Comparison of the protective effects of ginsenosides Rb1 and Rg1 on improving cognitive deficits in SAMP8 mice based on anti-neuroinflammation mechanism

This present study was designed to investigate the different effects of ginsenosides Rb1 and Rg1 on improving cognitive deficits in 4-month-old SAMP8 mice. Mice were divided into six groups, including the SAMP8 group, the SAMP8 + Donepezil (1.6 mg/kg) group, the SAMP8 + Rb1 (30 and 60 µmol/kg), and SAMP8 + Rg1 (30 and 60 µmol/kg) groups. SAMR1 mice of the same age were used as the control group. Ginsenosides and donepezil were administrated orally to animals for 8 weeks, then the learning and memory ability of mice were measured by using Morris water maze (MWM) test, object recognition test and passive avoidance experiments. The possible mechanisms were studied including the anti-glial inflammation of Rb1 and Rg1 using HE staining, immunohistochemistry and western blot experiments. Results revealed that Rb1 and Rg1 treatment significantly improved the discrimination index of SAMP8 mice in the object recognition test. Rb1 (60 µmol/kg) and Rg1 (30, 60 µmol/kg) could significantly shorten the escape latency in the acquisition test of the MWM test in SAMP8 mice. Furthermore, Rb1 and Rg1 treatments effectively reduced the number of errors in the passive avoidance task in SAMP8 mice. Western blot experiments revealed that Rb1 showed higher effect than Rg1 in decreasing protein expression levels of ASC, caspase-1 and Aβ in the hippocampus of SAMP8 mice, while Rg1 was more effective than Rb1 in decreasing the protein levels of iNOS. In addition, although Rb1 and Rg1 treatments showed significant protective effects in repairing neuronal cells loss and inhibiting the activation of astrocyte and microglia in hippocampus of SAMP8 mice, Rb1 was more effective than Rg1. These results suggest that Rb1 and Rg1 could improve the cognitive impairment in SAMP8 mice, and they have different mechanisms for the treatment of Alzheimer's disease.This work was supported by the National Key Research and Development Program of China (2016YFE0131800), Science & Technology department of Sichuan province (2019YFH0023), Office of Sciences & Technology and Talent work of Luzhou (2018LZXNYD-ZK32), the High - end Talents Recruitment Program (Liu Xinmin group) of Luzhou Municipal People's Government

Force spectroscopy reveals the presence of structurally modified dimers in transthyretin amyloid annular oligomers.

Toxicity in amyloidogenic protein misfolding disorders is thought to involve intermediate states of aggregation associated with the formation of amyloid fibrils. Despite their relevance, the heterogeneity and transience of these oligomers have placed great barriers in our understanding of their structural properties. Among amyloid intermediates, annular oligomers or annular protofibrils have raised considerable interest because they may contribute to a mechanism of cellular toxicity via membrane permeation. Here we investigated, by using AFM force spectroscopy, the structural detail of amyloid annular oligomers from transthyretin (TTR), a protein involved in systemic and neurodegenerative amyloidogenic disorders. Manipulation was performed in situ, in the absence of molecular handles and using persistence length-fit values to select relevant curves. Force curves reveal the presence of dimers in TTR annular oligomers that unfold via a series of structural intermediates. This is in contrast with the manipulation of native TTR that was more often manipulated over length scales compatible with a TTR monomer and without unfolding intermediates. Imaging and force spectroscopy data suggest that dimers are formed by the assembly of monomers in a head-to-head orientation with a nonnative interface along their beta-strands. Furthermore, these dimers stack through nonnative contacts that may enhance the stability of the misfolded structure

HIV prevalence among female sex workers, drug users and men who have sex with men in Brazil: A Systematic Review and Meta-analysis

<p>Abstract</p> <p>Background</p> <p>The Brazilian response towards AIDS epidemic is well known, but the absence of a systematic review of vulnerable populations ─ men who have sex with men (MSM), female sex workers (FSW), and drug users (DU) remains a main gap in the available literature. Our goal was to conduct a systematic review and meta-analysis of studies assessing HIV prevalence among MSM, FSW and DU, calculating a combined pooled prevalence and summarizing factors associated the pooled prevalence for each group.</p> <p>Methods</p> <p>Nine electronic databases (MEDLINE via PubMed, EMBASE, Cochrane CENTRAL, AIDSLINE, AMED, CINAHL, TOXNET, SciELO, and ISI-Web of Science) were searched for peer-reviewed papers published in English, French, Spanish or Portuguese, from 1999 to 2009. To be included in the review, studies had to measure HIV prevalence and/or incidence as the primary outcome among at least one specific population under analysis.</p> <p>Results</p> <p>The studies targeting the three populations analyzed mostly young participants aged 30 years or less. Among FSW, eight studies were selected (3,625 participants), consistently identifying higher condom use with sexual clients than with occasional and stable partners. The combined HIV prevalence for FSW was 6.2 (95% CI: 4.4-8.3). Ten studies targeting MSM were identified (6,475 participants). Unprotected anal intercourse was commonly reported on those studies, but with great variability according to the nature of the relationship - stable vs. occasional sex partners - and sexual practice - receptive vs. insertive anal sex. Pooled HIV prevalence for MSM was 13.6 (95% CI: 8.2-20.2). Twenty nine studies targeting DU were identified (13,063 participants). Those studies consistently identified injection drug use and syringe/needle sharing as key predictors of HIV-infection, as well as engagement in sex work and male-to-male sex. The combined HIV prevalence across studies targeting DU was 23.1 (95% CI: 16.7-30.2).</p> <p>Conclusions</p> <p>FSW, MSM and DU from Brazil have a much risk of acquiring HIV infection compared to the general population, among which HIV prevalence has been relatively low (~0.6%). Those vulnerable populations should be targeted by focused prevention strategies that provide accurate information, counseling and testing, as well as concrete means to foster behavior change (e.g. access to condoms, drug abuse treatment, and clean syringes in the case of active injecting drug users), tailored to gender and culture-specific needs. Programs that provide these services need to be implemented on public health services throughout the country, in order to decrease the vulnerability of those populations to HIV infection.</p

Biased-corrected richness estimates for the Amazonian tree flora

Amazonian forests are extraordinarily diverse, but the estimated species richness is very much debated. Here, we apply an ensemble of parametric estimators and a novel technique that includes conspecific spatial aggregation to an extended database of forest plots with up-to-date taxonomy. We show that the species abundance distribution of Amazonia is best approximated by a logseries with aggregated individuals, where aggregation increases with rarity. By averaging several methods to estimate total richness, we confirm that over 15,000 tree species are expected to occur in Amazonia. We also show that using ten times the number of plots would result in an increase to just ~50% of those 15,000 estimated species. To get a more complete sample of all tree species, rigorous field campaigns may be needed but the number of trees in Amazonia will remain an estimate for years to come