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  • 机译 缺血再灌注损伤后硫化氢减弱肌肉功能的机制:对Akt信号转导,线粒体功能和凋亡的影响
    摘要:Ischemia–reperfusion injury is caused by a period of ischemia followed by massive blood flow into a tissue that had experienced restricted blood flow. The severity of the injury is dependent on the time the tissue was restricted from blood flow, becoming more severe after longer ischemia times. This can lead to many complications such as tissue necrosis, cellular apoptosis, inflammation, metabolic and mitochondrial dysfunction, and even organ failure. One of the emerging therapies to combat ischemic reperfusion injury complications is hydrogen sulfide, which is a gasotransmitter that diffuses across cell membranes to exert effects on various signaling pathways regulating cell survival such as Akt, mitochondrial activity, and apoptosis. Although commonly thought of as a toxic gas, low concentrations of hydrogen sulfide have been shown to be beneficial in promoting tissue survival post-ischemia, and modulate a wide variety of cellular responses. This review will detail the mechanisms of hydrogen sulfide in affecting the Akt signaling pathway, mitochondrial function, and apoptosis, particularly in regards to ischemic reperfusion injury in muscle tissue. It will conclude with potential clinical applications of hydrogen sulfide, combinations with other therapies, and perspectives for future studies.
  • 机译 产生随机性:充分利用无序错误将错误的命令变成真实的命令
    • 作者:Yaron Ilan
    • 刊名:Journal of Translational Medicine
    • 2019年第期
    摘要:Randomness is far from a disturbing disorder in nature. Rather, it underlies many processes and functions. Randomness can be used to improve the efficacy of development and of systems under certain conditions. Moreover, valid unpredictable random-number generators are needed for secure communication, rendering predictable pseudorandom strings unsuitable. This paper reviews methods of generating randomness in various fields. The potential use of these methods is also discussed. It is suggested that by disordering a “false order,” an effective disorder can be generated to improve the function of systems.
  • 机译 mRNA治疗药物如何进入单克隆抗体领域
    摘要:In 1975, Milstein and Köhler revolutionized the medical world with the development of the hybridoma technique to produce monoclonal antibodies. Since then, monoclonal antibodies have entered almost every branch of biomedical research. Antibodies are now used as frontline therapeutics in highly divergent indications, ranging from autoimmune disease over allergic asthma to cancer. Wider accessibility and implementation of antibody-based therapeutics is however hindered by manufacturing challenges and high development costs inherent to protein-based drugs. For these reasons, alternative ways are being pursued to produce and deliver antibodies more cost-effectively without hampering safety. Over the past decade, messenger RNA (mRNA) based drugs have emerged as a highly appealing new class of biologics that can be used to encode any protein of interest directly in vivo. Whereas current clinical efforts to use mRNA as a drug are mainly situated at the level of prophylactic and therapeutic vaccination, three recent preclinical studies have addressed the feasibility of using mRNA to encode therapeutic antibodies directly in vivo. Here, we highlight the potential of mRNA-based approaches to solve several of the issues associated with antibodies produced and delivered in protein format. Nonetheless, we also identify key hurdles that mRNA-based approaches still need to take to fulfill this potential and ultimately replace the current protein antibody format.
  • 机译 小儿睡眠障碍和褪黑激素治疗
    摘要:BackgroundThere are no guidelines concerning the best approach to improving sleep, but it has been shown that it can benefit the affected children and their entire families. The aim of this review is to analyse the efficacy and safety of melatonin in treating pediatric insomnia and sleep disturbances.
  • 机译 儿童维生素D和生长激素:对当前科学知识的回顾
    摘要:BackgroundHuman growth is a complex mechanism that depends on genetic, environmental, nutritional and hormonal factors. The main hormone involved in growth at each stage of development is growth hormone (GH) and its mediator, insulin-like growth factor 1 (IGF-1). In contrast, vitamin D is involved in the processes of bone growth and mineralization through the regulation of calcium and phosphorus metabolism. Nevertheless, no scientific study has yet elucidated how they interact with one another, especially as a dysfunction in which one influences the other, even if numerous biochemical and clinical studies confirm the presence of a close relationship.
  • 机译 精密医学领域的创新和新技术是否为以患者为中心的护理铺平了新纪元?
    摘要:Healthcare is undergoing a transformation, and it is imperative to leverage new technologies to generate new data and support the advent of precision medicine (PM). Recent scientific breakthroughs and technological advancements have improved our understanding of disease pathogenesis and changed the way we diagnose and treat disease leading to more precise, predictable and powerful health care that is customized for the individual patient. Genetic, genomics, and epigenetic alterations appear to be contributing to different diseases. Deep clinical phenotyping, combined with advanced molecular phenotypic profiling, enables the construction of causal network models in which a genomic region is proposed to influence the levels of transcripts, proteins, and metabolites. Phenotypic analysis bears great importance to elucidat the pathophysiology of networks at the molecular and cellular level. Digital biomarkers (BMs) can have several applications beyond clinical trials in diagnostics—to identify patients affected by a disease or to guide treatment. Digital BMs present a big opportunity to measure clinical endpoints in a remote, objective and unbiased manner. However, the use of “omics” technologies and large sample sizes have generated massive amounts of data sets, and their analyses have become a major bottleneck requiring sophisticated computational and statistical methods. With the wealth of information for different diseases and its link to intrinsic biology, the challenge is now to turn the multi-parametric taxonomic classification of a disease into better clinical decision-making by more precisely defining a disease. As a result, the big data revolution has provided an opportunity to apply artificial intelligence (AI) and machine learning algorithms to this vast data set. The advancements in digital health opportunities have also arisen numerous questions and concerns on the future of healthcare practices in particular with what regards the reliability of AI diagnostic tools, the impact on clinical practice and vulnerability of algorithms. AI, machine learning algorithms, computational biology, and digital BMs will offer an opportunity to translate new data into actionable information thus, allowing earlier diagnosis and precise treatment options. A better understanding and cohesiveness of the different components of the knowledge network is a must to fully exploit the potential of it.
  • 机译 Hippo途径在癌症中的作用分析
    • 作者:Yanyan Han
    • 刊名:Journal of Translational Medicine
    • 2019年第期
    摘要:Cancer is a serious health issue in the world due to a large body of cancer-related human deaths, and there is no current treatment available to efficiently treat the disease as the tumor is often diagnosed at a serious stage. Moreover, Cancer cells are often resistant to chemotherapy, radiotherapy, and molecular-targeted therapy. Upon further knowledge of mechanisms of tumorigenesis, aggressiveness, metastasis, and resistance to treatments, it is necessary to detect the disease at an earlier stage and for a better response to therapy. The hippo pathway possesses the unique capacity to lead to tumorigenesis. Mutations and altered expression of its core components (MST1/2, LATS1/2, YAP and TAZ) promote the migration, invasion, malignancy of cancer cells. The biological significance and deregulation of it have received a large body of interests in the past few years. Further understanding of hippo pathway will be responsible for cancer treatment. In this review, we try to discover the function of hippo pathway in different diversity of cancers, and discuss how Hippo pathway contributes to other cellular signaling pathways. Also, we try to describe how microRNAs, circRNAs, and ZNFs regulate hippo pathway in the process of cancer. It is necessary to find new therapy strategies for cancer.
  • 机译 针对急性肾损伤的线粒体功能障碍的间充质干细胞疗法
    摘要:Mitochondria take part in a network of cellular processes that regulate cell homeostasis. Defects in mitochondrial function are key pathophysiological changes during acute kidney injury (AKI). Mesenchymal stem cells (MSCs) have shown promising regenerative effects in experimental AKI models, but the specific mechanism is still unclear. Some studies have demonstrated that MSCs are able to target mitochondrial dysfunction during AKI. In this review, we summarize these articles, providing an integral and updated view of MSC therapy targeting mitochondrial dysfunction during AKI, which is aimed at promoting the therapeutic effect of MSCs in AKI patients.
  • 机译 为什么原发性肥胖是一种疾病?
    摘要:Obesity must be considered a real pathology. In the world wide, obesity represent one of the major public health issue associated with increased morbidity and mortality. Overweight or obesity, in fact, significantly increases the risk of contracting diseases, such as: arterial hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, cerebral vasculopathy, gallbladder lithiasis, arthropathy, ovarian polycytosis, sleep apnea syndrome, and some neoplasms. Despite numerous informative campaigns, unfortunately, the fight against obesity does not seem to work: in the last years, the prevalence continued to increase. The progressive and rapid increase in the incidence of obesity, which has characterized most of the economically advanced countries in the last decade, has been the main stimulus for the research of the mechanisms underlying this pathology and the related disorders. The aims of this review is to provide a revision of the literature in order to define obesity as diseases, secondly to highlight the limits and the inaccuracy of common tools used for the diagnosis of obesity, and as a third thing to strengthen the concept of the complexity of obesity as a disease among political health care providers. Obesity may be viewed as a multifactorial pathology and chronic low-grade inflammatory disease. In fact, people affected by obesity have greater risk of developing comorbility and morbility, respect to healthy. Hence, the absolute therapeutic benefit is directly proportional to the basic risk. So, internationally interest on early diagnosis of obesity is growing to avoid under- and overdiagnosis consequences. Therefore, the consequences are an aggravation of the disease and an increase in obesity related pathology like diabetes, cardiovascular disease, and cancer. The most widely used parameter for diagnosis, body mass index (BMI) is not suitable for assessing the body fat. In fact, several studies demonstrate that BMI alone cannot define obesity, which consists not so much in weight gain as in excess fat mass. The use of suitable tools for the assessment of fat mass percentage combined with clinical and genetic analysis allowed to identify different phenotypes of obesity, which explain the various paradoxes of obesity. It is essential to adopt all possible strategies to be able to combat obesity, ameliorate the suffering of patients, and reduce the social and treatment costs of obesity.
  • 机译 卫生保健中的生物银行:演变和未来方向
    摘要:BackgroundThe aim of the present review is to discuss how the promising field of biobanking can support health care research strategies. As the concept has evolved over time, biobanks have grown from simple biological sample repositories to complex and dynamic units belonging to large infrastructure networks, such as the Pan-European Biobanking and Biomolecular Resources Research Infrastructure (BBMRI). Biobanks were established to support scientific knowledge. Different professional figures with varied expertise collaborate to obtain and collect biological and clinical data from human subjects. At same time biobanks preserve the human and legal rights of each person that offers biomaterial for research.
  • 机译 细胞因子在慢性疲劳综合征中的临床价值
    摘要:Chronic fatigue syndrome (CFS) is a heterogeneous disorder with uncertain pathogenesis. Without effective therapy, CFS is characterized by disabling fatigue, depression, memory loss, and somatic discomfort. This comprehensive and impartial review aimed to assess the available evidence and examined the potential clinical value of using cytokines for the monitoring of CFS and as targets for the treatment of CFS. Inflammatory reactions and immune modulation are considered to contribute to the pathophysiology of CFS, and it is well documented that cytokines present in both blood and cerebrospinal fluid (CSF) are closely associated with the progression and severity of CFS. However, pathophysiological and methodological limitations prevent using circulating cytokines as independent diagnostic indices. Moreover, there is no evidence to support the use of CSF cytokines as independent diagnostic indices. Nevertheless, a comprehensive evaluation of changes in circulating and CSF cytokines may improve clinical understanding of the pathophysiology of patients with CFS, aiding in the establishment of an appropriate diagnosis. Importantly, the available evidence does not support the value of cytokines as therapeutic targets. We believe that an improved understanding of cytokine-related mechanisms will be helpful to explore new cytokine-related therapeutic targets.
  • 机译 伊朗患者中乳腺癌的遗传和分子生​​物学
    • 作者:Meysam Moghbeli
    • 刊名:Journal of Translational Medicine
    • 2019年第期
    摘要:AbstractBackground, Breast cancer (BC) is one of the leading causes of cancer related deaths in Iran. This high ratio of mortality had a rising trend during the recent years which is probably associated with late diagnosis.
  • 机译 动物到人类的翻译:报告的一致性率的系统范围界定
    摘要:BackgroundDrug development is currently hampered by high attrition rates; many developed treatments fail during clinical testing. Part of the attrition may be due to low animal-to-human translational success rates; so-called “translational failure”. As far as we know, no systematic overview of published translational success rates exists.
  • 机译 口腔,气道,肠道和一些系统性疾病中的吸烟和微生物组
    摘要:The human microbiome harbors a diverse array of microbes which establishes a mutually beneficial relation with the host in healthy conditions, however, the dynamic homeostasis is influenced by both host and environmental factors. Smoking contributes to modifications of the oral, lung and gut microbiome, leading to various diseases, such as periodontitis, asthma, chronic obstructive pulmonary disease, Crohn’s disease, ulcerative colitis and cancers. However, the exact causal relationship between smoking and microbiome alteration remains to be further explored.
  • 机译 Wolfram综合征,一种罕见的神经退行性疾病:从发病机理到未来治疗的观点
    摘要:BackgroundWolfram syndrome (WS), a rare genetic disorder, is considered the best prototype of endoplasmic reticulum (ER) diseases. Classical WS features are childhood-onset diabetes mellitus, optic atrophy, deafness, diabetes insipidus, neurological signs, and other abnormalities. Two causative genes (WFS1 and WFS2) have been identified. The transmission of the disease takes place in an autosomal recessive mode but autosomal dominant mutations responsible for WS-related disorders have been described. Prognosis is poor, death occurs at the median age of 39 years with a major cause represented by respiratory failure as a consequence of brain stem atrophy and neurodegeneration. The aim of this narrative review is to focus on etiology, pathogenesis and natural history of WS for an adequate patient management and for the discussion of future therapeutic interventions.
  • 机译 儿童嗜酸性食管炎:疑问和未来展望
    摘要:BackgroundEosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disorder and represents the leading cause of food impaction. The pathogenesis of EoE is the result of an interplay between genetic, environmental and host immune system factors. New therapeutic approaches for EoE have been proposed. In this manuscript we review the current evidence regarding EoE management in pediatric age, with a particular focus on new findings related to the efficacy and safety of monoclonal antibodies.
  • 机译 III期黑色素瘤的新范例:从手术到辅助治疗
    摘要:BackgroundRecently the 8th version of the American Joint Committee on Cancer (AJCC) classification has been introduced, and has attempted to define a more accurate and precise definition of prognosis in line with the major progresses in understanding the biology and pathogenesis of melanoma. This new staging system introduces major changes in the stage III staging system. Indeed, surgical practice is changing in stage III patients, since, according to recent evidence, there is no survival benefit in radical lymph node dissection following a positive sentinel lymph node dissection. Therefore, some patients currently staged IIIB-C after dissection could be downgraded to IIIA (as in the case of patients with metastatic non-sentinel lymph nodes) since many completion lymph node dissections will no longer be performed. Moreover, new and effective targeted and immune strategies are being introduced in the pharmacological armamentarium in the adjuvant setting, showing major efficacy.
  • 机译 基因测试在生殖医学中的发展作用
    摘要:Infertility is considered a major public health issue, and approximately 1 out of 6 people worldwide suffer from infertility during their reproductive lifespans. Thanks to technological advances, genetic tests are becoming increasingly relevant in reproductive medicine. More genetic tests are required to identify the cause of male and/or female infertility, identify carriers of inherited diseases and plan antenatal testing. Furthermore, genetic tests provide direction toward the most appropriate assisted reproductive techniques. Nevertheless, the use of molecular analysis in this field is still fragmented and cumbersome. The aim of this review is to highlight the conditions in which a genetic evaluation (counselling and testing) plays a role in improving the reproductive outcomes of infertile couples. We conducted a review of the literature, and starting from the observation of specific signs and symptoms, we describe the available molecular tests. To conceive a child, both partners' reproductive systems need to function in a precisely choreographed manner. Hence to treat infertility, it is key to assess both partners. Our results highlight the increasing importance of molecular testing in reproductive medicine.
  • 机译 芳烃受体激活介导肾脏疾病和肾细胞癌
    摘要:The aryl hydrocarbon receptor (AhR) is a well-known ligand-activated cytoplasmic transcription factor that contributes to cellular responses against environmental toxins and carcinogens. AhR is activated by a range of structurally diverse compounds from the environment, microbiome, natural products, and host metabolism, suggesting that AhR possesses a rather promiscuous ligand binding site. Increasing studies have indicated that AhR can be activated by a variety of endogenous ligands and induce the expression of a battery of genes. AhR regulates a variety of physiopathological events, including cell proliferation, differentiation, apoptosis, adhesion and migration. These new roles have expanded our understanding of the AhR signalling pathways and endogenous metabolites interacting with AhR under homeostatic and pathological conditions. Recent studies have demonstrated that AhR is linked to cardiovascular disease (CVD), chronic kidney disease (CKD) and renal cell carcinoma (RCC). In this review, we summarize gut microbiota-derived ligands inducing AhR activity in patients with CKD, CVD, diabetic nephropathy and RCC that may provide a new diagnostic and prognostic approach for complex renal damage. We further highlight polyphenols from natural products as AhR agonists or antagonists that regulate AhR activity. A better understanding of structurally diverse polyphenols and AhR biological activities would allow us to illuminate their molecular mechanism and discover potential therapeutic strategies targeting AhR activation.
  • 机译 在大鼠中建模创伤:与人类的相似性以及需要考虑的潜在陷阱
    摘要:Trauma is the leading cause of mortality in humans below the age of 40. Patients injured by accidents frequently suffer severe multiple trauma, which is life-threatening and leads to death in many cases. In multiply injured patients, thoracic trauma constitutes the third most common cause of mortality after abdominal injury and head trauma. Furthermore, 40–50% of all trauma-related deaths within the first 48 h after hospital admission result from uncontrolled hemorrhage. Physical trauma and hemorrhage are frequently associated with complex pathophysiological and immunological responses. To develop a greater understanding of the mechanisms of single and/or multiple trauma, reliable and reproducible animal models, fulfilling the ethical 3 R’s criteria (Replacement, Reduction and Refinement), established by Russell and Burch in ‘The Principles of Human Experimental Technique’ (published 1959), are required. These should reflect both the complex pathophysiological and the immunological alterations induced by trauma, with the objective to translate the findings to the human situation, providing new clinical treatment approaches for patients affected by severe trauma. Small animal models are the most frequently used in trauma research. Rattus norvegicus was the first mammalian species domesticated for scientific research, dating back to 1830. To date, there exist numerous well-established procedures to mimic different forms of injury patterns in rats, animals that are uncomplicated in handling and housing. Nevertheless, there are some physiological and genetic differences between humans and rats, which should be carefully considered when rats are chosen as a model organism. The aim of this review is to illustrate the advantages as well as the disadvantages of rat models, which should be considered in trauma research when selecting an appropriate in vivo model. Being the most common and important models in trauma research, this review focuses on hemorrhagic shock, blunt chest trauma, bone fracture, skin and soft-tissue trauma, burns, traumatic brain injury and polytrauma.

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