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The proteolytic autophagy system is involved in a major regulatory pathway in dexamethasone (Dex)-induced muscle atrophy. Sirtuin 2 (SIRT2) is known to modulate autophagy signaling, exerting effects in skeletal muscle atrophy. We examined the effects of SIRT2 on autophagy in Dex-induced myoatrophy. Tostudy this, mice were randomly distributed among the normal, Dex, and sirtinol groups. C2C12 cells were differentiated into myotubes and transduced with lentivirus carrying Sirt2--green fluorescent protein (GFP) or Sirt2 short hairpin RNA (Sirt2-shRNA)--GFP. To evaluate the mass and function of skeletal muscles, we measured myofiber cross-sectional area, myotube size, gastrocnemius (GA) muscle wet mass: body mass ratio (%), and time to exhaustion. The expression levels of SIRT2, myosin heavy chain, microtubule-associated protein 1 light chain 3 (LC3), and Beclin-1 were measured using Western blotting and quantitative reverse transcription--polymerase chain reaction. Inhibition of SIRT2 markedly attenuated GA muscle mass and endurance capacity. The same phenotype was observed in Sirt2-shRNA-treated myotubes, as evidenced by their decreased size. Conversely, overexpression of SIRT2 alleviated Dex-induced myoatrophy in vitro. Moreover, SIRT2 negatively regulated the expression of LC3b and Beclin-1 in skeletal muscles. These findings suggest that SIRT2 activation protects myotubes against Dex-induced atrophy through inhibition of the autophagy system; this phenomenon may serve as a target for treating glucocorticoid-induced myopathy. Key words: sirtuin 2, dexamethasone, skeletal muscle atrophy, autophagy, myotube. Le système protéolytique d'autophagie est impliqué dans une voie de régulation majeure dans l'atrophie musculaire induite par la dexaméthasone (Dex). La sirtuine 2 (SIRT2) est connue pour participer à la modulation de la signalisation de l'autophagie, exerçant ses effets dans l'atrophie du muscle squelettique. Les auteurs cherchaient à déterminer les effets de la SIRT2 sur l'autophagie dans la myoatrophie induite par la Dex. Des souris ont été réparties au hasard entre les groupes normal, Dex et sirtinol. Les cellules C2C12 ont été différenciées en myotubes et transfectées avec un lentivirus comportant un court ARN en épingle à cheveux de Sirt2 (ARNsh-Sirt2) marqué à la protéine fluorescente verte (GFP) ou un lentivirus Sirt2-GFP. Pour évaluer la masse et la fonction des muscles squelettiques, ils ont mesuré la surface transversale des myofibres, la taille des myotubes, le rapport (%) entre le poids humide du muscle gastrocnémien (GA) et le poids corporel et le temps d'épuisement. Les niveaux d'expression de la SIRT2, de la chaîne lourde de la myosine (MyHC), de la LC3 et de la bécline-1 ont été détectés par buvardage Western et par réaction en chaîne par polymérase quantitative couplée à une transcription inverse. L'inhibition de la SIRT2 diminuait nettement la masse musculaire et la capacité d'endurance du GA. Le même phénotype était observé dans les myotubes traités par l'ARNsh-Sirt2, comme en témoignait leur taille réduite. À l'inverse, la surexpression de SIRT2 atténuait la myoatrophie induite par le Dex in vitro. De plus, la SIRT2 régulait négativement l'expression de la LC3b et de la bécline-1 dans les muscles squelettiques. Ces résultats suggèraient que l'activation de la SIRT2 protège les myotubes contre l'atrophie induite par la Dex par l'inhibition du système d'autophagie; ce phénomène pourrait potentiellement servir de cible pour le traitement de la myopathie induite par les glucocorticoïdes. [Traduit par la Rédaction] Mots-clés : sirtuine 2, dexaméthasone, atrophie des muscles squelettiques, autophagie, myotube., Introduction Dexamethasone (Dex) is one of the most commonly prescribed synthetic glucocorticoids, owing to its strong pharmacological action in treating endocrine, respiratory, hematologic, and neoplastic conditions (Kadmiel and Cidlowski 2013; [...]

As one of mature theories, formal concept analysis (FCA) possesses remarkable mathematical properties, but it may generate massive concepts and complicated lattice structure when dealing with large-scale data. With a view to the fact that granular computing (GrC) can significantly lower the difficulty by selecting larger and appropriate granulations when processing large-scale data or solving complicated problems, the paper introduces GrC into FCA, it not only helps to expand the extent and intent of classical concept, but also can effectively reduce the time complexity and space complexity of FCA in knowledge acquisition to some degree. In modeling, concept-base, as a kind of low-level knowledge, plays an important role in the whole process of information granularity. Based on concept-base, attribute granules, object granules and relation granules in formal contexts are studied. Meanwhile, supremum and infimum operations are introduced in the precess of information granularity, whose biggest distinction from traditional models is integrating the structural information of concept lattice. In addition, the paper also probes into reduction, core, and implication rules in granularity formal contexts. Theories and examples verify the reasonability and effectiveness of the conclusions drawn in the paper. In short, the paper not only can be viewed as an effective means for the expansion of FCA, but also is an attempt for the fusion study of the two theories. [ABSTRACT FROM AUTHOR]

As one of core problems in rough set theory, normally, classification analysis requires that “all” rather than “most”elements in one class are similar to each other. Nevertheless, the situation is just opposite to that in many actual applications. This means users actually just require “most” rather than “all”elements in a class are similar to each other. In the case, to further enhance the robustness and generalization ability of rough set based on tolerance relation, this paper, with concept lattice as theoretical foundation, presents a variable precision rough set model based on the granularity of tolerance relation, in which users can flexibly adjust parameters so as to meet the actual needs. The so-called relation granularity means that the tolerance relation can be decomposed into several strongly connected sub-relations and several weakly connected sub-relations. In essence, classes defined by people usually correspond to strongly connected sub-relations, but classes defined in the paper always correspond to weakly connected sub-relations. In the paper, an algebraic structure can be inferred from an information system, which can organize all hidden covers or partitions in the form of lattice structure. In addition, solutions to the problems are studied, such as reduction, core and dependency. In short, the paper offers a new idea for the expansion of classical rough set models from the perspective of concept lattice. [ABSTRACT FROM AUTHOR]

In plenty of realistic situations, multi-attribute group decision-making (MAGDM) is ubiquitous and significant in daily activities of individuals and organizations. Among diverse tools for coping with MAGDM, granular computing-based approaches constitute a series of viable and efficient theories by means of multi-view problem solving strategies. In this paper, in order to handle MAGDM issues with interval-valued neutrosophic (IN) information, we adopt one of the granular computing (GrC)-based approaches, known as multigranulation probabilistic models, to address IN MAGDM problems. More specifically, after revisiting the related fundamental knowledge, three types of IN multigranulation probabilistic models are designed at first. Then, some key properties of the developed theoretical models are explored. Afterwards, a MAGDM algorithm for merger and acquisition target selections (M&A TSs) with IN information is summed up. Finally, a real-life case study together with several detailed discussions is investigated to present the validity of the developed models. [ABSTRACT FROM AUTHOR]

A chronically elevated glucocorticoid level impairs memory and cognition. Manninotriose is the main oligosaccharide of Prepared Radix Rehmanniae, and Astragaloside IV (AS-IV) is the primary ingredient of Astragali Radix; they have been reported to possess neuroprotective effects. The aim of the present study was to investigate the protective effects of Manninotriose and AS-IV on corticosterone (CORT) induced neurotoxicity and the underlying mechanisms. Primary cultured hippocampal neurons from newborn Sprague Dawley rats were treated with CORT in the absence or presence of Manninotriose and AS-IV. Cell Counting Kit-8 experiments and fluorescein diacetate (FDA)/propidium iodide (PI) double staining were conducted to assess the activity and survival rate of neurons. Quantitative Real-time PCR (qRT-PCR) and western blot analysis were performed to detect the expression of glucocorticoid receptor (GR), zinc finger protein (Zif268) and synapsin 1 (SYN1). DNA methylation of the gene promoter was assessed by bisulfite sequencing (BSP) analysis. The results demonstrated that pre-treatment with Manninotriose and AS-IV significantly improved cell viability and survival rate, and ameliorated the downregulation of GR, Zif268 and SYN1 genes in CORT injured neurons. BSP analysis revealed that CORT was able to improve the CpG island methylation rate of SYN1. AS-IV was observed to decrease the hypermethylation of the SYN1 gene induced by CORT. The results of the present study indicated that Manninotriose and AS-IV may have a protective effect against CORT-induced damage and the downregulation of learning and memory associated genes in hippocampal neurons. Regulation of DNA methylation may be important in the pharmaceutical activities of AS-IV. Thus, Manninotriose and AS-IV may be effective agents against learning and memory impairment. [ABSTRACT FROM AUTHOR]

Growing evidence indicates that silibinin (SLB), a main component extracted from Chinese herb Silybum marianum , can effectively antagonize doxorubicin (DOX) induced myocardial injury (DIMI), but the specific molecular mechanism is still unelucidated. Herein, DOX induced human AC16 cardiomyocyte injury model and Network Pharmacology are used to predict and verify the potential mechanism. The analysis results of the core PPI network of SLB against DIMI show that JAK/STAT signaling pathway and autophagy are significantly enriched. Molecular docking results indicate that SLB has stronger binding ability to signaling key proteins IL6ST, JAK2 and STAT3 (affinity ≤ −7.0 kcal/mol). The detection results of pathway activation and autophagy level demonstrate that SLB significantly alleviates DOX induced IL6ST/JAK2/STAT3 signaling pathway inhibition and autophagy inhibition, reduces the death rate of cardiomyocytes. This protective effect of SLB is eliminated when key pathway proteins (IL6ST, JAK2, STAT3) are knocked down or autophagy is inhibited (3-MA or Beclin1 knockdown). These results suggest that the regulation of IL6ST/JAK2/STAT3 signaling pathway and autophagy may be important mechanism for SLB's protective effect on DOX injured cardiomyocytes. Further experimental results prove that knockdown of IL6ST, JAK2 and STAT3 eliminate the mitochondrial ROS scavenging effect and autophagy promoting effect of SLB. In sum, SLB can decrease the mitochondrial ROS and restore autophagy to antagonize DOX-induced cardiomyocyte injury by activating IL6ST/JAK2/STAT3 signaling pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Chemokines secreted by astrocytes play multiple roles in the pathology of Alzheimer's disease, a chronic inflammation disorder of central nervous system. The level of chemokines in serum, cerebrospinal fluid and brain tissue and their receptors both significantly changed in patients with Alzheimer's disease. In this review, we briefly summarized the involvement of astrocytes and chemokines in Alzheimer's disease, and the role of chemokine/chemokine receptors in the occurrence and development of Alzheimer's disease. Clarification of the involvement of chemokines and their receptors, such as MCP-1/CCR2, fractalkine/CX3CR1, SDF-1α/CXCR4, MIP-1α/CCR5, IP-10/CXCR3, IL-8/CXCR1, CXCR2, and RANTES/CCR1, CCR3, CCR5, will provide a new strategy and more specific targets for the treatment of Alzheimer's disease.