ResearchPad - mini‐review https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Risks of ACE Inhibitor and ARB Usage in COVID‐19: Evaluating the Evidence]]> https://www.researchpad.co/article/elastic_article_16572 Concerns have been raised regarding the safety of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with coronavirus disease of 2019 (COVID‐19), based on the hypothesis that such medications may raise expression of ACE2, the receptor for severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). We conducted a literature review of studies (= 12) in experimental animals and human subjects (= 12) and evaluated the evidence regarding the impact of administration of ACEIs and ARBs on ACE2 expression. We prioritized studies that assessed ACE2 protein expression data, measured directly or inferred from ACE2 activity assays. The findings in animals are inconsistent with respect to an increase in ACE2 expression in response to treatment with ACEIs or ARBs. Control/sham animals show little to no effect in the plurality of studies. Those studies that report increases in ACE2 expression tend to involve acute injury models and/or higher doses of ACEIs or ARBs than are typically administered to patients. Data from human studies overwhelmingly imply that administration of ACEIs/ARBs does not increase ACE2 expression. Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID‐19. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.

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<![CDATA[Airborne signals and abiotic factors: the neglected side of the plant communication]]> https://www.researchpad.co/article/elastic_article_15003 A relevant number of reports have examined the role of airborne signals in plant-plant communication, indicating that volatile organic compounds (VOCs) can prime neighboring plants against pathogen and/or herbivore attacks. Conversely, there is very limited information available on the possibility of the emission of VOCs by emitter plants under abiotic stress conditions, which may alert neighboring unstressed plants and prime these individuals (receivers) against the same stressors. The present opinion paper briefly reviews a few reports examining the effect of infochemicals produced by emitters on receiver plants subjected to abiotic stresses typical of global climate change. The ecological implications of these dynamics, as well as some concerns related to the potential roles of inter-plant communication in environmentally controlled experiments, have arisen. Some possible inter-plant communications applications (biomonitoring and biostimulation), mediated by airborne signals, and some directions for future studies on this topic, are also provided.

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<![CDATA[Host Immunity to <i>Malassezia</i> in Health and Disease]]> https://www.researchpad.co/article/elastic_article_14102 The microbiota plays an integral role in shaping physical and functional aspects of the skin. While a healthy microbiota contributes to the maintenance of immune homeostasis, dysbiosis can result in the development of diverse skin pathologies. This dichotomous feature of the skin microbiota holds true not only for bacteria, but also for fungi that colonize the skin. As such, the yeast Malassezia, which is by far the most abundant component of the skin mycobiota, is associated with a variety of skin disorders, of which some can be chronic and severe and have a significant impact on the quality of life of those affected. Understanding the causative relationship between Malassezia and the development of such skin disorders requires in-depth knowledge of the mechanism by which the immune system interacts with and responds to the fungus. In this review, we will discuss recent advances in our understanding of the immune response to Malassezia and how the implicated cells and cytokine pathways prevent uncontrolled fungal growth to maintain commensalism in the mammalian skin. We also review how the antifungal response is currently thought to affect the development and severity of inflammatory disorders of the skin and at distant sites.

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<![CDATA[Endothelial-to-Mesenchymal Transition, Vascular Inflammation, and Atherosclerosis]]> https://www.researchpad.co/article/elastic_article_14073 Atherosclerosis is a chronic progressive disease characterized by vascular inflammation and growth of atherosclerotic plaque that eventually lead to compromise of blood flow. The disease has proven to be remarkably resistant to multiple attempts at meaningful reversal including recent strategies targeting selective inflammatory mediators. Endothelial-to-mesenchymal transition (EndMT) has emerged as a key driver of both vascular inflammation and plaque growth. A deeper understanding of EndMT provides new insights into the underlying biology of atherosclerosis, suggests likely molecular mechanism of atherosclerotic resistance, and identifies potential new therapeutic targets.

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<![CDATA[Crossing the Cleft: Communication Challenges Between Neuroscience and Artificial Intelligence]]> https://www.researchpad.co/article/elastic_article_14004 Historically, neuroscience principles have heavily influenced artificial intelligence (AI), for example the influence of the perceptron model, essentially a simple model of a biological neuron, on artificial neural networks. More recently, notable recent AI advances, for example the growing popularity of reinforcement learning, often appear more aligned with cognitive neuroscience or psychology, focusing on function at a relatively abstract level. At the same time, neuroscience stands poised to enter a new era of large-scale high-resolution data and appears more focused on underlying neural mechanisms or architectures that can, at times, seem rather removed from functional descriptions. While this might seem to foretell a new generation of AI approaches arising from a deeper exploration of neuroscience specifically for AI, the most direct path for achieving this is unclear. Here we discuss cultural differences between the two fields, including divergent priorities that should be considered when leveraging modern-day neuroscience for AI. For example, the two fields feed two very different applications that at times require potentially conflicting perspectives. We highlight small but significant cultural shifts that we feel would greatly facilitate increased synergy between the two fields.

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<![CDATA[<i>Mycobacterium tuberculosis</i> Infection-Driven Foamy Macrophages and Their Implications in Tuberculosis Control as Targets for Host-Directed Therapy]]> https://www.researchpad.co/article/elastic_article_13969 Tuberculosis (TB) is a leading cause of death worldwide following infection with Mycobacterium tuberculosis (Mtb), with 1.5 million deaths from this disease reported in 2018. Once the bacilli are inhaled, alveolar and interstitial macrophages become infected with Mtb and differentiate into lipid-laden foamy macrophages leading to lung inflammation. Thus, the presence of lipid-laden foamy macrophages is the hallmark of TB granuloma; these Mtb-infected foamy macrophages are the major niche for Mtb survival. The fate of TB pathogenesis is likely determined by the altered function of Mtb-infected macrophages, which initiate and mediate TB-related lung inflammation. As Mtb-infected foamy macrophages play central roles in the pathogenesis of Mtb, they may be important in the development of host-directed therapy against TB. Here, we summarize and discuss the current understanding of the alterations in alveolar and interstitial macrophages in the regulation of Mtb infection-induced immune responses. Metabolic reprogramming of lipid-laden foamy macrophages following Mtb infection or virulence factors are also summarized. Furthermore, we review the therapeutic interventions targeting immune responses and metabolic pathways, from in vitro, in vivo, and clinical studies. This review will further our understanding of the Mtb-infected foamy macrophages, which are both the major Mtb niche and therapeutic targets against TB.

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<![CDATA[Are Health e-Mavens the New Patient Influencers?]]> https://www.researchpad.co/article/elastic_article_13031 Even though the healthcare industry is usually considered a rather traditional and slowly evolving sector, change is happening. Digitalization is transforming the way of obtaining medical advice and treatment and the Internet has become a key source for the seeking of healthcare information. It has allowed people to turn into more active collaborators in matters of their own health by enabling them to easily search and share information with other patients. Although research points out the growing importance of user-generated content in many sectors and its positive impact on information credibility, trust, engagement, and, ultimately, customer behavior (Malthouse et al., 2016), there is a lack of attention to this topic in healthcare. In this brief review, we address this gap by analyzing the role of health e-mavens, which are a particular type of influencers that possesses both expertise and online social influence. We lastly illustrate possible benefits of their impact on other to the different parties involved and affected by this phenomenon.

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<![CDATA[The Beneficial Role of Exercise Training for Myocardial Infarction Treatment in Elderly]]> https://www.researchpad.co/article/elastic_article_12883 Worldwide, elderly people have a higher prevalence of myocardial infarction (MI), which is associated with body function aging and a sedentary lifestyle. In addition to medication, exercise training is a well-established supplementary method to prevent and treat cardiovascular diseases (CVDs). Substantial evidence has shown the value of different intensity exercise programs in the prevention and treatment of MI, and exercise rehabilitation programs are also applicable to elderly patients with MI. Although exercise rehabilitation programs could significantly improve function, quality of life (QoL), and lower mortality and morbidity for people with MI, such programs are underused because their mechanisms are not accurately elucidated. To promote the application of exercise therapy for MI, this review summarizes the benefits and mechanisms of exercise rehabilitation for post-MI patients and provides rationalized proposals for outpatient cardiac rehabilitation.

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<![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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