Bioscience Reports最新文献

Diabetes mellitus is a complex metabolic disorder associated with severe complications affecting various organs, including the kidneys, nerves, heart, and blood vessels. Managing these complications remains a significant clinical challenge, necessitating the exploration of novel therapeutic approaches. This review focuses on polydatin, a naturally occurring glycoside from Polygonum cuspidatum, highlighting its potential as a multitargeted therapeutic agent against diabetic complications. Evidence indicates that polydatin effectively improves insulin sensitivity, lowers blood glucose levels, and exhibits antioxidant properties. In diabetic nephropathy, polydatin has been shown to reduce oxidative stress, inflammation, and podocyte apoptosis, thereby preserving renal function. Furthermore, it enhances mitochondrial function and Sirt1 expression in diabetic neuropathy, promoting nerve regeneration and alleviating pain. In cardiac studies, polydatin protects against diabetic cardiomyopathy by enhancing autophagy and reducing oxidative stress, ultimately improving cardiac function. Additionally, polydatin restores endothelial function in vascular complications associated with diabetes. Polydatin presents a promising natural therapy with the potential to mitigate multiple complications of diabetes through its antioxidant, anti-inflammatory, and cytoprotective effects. Although findings from animal models and in vitro studies are promising, further clinical research is essential to validate its efficacy and safety in human subjects. By integrating polydatin into diabetes management strategies, there is potential for improved health outcomes and quality of life for individuals affected by this chronic condition.

Abdominal aortic aneurysms (AAAs) are life-threatening due to the rupture of aorta. Different vascular cell types are known to be involved in AAA development. However, whether any specific cell cluster plays a critical role during AAA formation is unknown. Angiotensin II (Ang II) infused mouse AAA models are commonly used to study the development and progression of AAA. We here investigate the incidence of AAA at different ages or different doses of Ang II in C57BL/6J mice. There was no AAA formation at a concentration of 1.44 mg/kg/day or 2.16 mg/kg/day at the age of 14 weeks. At the age of 20 weeks and 32 weeks, the incidence of AAA was 18.2% (6/21) and 57.1% (4/7), respectively, with a concentration of 1.44 mg/kg/day. Using single-cell RNA sequencing, we found that increased clusters of monocytes and neutrophils, macrophages, T cells, and B cells were the typical changes in AAA. A special cluster transformed from endothelial cells (malignant ECs) was identified, in which genesinvolved in lipid metabolism, including Cd36, Lpl, Gpihbp1, Fabp4, and Pparg, were highly expressed. Mice receiving Ang II treatment without AAA development showed increased fibroblasts, which may prevent the occurrence of AAA. Through cell-cell interaction analysis, we found that the Cxcl12-Cxcr4/Ackr3 axis, which functions in inflammatory ligand- receptor binding, may play a role in AAA formation. Our results reveal that specific cell clusters may contribute to the progression or prevention of AAA formation. These findings provide new clues for the pathogenesis and intervention of AAA.

Phosphorylation/dephosphorylation is fundamental for transduction of external stimuli into physiological responses. In photosynthetic dinoflagellates Symbiodinium microadriaticum CassKB8, Thr-phosphorylated SBiP1 under dark conditions, undergoes significant dephosphorylation upon light stimuli. We evaluated the effect of protein synthesis inhibitors on light modulated Thr phosphorylation of SBiP1. Inhibition of cytoplasmic protein synthesis by cycloheximide but not of chloroplastic protein synthesis by chloramphenicol, prevented Thr dephosphorylation of the protein under the light. Additionally, inhibition of glutamine synthetase by glufosinate produced a delay in the light induced dephosphorylation of the chaperone. Heat shock reverted the effect in cycloheximide-treated cells suggesting that heat stress overrides the cycloheximide-induced inhibition of SBiP1 dephosphorylation to hypothetically restore chaperone activity. These results suggest that light and stress are critical switches of SBiP1 chaperone activity that function along with common pathways of protein synthesis and ammonia assimilation, and further confirm that the light induced SBiP1 Thr dephosphorylation is independent of photosynthesis.

Inflammatory bowel disease (IBD) is a gastrointestinal disorder characterised by elevated colonic neutrophil extracellular traps (NETs), which are associated with disease severity. Formation of NETs is primarily driven by peptidyl arginine deaminase IV (PAD4) and other enzymes including myeloperoxidase (MPO) and neutrophil elastase. The present study evaluated the effect of MPO and PAD4 inhibition in dextran sodium sulfate (DSS)-induced colitis. Experimental colitis was induced in male C57BL/6 mice by 2% w/v DSS in drinking water ad libitum. Treatment groups received daily oral administration of MPO inhibitor (AZD3241; 30 mg/kg) and/or intraperitoneal injection of PAD4 inhibitor (GSK484; 4 mg/kg) 4 times over 9 Inhibition of PAD4 significantly diminished NET density in the colonic mucosa of mice insulted with DSS, reaching levels similar to that detected in control mice. Both inhibitors offered limited improvement in disease-activity-index, a scoring system that considers the extent of weight loss, stool consistency and rectal bleeding. Histology showed that MPO and/or PAD4 inhibition did not recover DSS-induced colon histoarchitectural damage whilst Alcian blue staining demonstrated that PAD4 failed to reduce goblet cell loss. The selected dosage of PAD4 inhibition also yielded no effect on inflammatory markers and antioxidant protein levels. These data sets suggest that other mechanisms may be involved in the pathogenesis of IBD, and the appropriate dosage of GSK484 requires thorough investigation.

Biosurfactants are surface-active compounds that have many benefits. This research aims to isolate and identify biosurfactants produced by B. subtilis 3KP when cultured on a molasses substrate. The isolation and purification procedure included gradual ammonium sulfate precipitation, ion exchange and adsorption chromatography. Identification and characterization using high-pressure liquid chromatography, gas chromatography-mass spectrometry, amino acid analyzer, UV-V is spectroscopy, and infrared spectroscopy confirmed that B. subtilis 3KP biosurfactant is a lipopeptide. The biosurfactant produced by B. subtilis 3KP was determined to be a surfactin isoform, characterized by a 16-carbon fatty acid chain. The purified biosurfactant successfully decreased the surface tension from 72 mN/m to 27 mN/m and reached the critical micelle concentration at a precise value of 20.01 mg/L. This biosurfactant product is stable at 30°C-65°C, pH 4-8, and salinity 0-4 M. Therefore, the presented isolate has tremendous potential to produce surfactin-type biosurfactants which can be developed and utilized for various industrial fields.

Bacteriocins are considered promising natural biopreservatives in the food industry because of their broad spectrum of antimicrobial activity against Gram-positive bacteria and foodborne pathogens. This review provides information on several bacteriocins (nisin, pediocin, Micocin®, lacticin 3147, and enterocin AS-48), their mechanisms of action, applications, and discussion of regulatory requirements for their approval as food additives by the Food and Drug Administration (FDA) and the European Union to improve food safety. Nisin (the most studied bacteriocin), recognized as generally regarded as safe by the FDA, is used as a food preservative. Pediocin, derived from Pediococcus acidilactici, shows efficacy against Listeria species and is used in vegetable and meat products. Micocin®, a mixture of bacteriocins produced by Carnobacterium maltaromaticum CB1, is effective against Clostridium botulinum and Listeria monocytogenes. Lacticin 3147, composed of two peptides: Ltnα and Ltnβ, shows synergistic antibacterial activity with potential applications in the control of pathogens in dairy products. Enterococcin AS-48, produced by Enterococcus faecalis subsp. liquefaciens S-48, exhibits broad-spectrum antimicrobial activity against several Gram-positive bacteria and has been studied for biopreservation in a number of food products. For regulatory approval, the following criteria must be met: determination of identity, chemical composition, safety assessments, and recommended concentrations for use. Despite the difficulties posed by their large-scale production and purification, bacteriocins hold enormous potential for improving food safety and shelf life; however, further research is required to harness bacteriocins as future food preservation strategies.

In Clostridium thermocellum, there are nine RsgI factors responsible for sensing different types of substrates and regulating the transcription and expression of cellulosome genes. Within the signaling pathway of RsgI, the membrane protease RseP cleaves RsgI in its transmembrane helix, thus releasing the N-terminal fragment of RsgI from the membrane. This released RsgI N-terminal fragment is subsequently recognized and degraded by a cytoplasmic protease complex consisting of an AAA+ ATPase and ClpP protease. Previous research showed that the ClpXP complex, comprising ClpX and ClpP, is capable of recognizing and degrading the N-terminal fragment of RsgI6. However, due to the low conservation of the transmembrane helical region of RsgI, it remains unclear whether other RsgIs are similarly recognized and degraded by the same unfoldase. In this study, we employed in vitro protease assays to examine the recognition and degradation of the N-terminal fragment of each RsgI by various ClpP-unfoldase complexes. Results confirm that ClpXP is responsible for degrading the N-terminal fragments of all RsgI proteins in C. thermocellum, suggesting a degree of sequence promiscuity in substrate recognition by ClpXP. ClpXP can recognize multiple XAA sites in the transmembrane helix region of RsgI. Moreover, we unexpectedly discovered that the cytoplasmic domain influences the degradation of RsgI2-NF by ClpXP in our in vitro assay. This study provides new insights into understanding the complex regulatory mechanisms of cellulosome genes and the role of AAA+ proteases in C. thermocellum, thereby offering critical clues for unraveling the internal regulatory networks of bacteria.

The allostatic load (AL) concept measures physiological dysregulation in response to internal and external stressors that accumulate across the life course. AL has been consistently linked to chronic disease risk across studies. However, there is considerable variation in its operationalization. In the present study, DNA methylation (DNAm) data (using the Illumina Infinium MethylationEPIC BeadChip array) from the Swiss Kidney Project on Genes in Hypertension (SKIPOGH) cohort, a Swiss-based family cohort study, were used in a discovery epigenome-wide association study to identify cytosine-guanine nucleotide sites associated with phenotypic measures of AL. Elastic net linear regression models were used to estimate an epigenetic signature of AL (methAL), including an Illumina HumanMethylation450K (HM450K) assay-compatible signature (methALT). The methALT signature was validated in the 1936 Lothian Birth Cohort (LBC1936), population-based prospective cohort study. We found that the methAL signature was positively associated with the clinical phenotype of AL in both the SKIPOGH (R2 = 0.59) and LBC1936 (R2 = 0.16) cohorts. In the validation cohort, a one standard deviation increase in methALT signature was associated with 25% higher odds of reported history of cardiovascular disease (CVD) (odd ratio [OR] = 1.25, 95% confidence interval [CI] = 1.05-1.50), and a nearly two-fold increase in all-cause mortality rate at the beginning of follow-up (hazard ratio = 1.68, 95% CI = 1.33-2.13) when adjusting for all potential confounders. In conclusion, the epigenetic signature for AL not only correlated well with phenotype-based AL scores but also exhibited a stronger association with the history of CVD and all-cause mortality compared with AL scores. The methAL signature could help assuage issues of comparison across studies.

Intervertebral disc degeneration (IVDD) is a prevalent musculoskeletal disorder characterized by the deterioration of nucleus pulposus (NP) cells, leading to significant impairments in patients' quality of life. Elucidating the molecular mechanisms underlying IVDD is essential for developing effective therapeutic strategies. In this study, we utilized weighted gene co-expression network analysis to identify key module eigengenes (MEs) from the GSE124272 dataset, combined with differential gene expression analysis to pinpoint differentially expressed genes (DEGs). Functional enrichment analysis revealed that MEs were primarily associated with lipid metabolism and immune response, while DEGs were enriched in immune response and cell proliferation pathways. By integrating MEs, DEGs, and ferroptosis-related genes, we identified six hub genes (acyl-CoA synthetase long-chain family member 1 [ACSL1], BACH1, CBS, CP, AKR1C1, and AKR1C3). Consensus clustering analysis classified samples into two immune-related subgroups, C1 and C2, with single-sample gene set enrichment analysis demonstrating distinct immune scores between the subgroups. Notably, ACSL1 showed the strongest correlation with immune cell infiltration and was significantly up-regulated in the C1 subgroup, which exhibited higher immune scores. In vitro experiments confirmed elevated ACSL1 expression in an IL-1β-induced degenerative NP cell model. Silencing ACSL1 improved cell viability, reduced apoptosis, and restored mitochondrial membrane potential, alongside significant changes in intracellular Fe2+, malondialdehyde, and glutathione levels. In vivo experiments further validated increased ACSL1 expression in intervertebral disc tissues of IVDD rats. Collectively, these findings highlight ACSL1 as a potential biomarker for the early diagnosis of IVDD and a promising therapeutic target.