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Trigonelline: An Emerging Paradigm for Effective Therapy in Diabetes Mellitus 葫芦巴碱:糖尿病有效治疗的新范例
Pub Date : 2023-05-12 DOI: 10.18311/jer/2023/29609
M. Walvekar, Namrata Jadhav, J. A. Daunde, N. D. Potphode, S. S. Desai
Diabetes Mellitus (DM) is recognized as a critical priority because of its epidemic nature. Successful diabetes treatment is not yet established and nowadays, diabetes is considered a global problem. Recent medications have not proved to be complete treating agents because, until now no one had completely cured diabetes. Current antidiabetic drugs have many undesirable side effects. So, an alternative therapy is required. Nowadays, various plant species are used worldwide as hypoglycemic, antihyperglycemic, antidiabetic and antihyperlipidemic agents. A number of plants contain active metabolites such as alkaloids, flavonoids, glycosides, carotenoids, terpenoids, etc., which are extensively used in antidiabetic drugs. About 400 plant species have been reported as having hypoglycemic activity. From these medicinal plants and their active components, various herbal drugs are being formed. This review aims to understand different plant species used to date for treating diabetes, the therapeutic potential of fenugreek, the active compounds isolated from fenugreek, the chemical structure of trigonelline, therapeutic uses of trigonelline as an antidiabetic agent. Research papers, manuscripts and review papers were searched and relevant contents were studied. One hundred sixty-three papers were included in this review. The review resulted in a better understanding of the use of trigonelline in diabetes treatment.
糖尿病(DM)由于其流行病的性质而被认为是一个关键的优先事项。目前,成功的糖尿病治疗尚未建立,糖尿病被认为是一个全球性的问题。最近的药物还没有被证明是完全的治疗药物,因为直到现在还没有人完全治愈糖尿病。目前的抗糖尿病药物有许多不良的副作用。因此,需要一种替代疗法。目前,世界上有多种植物被用作降血糖、降高血糖、降糖尿病和降血脂的药物。许多植物含有活性代谢物,如生物碱、黄酮类、糖苷类、类胡萝卜素、萜类等,广泛应用于降糖药中。据报道,大约有400种植物具有降血糖活性。从这些药用植物和它们的有效成分中,各种草药正在形成。本文综述了迄今为止用于治疗糖尿病的不同植物种类,胡芦巴的治疗潜力,胡芦巴中分离的活性化合物,葫芦巴碱的化学结构,葫芦巴碱作为抗糖尿病药物的治疗用途。检索研究论文、原稿和综述论文,研究相关内容。本综述共纳入163篇论文。该综述使人们对葫芦巴碱在糖尿病治疗中的应用有了更好的了解。
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引用次数: 0
Relationship between Serum Levels of Oxidative Stress Markers and Metabolic Syndrome Components in PCOS Women PCOS妇女血清氧化应激标志物水平与代谢综合征成分的关系
Pub Date : 2023-05-12 DOI: 10.18311/jer/2023/33508
K. Lakshmi, S. S. Malini
Background: Polycystic Ovarian Syndrome (PCOS) is a common endocrinological problem that leads to infertility in reproductive age. It is strongly associated with oxidative stress, which increases the risk of Metabolic Syndrome (Met-S) in women. This study aimed to evaluate the relationship between oxidative stress markers and metabolic syndrome parameters in PCOS women. Methods: In this cross-sectional study, we included age-matched 100 control and 150 PCOS (according to Rotterdam criteria). Anthropometric measurements were obtained from each subject. Lipid profile, Fasting Plasma Glucose (FPG), and insulin were determined. Serum Malondialdehyde (MDA), Nitric Oxide (NO), and Reactive Oxygen Species (ROS) levels are pro-oxidant indicators, while for antioxidant activities, Superoxide Dismutase (SOD), Catalase (CAT), Glutathione (GSH), Vitamin-C (Vit C), and Total Antioxidant Capacity (TAC) activity were measured by spectrophotometry. Results: In the PCOS group the SOD, CAT, GSH, Vit C, and TAC activity were significantly low, whereas NO, ROS, and MDA were significantly high (p < 0.05). In the PCOS group, the pro-oxidant MDA showed a negative correlation with HDL and a positive correlation with DBP. The antioxidants SOD and CAT showed a negative correlation with fasting blood glucose and triglycerides. Conclusion: The metabolic syndrome components of PCOS can induce oxidative stress, which is evidenced by a decrease in antioxidant defence mechanisms. It is probably because oxidative stress itself is the consequence of PCOS, more so with Met-S which increases the pro-oxidant state and decreases the anti-oxidant capacity in women.
背景:多囊卵巢综合征(PCOS)是导致育龄期不孕的常见内分泌问题。它与氧化应激密切相关,而氧化应激会增加女性代谢综合征(Met-S)的风险。本研究旨在评估PCOS女性氧化应激标志物与代谢综合征参数的关系。方法:在这项横断面研究中,我们纳入了年龄匹配的100名对照组和150名PCOS患者(根据鹿特丹标准)。对每个受试者进行人体测量。测定血脂、空腹血糖(FPG)和胰岛素。血清丙二醛(MDA)、一氧化氮(NO)和活性氧(ROS)水平为促氧化指标,抗氧化活性以超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽(GSH)、维生素C (Vit C)和总抗氧化能力(TAC)活性为测定指标。结果:PCOS组SOD、CAT、GSH、Vit C、TAC活性显著降低,NO、ROS、MDA活性显著升高(p < 0.05)。在PCOS组,促氧化剂MDA与HDL呈负相关,与DBP呈正相关。抗氧化剂SOD和CAT与空腹血糖和甘油三酯呈负相关。结论:多囊卵巢综合征代谢综合征成分可诱导氧化应激,其机制表现为抗氧化防御机制的降低。这可能是因为氧化应激本身就是多囊卵巢综合征的后果,而Met-S的作用更大,它会增加女性的促氧化状态,降低抗氧化能力。
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引用次数: 0
Alterations in the Epigenetic Landscape Underlying Later-Life Health Effects Due to In-utero Exposure to Endocrine Disrupting Chemicals: A Review of Outcomes from Mice to Men 子宫内暴露于内分泌干扰化学物质对后期健康影响的表观遗传景观的改变:从小鼠到男性的结果综述
Pub Date : 2021-07-20 DOI: 10.18311/JER/2021/28038
S. Santosh, Christy Lite, Glancis Luzeena Raja, K. D. Subhashree, Kamalini Esther Kantayya, S. Barathi
Widespread persistence of Endocrine Disrupting Chemicals (EDCs) in the environment has mandated the need to study their potential long-term effects on human health, after acute as well aschronic exposures. The particular focus is on in utero exposure to EDCs in rodent models to look at altered epigenetic programming to result in transgenerational effects in later life of the offspring. This potentially contributes to reproductive and immune dysfunctions, obesity, cancer, and altered brain development and neurobehavioral outcomes. The literature to date establishes the transgenerational effects associated with in utero exposure to EDCs in rodent models. Hence, the aim of this review is to provide a comprehensive overview of epigenetic programming and its regulation in mammals, specially focussing on epigenetic plasticity and susceptibility to exogenous endocrine-active chemicals, EDCs, during the early developmental period, and carried forward to later life using rodent models. The available reports suggest that the key mechanism behind the long-term impact of EDCs is caused by alterations in the epigenetic programming machinery, leading to dysregulated gene expression during adult life. Studies have reported the effect of prenatal exposure to EDCs in the ovarian microRNA expression and function, highlighting ovary as an organ undergoing in utero programming. It ascertains the heightened sensitivity of the organ to exogenous hormone-active compounds, particularly during early development. In addition to this, another key aspect in this review is increased susceptibility of the brain when exposed to even minute quantities of EDCs during embryonic development, resulting in profound alterations in the structural organization of the brain and neurobehavior. Detailed analyses of variables such as folic acid and phytoestrogen content in maternal diet need to be considered as crucial factors while designing experiments and therapeutic interventions. Apart from this, appropriate animal handling during the experimental procedures to eliminate stress in animal models to ensure unbiased results is recommended.
环境中广泛存在的内分泌干扰物(EDCs)要求研究它们在急性和慢性暴露后对人类健康的潜在长期影响。特别关注的是啮齿动物模型在子宫内暴露于EDCs,以观察改变的表观遗传程序对后代后期生活的跨代影响。这可能会导致生殖和免疫功能障碍、肥胖、癌症以及大脑发育和神经行为结果的改变。迄今为止的文献在啮齿动物模型中建立了与子宫内暴露于EDCs相关的跨代效应。因此,本文旨在对哺乳动物的表观遗传编程及其调控进行综述,特别是在早期发育阶段的表观遗传可塑性和对外源性内分泌活性化学物质(EDCs)的易感性,并利用啮齿动物模型进行后续研究。现有的报告表明,EDCs长期影响背后的关键机制是由表观遗传编程机制的改变引起的,导致成年期基因表达失调。研究报道了产前暴露于EDCs对卵巢microRNA表达和功能的影响,强调了卵巢作为一个在子宫内进行编程的器官。它确定了器官对外源性激素活性化合物的高度敏感性,特别是在早期发育期间。除此之外,本综述的另一个关键方面是,在胚胎发育期间,即使暴露于极少量的EDCs,也会增加大脑的易感性,从而导致大脑结构组织和神经行为的深刻改变。在设计实验和治疗干预措施时,需要考虑对母亲饮食中叶酸和植物雌激素含量等变量的详细分析。除此之外,建议在实验过程中适当处理动物以消除动物模型中的应激,以确保结果公正。
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引用次数: 0
Breaching the Barriers of Chemotherapeutics for Breast Cancer with Alternative Medicine 用替代医学突破乳腺癌化疗的障碍
Pub Date : 2021-07-20 DOI: 10.18311/JER/2021/27792
Khushali Upadhyay, F. Patel, A. Ramachandran, E. Robin, D. Baxi
Breast cancer is one of the most prevalent forms of cancers in women around the world. Owing to its biochemical variation and complexity, treatment with chemotherapy and/or radiotherapy is very complicated and often results in adverse side effects. This article reviews the widely practiced chemotherapeutic drugs, their modes of actions and side effects. The several breast cancer therapeutic approaches based on medicinal plants, hormones, nutritional supplements and/or some advanced drug delivery systems that may lead to faster recovery are also reviewed.
乳腺癌是世界上最常见的女性癌症之一。由于其生化变化和复杂性,化疗和/或放疗治疗非常复杂,往往导致不良副作用。本文综述了目前广泛应用的化疗药物及其作用方式和副作用。本文还综述了几种基于药用植物、激素、营养补充剂和/或一些先进的药物输送系统的乳腺癌治疗方法,这些方法可能导致更快的恢复。
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引用次数: 0
Comparative Immune-reactivity Patterns of Arginine Vasotocin (AVT) and Melatonin Receptors (Mel1a & Mel1b) in Hypothalamic Regions of Male Japanese Quail Coturnix coturnix japonica : Possible Role in Water-Electrolyte Balance 雄性日本鹌鹑下丘脑区精氨酸血管催产素(AVT)和褪黑激素受体(Mel1a和Mel1b)免疫反应模式的比较:可能在水电解质平衡中的作用
Pub Date : 2021-07-20 DOI: 10.18311/JER/2021/28023
C. Haldar, S. Yadav, S. Arora
Photoperiod influences circulatory Melatonin (Mel) and hypothalamic functions via retino-hypothalamic tract. However, interrelation between Mel receptors and Arginine Vasotocin (AVT), a water-electrolyte balancing hormone receptor expression in hypothalamic regions of avian brain has never been explored. We noted the expression pattern of two Mel receptors (Mel1a & Mel1b) along with AVT, in terms of neuronal immuno-positivity, in hypothalamic region of Japanese quail under different photoperiodic conditions with/without melatonin treatment. This is interesting and equally important because both Mel and AVT levels are regulated by light/dark cycle. Confocal imaging revealed specific regional localization of Mel1a/Mel1b in Supra-Chiasmatic Nucleus (SCN), Supra-Optic Nucleus (SON) and Para-Ventricular Nucleus (PVN), the intensity of which was dependent on the photoperiodic condition (long day, LD or short day, SD) and melatonin treatment. Mel1a/Mel1b was mostly co-localized along with AVT. Mel1b was abundant in hypothalamic regions in contrast to the Mel1a as reported in mammals. Mel1a immune-positivity was detected in SCN and SON regions of brain. Compared to control birds, a high intensity of Mel1a immunoreactivity was found in hypothalamic regions of birds under short photoperiod (SD, 8h L: 16h D) after Mel treatment. Further, Mel1b immunopositivity was high only in birds exposed to long days (LD, 16h L: 8h D). In SCN, abundant Mel1a and AVT immunoreative cells were found in Mel pretreated and SDexposed birds compared to LD-exposed ones. Mel1a and AVT immunoreative cells were less in PVN of both SD and LD exposed birds. Our data of co-localization of Mel receptor(s) along with AVT in hypothalamic regions (exposed to short or long days with/without melatonin administration) strongly suggest a role for Mel along with AVT in water-electrolyte balance of birds which is important during long duration nuptial migration/flight.
光周期通过视网膜-下丘脑束影响循环褪黑素(Mel)和下丘脑功能。然而,Mel受体与AVT (Arginine vaso催产素,一种水电解质平衡激素受体)在鸟类下丘脑区域的表达之间的相互关系尚未被研究。我们注意到在不同的光周期条件下,日本鹌鹑下丘脑区域两种Mel受体(Mel1a和Mel1b)与AVT在神经元免疫阳性方面的表达模式,有/没有褪黑激素治疗。这很有趣,也同样重要,因为Mel和AVT水平都是由光/暗周期调节的。共聚焦成像显示Mel1a/Mel1b在交叉上核(SCN)、视上核(SON)和室旁核(PVN)中有特定的区域定位,其强度取决于光周期条件(长昼,LD或短昼,SD)和褪黑素治疗。Mel1a/Mel1b多与AVT共定位。Mel1b在下丘脑区域丰富,这与在哺乳动物中报道的Mel1a相反。脑SCN和SON区检测到Mel1a免疫阳性。与对照组相比,Mel处理后短光周期(SD, 8h L: 16h D)下丘脑区域Mel1a免疫反应性较高。此外,Mel1b免疫阳性仅在暴露于长时间(LD, 16小时L: 8小时D)的鸟类中较高。在SCN中,与暴露于LD的鸟类相比,Mel预处理和s暴露的鸟类中发现了丰富的Mel1a和AVT免疫反应细胞。SD和LD暴露的鸟类PVN中Mel1a和AVT免疫反应细胞较少。我们关于Mel受体和AVT在下丘脑区域共定位的数据(暴露于有/没有褪黑激素的短或长时间)强烈表明Mel和AVT在鸟类的水电解质平衡中起着重要作用,这在长时间的婚礼迁徙/飞行中很重要。
{"title":"Comparative Immune-reactivity Patterns of Arginine Vasotocin (AVT) and Melatonin Receptors (Mel1a & Mel1b) in Hypothalamic Regions of Male Japanese Quail Coturnix coturnix japonica : Possible Role in Water-Electrolyte Balance","authors":"C. Haldar, S. Yadav, S. Arora","doi":"10.18311/JER/2021/28023","DOIUrl":"https://doi.org/10.18311/JER/2021/28023","url":null,"abstract":"Photoperiod influences circulatory Melatonin (Mel) and hypothalamic functions via retino-hypothalamic tract. However, interrelation between Mel receptors and Arginine Vasotocin (AVT), a water-electrolyte balancing hormone receptor expression in hypothalamic regions of avian brain has never been explored. We noted the expression pattern of two Mel receptors (Mel1a & Mel1b) along with AVT, in terms of neuronal immuno-positivity, in hypothalamic region of Japanese quail under different photoperiodic conditions with/without melatonin treatment. This is interesting and equally important because both Mel and AVT levels are regulated by light/dark cycle. Confocal imaging revealed specific regional localization of Mel1a/Mel1b in Supra-Chiasmatic Nucleus (SCN), Supra-Optic Nucleus (SON) and Para-Ventricular Nucleus (PVN), the intensity of which was dependent on the photoperiodic condition (long day, LD or short day, SD) and melatonin treatment. Mel1a/Mel1b was mostly co-localized along with AVT. Mel1b was abundant in hypothalamic regions in contrast to the Mel1a as reported in mammals. Mel1a immune-positivity was detected in SCN and SON regions of brain. Compared to control birds, a high intensity of Mel1a immunoreactivity was found in hypothalamic regions of birds under short photoperiod (SD, 8h L: 16h D) after Mel treatment. Further, Mel1b immunopositivity was high only in birds exposed to long days (LD, 16h L: 8h D). In SCN, abundant Mel1a and AVT immunoreative cells were found in Mel pretreated and SDexposed birds compared to LD-exposed ones. Mel1a and AVT immunoreative cells were less in PVN of both SD and LD exposed birds. Our data of co-localization of Mel receptor(s) along with AVT in hypothalamic regions (exposed to short or long days with/without melatonin administration) strongly suggest a role for Mel along with AVT in water-electrolyte balance of birds which is important during long duration nuptial migration/flight.","PeriodicalId":15664,"journal":{"name":"Journal of Endocrinology and Reproduction","volume":"45 1","pages":"51-63"},"PeriodicalIF":0.0,"publicationDate":"2021-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79411845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Female Fertility Clock Closes to Tick around the Age of 43 女性生育时钟在43岁左右停止转动
Pub Date : 2021-07-20 DOI: 10.18311/JER/2021/27816
B. Chakravarty, R. Chattopadhyay, Kuladip Jana, P. Chakraborty
Objective: To investigate if attempting In Vitro Fertilization (IVF) in women over 40 is of worth. Materials & Methods: Two hundred and thirty nine women over 40 years of age undergoing IVF were enrolled. Long protocol was used for downregulation followed by stimulation and IVF-ET. The primary outcome measure was live-birth rate. Secondary outcomes included rates of miscarriage, cycle cancellation, obstetrical complications, and maternal and fetal adverse events. Results: Clinical pregnancy rates per cycle were 42.85 %, 39.34 %, 34.09 %, 27.27 % and 16.66 % for 40, 41, 42, 43 and 44 years old, respectively. Absolute difference in live birth rate in age 40 - 44 vs control, -15 percentage points; 95 % Confidence Interval (CI) -45 to 15.1, -18.77 percentage points; 95 % CI,(-56.31 to 18.79), -23.77 percentage points; 95 % CI,(-71.31 to 23.81), -25.82 percentage points; 95 % CI, (-77.48 to 25.84) and, - 27.72 percentage points; 95 % CI, (-83.16 to 27.76), respectively. Intra-uterine growth restriction and preterm delivery occurred significantly more frequently in the age group of 42 and above. Only one IVF cycle in patients aged 44 resulted in delivery. Conclusion: It appears that IVF treatment should be limited to patients not older than 43 years, with adequate ovarian response.
目的:探讨40岁以上妇女尝试体外受精(IVF)是否值得。材料与方法:纳入239名40岁以上接受体外受精的女性。长期方案用于下调,随后刺激和IVF-ET。主要结局指标为活产率。次要结局包括流产率、周期取消、产科并发症和母婴不良事件。结果:40岁、41岁、42岁、43岁、44岁患者临床单周期妊娠率分别为42.85%、39.34%、34.09%、27.27%、16.66%。40 - 44岁年龄组活产率与对照组的绝对差异为-15个百分点;95%置信区间(CI) -45至15.1,-18.77个百分点;95% CI,(-56.31 ~ 18.79), -23.77个百分点;95% CI,(-71.31 ~ 23.81), -25.82个百分点;95% CI,(-77.48至25.84)和- 27.72个百分点;95% CI分别为(-83.16 ~ 27.76)。子宫内生长受限和早产在42岁及以上年龄组中更为常见。在44岁的患者中,只有一个试管婴儿周期成功分娩。结论:体外受精治疗应局限于年龄不超过43岁,卵巢有足够反应的患者。
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引用次数: 0
Anti-diabetic Activity of Partially Purified Santalin A from the Heartwood of Pterocarpus santalinus L.f. in Alloxan-induced Diabetic Wistar Rat 山菖蒲心材部分纯化Santalin A对四氧嘧啶诱导的糖尿病大鼠的抗糖尿病活性
Pub Date : 2021-07-20 DOI: 10.18311/JER/2021/28024
Jyothi Chaitanya Pagadala, S. Yenugu, Padmaja Gudipalli
The ever-increasing use of plant-based pharmaceuticals as alternatives to conventional drugs for disease management demands identification, isolation, and characterization of novel compounds. Despite the potential of plant extracts to mitigate the morbidity of diseases, several active principles are preferred to avoid the interference of other compounds. The promising health benefits of the extracts and isolated compounds of Pterocarpus santalinus in the treatment of diabetes, cardiovascular disease, cancer, and infections have been described. However, such studies on the active principle, namely, santalins, are not reported. In this study, we standardized the isolation of a mixture of santalins A and B from the heartwood of P. santalinus by column chromatography followed by preparative TLC and HPLC. The partially purified santalins were characterized by LC-MS, HR-MS, and 1 H NMR analyses. The isolated combination of santalins displayed higher total antioxidant and DPPH free radical scavenging activity in vitro than the crude heartwood extracts. Administration of the mixture of santalins A and B did not exhibit any antihyperglycemic activity in the liver, kidney, and pancreas of alloxan-induced diabetic rats. However, pretreatment of rats with a mixture of santalins at a dose of 1.0 mg/kg body weight prevented alloxan-induced diabetes as indicated by the normal blood glucose levels. Hyperglycemia-associated lipid peroxidation was abrogated in santalin-pretreated rats that did not develop alloxan-induced diabetes. Furthermore, the alterations in catalase, glutathione peroxidase, and glutathione-S-transferase activities in the pancreas of santalinpretreated rats could be responsible for preventing damage to the pancreas and thus non-induction of diabetes following alloxan treatment. Therefore, for the first time, we report the simplified procedure for isolating a mixture of santalins, including their ability to prevent the induction of diabetes in Wistar rats. The outcome of our study has significant clinical importance to the fact that supplementation of santalins may potentially avoid or delay the onset of diabetes in high-risk individuals.
越来越多地使用植物性药物作为疾病管理常规药物的替代品,需要对新化合物进行鉴定、分离和表征。尽管植物提取物具有减轻疾病发病率的潜力,但为了避免其他化合物的干扰,一些活性原理是首选的。在治疗糖尿病、心血管疾病、癌症和感染方面,已经描述了翼龙桃的提取物和分离化合物的有希望的健康益处。然而,这种对活性原理,即桑塔林的研究,并没有报道。本研究采用柱层析-制备层析-高效液相色谱法,从桑菖蒲心材中分离纯化桑菖蒲苷a和B。采用LC-MS、HR-MS和1h NMR对部分纯化的唐芦苷进行了表征。与心材粗提物相比,唐缕素组合体外总抗氧化活性和DPPH自由基清除活性更高。在四氧嘧啶诱导的糖尿病大鼠的肝脏、肾脏和胰腺中,桑他林A和B的混合物没有表现出任何降糖活性。然而,预处理大鼠1.0 mg/kg体重的桑他林混合物,可以防止四氧嘧啶诱导的糖尿病,血糖水平正常。在未发生四氧嘧啶诱导的糖尿病的santalin预处理大鼠中,高血糖相关的脂质过氧化被消除。此外,santalin预处理大鼠胰腺中过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽s -转移酶活性的改变可能是防止胰腺损伤的原因,因此不会在四氧嘧啶治疗后诱发糖尿病。因此,我们首次报道了分离santalins混合物的简化程序,包括它们在Wistar大鼠中预防诱导糖尿病的能力。我们的研究结果具有重要的临床意义,即补充桑他林可能潜在地避免或延迟高危人群糖尿病的发病。
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引用次数: 0
Peptidyl Arginine Deiminase 2 (PADI2) is Expressed in Post-Meiotic Germ Cells in the Mouse Testis and is Localized Heavily on the Acrosomal Region of Spermatozoa 肽基精氨酸脱亚胺酶2 (PADI2)在小鼠睾丸减数分裂后生殖细胞中表达,主要定位于精子顶体区域
Pub Date : 2021-07-20 DOI: 10.18311/JER/2021/27986
M. Sahadevan, Pradeep G. Kumar
Peptidyl Arginine Deiminase 2 (PADI2) is a widely expressed Ca 2+ ion-dependent enzyme in rodents and humans belonging to Peptidyl Arginine Deiminases (PAD) family. It regulates various cellular processes like proliferation, differentiation, apoptosis, migration, epithelial-mesenchymal transition and chromatin organization. Altered expression of PADI2 was associated with various autoimmune diseases, neurological disorders and different types of cancers. Based on our previously published miRNA-mRNA network during the first wave of spermatogenesis in the mouse, Padi2 appeared to be a common potential target of miR-34c and miR-449a in the mouse testes. In the present study, the expression of Padi2 in the mouse testes during the first wave of spermatogenesis was evaluated using real-time PCR, western blot analysis and immunohistochemistry. Transcript levels of Padi2 showed progressive down-regulation during the first wave of spermatogenesis. However, we detected a progressive increase in the levels of PADI2 as the first wave of spermatogenesis progressed, with heavy expression of this protein in post-meiotic germ cells. Additionally, a prominent localization of PADI2 in the acrosomal region of late spermatids and spermatozoa was identified through immunohistochemical analysis. Padi2 expression was identified in germ cell-derived cell lines, C18-4 and GC-1 spg as well. Thus, the present study illustrates for the first time the expression of PADI2 in germ cells in the testis and its predominant localization on the acrosome region of spermatozoa, suggesting its potential role in fertilization.
肽基精氨酸脱亚胺酶2 (PADI2)是一种在啮齿动物和人类体内广泛表达的ca2 +离子依赖性酶,属于肽基精氨酸脱亚胺酶(PAD)家族。它调节多种细胞过程,如增殖、分化、凋亡、迁移、上皮-间质转化和染色质组织。PADI2表达的改变与多种自身免疫性疾病、神经系统疾病和不同类型的癌症有关。基于我们之前发表的小鼠精子发生第一波期间的miRNA-mRNA网络,Padi2似乎是小鼠睾丸中miR-34c和miR-449a的共同潜在靶点。本研究采用实时荧光定量PCR、western blot分析和免疫组织化学方法,对第一波精子发生过程中小鼠睾丸中Padi2的表达进行了检测。在精子发生的第一波过程中,Padi2的转录水平呈进行性下调。然而,我们发现随着第一波精子发生的进展,PADI2的水平逐渐增加,在减数分裂后的生殖细胞中大量表达该蛋白。此外,通过免疫组织化学分析,我们发现PADI2在晚期精子和精子的顶体区域有明显的定位。在生殖细胞衍生细胞系C18-4和GC-1 spg中也发现了Padi2的表达。因此,本研究首次阐明了PADI2在睾丸生殖细胞中的表达及其在精子顶体区域的主要定位,提示其在受精中的潜在作用。
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引用次数: 2
Expression of SARS-CoV2 Infectivity Machinery in the Male Reproductive Tract: Possible Outcomes on Fertility SARS-CoV2感染机制在男性生殖道中的表达:对生育能力的可能影响
Pub Date : 2021-06-11 DOI: 10.18311/JER/2020/27709
J. Aisha, A. R. Ravula, M. Mounika, Patra Priyadarshini Priyanka, K. Sangeeta, Munipalli Suresh Babu, S. Yenugu
Emergence of the COVID-19 pandemic continues to rage and rattles the entire world causing multifaceted hardships. Though initially thought to be a disease that primarily affects the lungs, latest evidence suggests its possible Long-term effects on multiple organ systems. SARS-Cov-2, the virus responsible for this disease infects the cells through ACE2 receptor and the serine protease TMPRSS2. In light of the fact that ACE2 expression is very high in the testis and the expression of TMPRSS2 in other reproductive organs, there has been growing interest to determine the effect of SARS-Cov-2 infection on the male reproductive system, especially on fertility. Through bioinformatics analyses, in vitro and cohort studies, the effects on SARS-Cov-2 infection at the molecular to physiological levels are proposed. Perturbations in hormonal levels, damage to the anatomical structure and inflammation in reproductive organs, decline in sperm count and sperm function have been reported. Thus, the significance of COVID-19 on global reproductive health has gained importance. In this article, we summarize the reported facts related to SARS-Cov-2 infectivity on male reproductive system. Such a comprehensive summation herein will help the researchers to have an up to date knowledge in this area of research and to coronavirus newer studies to address the effects of the COVID-19 pandemic on male reproduction, especially fertility.
新冠肺炎疫情持续肆虐,给全球带来了多方面的困难。虽然最初认为这是一种主要影响肺部的疾病,但最新证据表明,它可能对多个器官系统产生长期影响。导致这种疾病的SARS-Cov-2病毒通过ACE2受体和丝氨酸蛋白酶TMPRSS2感染细胞。鉴于ACE2在睾丸中的表达非常高,而TMPRSS2在其他生殖器官中的表达也非常高,因此人们越来越感兴趣确定SARS-Cov-2感染对男性生殖系统,特别是生育能力的影响。通过生物信息学分析、体外和队列研究,提出了从分子到生理水平对SARS-Cov-2感染的影响。据报道,激素水平紊乱,解剖结构损伤和生殖器官炎症,精子数量和精子功能下降。因此,COVID-19对全球生殖健康的重要性日益凸显。本文就SARS-Cov-2感染男性生殖系统的相关报道进行综述。本文的全面总结将有助于研究人员掌握这一研究领域的最新知识,并有助于开展新的冠状病毒研究,以解决COVID-19大流行对男性生殖,特别是生育能力的影响。
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引用次数: 0
Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry: Complementary Approaches to Analyze the Metabolome 核磁共振波谱和质谱:代谢组分析的互补方法
Pub Date : 2021-04-16 DOI: 10.18311/JER/2020/27221
Saleem Yousf, Jeetender Chugh
Over the last decade, the rapid advancement of analytical technologies has made it feasible for researchers to target a wider area of any given biological sample. Metabolomics, an emerging field of scientific research, involves studying the endogenously synthesized small molecules within the biological system. This recently developed ‘omics’ platform has been used for the discovery of disease-specific biomarkers; and for providing deep insights into the etiology and progression of a variety of endocrine disorders, including type 2 diabetes, polycystic ovarian syndrome, Addison’s disease, etc. Nuclear Magnetic Resonance (NMR) spectroscopy and Mass Spectrometry (MS) are the two most powerful and information-rich analytical platforms that have currently been employed in metabolomics studies worldwide. The unique properties of NMR, including a high degree of reproducibility, relative ease of sample preparation, highly quantitative nature, and inherently non-destructive nature, have made it an eminent technique useful in several disciplines of metabolomics. However, a major drawback of this approach is its low sensitivity (≥ 1 μM) when compared with MS. Conversely, MS has the potential to detect the metabolites in the femtomolar to the attomolar range and has a higher resolution (∼10 3 -10 4 ) relative to NMR, but quantification and sample preparation are a little cumbersome. This mini-review discusses the assets and limitations of NMR and MS approaches for metabolomic studies and the latest emerging technological developments that are being used to cope with these limitations in metabolic applications.
在过去的十年里,分析技术的快速发展使得研究人员可以针对任何给定的生物样本进行更广泛的研究。代谢组学是一门新兴的科学研究领域,主要研究生物系统内内源性合成的小分子。这个最近开发的“组学”平台已被用于发现疾病特异性生物标志物;并对多种内分泌疾病的病因和进展提供了深入的见解,包括2型糖尿病、多囊卵巢综合征、艾迪生病等。核磁共振(NMR)光谱和质谱(MS)是目前世界范围内用于代谢组学研究的两个最强大和信息最丰富的分析平台。核磁共振的独特性质,包括高度的可重复性、相对容易的样品制备、高度定量和固有的非破坏性,使其成为代谢组学几个学科中有用的杰出技术。然而,与质谱相比,这种方法的主要缺点是灵敏度低(≥1 μM)。相反,质谱有可能检测飞摩尔到原子摩尔范围内的代谢物,并且相对于核磁共振具有更高的分辨率(~ 10 3 -10 4),但定量和样品制备有点麻烦。这篇小综述讨论了核磁共振和质谱方法在代谢组学研究中的优点和局限性,以及用于应对代谢应用中这些局限性的最新新兴技术发展。
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引用次数: 1
期刊
Journal of Endocrinology and Reproduction
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