Dynamic Distribution of HIG2A between the Mitochondria and the Nucleus in Response to Hypoxia and Oxidative Stress

Mitochondrial respiratory supercomplex formation requires HIG2A protein, which also has been associated with cell proliferation and cell survival under hypoxia. HIG2A protein localizes in mitochondria and nucleus. DNA methylation and mRNA expression of the HIGD2A gene show significant alterations in several cancers, suggesting a role for HIG2A in cancer biology. The present work aims to understand the dynamics of the HIG2A subcellular localization under cellular stress. We found that HIG2A protein levels increase under oxidative stress. H₂O₂ shifts HIG2A localization to the mitochondria, while rotenone shifts it to the nucleus. HIG2A protein colocalized at a higher level in the nucleus concerning the mitochondrial network under normoxia and hypoxia (2% O₂). Hypoxia (2% O₂) significantly increases HIG2A nuclear colocalization in C2C12 cells. In HEK293 cells, chemical hypoxia with CoCl₂ (>1% O₂) and FCCP mitochondrial uncoupling, the HIG2A protein decreased its nuclear localization and shifted to the mitochondria. This suggests that the HIG2A distribution pattern between the mitochondria and the nucleus depends on stress and cell type. HIG2A protein expression levels increase under cellular stresses such as hypoxia and oxidative stress. Its dynamic distribution between mitochondria and the nucleus in response to stress factors suggests a new communication system between the mitochondria and the nucleus.     

磷脂酶在植物逆境胁迫信号传导中的作用

磷脂酰肌醇是构成细胞膜的重要组分,它在磷脂酶的作用下水解产生三磷酸肌醇、二酰基甘油、磷脂酸、溶血磷脂、不饱和脂肪酸等,不仅可以作为磷脂的合成原料,而且在细胞感受外界刺激及其信号传导过程中也起着重要作用.磷脂酰肌醇信号传导途径与光合作用、激素调控等影响植物生长发育过程及抗逆信号传导关系密切,由于磷脂酶的活性直接影响这些信号分子的产生,磷脂酶在磷脂酰肌醇信号传导途径中处于一个中心地位,根据磷酯不同水解位点所分类的磷脂酶PLA2,PLC和PLD具有多种同功酶形式,分别在植物生长发育的不同阶段及对外界环境因子应答的信号传导过程中起着重要的调节作用.     

The Wnt Signaling Pathway Inhibitors Improve the Therapeutic Activity of Glycolysis Modulators against Tongue Cancer Cells

Excessive glucose metabolism and disruptions in Wnt signaling are important molecular changes present in oral cancer cells. The aim of this study was to evaluate the effects of the combinatorial use of glycolysis and Wnt signaling inhibitors on viability, cytotoxicity, apoptosis induction, cell cycle distribution and the glycolytic activity of tongue carcinoma cells. CAL 27, SCC-25 and BICR 22 tongue cancer cell lines were used. Cells were treated with inhibitors of glycolysis (2-deoxyglucose and lonidamine) and of Wnt signaling (PRI-724 and IWP-O1). The effects of the compounds on cell viability and cytotoxicity were evaluated with MTS and CellTox Green tests, respectively. Apoptosis was evaluated by MitoPotential Dye staining and cell cycle distribution by staining with propidium iodide, followed by flow cytometric cell analysis. Glucose and lactate concentrations in a culture medium were evaluated luminometrically. Combinations of 2-deoxyglucose and lonidamine with Wnt pathway inhibitors were similarly effective in the impairment of oral cancer cells’ survival. However, the inhibition of the canonical Wnt pathway by PRI-724 was more beneficial, based on the glycolytic activity of the cells. The results point to the therapeutic potential of the combination of low concentrations of glycolytic modulators with Wnt pathway inhibitors in oral cancer cells.     

Physiologic Insulin Resensitization as a Treatment Modality for Insulin Resistance Pathophysiology

Prevalence of type 2 diabetes increased from 2.5% of the US population in 1990 to 10.5% in 2018. This creates a major public health problem, due to increases in long-term complications of diabetes, including neuropathy, retinopathy, nephropathy, skin ulcers, amputations, and atherosclerotic cardiovascular disease. In this review, we evaluated the scientific basis that supports the use of physiologic insulin resensitization. Insulin resistance is the primary cause of type 2 diabetes. Insulin resistance leads to increasing insulin secretion, leading to beta-cell exhaustion or burnout. This triggers a cascade leading to islet cell destruction and the long-term complications of type 2 diabetes. Concurrent with insulin resistance, the regular bursts of insulin from the pancreas become irregular. This has been treated by the precise administration of insulin more physiologically. There is consistent evidence that this treatment modality can reverse the diabetes-associated complications of neuropathy, diabetic ulcers, nephropathy, and retinopathy, and that it lowers HbA1c. In conclusion, physiologic insulin resensitization has a persuasive scientific basis, significant treatment potential, and likely cost benefits.     

食品中展青霉素的产生机制及污染防控策略

展青霉素是由真菌产生的一种聚酮类次级代谢产物,是污染水果及其加工制品的最重要的真菌毒素之一。食品中污染的展青霉素主要由扩展青霉(Penicillium expansum)产生。P.expansum是常见大宗和特色果品的主要采后病原菌,其在引起果实腐烂的同时产生大量的展青霉素,伴随鲜食流通和加工过程进入食物链,危害消费者的健康。展青霉素可侵害人和动物的多个器官,引起急性和慢性症状。由展青霉素污染引起的食品安全问题越来越得到重视,展青霉素的相关研究逐渐成为热点。对展青霉素的产生和调控机制研究进行了系统的总结,介绍了展青霉素生物合成基因簇的组成,生物合成途径中不同步骤的催化酶,展青霉素生物合成和中间产物转运的分子路径;从合成途径特异性调控因子,光、pH值、碳源、硫源等环境信号-全局性调控因子,以及参与组蛋白甲基化和乙酰化修饰的表观遗传因子等不同层次归纳了展青霉素生物合成的复杂调控网络。从源头防控和直接脱除2个方面阐述了食品中展青霉素污染的防控策略,分别概述了基于物理、化学和生物原理的主要防控技术,并讨论了不同防控策略的优缺点。最后,讨论了展青霉素产生机制研究与污染防控技术研发的关系,并指出绿...     

The Association between Gut Microbiota and Osteoarthritis: Does the Disease Begin in the Gut?

Some say that all diseases begin in the gut. Interestingly, this concept is actually quite old, since it is attributed to the Ancient Greek physician Hippocrates, who proposed the hypothesis nearly 2500 years ago. The continuous breakthroughs in modern medicine have transformed our classic understanding of the gastrointestinal tract (GIT) and human health. Although the gut microbiota (GMB) has proven to be a core component of human health under standard metabolic conditions, there is now also a strong link connecting the composition and function of the GMB to the development of numerous diseases, especially the ones of musculoskeletal nature. The symbiotic microbes that reside in the gastrointestinal tract are very sensitive to biochemical stimuli and may respond in many different ways depending on the nature of these biological signals. Certain variables such as nutrition and physical modulation can either enhance or disrupt the equilibrium between the various species of gut microbes. In fact, fat-rich diets can cause dysbiosis, which decreases the number of protective bacteria and compromises the integrity of the epithelial barrier in the GIT. Overgrowth of pathogenic microbes then release higher quantities of toxic metabolites into the circulatory system, especially the pro-inflammatory cytokines detected in osteoarthritis (OA), thereby promoting inflammation and the initiation of many disease processes throughout the body. Although many studies link OA with GMB perturbations, further research is still needed.     

Sleep Disturbance and Metabolic Dysfunction: The Roles of Adipokines

Adipokines are a growing group of peptide or protein hormones that play important roles in whole body metabolism and metabolic diseases. Sleep is an integral component of energy metabolism, and sleep disturbance has been implicated in a wide range of metabolic disorders. Accumulating evidence suggests that adipokines may play a role in mediating the close association between sleep disorders and systemic metabolic derangements. In this review, we briefly summarize a group of selected adipokines and their identified function in metabolism. Moreover, we provide a balanced overview of these adipokines and their roles in sleep physiology and sleep disorders from recent human and animal studies. These studies collectively demonstrate that the functions of adipokine in sleep physiology and disorders could be largely twofold: (1) adipokines have multifaceted roles in sleep physiology and sleep disorders, and (2) sleep disturbance can in turn affect adipokine functions that likely contribute to systemic metabolic derangements.     

Adipose Stromal/Stem Cell-Derived Extracellular Vesicles: Potential Next-Generation Anti-Obesity Agents

Over the last decade, several compounds have been identified for the treatment of obesity. However, due to the complexity of the disease, many pharmacological interventions have raised concerns about their efficacy and safety. Therefore, it is important to discover new factors involved in the induction/progression of obesity. Adipose stromal/stem cells (ASCs), which are mostly isolated from subcutaneous adipose tissue, are the primary cells contributing to the expansion of fat mass. Like other cells, ASCs release nanoparticles known as extracellular vesicles (EVs), which are being actively studied for their potential applications in a variety of diseases. Here, we focused on the importance of the contribution of ASC-derived EVs in the regulation of metabolic processes. In addition, we outlined the advantages/disadvantages of the use of EVs as potential next-generation anti-obesity agents.     

细菌纤维素合成与鉴定研究综述

细菌纤维素（BC）因其独特性能被广泛应用于医药、食品等领域,目前其高产量菌株筛选、合成成本降低及合成途径改良等成为研究热点。本文依据国内外文献并结合团队研究成果对BC合成与鉴定的相关研究进行综述。首先对BC合成菌筛选及碳源利用的研究进行了分析,总结了降低BC合成成本的研究思路。其次对鉴定菌株合成产物的方法进行了归纳,总结了不同方法的特点。然后结合本团队筛选出的BC生产菌XJL-06-4 BC合成酶基因分析结果,综述了BC合成途径、合成酶存在形式以及基因水平调控作用,为BC在分子水平上通过改变合成途径提高产量提供新思路。最后,总结BC微生物发酵生产存在的问题,多角度提出解决方案。