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Cranial nerve VII on gadolinium contrast-enhanced magnetic resonance imaging in the case of Bell’s palsy 颅神经VII在贝尔麻痹病例中的钆增强磁共振成像
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-23 DOI: 10.37349/emed.2023.00169
Alvarez Alvarez, Asif Becher, Thomas Chandy Varkey, Avtar Singh
Bell’s palsy is a rapid unilateral peripheral paralysis of cranial nerve VII whose etiology is varied, most commonly associated with an acute infectious or inflammatory demyelinating process. Nerve injury can result in edema because of increased permeability of vascular structures, which can sometimes be seen as a locus of enhancement of magnetic resonance imaging (MRI). Bell’s palsy is typically considered a clinical diagnosis and the specificity and sensitivity of imaging have been poorly studied. Herein is describe a case of a 73-year-old male who presented to the emergency department with left-sided facial droop and no other focal neurological abnormalities. With a history of a Janus kinase 2 (JAK2) mutation and the new initial facial drooping, acute cerebrovascular insult was high on the differential. Initial labs and computerized tomography (CT) head were inconclusive, but MRI showed pronounced enhancement of the left distal internal carotid artery (ICA) with contiguous enhancement of the labyrinthine, geniculate, and tympanic segments of the left facial nerve. Diagnosing Bell’s palsy can be a challenge as there are numerous postulated etiologies stemming from trauma, infection, and neoplasm; with infection (particularly viral) postulated to be the most likely source. Though MRI is currently not validated as a tool in expediting Bell’s palsy diagnosis, findings such as the enhancement seen here provide some insight into the benefit of MRI as a diagnostic modality in some cases. This case is unique both for the diagnostic dilemma between stroke and Bell’s palsy and the potential for MRI imaging to help guide clinical decision-making into treatment.
贝尔麻痹是一种快速单侧颅神经周围性麻痹,其病因多种多样,最常与急性感染性或炎性脱髓鞘过程有关。神经损伤可导致水肿,因为血管结构的通透性增加,这有时可以被视为磁共振成像(MRI)增强的一个位点。贝尔麻痹通常被认为是一种临床诊断,影像学的特异性和敏感性研究很少。这里是一个73岁的男性谁提出的情况下,以左侧面部下垂和其他局灶性神经异常急诊科。有JAK2激酶突变史和新的初始面部下垂,急性脑血管损伤在鉴别上很高。最初的实验室和计算机断层扫描(CT)头部没有确定,但MRI显示左侧颈动脉远端(ICA)明显增强,左侧面神经的迷路节、膝曲节和鼓室节连续增强。诊断贝尔氏麻痹可能是一个挑战,因为有许多假定的病因源于创伤,感染和肿瘤;感染(特别是病毒)被认为是最可能的来源。虽然MRI目前还没有被证实是加速贝尔麻痹诊断的工具,但在某些情况下,MRI作为一种诊断方式的好处,在这里看到的增强等发现提供了一些见解。这个病例的独特之处在于中风和贝尔氏麻痹之间的诊断困境,以及MRI成像在帮助指导临床决策治疗方面的潜力。
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引用次数: 0
Self-replicating RNA viruses in vaccine development 疫苗开发中的自我复制RNA病毒
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-10 DOI: 10.37349/emed.2023.00168
Kenneth Lundstrom
Self-replicating RNA viruses such as alphaviruses, flaviviruses, paramyxoviruses, and rhabdoviruses have been engineered as expression vectors for vaccine development. The prominent feature of self-replicating RNA viruses is their RNA-dependent RNA polymerase activity, which generates massive self-amplification of RNA in the cytoplasm of infected host cells leading to extreme levels of transgene expression. Infectious diseases have been targeted by overexpression of surface proteins of pathogens as antigens for vaccine development. Moreover, overexpression of tumor-associated antigens and immunostimulatory genes has been the basis for cancer vaccines. Proof-of-concept of robust antigen-specific immune responses and protection against challenges with lethal doses of infectious agents have been demonstrated. Likewise, vaccine development against various cancers has elicited strong immune responses and resulted in tumor regression and eradication, cure, and prolonged survival in animal tumor models. Good safety and immune responses have been achieved in clinical trials. The ERVEBO® vaccine, based on the vesicular stomatitis virus, has been approved for immunization against the Ebola virus disease.
自我复制的RNA病毒,如甲病毒、黄病毒、副粘病毒和横纹肌病毒已被设计为疫苗开发的表达载体。自我复制的RNA病毒的突出特点是其RNA依赖的RNA聚合酶活性,它在被感染的宿主细胞的细胞质中产生大量的RNA自我扩增,从而导致极端水平的转基因表达。病原体表面蛋白的过度表达已成为传染病疫苗开发的靶标。此外,肿瘤相关抗原和免疫刺激基因的过度表达已成为癌症疫苗的基础。已经证明了强大的抗原特异性免疫反应和对致命剂量感染原的挑战的保护的概念证明。同样,针对各种癌症的疫苗开发也引发了强烈的免疫反应,并在动物肿瘤模型中导致肿瘤消退、根除、治愈和延长生存期。在临床试验中取得了良好的安全性和免疫应答。基于水疱性口炎病毒的ERVEBO®疫苗已被批准用于预防埃博拉病毒病的免疫。
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引用次数: 0
Diabetes and substance use: a perspective within drug rehabilitation 糖尿病和药物使用:药物康复的视角
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-08 DOI: 10.37349/emed.2023.00167
Abuelgasim Elrasheed A. Alhassan, Weaam Elrashid, Aref Alshehhi, Samya Al Mamari, Mahmoud Abu Raddaha, Mansour Assaf, Simon Elliott
Diabetes mellitus has become increasingly more common and diagnosed within the global population. Coupled with the continued prevalence of substance use, there are some distinct considerations for users suffering (knowingly or unknowingly) from type 1 or type 2 diabetes. The various different types of drugs of abuse including central nervous system stimulants, depressants, and hallucinogens present varying direct and indirect complications for diabetes based on their physiological and psychological effects ranging from non-compliance with medication to an increased risk of hypoglycaemia, hyperglycaemia, and/or ketoacidosis. This perspective highlights these issues supported by the drug history and toxicological findings in patients undergoing drug rehabilitation in the United Arab Emirates (UAE) demonstrating the use of alcohol, amphetamines, benzodiazepines, cannabis, opiates/opioids (especially tramadol), pregabalin, and synthetic cannabinoids. Physicians and drug clinic professionals should be aware of the contraindications of substance use and diabetes with a view to educating patients and healthcare professionals within such clinical settings.
糖尿病在全球人口中变得越来越普遍和确诊。再加上药物使用的持续流行,对于患有(有意或无意)1型或2型糖尿病的用户有一些不同的考虑。滥用各种不同类型的药物,包括中枢神经系统兴奋剂、抑制剂和致幻剂,根据其生理和心理影响,从不遵守药物治疗到低血糖、高血糖和/或酮症酸中毒的风险增加,会出现各种直接和间接的糖尿病并发症。这一观点强调了这些问题,这些问题得到了阿拉伯联合酋长国(UAE)接受药物康复的患者的药物史和毒理学调查结果的支持,这些结果表明使用酒精、安非他明、苯二氮卓类药物、大麻、阿片类药物/阿片类药物(特别是曲马多)、普瑞巴林和合成大麻素。医生和药物诊所专业人员应了解药物使用和糖尿病的禁忌症,以便在此类临床环境中对患者和保健专业人员进行教育。
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引用次数: 0
Mechanistic insights on anticancer drugs with specific biological targets and signalling pathways 具有特定生物学靶点和信号通路的抗癌药物的机制见解
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-15 DOI: 10.37349/emed.2023.00166
Mohsina Patwekar, Faheem Patwekar, Anuradha Medikeri, Shaikh Daniyal, Mohammad A. Kamal, Gulzar Ahmed Rather, Rohit Sharma
Complex enzyme interactions play a role in the spread of cancer, a process fueled by unregulated cell proliferation. DNA topoisomerases, which are important for fixing DNA topological problems, have drawn a lot of interest as potential targets for anti-cancer medications. Cancer treatment, which includes radiation, surgery, and chemotherapy, tries to control cell survival, demise, and mobility, which are mediated by ion transportation across cell membranes via channels and carriers. The malignant transition is characterised by altered channels and carriers. Chemoresistance, which commonly develops after chemotherapy, denotes decreased therapeutic effectiveness against cancer progression. Chemosensitizers are used in combination with anti-cancer medications to overcome this resistance, particularly against adenosine triphosphate (ATP)-binding cassette (ABC) transporters including P-glycoprotein, multidrug resistance-associated protein 1 (MRP1), breast cancer resistance protein (BCRP). Effective targets for treatment are transcription factors, which play a key role in the development of cancer. With the use of interactions with receptors, enzymes, ion channels, transporters, and TFs, nanotechnology improves the safety of tumour localization, treatment, and diagnostics. As a result of mutations or altered signalling, rat sarcoma (RAS) proteins regulate signalling, which is essential for both healthy growth and the development of cancer. Rational treatments that target RAS pathways have the potential to inhibit the growth and spread of tumours. New treatments are still being developed, and they are showing promise in clinical settings. The roles of receptors on tumour cells, their significance for cancer therapy, and recent advancements in preclinical and clinical research are all included in this overview.
复杂的酶相互作用在癌症的扩散中发挥作用,这是一个由不受调节的细胞增殖推动的过程。DNA拓扑异构酶对于修复DNA拓扑问题具有重要意义,作为抗癌药物的潜在靶点引起了人们的广泛关注。癌症治疗包括放疗、手术和化疗,试图控制细胞的生存、死亡和迁移,这些都是由离子通过通道和载体在细胞膜上运输介导的。恶性转移的特征是通道和载体的改变。化疗耐药通常发生在化疗后,表明治疗癌症进展的有效性下降。化疗增敏剂与抗癌药物联合使用以克服这种耐药性,特别是针对三磷酸腺苷(ATP)结合盒(ABC)转运体,包括p -糖蛋白,多药耐药相关蛋白1 (MRP1),乳腺癌耐药蛋白(BCRP)。有效的治疗靶点是转录因子,它在癌症的发展中起着关键作用。利用与受体、酶、离子通道、转运体和tf的相互作用,纳米技术提高了肿瘤定位、治疗和诊断的安全性。由于突变或信号改变,大鼠肉瘤(RAS)蛋白调节信号,这对于健康生长和癌症的发展都是必不可少的。针对RAS通路的合理治疗有可能抑制肿瘤的生长和扩散。新的治疗方法仍在开发中,它们在临床环境中显示出希望。受体在肿瘤细胞上的作用,它们对癌症治疗的意义,以及临床前和临床研究的最新进展都包括在这篇综述中。
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引用次数: 0
Body mass, blood pressure, and cognitive functioning among octogenarians and centenarians 八十岁和百岁老人的体重、血压和认知功能
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-15 DOI: 10.37349/emed.2023.00165
Peter Martin, Rotem Arieli, Mai Kabayama, Kayo Godai, Yasuyuki Gondo, Mary Ann Johnson, Leonard W. Poon
Aim: The purpose of this study was to examine the association among body mass, blood pressure (BP), and cognitive functioning for octogenarians and centenarians. Methods: A total of 300 participants (221 centenarians and 79 octogenarians) from the Georgia Centenarian Study were included in this study. Demographic variables included age, gender, and ethnicity. Body mass was measured with the body mass index (BMI), and systolic and diastolic BP, as well as mean arterial pressure (MAP) and the Mini-Mental Status Examination (MMSE) were assessed. Results: Results showed age differences indicating that centenarians had lower BMI and MMSE scores when compared to octogenarians. Women had lower cognitive functioning scores compared to men. Black Americans had higher BMI and BP as well as lower MMSE scores. Participants with low BMI values (< 18.5 kg/m2) and normal BP had a significantly lower MMSE score when compared to those with elevated BMI values (≥ 25 kg/m2 to < 30 kg/m2) and high BP. Multiple regression analyses determined that age, gender, ethnicity, and BMI were significantly associated with cognitive function in very late life. Conclusions: The results suggest that extreme values of body mass (low and high) in combination with normal BP (< 130 mmHg) are potential risk factors for compromised cognition.
目的:本研究的目的是研究八十岁和百岁老人的体重、血压(BP)和认知功能之间的关系。方法:从乔治亚州百岁老人研究中选取300名参与者(221名百岁老人和79名八十岁老人)进行研究。人口统计变量包括年龄、性别和种族。用体重指数(BMI)测量体重,并评估收缩压和舒张压、平均动脉压(MAP)和最小精神状态检查(MMSE)。结果:结果显示年龄差异表明百岁老人的BMI和MMSE评分低于80岁老人。与男性相比,女性的认知功能得分较低。美国黑人的身体质量指数和血压较高,MMSE得分较低。BMI值较低的参与者(<18.5 kg/m2)和正常血压的患者的MMSE评分明显低于BMI值升高的患者(≥25 kg/m2至<30kg /m2),血压高。多元回归分析表明,年龄、性别、种族和身体质量指数与晚年的认知功能显著相关。结论:体重极值(低、高)与正常血压(<130毫米汞柱)是认知功能受损的潜在危险因素。
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引用次数: 0
An overview of current advances and pharmaceutical uses of 3D and 4D printing 概述了3D和4D打印的当前进展和制药用途
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-08-31 DOI: 10.37349/emed.2023.00161
Pankaj Sharma, Vinay Jain
The development of patient-specific prosthetics, medication administration, the manufacture of tissues and organs, and surgical planning have all benefited significantly from the use of three-dimensional (3D) printing during the past few decades. The enthusiasm for customized healthcare has increased because the United States of America launched its Precision Medicine Initiative in 2015. In a nutshell, the phrase “personalized medicine” refers to medical care that is tailored to the patient. Nevertheless, the biomedical materials utilized in 3D printing are often stable and can’t react or be adaptive and intelligent in the body’s interior environment. Ex-situ fabrication of these substances, which includes printing on a flat substrate before releasing it onto the target surface, may cause a discrepancy between the printed portion and the target areas. The 3D printing is one method that might be used to provide customized treatment. The four-dimensional (4D) printing is developed while employing components that can be tweaked with stimulation. Several researchers have been looking at a new area recently that blends medicines with 3D and 4D printing. The development of 4D printing overcomes a number of these issues and creates a promising future for the biomedical industry. Smart materials that have been pre-programmed can be used in 4D printing to create structures that react interactively to outside stimuli. Despite these benefits, dynamic materials created using 4D technology remain in their development. As a result, several ideas for pharmaceutical products and formulas that may be customized and printed have emerged. Furthermore, Spritam®, the first medicine produced by 3D printing, has indeed reached a medical facility. This paper offers a summary of several 3D and 4D printing technologies and how they are used in the pharmaceutical industry for customized medicine and drug delivery systems.
在过去的几十年里,患者特异性假肢的发展、药物管理、组织和器官的制造以及手术计划都从三维(3D)打印的使用中受益匪浅。由于美国在2015年推出了精准医疗计划,定制医疗的热情有所增加。简而言之,“个性化医疗”一词指的是为患者量身定制的医疗服务。然而,3D打印中使用的生物医学材料往往是稳定的,不能对人体内部环境做出反应或自适应和智能。这些物质的非原位制造,包括在将其释放到目标表面之前在平面基板上打印,可能导致打印部分和目标区域之间的差异。3D打印是一种可能用于提供定制治疗的方法。这种四维(4D)打印技术是在使用可以随刺激调整的组件的同时开发出来的。几位研究人员最近一直在研究将药物与3D和4D打印相结合的新领域。4D打印的发展克服了许多这些问题,并为生物医学行业创造了一个充满希望的未来。预先编程的智能材料可用于4D打印,以创建对外界刺激进行交互反应的结构。尽管有这些好处,使用4D技术创建的动态材料仍在发展中。因此,出现了一些可以定制和印刷的药品和配方的想法。此外,Spritam®,第一种由3D打印生产的药物,确实已经进入医疗机构。本文概述了几种3D和4D打印技术,以及它们如何在制药行业中用于定制药物和药物输送系统。
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引用次数: 0
Utility of fibroblasts derived from broncho-alveolar lavage of patients with idiopathic pulmonary fibrosis or related disorders to develop in vitro models 特发性肺纤维化或相关疾病患者支气管肺泡灌洗成纤维细胞在体外模型开发中的作用
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-08-31 DOI: 10.37349/emed.2023.00156
P. Giannoni, E. Barisione, M. Grosso, D. de Totero
Broncho-alveolar lavage (BAL) represents a safe tool for the differential diagnosis of various pulmonary fibrotic diseases. Idiopathic pulmonary fibrosis (IPF) belongs to a heterogeneous group of diseases, interstitial lung disease (ILD), presenting a progressive impairment of pulmonary functions. IPF is characterized by the excessive accumulation of extracellular matrix (ECM) in the alveolar parenchyma that may lead to irreversible pulmonary remodeling. Although the exact pathogenetic mechanisms leading to IPF development are still unclear it has been demonstrated that fibroblasts differentiating toward myofibroblasts are the major actors involved in this process. The possibility of obtaining and expanding fibroblasts from the BAL of ILD patients for research purposes has been recently explored. This approach is discussed here as a reliable chance, helpful to advance the scientific community knowledge and to devise two- and three-dimensional (2D/3D) pre-clinical in vitro models of these diseases, further overcoming technical and ethical concerns related to the use of fibroblasts derived from tissue biopsy.
支气管肺泡灌洗(BAL)是鉴别诊断各种肺纤维化疾病的安全工具。特发性肺纤维化(IPF)属于异质性疾病,间质性肺疾病(ILD),表现为肺功能的进行性损害。IPF的特征是细胞外基质(ECM)在肺泡实质中的过度积累,可能导致不可逆的肺重塑。虽然导致IPF发育的确切发病机制尚不清楚,但已证明成纤维细胞向肌成纤维细胞分化是这一过程的主要参与者。从ILD患者BAL中获取和扩增成纤维细胞用于研究目的的可能性最近得到了探索。本文将这种方法作为一种可靠的机会进行讨论,有助于推进科学界的知识,并设计这些疾病的二维和三维(2D/3D)临床前体外模型,进一步克服与使用来自组织活检的成纤维细胞相关的技术和伦理问题。
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引用次数: 0
Comparison of eating habits and gut microbiota of preschool children with obesity 学龄前肥胖儿童饮食习惯和肠道微生物群的比较
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-08-31 DOI: 10.37349/emed.2023.00164
Shymaa M. Al-Jabri, Effat A. Al-Judaibi, Yasser A. Al-Gamdee, A. Al-Judaibi
Aim: Childhood obesity is a global health concern that affects the daily life of children. It has a complex pathogenesis that involves genetic and nutritional factors among others. Moreover, the dysbiosis of gut microbiota has been recently associated with the development and progression of obesity.Methods: A total of 43 faecal samples were collected from Saudi children; among them, 26 were normal and 17 were obese. Whole genomic DNA was extracted from their faecal samples and sequenced using an Illumina Sequencing platform.Results: The gut microbiota was dominated by Phyla Firmicutes (69.00%) and Bacteroidetes (20.00%), followed by Actinobacteria (8.50%). In children with obesity, the abundance of Firmicutes was decreased, while Bacteroidetes was relatively enriched. Verrucomicrobia and Proteobacteria were not detected in the obese group, but they were found in low abundance in the control group. Phylum Firmicutes was dominated by the families Ruminococcaceae (17.86%) and Lachnospiraceae (41.20%). Less Ruminococcaceae was found in the obese group. Phylum Bacteroidetes was dominated by families Bacteroidaceae (12.98%) and Prevotellaceae (4.10%), which were enriched in the obese group. Genus Blautia (14.29%) was highly abundant, followed by Bacteroides (12.98%), Faecalibacterium (10.08%), Bifidobacterium (7.96%), and Prevotella (5.04%). Ruminococcus_g2 and _g4, Subdoligranulum, Roseburia, Fusicatenibacter, Anaerostipes, and Faecalibacterium were decreased (P > 0.05) in the obese group, while Streptococcus, Agathobacter, Prevotella, Bacteroides, and Bifidobacterium were increased (P > 0.05).Conclusions: In conclusion, a diverse bacterial community was profiled in Saudi preschool children, and changes in bacterial community composition were observed between obese- and normal-weight children.
目的:儿童肥胖是影响儿童日常生活的全球性健康问题。它有一个复杂的发病机制,涉及遗传和营养因素等。此外,肠道微生物群的微生态失调最近与肥胖的发展和进展有关。方法:共采集沙特儿童粪便43份;其中正常26例,肥胖17例。从他们的粪便样本中提取全基因组DNA,并使用Illumina测序平台进行测序。结果:肠道微生物群以厚壁菌门(69.00%)和拟杆菌门(20.00%)为主,其次是放线菌门(8.50%)。在肥胖儿童中,厚壁菌的丰度降低,而拟杆菌门相对富集。在肥胖组中未检测到Verrucomirobia和变形杆菌,但在对照组中发现它们的丰度较低。厚壁菌门(Phylum Firmicutes)以瘤胃球菌科(17.86%)和钩藤科(41.20%)为主,肥胖组瘤胃球菌科较少。拟杆菌门以拟杆菌科(12.98%)和普雷沃菌科(4.10%)为主,它们在肥胖组中富集。Blautia属(14.29%)非常丰富,其次是拟杆菌属(12.98%)、粪杆菌属(10.08%)、双歧杆菌属(7.96%)和普雷沃氏菌属(5.04%)。瘤胃球菌_g2和_g4、亚多颗粒菌、罗斯伯里菌、镰刀菌属、Anaerostipes和粪杆菌在肥胖组中减少(P>0.05),结论:沙特学龄前儿童细菌群落多样,肥胖儿童和正常体重儿童细菌群落组成发生变化。
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引用次数: 0
Autophagy and diabetes 自噬与糖尿病
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-08-31 DOI: 10.37349/emed.2023.00162
M. Obradović, S. Zafirovic, Z. Gluvić, Jelena Radovanović, E. Isenovic
The current literature findings on autophagy’s beneficial and detrimental roles in diabetes mellitus (DM) and diabetes-related comorbidities were reviewed. The effects of oral hypoglycaemic medicines and autophagy in DM. Autophagy plays an important function in cellular homeostasis by promoting cell survival or initiating cell death in physiological settings was also assessed. Although autophagy protects insulin-target tissues, organelle failure caused by autophagy malfunction influences DM and other metabolic diseases. Endoplasmic reticulum and oxidative stress enhance autophagy levels, making it easier to regulate stress-induced intracellular changes. Evidence suggests that autophagy-caused cell death can occur when autophagy is overstimulated and constitutively activated, which might prevent or develop DM. Even though the precise role of autophagy in DM complications is uncertain, deregulation of the autophagic machinery is strongly linked to beta cell destruction and the aetiology of DM. Thus, improving autophagy dysfunction is a possible therapeutic objective in treating DM and other metabolic disorders.
综述了目前关于自噬在糖尿病(DM)和糖尿病相关合并症中的有益和有害作用的文献研究结果。口服低血糖药物和自噬在糖尿病中的作用。还评估了自噬在生理环境中通过促进细胞存活或引发细胞死亡在细胞稳态中发挥重要作用。尽管自噬可以保护胰岛素靶组织,但自噬功能障碍引起的细胞器衰竭会影响糖尿病和其他代谢性疾病。内质网和氧化应激增强了自噬水平,使其更容易调节应激诱导的细胞内变化。有证据表明,当自噬被过度刺激和组成性激活时,可能会发生自噬引起的细胞死亡,这可能会预防或发展为糖尿病。尽管自噬在糖尿病并发症中的确切作用尚不确定,但自噬机制的失调与β细胞破坏和糖尿病的病因密切相关。因此,改善自噬功能障碍是治疗糖尿病和其他代谢紊乱的一个可能的治疗目标。
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引用次数: 0
Lactate metabolic pathway regulates tumor cell metastasis and its use as a new therapeutic target 乳酸代谢途径调控肿瘤细胞转移及其作为新的治疗靶点
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-08-31 DOI: 10.37349/emed.2023.00160
Weimei Xing, Xiaowei Li, Yuli Zhou, Mengsen Li, Mingyue Zhu
Abnormal energy metabolism is one of the ten hallmarks of tumors, and tumor cell metabolism provides energy and a suitable microenvironment for tumorigenesis and metastasis. Tumor cells can consume large amounts of glucose and produce large amounts of lactate through glycolysis even in the presence of oxygen, a process called aerobic glycolysis, also known as the Warburg effect. Lactate is the end product of the aerobic glycolysis. Lactate dehydrogenase A (LDHA), which is highly expressed in cancer cells, promotes lactate production and transports lactate to the tumor microenvironment and is taken up by surrounding stromal cells under the action of monocarboxylate transporter 1/4 (MCT1/4), which in turn influences the immune response and enhances the invasion and metastasis of cancer cells. Therapeutic strategies targeting lactate metabolism have been intensively investigated, focusing on its metastasis-promoting properties and various target inhibitors; AZD3965, an MCT1 inhibitor, has entered phase I clinical trials, and the LDHA inhibitor N-hydroxyindole (NHI) has shown cancer therapeutic activity in pre-clinical studies. Interventions targeting lactate metabolism are emerging as a promising option for cancer therapy, with chemotherapy or radiotherapy combined with lactate-metabolism-targeted drugs adding to the effectiveness of cancer treatment. Based on current research, this article outlines the role of lactate metabolism in tumor metastasis and the potential value of inhibitors targeting lactate metabolism in cancer therapy.
能量代谢异常是肿瘤的十大标志之一,肿瘤细胞代谢为肿瘤的发生和转移提供了能量和适宜的微环境。肿瘤细胞即使在氧气存在的情况下也能通过糖酵解消耗大量葡萄糖并产生大量乳酸,这一过程被称为有氧糖酵解,也被称为Warburg效应。乳酸是有氧糖酵解的最终产物。乳酸脱氢酶A (Lactate dehydrogenase A, LDHA)在癌细胞中高表达,在单羧酸转运蛋白1/4 (MCT1/4)的作用下,促进乳酸生成并将乳酸转运到肿瘤微环境,被周围基质细胞摄取,进而影响免疫应答,增强癌细胞的侵袭和转移。针对乳酸代谢的治疗策略已被深入研究,重点关注其促进转移的特性和各种靶标抑制剂;MCT1抑制剂AZD3965已进入I期临床试验,LDHA抑制剂n -羟基吲哚(NHI)已在临床前研究中显示出癌症治疗活性。针对乳酸代谢的干预措施正在成为癌症治疗的一个有希望的选择,化疗或放疗结合乳酸代谢靶向药物增加了癌症治疗的有效性。基于目前的研究,本文概述了乳酸代谢在肿瘤转移中的作用以及靶向乳酸代谢抑制剂在肿瘤治疗中的潜在价值。
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引用次数: 0
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Exploration of medicine
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