In the current study,Bacillus velezensisAG6 was isolated from sediment samples in the Red Sea, identified by traditional microbiological techniques and phylogenetic 16S rRNA sequences.

Human colon microbiota produce a metabolite called urolithin A (URO A) from ellagic acid and linked compounds, and this metabolite has been demonstrated to have antioxidant, anti-inflammatory, and antiapoptotic activities. The current work examines the various mechanisms through which URO A protects against doxorubicin (DOX)-induced liver injury in Wistar rats. In this experiment, Wistar rats were administered DOX intraperitoneally (20 mg kg⁻¹) on day 7 while given URO A intraperitoneally (2.5 or 5 mg kg⁻¹ d⁻¹) for 14 days. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) were measured. Hematoxylin and eosin (HE) staining was used to evaluate histopathological characteristics, and then antioxidant and anti-inflammatory properties were evaluated in tissue and serum, respectively. We also looked at how active caspase 3 and cytochrome c oxidase were in the liver. The findings demonstrated that supplementary URO A therapy clearly mitigated DOX-induced liver damage. The antioxidant enzymes SOD and CAT were elevated in the liver, and the levels of inflammatory cytokines, such as TNF-α, NF-kB, and IL-6, in the tissue were significantly attenuated, all of which complemented the beneficial effects of URO A in DOX-induced liver injury. In addition, URO A was able to alter the expression of caspase 3 and cytochrome c oxidase in the livers of rats that were subjected to DOX stress. These results showed that URO A reduced DOX-induced liver injury by reducing oxidative stress, inflammation, and apoptosis.

Mitochondrial dysfunction is a feature of type I and type II diabetes, but there is a lack of consistency between reports and links to disease development. We aimed to investigate if mitochondrial structure–function remodelling occurs in the early stages of diabetes by employing a mouse model (GENA348) of Maturity Onset Diabetes in the Young, exhibiting hyperglycemia, but not hyperinsulinemia, with mild left ventricular dysfunction. Employing 3-D electron microscopy (SBF-SEM) we determined that compared to wild-type, WT, the GENA348 subsarcolemma mitochondria (SSM) are ~ 2-fold larger, consistent with up-regulation of fusion proteins Mfn1, Mfn2 and Opa1. Further, in comparison, GENA348 mitochondria are more irregular in shape, have more tubular projections with SSM projections being longer and wider. Mitochondrial density is also increased in the GENA348 myocardium consistent with up-regulation of PGC1-α and stalled mitophagy (down-regulation of PINK1, Parkin and Miro1). GENA348 mitochondria have more irregular cristae arrangements but cristae dimensions and density are similar to WT. GENA348 Complex activity (I, II, IV, V) activity is decreased but the OCR is increased, potentially linked to a shift towards fatty acid oxidation due to impaired glycolysis. These novel data reveal that dysregulated mitochondrial morphology, dynamics and function develop in the early stages of diabetes.

A hallmark of heart failure is mitochondrial dysfunction leading to a bioenergetics imbalance in the myocardium. Consequently, there is much interest in targeting mitochondrial abnormalities to attenuate the pathogenesis of heart failure. This review discusses (i) how electron microscopy (EM) techniques have been fundamental for the current understanding of mitochondrial structure–function, (ii) the paradigm shift in resolutions now achievable by 3‐D EM techniques due to the introduction of direct detection devices and phase plate technology, and (iii) the application of EM for unravelling mitochondrial pathological remodelling in heart failure. We further consider the tremendous potential of multi‐scale EM techniques for the development of therapeutics, structure‐based ligand design and for delineating how a drug elicits nanostructural effects at the molecular, organelle and cellular levels. In conclusion, 3‐D EM techniques have entered a new era of structural biology and are poised to play a pivotal role in discovering new therapies targeting mitochondria for treating heart failure.Linked Articles: This article is part of a themed section on Mitochondrial Pharmacology: Featured Mechanisms and Approaches for Therapy Translation. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.22/issuetoc

Microbial exopolysaccharides (EPSs) are gaining interest as alternatives to chemical antioxidants and pharmaceuticals. This study mines the promising biomedical and antimicrobial potential of a marine bacterium, a prolific EPS producer, isolated from the Red Sea. Pseudomonas sp. strain AHG22 generated an EPS weighing 6.98 g·L⁻¹, coded EPSF8, subjected to FT-IR and HPLC chemical analysis. EPSF8 was then investigated for antioxidant assessment by 2,2-diphenyl-1-picrylhydrazyl (DPPH), H₂O₂, ABTS˙ ⁺ , nitric oxide, total antioxidant capacity (TAC), and ferric reducing antioxidant power (FRAP). EPSF8 had an IC₅₀ of 46.99 μg·mL⁻¹ in the DPPH antioxidant assay and antioxidant capacities of 219.45 μg·mg⁻¹ ascorbic acid equivalent (AAE) in the TAC assay and 54.15 μg·mg⁻¹ AAE in the FRAP assay. The in vitro anti-inflammatory effect of EPSF8 was tested against 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) enzymes and compared with the drugs ibuprofen and celecoxib used as controls. The IC₅₀ values of 5-LOX, COX-2, ibuprofen, and celecoxib were found to be 14.82, 15.49, 1.5, and 0.28 μg·mL⁻¹, respectively. Additionally, EPSF8 revealed antidiabetic activity toward α-amylase and α-glucosidase, and the IC₅₀ values were 93.1 and 127.28 μg·mL⁻¹, compared to those of acarbose (50.93 and 4.13 μg·mL⁻¹, respectively). Anti-obesity activity of EPSF8 by lipase inhibition revealed IC₅₀ = 56.12 μg·mL⁻¹ compared to orlistat (IC₅₀ = 20.08 μg·mL⁻¹) as a control. EPSF8 displayed antibiofilm and bactericidal activity against Gram-positive (G +ve) and Gram-negative (G −ve) ATCC pathogenic bacterial strains. It had a minimum bactericidal concentration/minimum inhibitory concentration ratio ≤2, indicating a broad bactericidal spectrum. Furthermore, EPSF8 is evidenced to have a promising anti-butyrylcholinesterase activity for the control of Alzheimer’s disease. The findings of the present analysis suggest that the isolated Pseudomonas sp. strain AHG22 EPS can potentially be explored as a promising green therapeutic compound.

Background and Objectives: Dyslipidemia is a major risk factor for cardiovascular disease (CVD). The identification of new biomarkers that may enhance the risk assessment of lipid abnormalities is a promising approach in improving risk prediction of CVD. There is no information on the association of the hemoglobin, albumin, lymphocyte, and platelet (HALP) score with dyslipidemia. The aim of this study was to investigate the clinical utility of the HALP score in light of dyslipidemia. Materials and Methods: A retrospective analysis of 7192 subjects was initiated to assess the association between the HALP score and disturbed lipid markers. Medians were compared by Mann–Whitney U or Kruskal–Wallis tests and the diagnostic performance and risk assessment were calculated. Results: Median HALP score among all subjects was 53.3, with varying values between males and females. Notably, median HALP was significantly elevated in all forms of dyslipidemia and among males and females irrespective of age. The odds of having elevated HALP score values were significantly higher in all lipid abnormalities. Moreover, HALP score was significantly yet weakly correlated with lipid markers, while the highest diagnostic accuracy of the HALP score was observed with an elevated ratio of total cholesterol to high-density lipoprotein (TC/HDL) (area under the curve, AUC = 0.6411, p < 0.0001). The decision curve analysis (DCA) showed that the HALP score can reliably predict the presence of dyslipidemia. Conclusions: This study demonstrates that the HALP score is a novel, cost-effective index that is associated with a disturbed lipid profile. Further investigation of the nature of this association is needed.