Fecal microbiota transplantation and short-chain fatty acids protected against cognitive dysfunction in a rat model of chronic cerebral hypoperfusion.

AIMS: Clear roles and mechanisms in explaining gut microbial dysbiosis and microbial metabolites short-chain fatty acids (SCFAs) alterations in chronic cerebral ischemic pathogenesis have yet to be explored. In this study, we investigated chronic cerebral hypoperfusion (CCH)-induced gut microbiota and metabolic profiles of SCFAs as well as the effects and mechanisms of fecal microbiota transplantation (FMT) and SCFAs treatment on CCH-induced hippocampal neuronal injury. METHODS: Bilateral common carotid artery occlusion (BCCAo) was used to establish the CCH model. Gut microbiota and SCFAs profiles in feces and hippocampus were evaluated by 16S ribosomal RNA sequencing and gas chromatography-mass spectrometry. RNA sequencing analysis was performed in hippocampal tissues. The potential molecular pathways and differential genes were verified through western blot, immunoprecipitation, immunofluorescence, and ELISA. Cognitive function was assessed via the Morris water maze test. Ultrastructures of mitochondria and synapses were tested through a transmission electron microscope. RESULTS: Chronic cerebral hypoperfusion induced decreased fecal acetic and propionic acid and reduced hippocampal acetic acid, which were reversed after FMT and SCFAs administration by changing fecal microbial community structure and compositions. Furthermore, in the hippocampus, FMT and SCFAs replenishment exerted anti-neuroinflammatory effects through inhibiting microglial and astrocytic activation as well as switching microglial phenotype from M1 toward M2. Moreover, FMT and SCFAs treatment alleviated neuronal loss and microglia-mediated synaptic loss and maintained the normal process of synaptic vesicle fusion and release, resulting in the improvement of synaptic plasticity. In addition, FMT and SCFAs supplement prevented oxidative phosphorylation dysfunction via mitochondrial metabolic reprogramming. The above effects of FMT and SCFAs treatment led to the inhibition of CCH-induced cognitive impairment. CONCLUSION: Our findings highlight FMT and SCFAs replenishment would be the feasible gut microbiota-based strategy to mitigate chronic cerebral ischemia-induced neuronal injury.

Effect of Xanthium Strumarium on HIV-1 5'-LTR Transcriptional Activity and Viral Reactivation in Latently Infected Cells.

Chinese herbal medicines (CHMs) are widely used in Asian countries. They show multiple pharmacological activities, including antiviral activities. The 5'-long terminal repeat (LTR) region of HIV-1, required for viral transcription, is a potential drug target for HIV-1 reactivation and intrinsic cell death induction of infected or latently infected cells. Modulation of HIV-1 reactivation requires interactions between host cell proteins and viral 5'-LTR elements. By evaluation of two CHMs- Xanthium strumarium and Pueraria montana, we found that 1) X. strumarium reactivated HIV-1 latently infected cells in J-Lat 8.4, J-Lat 9.2, U1, and ACH-2 cells in vitro; 2) 27 nuclear regulatory proteins were associated with HIV-1 5'-LTR using deoxyribonucleic acid affinity pull-down and LC-MS/MS analyses; and 3) among them, silencing of XRCC6 reactivated HIV-1 5'-LTR transcriptional activity. We found that X. strumarium inhibits the 5'-LTR associated XRCC6 nuclear regulatory proteins, increases its viral 5'-LTR promoter transcriptional activity, and reactivates HIV-1 latently infected cells in vitro. These findings may contribute to understanding the 5'-LTR activity and the host cell nuclear regulatory protein machinery for reactivating HIV-1 and for future investigations to eradicate and cure HIV-1 infection.

Effects of Chinese herbal medicine therapy on survival and hepatic outcomes in patients with hepatitis C virus infection in Taiwan.

BACKGROUND: Chinese herbal medicine (CHM) is a complementary natural medicine that is used widely for the treatment of hepatic diseases. The aim of this study was to investigate the effects of the long-term use of CHM for the treatment of liver diseases, as prescribed by TCM doctors, on overall mortality and hepatic outcomes in patients with HCV. PATIENTS AND METHODS: We identified 98788 patients with HCV. Of these, 829 and 829 patients who were users and non-users of CHM, respectively, were matched for age, gender, CCI, and comorbidities prior to CHM treatment. The chi-squared test, Cox proportional hazard model, Kaplan--Meier method, and log-rank test were used for comparisons. RESULTS: CHM users had a lower risk of overall mortality than non-users after adjustment for comorbidities by using a multivariate Cox proportional hazard model (p-value < 0.001; HR: 0.12, 95% CI: 0.06-0.26). In addition,the CHM users had a lower risk of liver cirrhosis than non-users after adjustment for comorbidities (p-value = 0.028; HR: 0.29, 95% CI: 0.09-0.88). The 12-year cumulative incidences of overall mortality and liver cirrhosis were lower in the CHM group (p-value < 0.05 for both, log rank test). The CHM co-prescription for Dan-Shen, Bie-Jia, Jia-Wei-Xiao-Yao-San => E-Shu was found to occur most often associated for the specific treatment of HCV infection. CONCLUSION: CHM as adjunctive therapy may reduce the overall mortality and the risk of liver cirrhosis in patients with HCV. The comprehensive list of the herbal medicines that may be used for the treatment of patients with HCV may be useful in future scientific investigations or for future therapeutic interventions to prevent negative hepatic outcomes in patients with HCV.

Molecular structure and vibrational bands and 13C chemical shift assignments of both enmein-type diterpenoids by DFT study.

We report here theoretical and experimental studies on the molecular structure and vibrational and NMR spectra of both natural enmein type diterpenoids molecule (6, 7-seco-ent-kaurenes enmein type), isolated from the leaves of Isodon japonica (Burm.f.) Hara var. galaucocalyx (maxin) Hara. The optimized geometry, total energy, NMR chemical shifts and vibrational wavenumbers of epinodosinol and epinodosin have been determined using B3LYP method with 6-311G (d,p) basis set. A complete vibrational assignment is provided for the observed IR spectra of studied compounds. The calculated wavenumbers and 13C c.s. are in an excellent agreement with the experimental values. Quantum chemical calculations at the B3LYP/6-311G (d,p) level of theory have been carried out on studied compounds to obtain a set of molecular electronic properties (MEP,HOMO, LUMO and gap energies ΔEg). Electrostatic potential surfaces have been mapped over the electron density isosurfaces to obtain information about the size, shape, charge density distribution and chemical reactivity of the molecules.