Alzheimer’s disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aβ aggregation and attenuating Aβ-induced oxidation in vitro. When given before or after the onset of Aβ deposition via i.p. injection, Edaravone substantially reduces Aβ deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.
Microarray showed that lncRNA RMST was differentially expressed in cervical cancer. Further experiments were conducted to detect the expression and biological function of RMST in triple-negative breast cancer (TNBC). Microarray was used to screen the differentially expressed lncRNAs in TNBC. QRT-PCR was applied to uncover the expression of RMST in TNBC tissues. The cell viability of RMST-transfected TNBC cells were probed by CKK-8 assay and colony formation assay. TUNEL assay was conducted to test the cell apoptosis and FCM assay was exerted to detect the cell cycle. The invasion and migration ability of transfected cells were examined by transwell assay. RMST played its biological function through regulating the mRNA or protein expression in cytoplasm. CCK-8 and colony formation assay unveiled that RMST could slow down the proliferation of TNBC cells to influence the tumor progression. TUNEL results revealed that RMST could enhance cell apoptosis in TNBC. The cell cycle detected by FCM assay indicated that RMST might induce the block of G0/G1 phase thus inhibiting TNBC cell proliferation. RMST overexpression could also restrain the invasion and migration abilities of TNBC cells. RMST played a role of tumor suppressor in TNBC through inhibiting cell proliferation, invasion and migration, enhancing cell apoptosis, and regulating cell cycle.
Atomically
dispersed single-atom catalysts are among the most attractive
electrocatalysts for the CO2 reduction reaction (CRR).
To elucidate the origin of the exceptional activity of atomically
dispersed Fe–N–C catalyst in CRR, we have performed
operando 57Fe Mössbauer spectroscopic studies on
a model single-Fe-atom catalyst with a well-defined N coordination
environment. Combining with operando X-ray absorption spectroscopy,
the in situ-generated four pyrrolic nitrogen atom-coordinated low-spin
Fe(I) (LS FeIN4) featuring monovalent iron is
identified as the reactive center for the conversion of CO2 to CO. Furthermore, density functional theory calculations reveal
that the optimal binding strength of CO2 to the LS FeIN4 site, with strong orbital interactions between
the singly occupied d
z
2
orbital of the Fe(I) site and the singly occupied π*
orbital of [COOH] fragment, is the key factor for the excellent CRR
performance.
Liver cancer is a common and aggressive malignancy, but available treatment approaches remain suboptimal. Cancer targeting Gene-Viro-Therapy (CTGVT) has shown excellent anti-tumor effects in a preclinical study. CTGVT takes advantage of both gene therapy and virotherapy by incorporating an anti-tumor gene into an oncolytic virus vector. Potent anti-tumor activity is achieved by virus replication and exogenous expression of the anti-tumor gene. A dual-regulated oncolytic adenoviral vector designated AdÁAFPÁE1AÁE1B (D55) (AdÁAFPÁD55 for short thereafter) was constructed by replacing the native viral E1A promoter with the simian virus 40 enhancer/a-fetoprotein (AFP) composite promoter (AFPep) based on an E1B-55K-deleted construct, ZD55. AdÁAFPÁD55 showed specific replication and cytotoxicity in AFP-positive hepatoma cells. It also showed enhanced safety in normal cells when compared with the mono-regulated vector ZD55. To improve the anti-hepatoma activities of the virus, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene was introduced into AdÁAFPÁD55. AdÁAFPÁD55-TRAIL exhibited remarkable anti-tumor activities in vitro and in vivo. Treatment with AdÁAFPÁD55-TRAIL can induce both autophagy owing to the AdÁAFPÁD55 vector and caspase-dependent apoptosis owing to the TRAIL protein. Therefore, AdÁAFPÁD55-TRAIL could be a potential anti-hepatoma agent with anti-tumor activities due to AFP-specific replication and TRAIL-induced apoptosis.
Ginsenoside Rg1 (GRg1) has neuroprotective effects on Alzheimer's disease (AD). The occurrence and progression of AD are closely related to gut microbiota. Few studies have learned the direct relationship between GRg1 and gut microbiota. In this study, we found an original way to research this relationship by using GRg1 in the AD model of tree shrews. Morris water maze and immunohistochemistry were performed to test the cognition repairing function of GRg1 by tree shrews and 16S ribosomal RNA sequencing was used to explore the composition and abundance of gut microbiota. After GRg1 treatment, the result of Morris water maze showed an improvement in cognitive function, and immunohistochemistry revealed a decrease in tau protein. Moreover, 16SrRNA sequencing results showed the abundances of Proteobacteria and Verrucomicrobia were significantly different, and Lactobacillaceae was significantly increased in the GRg1 treatment group. It also showed that the gut microbiome with middle and high doses of GRg1 was close to the normal group. In conclusion, this study suggests that GRg1 at middle and high doses may change the abundance of gut microbiota to improve AD, and thatProteobacteria and Verrucomicrobia are key microbiota. This is the first report that has ever studied the relationship between GRg1 and gut microbiota in tree shrews.
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