Inhibition of VDAC1 Rescues Aß 1-42-Induced Mitochondrial Dysfunction and Ferroptosis via Activation of AMPK and Wnt/ß-Catenin Pathways.

Beta-amyloid (Aß) accumulation in the brains of Alzheimer's disease (AD) patients leads to mitochondrial dysfunction and ferroptosis in neurons. Voltage-dependent anion channel 1 (VDAC1) is a major protein in the mitochondrial outer membrane. It has been reported that VDAC1 associated with mitochondrial dysfunction and ferroptosis. However, the mechanism by which VDAC1 regulates mitochondrial dysfunction and ferroptosis of neurons in AD remains unclear. This study is aimed at investigating the mechanism of action of VDAC1 in mitochondrial dysfunction and ferroptosis in neurons of the AD model. In this study, we determined cell viability after treatment with Aß 1-42 via the MTT assay. The SOD, MDA, ROS, and MMP production was measured via the SOD kit, MDA kit, DCFDA staining, and JC-1 staining. The memory abilities of mice were detected via the Morris water maze test. The expression of AMPK/mTOR, Wnt/ß-catenin, and GPX4 regulated by VDAC1 was detected via western blotting. Our present study showed that PC12 cells had decreased cell viability, increased LDH release, and decreased GPX4 expression after Aß 1-42 treatment. Meanwhile, Aß 1-42 induced MMP and SOD downregulation and increased MDA and ROS generation in PC12 cells. In addition, the expression of VDAC1 is increased in the brain tissue of AD mice and Aß 1-42-treated PC12 cells. Further investigation of the role of VDAC1 in regulating AD found that all effects induced by Aß 1-42 were reversed by inhibition of VDAC1. Additionally, inhibition of VDAC1 activates the AMPK/mTOR and Wnt/ß-catenin pathways. Taken together, these findings demonstrate that inhibition of VDAC1 alleviates mitochondrial dysfunction and ferroptosis in AD neurons by activating AMPK/mTOR and Wnt/ß-catenin.

Separation of ofloxacin enantiomers by capillary electrophoresis with fluorescence detection using deoxyribonucleic acid oligonucleotides as chiral selectors.

This study used capillary electrophoresis with fluorescence detection- and a partial-filling mode-based method for chiral separation of ofloxacin. The deoxyribonucleic acid oligonucleotides with different base sequences were studied as potential chiral selectors including deoxyribonucleic acid tetrahedron, G-quadruplex, and G-riched double-strand deoxyribonucleic acid. Under the optimized conditions, all the deoxyribonucleic acid chiral selectors exhibited excellent chiral separation capabilities with a resolution higher than 1.5. The electrophoretic behavior of the ofloxacin enantiomer might result from the intermediate conjugate with different stabilities between chiral selectors and analytes by a combination of the hydrogen bond and spatial recognition structure. Moreover, satisfactory repeatability regarding run-to-run and interday repeatability was obtained, and all the relative standard deviation values of migration times and resolutions were below 4% (n = 6). Conclusively, both spatial structure and arrangement of the G bases potentiated the chiral separation capability of deoxyribonucleic acid for ofloxacin enantiomer. This work offered a stepping stone for enantioseparation using deoxyribonucleic acid as chiral selectors.

[Research progress on Toll-like receptor 2 (TLR2) with Mycobacterium tuberculosis infection].

Toll-like receptor 2 (TLR2) is a pattern recognition receptor expressed on the surface of leukocytes. Various ligands can activate or inhibit TLR2, therefore regulating the inflammation and apoptosis of immune cells. Mycobacterium tuberculosis (MTB) typically parasitizes macrophages. Further, after infecting the body, MTB can interact with TLR2 on the surface of various immune cells, including macrophages, leading to the release of cytokines that can affect the state and proliferation of MTB in the body. Additional research is needed to understand the polymorphism of TLR2 at the molecular level. Current studies indicate that the majority of TLR2 polymorphisms are not associated with susceptibility to MTB infection. This review provides an overview of the researches related to TLR2 and its ligands, the immune regulation activities of TLR2 following MTB infection, and the association of TLR2 polymorphism with susceptibility to MTB.

Collagen hydrogel with multiple antimicrobial mechanisms as anti-bacterial wound dressing.

Wound infection by multidrug-resistant bacteria seriously threatens human life. Chronic wounds, with necrosis, persistent inflammation, and covered by hypoxic tissue, seriously hinder anti-infection treatments. Herein, we have developed a multifunctional hydrogel dressing with antibacterial activity in the hypoxia environment to promote wound healing. The hydrogel comprises Cypate-conjugated antimicrobial peptides (AMP-Cypates), liposome-encapsulated perfluorodecalin, and recombinant type III collagen. AMP-Cypates exhibited outstanding antibacterial activity, jointly achieved through antimicrobial peptide (AMP) activity, photothermal therapy (PTT), and photodynamic therapy (PDT). The perfluorodecalin liposomes act as the oxygen carrier to mitigate wound hypoxia condition and enhance the efficacy of PDT. The recombinant type III collagen in the hydrogel further promoted the healing of the wounds together with the eradication of bacterial infection. Taken together, the hydrogel dressing provides a platform for integrating multiple antimicrobial mechanisms for the rapid removal of bacterial infection and the healing of chronic wounds.

Gelatinase Responsive Nanogel for Antibacterial Phototherapy and Wound Healing.

The unique bactericidal mechanism of metal nanoparticles (MNPs) is considered to be an effective strategy to deal with antibiotic resistance, but the oxidative stress damage caused by excessive accumulation of MNPs to normal cells cannot be ignored. Achieving on-demand release of nano-drugs in specific infection environments is highly attractive. Herein, we constructed a "core-shell" nanogel (G@CuS) based on a copper sulfide (CuS) antimicrobial agent and gelatin for targeted drug release and bacterial clearance in a gelatinase infected microenvironment. G@CuS produced heat and reactive oxygen species (ROS) under the irradiation of a laser, which together with the released Cu2+ cause irreversible and efficient physical damage to the bacteria. Moreover, the encapsulation of gelatin not only limits the biotoxicity of CuS nanodots (NDs), but also effectively promotes the proliferation of mammalian cells. Under the synergy of multiple mechanisms, G@CuS eradicated the colonized bacteria in the wound of mice infected with Staphylococcus aureus (S. aureus) and accelerated wound healing. The proposed application strategy of nanogel is expected to provide a new idea for clinical transformation.

Meta analysis of aerobic exercise improving intelligence and cognitive function in patients with Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is a neurodegenerative disease. This study aims to explore the intervention and treatment effects of aerobic exercise and different exercise modes on AD through meta-analysis. METHODS: Using the set inclusion and exclusion criteria, retrieve the China national knowledge infrastructure (CNKI), Wanfang Data Knowledge Service Platform, China Science and Technology Journal Database, Cochrane Library, and PubMed were searched from January 1, 2012, to December 31, 2021. Cochrane risk bias assessment tool was used to evaluate the quality of the included articles, and ReMan5.4.1 was used for forest plot analysis of mini-mental state exam (MMSE) score indicators included in the included articles. RESULTS: Twelve randomized controlled trials and 795 samples were included. Meta analysis of all articles: I2 = 91%, P ≤ .00001, (MD = 2.95, 95%CI [2.49, 3.40], P ≤ .00001). Meta analysis of 5 fit aerobics groups: I2 = 4%, P = .38, (MD = 1.53, 95%CI [0.72, 2.33], P = .0002); meta-analysis of three spinning groups: I2 = 3%, P = .36, (MD = 1.79, 95%CI [0.29, 3.29], P = .02). CONCLUSION: Aerobic exercise can effectively improve intellectual and cognitive impairment in AD patients, and for different forms of aerobic exercise, the therapeutic effect of spinning aerobic exercise is better than that of fit aerobics.

The catalytic activity of Ag2S-montmorillonites as peroxidase mimetic toward colorimetric detection of H2O2.

Nanocomposites based on silver sulfide (Ag2S) and Ca-montmorillonite (Ca(2+)-MMT) were synthesized by a simple hydrothermal method. The nanocomposites were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and Fourier transform infrared spectra (FTIR). The as-prepared Ag2S-MMT nanocomposites were firstly demonstrated to possess intrinsic peroxidase-like activity and could rapidly catalytically oxidize the substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2 to produce a blue product which can be seen by the naked eye in only one minute. The experimental results revealed that the Ag2S-MMT nanocomposites exhibit higher thermal durance. Based on the TMB-H2O2 catalyzed color reaction, the Ag2S-MMT nanocomposites were exploited as a new type of biosensor for detection and estimation of H2O2 through a simple, cheap and selective colorimetric method.