ResearchPad - mini-review https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Closed-loop bioelectronic medicine for diabetes management]]> https://www.researchpad.co/article/elastic_article_9186 Modulation of the nervous system by delivering electrical or pharmaceutical agents has contributed to the development of novel treatments to serious health disorders. Recent advances in multidisciplinary research has enabled the emergence of a new powerful therapeutic approach called bioelectronic medicine. Bioelectronic medicine exploits the fact that every organ in our bodies is neurally innervated and thus electrical interfacing with peripheral nerves can be a potential pathway for diagnosing or treating diseases such as diabetes. In this context, a plethora of studies have confirmed the important role of the nervous system in maintaining a tight regulation of glucose homeostasis. This has initiated new research exploring the opportunities of bioelectronic medicine for improving glucose control in people with diabetes, including regulation of gastric emptying, insulin sensitivity, and secretion of pancreatic hormones. Moreover, the development of novel closed-loop strategies aims to provide effective, specific and safe interfacing with the nervous system, and thereby targeting the organ of interest. This is especially valuable in the context of chronic diseases such as diabetes, where closed-loop bioelectronic medicine promises to provide real-time, autonomous and patient-specific therapies. In this article, we present an overview of the state-of-the-art for closed-loop neuromodulation systems in relation to diabetes and discuss future related opportunities for management of this chronic disease.

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<![CDATA[Unraveling Adipocytes and Cancer Links: Is There a Role for Senescence?]]> https://www.researchpad.co/article/elastic_article_7541 Senescence is characterized by a permanent cell cycle arrest that is elicited in response to different stresses. In addition, senescent cells undergo multiple other phenotypic alterations, such as autophagy modulation, metabolic reprogramming, and the senescence-associated secretory phenotype (SASP). These senescence-related and inflammatory effects prevail within tumors and are strongly controlled by cancer properties, and inflammatory mediators further maintain and propagate the senescence process to adjacent cells. It is important to consider these detrimental effects that may drive tumorigenesis or cancer relapse. Importantly, cancer-associated adipocytes (CAAs) are one of the primary stromal cells in various tumor microenvironments and favor tumor progression by releasing various factors that can mediate local and systemic effects. However, it remains unclear whether CAAs possess senescent features. In this review, we discuss the complex relationship between senescence and CAAs and highlight important considerations for therapeutics.

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<![CDATA[MR1-Restricted T Cells Are Unprecedented Cancer Fighters]]> https://www.researchpad.co/article/elastic_article_7505 Non-polymorphic MHC class I-related molecule MR1 presents antigenic bacterial metabolites to mucosal-associated invariant T (MAIT) cells and self-antigens to MR1-restricted T (MR1T) cells. Both MR1-restricted T cell populations are readily identified in healthy individuals, with MAIT cells accounting for 1–10% of circulating T cells, while MR1T cells have frequencies comparable to peptide-specific T cells (<0.1%). Self-reactive MR1T cells display a heterogeneous phenotype, and are capable of releasing both TH1 and TH2 cytokines, supporting not only activation of inflammation but also contributing to its regulation. Importantly, MR1T cells recognize and kill a diverse range of MR1-expressing tumor cells. On the other hand, evidence suggests MAIT cells augment cancer growth and metastases. This review addresses the potential role of MR1-restricted T cells in controlling tumor cells, facilitating their elimination and regulating cancer immunity. We also discuss therapeutic opportunities surrounding MR1-restricted T cells in cancer.

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<![CDATA[Proline Homeostasis in <i>Saccharomyces cerevisiae</i>: How Does the Stress-Responsive Transcription Factor Msn2 Play a Role?]]> https://www.researchpad.co/article/elastic_article_7483 Overexpression of MSN2, which is the transcription factor gene in response to stress, is well-known to increase the tolerance of the yeast Saccharomyces cerevisiae cells to a wide variety of environmental stresses. Recent studies have found that the Msn2 is a feasible potential mediator of proline homeostasis in yeast. This result is based on the finding that overexpression of the MSN2 gene exacerbates the cytotoxicity of yeast to various amino acid analogs whose uptake is increased by the active amino acid permeases localized on the plasma membrane as a result of a dysfunctional deubiquitination process. Increased understanding of the cellular responses induced by the Msn2-mediated proline incorporation will provide better comprehension of how cells respond to and counteract to different kinds of stimuli and will also contribute to the breeding of industrial yeast strains with increased productivity.

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<![CDATA[MCT8 Deficiency: The Road to Therapies for a Rare Disease]]> https://www.researchpad.co/article/elastic_article_7435 Allan-Herndon-Dudley syndrome is a rare disease caused by inactivating mutations in the SLC16A2 gene, which encodes the monocarboxylate transporter 8 (MCT8), a transmembrane transporter specific for thyroid hormones (T3 and T4). Lack of MCT8 function produces serious neurological disturbances, most likely due to impaired transport of thyroid hormones across brain barriers during development resulting in severe brain hypothyroidism. Patients also suffer from thyrotoxicity in other organs due to the presence of a high concentration of T3 in the serum. An effective therapeutic strategy should restore thyroid hormone serum levels (both T3 and T4) and should address MCT8 transporter deficiency in brain barriers and neural cells, to enable the access of thyroid hormones to target neural cells. Unfortunately, targeted therapeutic options are currently scarce and their effect is limited to an improvement in the thyrotoxic state, with no sign of any neurological improvement. The use of thyroid hormone analogs such as TRIAC, DITPA, or sobetirome, that do not require MCT8 to cross cell membranes and whose controlled thyromimetic activity could potentially restore the normal function of the affected organs, are being explored to improve the cerebral availability of these analogs. Other strategies aiming to restore the transport of THs through MCT8 at the brain barriers and the cellular membranes include gene replacement therapy and the use of pharmacological chaperones. The design of an appropriate therapeutic strategy in combination with an early diagnosis (at prenatal stages), will be key aspects to improve the devastating alterations present in these patients.

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<![CDATA[Principles of Epilepsy Management for Women in Their Reproductive Years]]> https://www.researchpad.co/article/elastic_article_7380 In the United States, there are over one million women with epilepsy (WWE) in their childbearing years. Pregnancy can be challenging for this population. A number of international registries have documented that children born to these women are at increased risk for major congenital malformations (MCM), lower intelligence quotient scores and neurodevelopmental disorders, when the mother is managed on antiseizure medications (ASMs). To prevent poor neonatal outcomes for this population, safe and thoughtful management strategies are necessary. We propose to divide these management strategies into five principles. These include (I) choosing suitable ASMs for the patient's seizure type, (II) choosing an ASM with the least teratogenic and cognitive side effects, (III) dosing at the lowest possible effective dosage, (IV) selecting the best ASM regimen as promptly as possible, even before a woman has her first menses, and (V) supplementing these patients with folic acid in order to try to enhance cognition and reduce neural tube defects.

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<![CDATA[Diffusion Tensor Imaging Studies on Spontaneous Subarachnoid Hemorrhage-Related Brain Injury: A Mini-Review]]> https://www.researchpad.co/article/elastic_article_7375 Accurate diagnosis of the presence and severity of neural injury in patients with subarachnoid hemorrhage (SAH) is important in neurorehabilitation because it is essential for establishing appropriate therapeutic strategies and developing a prognosis. Diffusion tensor imaging has a unique advantage in the identification of microstructural white matter abnormalities which are not usually detectable on conventional brain magnetic resonance imaging. In this mini-review article, 12 diffusion tensor imaging studies on SAH-related brain injury were reviewed. These studies have demonstrated SAH-related brain injuries in various neural tracts or structures including the cingulum, fornix, hippocampus, dorsolateral prefrontal region, corticospinal tract, mamillothalamic tract, corticoreticular pathway, ascending reticular activating system, Papez circuit, optic radiation, and subcortical white matter. We believe that these reviewed studies provide information that would be helpful in science-based neurorehabilitation of patients with SAH. Furthermore, the results of these reviewed studies would also be useful for clarification of the pathophysiological mechanisms associated with SAH-related brain injury. However, considering the large number of neural tracts or neural structures in the brain, more research on SAH-related brain injury in other neural tracts or structures should be encouraged.

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<![CDATA[Functional roles of protein phosphatase 4 in multiple aspects of cellular physiology: a friend and a foe]]> https://www.researchpad.co/article/elastic_article_7310 Protein phosphatase 4 (PP4), one of serine/threonine phosphatases, is involved in many critical cellular pathways, including DNA damage response (DNA repair, cell cycle regulation, and apoptosis), tumorigenesis, cell migration, immune response, stem cell development, glucose metabolism, and diabetes. PP4 has been steadily studied over the past decade about wide spectrum of physiological activities in cells. Given the many vital functions in cells, PP4 has great potential to develop into the finding of key working mechanisms and effective treatments for related diseases such as cancer and diabetes. In this review, we provide an overview of the cellular and molecular mechanisms by which PP4 impacts and also discuss the functional significance of it in cell health.

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<![CDATA[COVID-19: an update on diagnostic and therapeutic approaches]]> https://www.researchpad.co/article/elastic_article_7302 The unexpected pandemic set off by the novel coronavirus 2019 (COVID-19) has caused severe panic among people worldwide. COVID-19 has created havoc, and scientists and physicians are urged to test the efficiency and safety of drugs used to treat this disease. In such a pandemic situation, various steps have been taken by the government to control and prevent the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). This pandemic situation has forced scientists to rework strategies to combat infectious diseases through drugs, treatment, and control measures. COVID-19 treatment requires both limiting viral multiplication and neutralizing tissue damage induced by an inappropriate immune reaction. Currently, various diagnostic kits to test for COVID-19 are available, and repurposing therapeutics for COVID-19 has shown to be clinically effective. As the global demand for diagnostics and therapeutics continues to rise, it is essential to rapidly develop various algorithms to successfully identify and contain the virus. This review discusses the updates on specimens/samples, recent efficient diagnostics, and therapeutic approaches to control the disease and repurposed drugs mainly focusing on chloroquine/hydroxychloroquine and convalescent plasma (CP). More research is required for further understanding of the influence of diagnostics and therapeutic approaches to develop vaccines and drugs for COVID-19.

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<![CDATA[Non-classical role of Galectin-3 in cancer progression: translocation to nucleus by carbohydrate-recognition independent manner]]> https://www.researchpad.co/article/elastic_article_7295 Galectin-3 is a carbohydrate-binding protein and regulates diverse functions, including cell proliferation and differentiation, mRNA splicing, apoptosis induction, immune surveillance and inflammation, cell adhesion, angiogenesis, and cancer-cell metastasis. Galectin-3 is also recommended as a diagnostic or prognostic biomarker of various diseases, including heart disease, kidney disease, and cancer. Galectin-3 exists as a cytosol, is secreted in extracellular spaces on cells, and is also detected in nuclei. It has been found that galectin-3 has different functions in cellular localization: (i) Extracellular galectin-3 mediates cell attachment and detachment. (ii) cytosolic galectin-3 regulates cell survival by blocking the intrinsic apoptotic pathway, and (iii) nuclear galectin-3 supports the ability of the transcriptional factor for target gene expression. In this review, we focused on the role of galectin-3 on translocation from cytosol to nucleus, because it happens in a way independent of carbohydrate recognition and accelerates cancer progression. We also suggested here that intracellular galecin-3 could be a potent therapeutic target in cancer therapy.

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<![CDATA[Trends in <i>Helicobacter pylori</i> resistance to clarithromycin: from phenotypic to genomic approaches]]> https://www.researchpad.co/article/N86463b18-e70d-4e66-bfe5-9094e820312d For a long time infections have been treated using the macrolide antibiotic, clarithromycin. Clarithromycin resistance is increasing worldwide and is the most common cause of treatment failure. Here we review the mechanisms of antibiotic resistance to clarithromycin, detailing the individual and combinations of point mutations found in the 23S rRNA gene associated with resistance. Additionally, we consider the methods used to detect clarithromycin resistance, emphasizing the use of high-throughput next-generation sequencing methods, which were applied to 17 newly sequenced pairs of strains isolated from the antrum and corpus of a recent colonized paediatric population. This set of isolates was composed of six pairs of resistant strains whose phenotype was associated with two point mutations found in the 23S rRNA gene: A2142C and A2143G. Other point mutations were found simultaneously in the same gene, but, according to our results, it is unlikely that they contribute to resistance. Further, among susceptible isolates, genomic variations compatible with mutations previously associated with clarithromycin resistance were detected. Exposure to clarithromycin may select low-frequency variants, resulting in a progressive increase in the resistance rate due to selection pressure.

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<![CDATA[Hydrogen peroxide and disease: towards a unified system of pathogenesis and therapeutics]]> https://www.researchpad.co/article/N15dd0101-d558-40d5-9ef7-5eeb516aff33 Although the immune response has a prominent role in the pathophysiology of ulcerative colitis, sepsis, and systemic lupus erythematosus, a primary immune causation has not been established to explain the pathogenesis of these diseases. However, studies have reported significantly elevated levels of colonic epithelial hydrogen peroxide (a known colitic agent) in ulcerative colitis prior to the appearance of colitis. And patients with sepsis are reported to have toxic levels of blood hydrogen peroxide, whose pathologic effects mirror the laboratory and clinical abnormalities observed in sepsis. More recently, evidence supports a causal role for cellular hydrogen peroxide (a potent apoptotic agent) in the enhanced apoptosis believed to be the driving force behind auto-antigenic exposure and chronic immune activation in systemic lupus erythematosus. The different biological properties of hydrogen peroxide exert distinct pathologic effects depending on the site of accumulation within the body resulting in a unique disease patho-phenotype. On a cellular level, the build-up of hydrogen peroxide triggers apoptosis resulting in systemic lupus erythematosus, on a tissue level (colonic epithelium) excess hydrogen peroxide leads to inflammation and ulcerative colitis, and on a systemic level the pathologic effects of toxic concentrations of blood hydrogen peroxide result in bioenergetic failure and microangiopathic dysfunction leading to multiple organ failure and circulatory shock, characteristic of advanced sepsis. The aim of this paper is to provide a unified evidence-based common causal role for hydrogen peroxide in the pathogenesis of ulcerative colitis, sepsis, and systemic lupus erythematosus. Based on this new theory of pathogenesis, a novel evidence-based treatment of sepsis is also discussed.

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<![CDATA[Permissive State of EMT: The Role of Immune Cell Compartment]]> https://www.researchpad.co/article/N786cf557-a5c5-4c41-a9c2-4edaf8401c0b The Epithelial to Mesenchymal Transition (EMT) type 3 is a reversible dynamic process recognized as a major determinant of the metastatic event, although many questions regarding its role throughout this process remain unanswered. The ability of cancer cells to migrate and colonize distant organs is a key aspect of tumor progression and evolution, requiring constant tumor cells and tumor microenvironment (TME) changes, as well as constant changes affecting the cross-talk between the two aforementioned compartments. Alterations affecting tumor cells, such as transcription factors, trans-membrane receptors, chromatin remodeling complexes and metabolic pathways, leading to the disappearance of the epithelial phenotype and concomitant gaining of the undifferentiated mesenchymal phenotype are undoubtedly major players of the EMT process. However, several lines of evidence point out toward a more critical role of TME composition in creating an “EMT-permissive state.” The “EMT-permissive state” consists in changes affecting physical and biochemical properties (i.e., stiffness and/or hypoxia) as well as changes of the TME cellular component (i.e., immune-cell, blood vessel, lymphatic vessels, fibroblasts, and fat cells) that favor and induce the epithelial mesenchymal transition. In this mini review, we will discuss the role of the tumor microenvironment cellular component that are involved in supporting the EMT, with particular emphasis on the immune-inflammatory cells component.

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<![CDATA[雷公藤内酯醇与非小细胞肺癌研究进展]]> https://www.researchpad.co/article/5b5b895b463d7e1effa460f4 雷公藤内酯醇对多种非小细胞肺癌(non-small cell lung cancer, NSCLC)细胞系具有杀伤作用,可通过干预细胞周期、激活caspase信号通路、抑制血管内皮生长因子(vascular endothelial growth factor, VEGF)的表达、抑制NF-κB活性等多种途径来促进肺癌细胞死亡。现将雷公藤内酯醇的抑瘤功能及其具体作用机制加以综述,为其在NSCLC中的科学研究及临床应用提供思路。

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<![CDATA[肺癌相关治疗与间质性肺病]]> https://www.researchpad.co/article/5b5b8923463d7e1effa460f3 间质性肺病是肺癌相关治疗引起的严重副反应之一,因诊断的复杂性及病情的多变性往往不能及时诊治甚至危及患者的生命,严重影响患者的预后。放、化疗及靶向治疗导致间质性肺炎的机制及相关因素尚不完全清楚。因此,如何减少、早期发现及诊治肺癌相关治疗引起的间质性肺病成为今后肺癌治疗过程中不可忽略的一个问题。

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<![CDATA[非小细胞肺癌术后辅助化疗研究进展]]> https://www.researchpad.co/article/5b5b8766463d7e1effa460eb 肺癌可分为非小细胞肺癌(non-small cell lung cancer, NSCLC)和小细胞肺癌,其发病率和死亡率均高居恶性肿瘤首位。本文主要就NSCLC术后辅助化疗的地位确立、辅助化疗的合适人群和化疗方案选择以及相关生物标志物研究进展作一综述。

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<![CDATA[胸腺瘤的分期进展]]> https://www.researchpad.co/article/5b5b8650463d7e1effa460e6 <![CDATA[肺上沟瘤的治疗进展]]> https://www.researchpad.co/article/5c053694d5eed0c4848be28b 肺上沟瘤是指发生在肺上沟区的的支气管源性肿瘤, 是非小细胞肺癌(non-small cell lung cancer, NSCLC)的一个独特的临床亚型, 占肺癌总数不足5%。它常侵犯第1肋、臂丛、锁骨下动静脉、交感神经链、星状神经节和(或)椎体等胸廓入口结构。近几十年, 肺上沟瘤的治疗取得了不断的进展, 最新发布的几个临床试验证实了同期放化疗加手术切除能够改善肿瘤的完整切除率、局部控制率和病理缓解率, 延长患者的总生存时间。已经成为肺上沟瘤的治疗最为有效的方式, 并成为美国国立综合癌症网络(National Comprehensive Cancer Network, NCCN)和美国胸科医师协会(American College of Chest Physicians, ACCP)指南推荐的肺上沟瘤治疗方案。本文回顾国内外相关文献, 简要介绍肺上沟瘤手术治疗及综合治疗的进展情况。

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<![CDATA[c-MET在非小细胞肺癌中的作用机制及其治疗和检测]]> https://www.researchpad.co/article/5c053078d5eed0c4848b0ca9 肝细胞生长因子/c-MET(hepatocyte growth factor/c-MET, HGF/c-MET)信号通路可通过多种机制如c-MET突变、扩增、过表达和HGF过表达被异常激活,并在非小细胞肺癌(non-small cell lung cancer, NSCLC)的发生发展以及表皮生长因子受体抑制剂(epidermal growth factor receptor tyrosine kinase inhibitor, EGFR-TKI)的耐药性方面发挥重要作用。因此,c-MET是继EGFR、ALK之后NSCLC的又一分子治疗靶点。目前c-MET抑制剂在一些临床试验中表现出了良好的的应用前景,但其在临床应用中的有效性和安全性的评估,以及对于c-MET检测方法的选择及判定标准还需进一步讨论。本文就c-MET在NSCLC中的作用机制、治疗前景和检测方法的选择作一综述。

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<![CDATA[放疗技术与放射性肺损伤:高剂量小体积还是低剂量大体积?]]> https://www.researchpad.co/article/5c053076d5eed0c4848b0c6c 放射治疗是肺癌的主要治疗手段之一,目前使用的主流技术是三维适形放疗(three-dimensional conformal radiation therapy, 3D-CRT)和调强适形放疗(intensity modulated radiation therapy, IMRT),两者各具特点。本文综述近年来两种放疗技术治疗肺癌的文献,重点讨论放射剂量在肺内的分布与放射性肺炎的关系,即高剂量分布在较小的肺体积与低剂量分布在较大的肺体积,两者哪种更易引发放射性肺炎(radiation pneumonitis, RP)。

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