A novel coronavirus (SCoV) is the etiological agent of severe acute respiratory syndrome (SARS). SCoV-like viruses were isolated from Himalayan palm civets found in a live-animal market in Guangdong, ...China. Evidence of virus infection was also detected in other animals (including a raccoon dog, Nyctereutes procyonoides) and in humans working at the same market. All the animal isolates retain a 29-nucleotide sequence that is not found in most human isolates. The detection of SCoV-like viruses in small, live wild mammals in a retail market indicates a route of interspecies transmission, although the natural reservoir is not known.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Objective
The manifestations of aging include cognitive deficits and muscular dysfunction, which are closely linked to impairment of mitochondrial biogenesis. Berberine, an isoquinoline alkaloid, ...presents multiple anti-diabetic pharmacological effects. Evidence has indicated that insulin resistance and cognitive impairment share the same pathogenesis, and berberine could reverse glucose metabolism abnormalities and muscle mitochondrial dysfunction induced by a high-fat diet. This study was used to investigate whether berberine could be used as an anti-aging drug to prevent cognitive deficits and muscular dysfunction in natural aging.
Methods
Biochemical indicators and an intraperitoneal glucose tolerance test were tested in 5-monthold rats (5 mo group), 24-month-old rats (24 mo group) and 24-month-old rats that had undergone 6 months of berberine treatment (BBR group). A Morris water maze test was conducted to assess the cognitive ability of the rats. Insulin resistance in whole-body was evaluated by intraperitoneal glucose tolerance test (IPGTT). The morphology of the skeletal muscle tissue was observed by hematoxylin-eosin (HE) staining. The levels of total cholesterol, triglyceride, ATP and reactive oxygen species (ROS) were assessed with corresponding reagent kits. The protein expressions of GLUT4, AMPK, SIRT1 and PGC-1α in skeletal muscle were examined by Western blot.
Results
The results showed that administration of berberine for 6 months significantly improved cognitive deficits and insulin resistance in naturally aging rats (p<0.01). Furthermore, berberine treatment helped normalize the disordered alignment and the decreased number of muscle fibers (p<0.01) in the skeletal muscle of 24 mo rats. Berberine decreased the levels of ROS in both the serum and the skeletal muscle of 24 mo rats (p<0.01). Berberine increased the protein expression of p-AMPK, SIRT1 and PGC-1α and increased the production of ATP in the skeletal muscle of aging rats (p<0.01).
Conclusions
Berberine markedly ameliorates aging-related reductions in cognitive ability and muscular function, and the activation of the AMPK/SIRT1/PGC-1α pathway in skeletal muscle may be the underlying protective mechanism of berberine on muscular function.
Highlights • NRG1 protects against OGD-induced cortical neuronal apoptosis. • NRG1-mediated neuroprotection is blocked by neutralizing NRG1 and ErbB4 inhibition. • GABA receptor agonists have no ...synergistic effect with NRG1. • NRG1-mediated neuroprotection is partly blocked by GABA receptor antagonists. • The NRG1 neuroprotection against brain ischemia is abolished in PV-ErbB4−/− mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Spinal cord stimulation (SCS) is a minimally invasive therapy used for the treatment of chronic neuropathic pain. SCS is a safe and effective alternative to medications such as opioids, and multiple ...randomized controlled studies have demonstrated efficacy for difficult‐to‐treat neuropathic conditions such as failed back surgery syndrome. Conventional SCS is believed mediate pain relief via activation of dorsal column Aβ fibers, resulting in variable effects on sensory and pain thresholds, and measurable alterations in higher order cortical processing. Although potentiation of inhibition, as suggested by Wall and Melzack's gate control theory, continues to be the leading explanatory model, other segmental and supraspinal mechanisms have been described. Novel, non‐standard, stimulation waveforms such as high‐frequency and burst have been shown in some studies to be clinically superior to conventional SCS, however their mechanisms of action remain to be determined. Additional studies are needed, both mechanistic and clinical, to better understand optimal stimulation strategies for different neuropathic conditions, improve patient selection and optimize efficacy.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The recent discovery of cancer stem cells (CSCs) has played a pivotal role in changing our view of carcinogenesis and chemotherapy. Based on this concept, CSCs are responsible for the formation and ...growth of neoplastic tissue and are naturally resistant to chemotherapy, explaining why traditional chemotherapies can initially shrink a tumor but fails to eradicate it in full, allowing eventual recurrence. Recently, we identified a CSC population in hepatocellular carcinoma (HCC) characterized by their CD133 phenotype. However, the molecular mechanism by which it escapes conventional therapies remains unknown. Here, we examined the sensitivity of these cells to chemotherapeutic agents (doxorubicin and fluorouracil) and the possible mechanistic pathway by which resistance may be regulated. Purified CD133+ HCC cells isolated from human HCC cell line and xenograft mouse models survived chemotherapy in increased proportions relative to most tumor cells which lack the CD133 phenotype; the underlying mechanism of which required the preferential expression of survival proteins involved in the Akt/PKB and Bcl-2 pathway. Treatment of CD133+ HCC cells with an AKT1 inhibitor, specific to the Akt/PKB pathway, significantly reduced the expression of the survival proteins that was normally expressed endogenously. In addition, treatment of unsorted HCC cells with both anticancer drugs in vitro significantly enriched the CD133+ subpopulation. In conclusion, our results show that CD133+ HCC cells contribute to chemoresistance through preferential activation of Akt/PKB and Bcl-2 cell survival response. Targeting of this specific survival signaling pathway in CD133+ HCC CSCs may provide a novel therapeutic model for the disease.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We propose a machine-learning approach based on Bayesian optimization to build global potential energy surfaces (PES) for reactive molecular systems using feedback from quantum scattering ...calculations. The method is designed to correct for the uncertainties of quantum chemistry calculations and yield potentials that reproduce accurately the reaction probabilities in a wide range of energies. These surfaces are obtained automatically and do not require manual fitting of the ab initio energies with analytical functions. The PES are built from a small number of ab initio points by an iterative process that incrementally samples the most relevant parts of the configuration space. Using the dynamical results of previous authors as targets, we show that such feedback loops produce accurate global PES with 30 ab initio energies for the three-dimensional H + H2 → H2 + H reaction and 290 ab inito energies for the six-dimensional OH + H2 → H2O + H reaction. These surfaces are obtained from 360 scattering calculations for H3 and 600 scattering calculations for OH3. We also introduce a method that quickly converges to an accurate PES without the a priori knowledge of the dynamical results. By construction, our method illustrates the lowest number of potential energy points (i.e. the minimum information) required for the non-parametric construction of global PES for quantum reactive scattering calculations.
Abstract This study examined the hypothesis that apoptotic inhibition via mitochondrial pathway was involved in hyperbaric oxygen preconditioning (HBO-PC)–induced neuroprotection on ...ischemia–reperfusion injury in rat brain. Male Sprague–Dawley rats (250∼280 g, n =144) were divided into control, middle cerebral artery occlusion (MCAO) for 90 min, and HBO-PC plus MCAO groups. HBO-PC was conducted four times by giving 100% oxygen at 2.5 atm absolute (ATA), for 1 h at 12 h intervals for 2 days. At 24 h after the last HBO-PC, MCAO was performed and at 24 h after MCAO, neurological function, brain water content, infarct volume, and cell death were evaluated. Enzymatic activity of capase-3 and −9, and expression of cytochrome c , Bcl-2 and Bax proteins were performed in the samples from hippocampus, ischemic penumbra and core of the brain cortex, respectively. HBO-PC reduced brain edema, decreased infarction volume, and improved neurological recovery. HBO-PC reduced cytoplasm cytochrome c levels, decreased caspase enzyme activity, upregulated the ratio of Bcl-2 and Bax expression, and abated the apoptosis of ischemic tissue. HBO-PC protects brain tissues from ischemia–reperfusion injury by suppressing mitochondrial apoptotic pathways.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Power line noise is known to affect the performance of broadband power-line communications significantly. This paper presents a frequency-domain approach to characterize and model the statistical ...variation of power-line noise. The model considers both the background noise and the impulsive noise. The background noise model is based on statistical analysis of the results from two long-term measurements of noise spectrum conducted at two separate sites of a laboratory and a residential apartment. On the other hand, the impulsive noise model is obtained by direct measurements from the noise sources (i.e., various electrical household appliances). The amount of impulse noise reaching a power-line communications (PLC) receiver can then be determined with consideration of the channel transfer characteristics between the noise sources and the PLC receiver. Using these noise models, the performance of two major classes of digital modulation schemes, namely single-carrier modulation and multicarrier modulation, are analyzed and compared. It is found that the multicarrier scheme performs better than the single-carrier scheme when subjected to the observed power-line noise with non-Gaussian statistics.
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