4-beta-glucanase activity, highlighting the complex regulatory networks involved in wheat's defense against F. graminearum. This study reveals the roles of methylation-related genes in susceptible wheat lines 2-2890, providing new insights into their potential impact on pathogen response and plant susceptibility.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04179-0.

The present study evaluated the antioxidant and anti-inflammatory properties of Cleome arabica (CA) fruit extract against bisphenol A (BPA)-induced ovarian injury in female Wistar rats. The antioxidant activity was estimated by the total antioxidant capacity (TAC) and superoxide radical (NBT) content. For the in vivo analyses, 24 animals were divided into the following 4 groups: the control group; the BPA group (50 mg/kg BW BPA for 30 days); the BPA  + CA group (50 mg/kg BW BPA and 50 mg/kg BW CA); and the CA group (50 mg/kg BW CA). The in vitro results demonstrated that CA exhibited strong antioxidant activity and scavenged O₂•- radicals. . Pharmacokinetic properties were also explored, reflecting the physiological dynamics of the five active molecules (quercetin, catechin, kaempferol, rosmarinic acid, and naringenin). The in vivo findings revealed a significant increase in body weight associated with a significant increase in plasma C-reactive protein (CRP), proinflammatory cytokines (IL-1, IL-6, and TNF-α), and testosterone levels (p < 0.01). In addition, ovarian histological disruption was observed. However, co-administration of CA extract significantly improved ovarian histological integrity and attenuated inflammatory and androgenic disturbances. Moreover, in silico investigations showed that CA compounds interacted more strongly with the active sites of IL-1β, IL-6, or TNF-α. The best binding energy was observed between catechin (five H-bonds) and IL-1β and IL-6, at -6.0 and -6.1 kcal/mol, respectively, and between rosmarinic acid (four H-bonds) and TNF-α, at -6.4 kcal/mol. The present study supports the use of Cleome arabica in the treatment of infertility for female polycystic ovary syndrome (PCOS) patients.

There is currently no effective treatment for Alzheimer's disease (AD). This research explored Shenzhiling Oral Liquid (SZLD) against AD by pinpointing crucial elements and understanding its molecular mechanisms through network pharmacology and in vitro experiment. First, we used network pharmacology to screen the main targets and mechanisms of SZLD to improve AD. Then we conducted experiments with Aβ42-induced SH-SY5Y cells to assess SZLD's impact, focusing particularly on apoptotic pathways, thereby uncovering its mechanism of action in AD. Through our analysis, we discovered a notable link between SZLD's effect on AD and apoptosis processes. Specifically, the critical proteins Casapse3 and BCL-2 showed strong correlations in this context. Through systematic data analysis and experimental verification, we unveiled the healing advantages and the foundational molecular mechanisms of SZLD in AD. These findings underscore the promising and compelling potential of targeting the PI3K/Akt signaling pathway and apoptosis with SZLD as a therapeutic strategy to ameliorate AD.

Visceral leishmaniasis (VL), caused by Leishmania donovani, remains challenging to treat due to severe side effects and increasing drug resistance associated with current chemotherapies. Our study investigates the anti-leishmanial potential of Rubus ellipticus from Uttarakhand, India, with extracts prepared from leaves and stems using ethanol and hexane. Advanced GC-MS analysis identified over 100 bioactive compounds, which were screened using molecular docking to assess their binding to LdHEL-67, a DDX3-DEAD box RNA helicase of L. donovani. Our results spotlighted nine major compounds with high binding energy, which were then further analyzed for ADMET properties and toxicity predictions, demonstrating their promising pharmacokinetic profiles. Among these, clionasterol emerged as the standout compound, displaying superior results in all in silico analyses compared to Amphotericin B (the control). Notably, clionasterol was present in significant proportions across all the mentioned extracts. Subsequent treatment with these extracts led to a remarkable reduction in the intracellular amastigote and axenic amastigote, and promastigote forms of L. donovani and non-toxic to THP-1-derived macrophages. Moreover, the extracts induced apoptotic effects, as evidenced by the fragmentation of parasitic genomic DNA. This study marks a significant leap in developing herbal-based, target-specific inhibitors against VL. Hence, our findings highlight the immense potential of R. ellipticus as a natural treatment for VL.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04183-4.

The etiology and pathogenesis of Alzheimer's disease (AD) are complex, and currently, no comprehensive treatment measures exist. In this study, we initially utilized ultra-high-performance liquid chromatography with quadrupole orbitrap mass spectrometry (UHPLC-QE-MS) to profile the bioactive constituents of SZLOL present in the bloodstream. Subsequent Y-maze experimental data demonstrated that SZLOL could ameliorate short-term memory deficits in APP/PS1 mice. Furthermore, micro-positron emission tomography (Micro-PET) experiments revealed that SZLOL enhanced glucose metabolism in the cerebral cortex of the mice. To model AD in vitro, we utilized Aβ42-induced SH-SY5Y cells and assessed the effects of SZLOL-containing serum on cell growth and migration using immunofluorescence and wound-healing assays. Both in vivo and in vitro Western blot analyses indicated that SZLOL and SZLOL-containing serum were capable of activating the PI3K/Akt signaling pathway, which modulates the expression of inflammatory mediators. In future studies, we will validate our findings in more animal and cell models.

The present study evaluated the effects of 5-methyltetrahydrofolate (5-MTHF) and Spirulina aqueous extract on diabetes. An in silico docking study with select Spirulina bioactive compounds showed strong binding affinities of folates with glucose metabolism-related proteins. In vitro assay showed 5-MTHF's superior inhibitory activity on alpha-amylase compared to folic acid. The protective effect of Spirulina aqueous extract and 5-MTHF were validated in vivo using an STZ-induced diabetic Wistar rat model. Supplementation with Spirulina extract through diet, and a higher dose of 5-MTHF through gavage effectively lowered fasting blood glucose levels and improved oral glucose tolerance and amylase content. Supplementation also countered hyperlipidemia, improved the levels of antioxidant enzymes, and reduced the inflammatory markers. Weight loss prevention, mitigation of kidney enlargement, and normalisation of the histology of the pancreas, kidney, and liver were also observed. The ameliorative effect of a higher dose of 5-MTHF was comparatively superior to Spirulina aqueous extract and a corresponding higher dose of folic acid. An increase in serum folate levels on supplementation with Spirulina aqueous extract suggests Spirulina to be a source of bioavailable folate. The positive effect of Spirulina aqueous extract suggests a potential synergistic role for folate along with its other bioactive phytochemicals. The study highlights the potential ameliorative effects of Spirulina aqueous extract and 5-MTHF as a dietary supplement on diabetes and associated complications.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04170-9.

The aim of this research is to investigate whether ferroptosis occurs in the pathogenesis of perioperative neurocognitive disorders (PND), and to explore the function and underlying molecular mechanism of tsRNA in the regulation of ferroptosis in PND. A PND aged mice model was established and behavioral changes and ferroptosis occurrence were confirmed. The effect of ferroptosis inhibitor ferrostatin-1 (Fer-1) on PND mice was detected. tsRNA expression profile in PND mice and the effect of tsRNA on ferroptosis in vitro were perfomed. We found that anxious exploration behavior and short-term working memory was declined in PND mice compared with control mice, and the levels of S100β and IL-6 were increased. Meanwhile, hippocampal neurons of PND mice were damaged and accompanied by ferroptosis. Fer-1 can improve cognitive impairment in PND mice, as reflected by improved anxious exploration behavior and short-term working memory, and the levels of S100β and IL-6 were decreased. The expression profile of tsRNA in PND mice is disordered, and the dysregulated tsRNAs were mainly enriched in biologic functions related to neuronal development and ferroptosis. The tsRNA-5006c, identified as a pivotal player, significantly suppressed ferroptosis in primary mice neurons. This study shows for the first time that the pathophysiological process of PND is accompanied by ferroptosis of neurons, and reveals that tsRNA-5006c regulates ferroptosis of hippocampal neurons to ameliorate PND, which is of great significance for the development of new treatment strategies.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04176-3.