Ginsenoside Rg1 Attenuates Oligomeric Aβ1-42-Induced Mitochondrial Dysfunction

Mitochondrial dysfunction is one of the major pathological changes seen in Alzheimer's disease (AD). Amyloid beta-peptide (Aβ), a neurotoxic peptide, accumulates in the brain of AD subjects and mediates mitochondrial and neuronal stress. Therefore, protecting mitochondrion from Aβ-induced toxicity holds potential benefits for halting and treating and perhaps preventing AD. Here, we report that administration of ginsenoside Rg1, a known neuroprotective drug, to primary cultured cortical neurons, rescues Aβ-mediated mitochondrial dysfunction as shown by increases in mitochondrial membrane potential, ATP levels, activity of cytochrome c oxidase (a key enzyme associated with mitochondrial respiratory function), and decreases in cytochrome c release. The protective effects of Rg1 on mitochondrial dysfunction correlate to neuronal injury in the presence of Aβ. This finding suggests that ginsenoside Rg1 may attenuate Aβ-induced neuronal death through the suppression of intracellular mitochondrial oxidative stress and may rescue neurons in AD

Multi-faced neuroprotectice effects of Ginsenoside Rg1 in an Alzheimer mouse model

There has been no extensive characterization of the effects of Ginsenoside Rg1, a pharmacological active component purified from the nature product ginseng, in an Alzheimer's disease mouse model. The well-characterized transgenic Alzheimer disease (AD) mice over expressing amyloid precursor protein (APP)/Aβ (Tg mAPP) and nontransgenic (nonTg) littermates at age of 6 and 9 months were treated with Rg 1 for three months via intraperitoneal injection. Mice were then evaluated for changes in amyloid pathology, neuropathology and behavior. Tg mAPP treated with Rg1 showed a significant reduction of cerebral Aβ levels, reversal of certain neuropathological changes, and preservation of spatial learning and memory, as compared to vehicle-treated mice. Rg1 treatment inhibited activity of γ-secretase in both Tg mAPP mice and B103-APP cells, indicating the involvement of Rg1 in APP regulation pathway. Furthermore, administration of Rg1 enhanced PKA/CREB pathway activation in mAPP mice and in cultured cortical neurons exposed to Aβ or glutamate-mediated synaptic stress. Most importantly, the beneficial effects on attenuation of cerebral Aβ accumulation, improvement in neuropathological and behavioral changes can be extended to the aged mAPP mice, even to 12–13 months old mice that had extensive amyloid pathology and severe neuropathological and cognitive malfunction. These studies indicate that Rg1 has profound multi-faced and neuroprotective effects in an AD mouse model. Rg1 induces neuroprotection through ameliorating amyloid pathology, modulating APP process, improving cognition, and activating PKA/CREB signaling. These findings provide a new perspective for the treatment of AD and demonstrate potential for a new class of drugs for AD treatment

Competing Demands of Prosociality & Equity in Monkeys

Prosocial decisions may lead to unequal payoffs among group members. Although an aversion to inequity has been found in empirical studies of both human and nonhuman primates, the contexts previously studied typically do not involve a trade-off between pro-sociality and inequity. Here we investigate the apparent co-existence of these two factors, specifically the competing demands of prosociality and equity. We directly compare the responses of brown capuchin monkeys (Cebus apella) among situations where pro-social preferences conflict with equality, using a paradigm comparable to other studies of cooperation and inequity in this species. By choosing to pull a tray towards themselves, subjects rewarded themselves and/or another in conditions in which the partner either received the same or different rewards, or the subject received no reward. In unequal payoff conditions, subjects could obtain equality by choosing not to pull in the tray, so that neither individual was rewarded. The monkeys showed prosocial preferences even in situations of moderate disadvantageous inequity, preferring to pull in the tray more often when a partner was present than absent. However when the discrepancy between rewards increased, prosocial behavior ceased

Association of Toll-Like Receptor 4 Gene Polymorphism and Expression with Urinary Tract Infection Types in Adults

Background: Innate immunity of which Toll-like receptor (TLR) 4 and CXCR1 are key elements plays a central role in the development of urinary tract infection (UTI). Although the relation between the genetics of TLR4 and CXCR1 and UTI is investigated partly, the polymorphisms and expression of TLR4 and CXCR1 in different types of UTI in adults are not extremely clear. Methodology/Principal Findings: This study investigates the presence of TLR4 A (896) G and CXCR1 G (2608) C polymorphisms in 129 UTI patients using RFLP-PCR. Gene and allelic prevalence were compared with 248 healthy controls. Flow cytometry was used to detect TLR4 and CXCR1 expression in the monocytes of UTI patients and healthy controls. TLR4 (896) AG genotype and TLR4 (896) G allele had higher prevalence in UTI (especially in acute cystitis and urethritis) patients, whereas CXCR1 (2608) GC genotype and CXCR1 (2608) C allele had lower prevalence in UTI patients than controls. TLR4 expression was significantly lower in chronic UTI patients than in acute pyelonephritis or healthy controls. CXCR1 expression was similar in both controls and patients. TLR4 expression in chronic UTI patients after astragalus treatment was higher than pre-treatment. Conclusions: The results indicate the relationship between the carrier status of TLR4 (896) G alleles and the development of UTI, especially acute cystitis and urethritis, in adults. TLR4 expression levels are correlated with chronic UTI

ALMA Observation of NGC5135: The Circumnuclear CO(6-5) and Dust Continuum Emission at 45 Parsec Resolution[⋆\star]

We present high-resolution (0.17\arcsec $\times$ 0.14\arcsec) Atacama Large Millimeter/submillimeter Array (ALMA) observations of the CO\,(6-5) line, and 435\um\ dust continuum emission within a $\sim$9\arcsec $\times$ 9\arcsec\ area centered on the nucleus of the galaxy NGC\,5135. NGC\,5135 is a well-studied luminous infrared galaxy that also harbors a Compton-thick active galactic nucleus (AGN). At the achieved resolution of 48 $\times$ 40\,pc, the CO\,(6-5) and dust emissions are resolved into gas "clumps" along the symmetrical dust lanes associated with the inner stellar bar. The clumps have radii between $\sim$45-180\,pc and CO\,(6-5) line widths of $\sim$60-88\,\kms. The CO\,(6-5) to dust continuum flux ratios vary among the clumps and show an increasing trend with the \FeII/Br-$\gamma$ ratios, which we interpret as evidence for supernova-driven shocked gas providing a significant contribution to the \co65\ emission. The central AGN is undetected in continuum, nor in CO\,(6-5) if its line velocity width is no less than $\sim$\,40\,\kms. We estimate that the AGN contributes at most 1\% of the integrated CO\,(6-5) flux of 512 $\pm$ 24$\,$Jy\kms\ within the ALMA field of view, which in turn accounts for $\sim$32\% of the CO\,(6-5) flux of the whole galaxy.Comment: 21 pages, 12 figures, Accepted for publication in Ap

Combining optogenetic stimulation and fMRI to validate a multivariate dynamical systems model for estimating causal brain interactions

State-space multivariate dynamical systems (MDS) (Ryali et al., 2011) and other causal estimation models are being increasingly used to identify directed functional interactions between brain regions. However, the validity and accuracy of such methods is poorly understood. Performance evaluation based on computer simulations of small artificial causal networks can address this problem to some extent, but they often involve simplifying assumptions that reduce biological validity of the resulting data. Here, we use a novel approach taking advantage of recently developed optogenetic fMRI (ofMRI) techniques to selectively stimulate brain regions while simultaneously recording high-resolution whole-brain fMRI data. ofMRI allows for a more direct investigation of causal influences from the stimulated site to brain regions activated downstream and is therefore ideal for evaluating causal estimation methods in vivo. We used ofMRI to investigate whether MDS models for fMRI can accurately estimate causal functional interactions between brain regions. Two cohorts of ofMRI data were acquired, one at Stanford University and the University of California Los Angeles (Cohort 1) and the other at the University of North Carolina Chapel Hill (Cohort 2). In each cohort optical stimulation was delivered to the right primary motor cortex (M1). General linear model analysis revealed prominent downstream thalamic activation in Cohort 1, and caudate-putamen (CPu) activation in Cohort 2. MDS accurately estimated causal interactions from M1 to thalamus and from M1 to CPu in Cohort 1 and Cohort 2, respectively. As predicted, no causal influences were found in the reverse direction. Additional control analyses demonstrated the specificity of causal interactions between stimulated and target sites. Our findings suggest that MDS state-space models can accurately and reliably estimate causal interactions in ofMRI data and further validate their use for estimating causal interactions in fMRI. More generally, our study demonstrates that the combined use of optogenetics and fMRI provides a powerful new tool for evaluating computational methods designed to estimate causal interactions between distributed brain regions

Ferroptosis in hematological malignant tumors

Ferroptosis is a kind of iron-dependent programmed cell death discovered in recent years. Its main feature is the accumulation of lipid reactive oxygen species in cells, eventually leading to oxidative stress and cell death. It plays a pivotal role in normal physical conditions and the occurrence and development of various diseases. Studies have shown that tumor cells of the blood system, such as leukemia cells and lymphoma cells, are sensitive to the response to ferroptosis. Regulators that modulate the Ferroptosis pathway can accelerate or inhibit tumor disease progression. This article reviews the mechanism of ferroptosis and its research status in hematological malignancies. Understanding the mechanisms of ferroptosis could provide practical guidance for treating and preventing these dreaded diseases