Decoding the role of gut microbiota in Alzheimer's pathogenesis and envisioning future therapeutic avenues.

Alzheimer's disease (AD) emerges as a perturbing neurodegenerative malady, with a profound comprehension of its underlying pathogenic mechanisms continuing to evade our intellectual grasp. Within the intricate tapestry of human health and affliction, the enteric microbial consortium, ensconced within the milieu of the human gastrointestinal tract, assumes a role of cardinal significance. Recent epochs have borne witness to investigations that posit marked divergences in the composition of the gut microbiota between individuals grappling with AD and those favored by robust health. The composite vicissitudes in the configuration of the enteric microbial assembly are posited to choreograph a participatory role in the inception and progression of AD, facilitated by the intricate conduit acknowledged as the gut-brain axis. Notwithstanding, the precise nature of this interlaced relationship remains enshrouded within the recesses of obscurity, poised for an exhaustive revelation. This review embarks upon the endeavor to focalize meticulously upon the mechanistic sway exerted by the enteric microbiota upon AD, plunging profoundly into the execution of interventions that govern the milieu of enteric microorganisms. In doing so, it bestows relevance upon the therapeutic stratagems that form the bedrock of AD's management, all whilst casting a prospective gaze into the horizon of medical advancements.

Selenium Deficiency Induces Apoptosis and Necroptosis Through ROS/MAPK Signal in Human Uterine Smooth Muscle Cells.

Selenium (Se) is one of the essential trace elements; its deficiency induces ROS production and cell death in cardiomyocytes, skeletal muscle cells, and vascular smooth muscle cells, but it is still not clear the impact of Se deficiency on human uterine smooth muscle cells (HUSMCs). To investigate the effect of low Se on the mRNA expression of selenoproteins, the mRNA and protein expression of apoptosis and necroptosis of HUSMCs and their mechanism, Se deficient HUSMCs mode was established through culturing with 1% FBS containing 0 ng/mL, 0.7 ng/mL, and 7 ng/mL Se, and 10% FBS was as the control group. Then, the apoptosis and necroptosis rates, intracellular ROS content and the expression levels of selenoproteins, apoptosis, necroptosis, MAPK pathway-related genes were examined under different Se concentrations. The results showed that Se deficiency led to the augment of cell apoptosis and necroptosis in HUSMCs (p < 0.05), downregulated (p < 0.05) 19 selenoproteins (GPX1, GPX2, GPX3, GPX4, GPX6, Dio3, Txnrd2, Txnrd3, SEPHS2, SEL15, SELH, SELI, SELM, SELN, SELO, SELS, SELT, SELV, and SELW), while Dio2, SELK, Txnrd1, and MSRB1 were not affected by Se deficiency (p ≥ 0.05). In addition, Se deficiency led to increased intracellular ROS content, p-P38 and p-JNK gene expression levels (p < 0.05), the mitochondrial apoptosis pathway Bax, Casp9 and Cle-Casp3 protein expression levels (p < 0.05), and decreased Bcl2 protein expression level (p < 0.05), simultaneously, increased necroptosis marker genes RIP1, RIP3, and MLKL protein expression levels (p < 0.05) with a dose-dependent pattern. The above results indicate that Se deficiency induces HUSMCs apoptosis and necroptosis through the ROS/MAPK pathway and is closely related to selenoproteins.

Schisandrin B attenuates bleomycin-induced pulmonary fibrosis in mice through the wingless/integrase-1 signaling pathway.

Purpose/Aim: Pulmonary fibrosis (PF) is characterized by the progressive and ultimately fatal accumulation of fibroblasts and extracellular matrix in the lung that distorts its architecture and compromises its function.Objective: The present study investigated the potential protective effects of schisandrin B (Sch B) on the Wingless/Integrase-1 (Wnt) signaling pathway in attenuating inflammation and oxidative stress in ICR mice.Methods: Sixty healthy ICR mice were randomly divided into the following groups: control group, bleomycin (BLM) group, Sch B low dose (Sch B-L) group, Sch B medium dose (Sch B-M) group, Sch B high dose (Sch B-H) group, and dexamethasone (DXM) group. The expression of transforming growth factor (TGF)-ß1 was examined by ELISA. In addition, the levels of superoxide dismutase (SOD), hydroxyproline (HYP), and the total antioxidant capacity (T-AOC) were determined. The protein and mRNA levels of matrix metalloproteinase 7 (MMP7) and ß-catenin in mice were analyzed by western blot and quantitative real -quantitative time PCR (qRT-PCR), respectively.Results: Lung tissues from the BLM group exhibited significantly more inflammatory changes and a significantly greater number of collagen fibers than lung tissues from the control group. In addition, the lung tissues from these BLM-treated mice exhibited slightly increased MMP7 and ß-catenin protein expression. Lung tissues from the Sch B-H group exhibited fewer inflammatory changes and fewer collagen fibers than lung tissues from the BLM group. Furthermore, the lung tissues from the Sch B-H mice exhibited decreased HYP and TGF-ß1 levels, but increased SOD and T-AOC levels.Conclusions: The present study provided evidence that Sch B may be a potential therapeutic agent for the treatment of PF.

Protective Effect of Buyang Huanwu Decoction on Neurovascular Unit in Alzheimer's Disease Cell Model via Inflammation and RAGE/LRP1 Pathway.

BACKGROUND The aim of this study was to investigate the protective mechanism of neurovascular unit of Buyang Huanwu decoction (BYHWD) in an Alzheimer's disease (AD) cell model via RAGE/LRP1 pathway and find a reliable target for Alzheimer's disease treatment. MATERIAL AND METHODS Rat brain microvessel endothelial cells (BMECs) were cultured in 10% FBS and 1% penicillin/streptomycin. The AD model was established by administration of 24 µmol/L amyloid-ß peptides 25~35. Different concentrations of BYHWD (0.1 mg/mL, 1 mg/mL, and 10 mg/mL) were added as the drug intervention. The morphology of the cells was observed by light microscopy and the ultrastructure of the cells was observed by microscopy. The inflammatory factors IL-1ß, IL-6, TNF-alpha, and Aß25-35 were detected by ELISA. Flow cytometry was used to assess the apoptosis rate. The expressions of RAGE, LRP1, ICAM-1, VCAM-1, Apo J, Apo E, and NF-kappaBp65 were detected by Western blotting. RESULTS The structure of cells in BYHWDM and BYHWDH gradually recovered with increasing dose. BYHWD decreased the apoptotic rate of BMECs induced by Aß25-35. The cells treated with different concentrations of BYHWD had significant difference in terms of anti-apoptotic effect. The therapeutic effect of BYHWD on AD was via the RAGE/LRP1 and NF-kappaBp65 pathways. CONCLUSIONS BYHWD regulates Aß metabolism via the RAGE/LRP1 pathway, inhibits vascular endothelial inflammation induced by ICAM-1 and VCAM-1 via the NF-kappaBP65 pathway, and promotes morphological changes induced by Aß-induced brain microvascular endothelial cell damage.

A polysaccharide purified from Radix Adenophorae promotes cell activation and pro-inflammatory cytokine production in murine RAW264.7 macrophages.

Radix Adenophorae, a traditional Chinese medicine, has been reported to have a variety of biological functions. In the present study, a polysaccharide component, Radix Adenophorae Polysaccharide (RAPS), was purified from Radix Adenophorae by decoloring with ADS-7 macroporous adsorption resin, DEAE-52 cellulose ion-exchange chromatography, and Sephacryl S-300HR gel chromatography, with the purity of 98.3% and a molecular weight of 1.8 × 10(4) Da. The cell viability assay and microscopic examination revealed that RAPS promoted the proliferation and activation of macrophages. At 400 µg·mL(-1), RAPS stimulated RAW264.7 cell proliferation by 1.91-fold compared with the control. Meanwhile, RAPS significantly increased the secretion of pro-inflammatory cytokines (TNF-α and IL-6) in a dose-dependent manner in the supernatant of RAW264.7 cell culture as determined by ELISA. At 400 µg·mL(-1), the production of TNF-iα was 20.8-fold higher than that of the control. Simultaneously, the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) were increased in RAW264.7 cells incubated with RAPS, as measured by Griess assay and Western blot analysis. The NO production of cells treated with RAPS (400 µg·mL(-1)) reached 15.8 µmol·L(-1), which was 30.4-fold higher than that of the control (0.53 µmol·L(-1)). These data suggested that RAPS may enhance the immune function and protect against exogenous pathogens by activating macrophages.