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Emphasizing the Role of Multi-omics Approach to Increase Survival Rate of Breast and Prostate Cancer Patients 强调多组学方法在提高乳腺癌和前列腺癌患者生存率中的作用
Pub Date : 2023-09-12 DOI: 10.18311/jer/2023/34985
Khushali Upadhyay, Foram Patel, Yashshvini Patel, A. V. Ramachandran, Darshee Baxi
The understanding of cancer biology has greatly advanced since the advent of genomics. A remarkable heterogeneity at the whole-genome (or omics) level exists amongst even histologically comparable cancers, demonstrating the enormous complexity of the cancer genome. A powerful resource that has the potential to translate high-throughput omics to better and quick overall survival is the massive accrual and public accessibility of multi-omics databases with accompanying clinical annotation, including tumor histology, patient response, and outcome. In this new era of high-throughput omics, this paper emphasizes the distinct benefits of a multidimensional approach to genomic analysis. It discusses the implications of translational omics research for the cancer population. Single-level data analysis of high-throughput technologies has constraints because it only displays a small window of cellular processes. Understanding the links across several cellular organization levels made possible by data integration across various platforms, including genomes, epigenomics, transcriptomics, proteomics, and metabolomics, is important. This review examines a few popular frameworks for integrating multi-omics data. It provides a general overview of multi-omics applications in tumor classification, prognosis, diagnostics, and the function of data integration in searching for novel biomarkers and treatment options.
自从基因组学出现以来,对癌症生物学的理解已经有了很大的进步。即使在组织学上具有可比性的癌症中,也存在着全基因组(或组学)水平上的显著异质性,这表明了癌症基因组的巨大复杂性。一个有潜力将高通量组学转化为更好和更快的总体生存的强大资源是多组学数据库的大量累积和公共可访问性,附带临床注释,包括肿瘤组织学,患者反应和结果。在这个高通量组学的新时代,本文强调了多维基因组分析方法的独特好处。它讨论了翻译组学研究对癌症人群的影响。高通量技术的单级数据分析具有局限性,因为它只显示细胞过程的一个小窗口。通过不同平台(包括基因组、表观基因组学、转录组学、蛋白质组学和代谢组学)的数据集成,了解多个细胞组织水平之间的联系是很重要的。本文综述了几种流行的集成多组学数据的框架。它概述了多组学在肿瘤分类、预后、诊断方面的应用,以及在寻找新的生物标志物和治疗方案方面的数据集成功能。
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引用次数: 0
Perspectives of PCOS Pathophysiology: Exploring the Interplay between PCOS and the Gut Microbiota 多囊卵巢综合征病理生理学的观点:探索多囊卵巢综合征与肠道微生物群之间的相互作用
Pub Date : 2023-09-12 DOI: 10.18311/jer/2023/34986
Komal Khade, Roshan Dadachanji, Srabani Mukherjee
PCOS is a gynecological and metabolic concern for numerous women of reproductive age. Its pathophysiology broadly entails hyperandrogenism, insulin resistance, and neuroendocrine dysfunction, and is heavily influenced by genetic and epigenetic factors. However, its precise aetiology remains unclear. The gut microbiome is a major endocrine organ and plays a key role in host metabolism through its metabolites which regulate diverse host physiology like metabolism, immunity, etc. Numerous studies have described associations of altered microbiota in the progress and development of major human diseases. The studies conducted on animals and humans have suggested that the gut microbiota and its metabolites are involved in the pathogenesis of PCOS and its associated attributes such as insulin resistance, obesity and inflammation. Moreover, supplementation of probiotics/prebiotics has been reported to relieve the adverse metabolic and hormonal parameters effectively. Knowledge of this link between gut dysbiosis and PCOS has also spurred research interest in exploring novel management of PCOS. In this review, we have discussed the role of gut microbiota dysbiosis and its metabolite in the progression and treatment of PCOS.
多囊卵巢综合征是许多育龄妇女的妇科和代谢问题。其病理生理学广泛涉及高雄激素、胰岛素抵抗和神经内分泌功能障碍,并受遗传和表观遗传因素的严重影响。然而,其确切的病因尚不清楚。肠道微生物群是一种重要的内分泌器官,通过代谢产物调节宿主代谢、免疫等多种生理机能,在宿主代谢中起着关键作用。许多研究已经描述了在人类主要疾病的进展和发展中改变的微生物群的关联。对动物和人类的研究表明,肠道微生物群及其代谢物参与了多囊卵巢综合征的发病机制及其相关特征,如胰岛素抵抗、肥胖和炎症。此外,据报道,补充益生菌/益生元可以有效缓解不良的代谢和激素参数。肠道生态失调与多囊卵巢综合征之间的联系也激发了探索多囊卵巢综合征新治疗方法的研究兴趣。在这篇综述中,我们讨论了肠道菌群失调及其代谢物在多囊卵巢综合征的进展和治疗中的作用。
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引用次数: 0
Menthol Attenuates Cholinergic Dysfunction and Neurotransmitter Imbalance in Experimental Diabetes 薄荷醇减轻实验性糖尿病胆碱能功能障碍和神经递质失衡
Pub Date : 2023-08-17 DOI: 10.18311/jer/2023/32989
S. Soumya, S. Mini
One of the most predominant enduring consequences of Diabetes Mellitus (DM) is Diabetic Encephalopathy (DE), which has neither a reliable treatment nor an effective preventive strategy. Cognitive dysfunction is the primary problem allied with DE. The current inquiry aims to determine the potency of menthol in reducing the risk of brain complications induced by Streptozotocin (STZ) in diabetic rats. A single STZ intraperitoneal injection (40 mg/kg body weight) was employed to induce DM in Sprague-Dawley male rats and animals were held without treatment for 30 days to develop DE. The Morris water maze test, followed by the supplementation of menthol and metformin for 60 days at 50 and 100 mg/kg body weight dosages, verified the cognitive deficit in diabetic rats. After 60 days of therapy, rats were sacrificed to obtain blood and brain tissues for biochemical investigation. Oral delivery of menthol enhanced cognitive function in DE rats. Furthermore, menthol markedly reduced fasting blood sugar, glycosylated Hemoglobin (HbA1c), and elevated plasma insulin levels. In the brain, menthol increases neurotransmitter levels and choline acetyltransferase activity while decreasing AChE activity. Menthol also downregulated the expressions of monoamine oxidase A and B. Thus, the study indicates that menthol was effective in attenuating the neurodegenerative alterations in DE rats. It had a therapeutic potential and could be effectively utilized as a dietary supplement for regulating complications associated with encephalopathy.
糖尿病(DM)最主要的持久后果之一是糖尿病性脑病(DE),既没有可靠的治疗方法,也没有有效的预防策略。认知功能障碍是与DE相关的主要问题。目前的研究旨在确定薄荷醇在降低糖尿病大鼠链脲佐菌素(STZ)诱导的脑并发症风险方面的效力。采用STZ单次腹腔注射(40 mg/kg体重)诱导Sprague-Dawley雄性大鼠发生DM,不给药30 d。Morris水迷宫实验后,以50和100 mg/kg体重剂量补充薄荷醇和二甲双胍60 d,证实糖尿病大鼠认知功能障碍。治疗60天后,处死大鼠取血、脑组织进行生化研究。口服薄荷醇可增强DE大鼠的认知功能。此外,薄荷醇显著降低空腹血糖、糖化血红蛋白(HbA1c)和血浆胰岛素水平升高。在大脑中,薄荷醇增加神经递质水平和胆碱乙酰转移酶活性,同时降低乙酰胆碱酯交换酶活性。薄荷醇还能下调单胺氧化酶A和单胺氧化酶b的表达,提示薄荷醇对DE大鼠神经退行性改变有一定的减轻作用。它具有治疗潜力,可以有效地作为一种膳食补充剂来调节脑病相关的并发症。
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引用次数: 0
The Effect of Methallibure (ICI Compound 33, 828) on Folliculogenesis and Steroidogenic Potential of Developing Ovary in the Lizard, Calotes versicolor (Daud.) 甲基甲醚(ICI化合物33,828)对花斑壁虎卵巢卵泡发生和甾体潜能的影响
Pub Date : 2023-08-17 DOI: 10.18311/jer/2023/34311
B. Y. Gouder, Rahul M. Handi, V. Vani, Gopal M. Advi Rao, Laxmi S. Inamdar (Doddamani)
In vertebrates, it is well established that gonadotropins are crucial for vertebrate ovarian development and its endocrine functions. The current investigation envisages determining how methallibure affects the histoanatomical structure and steroidogenic capacity of the developing ovary of 10-day-old female hatchlings of Calotes versicolor. The eggs were collected from gravid females during the breeding season and incubated at a female-producing temperature of 31.5±0.5 oC till hatching. Hatchlings were fed with live termites. Intraperitoneal injections of 6μg of methallibure in 0.05ml of 0.7% saline were injected into 10-day-old female hatchlings on alternate days for 21 days. The appropriate saline-treated hatchlings served as control. The results reveal that methallibure significantly reduces the number of oocytes (P<0.02) and primordial follicles, decreases their diameter, and increases the number of previtellogenic atretic follicles (P<0.001) with concomitant suppression of the progression of ovarian development when compared with that of baseline control. Three types of atretic follicles were noticed. The histoenzymatic activity of Δ5-3β-hydroxysteroid dehydrogenase in the ooplasm of the follicle and the stromal region showed a decreased intensity. The downregulation of steroidogenesis is probably due to the deprived secretion of gonadal steroids which disturbs the negative feedback mechanism because of the action of the drug at the hypothalamic-hypophyseal-ovarian axis. The present study unveils that methallibure acts as an antigonadotrophic drug altering the synthesis/secretion of gonadotrophin by hypophysis. It is inferred that methallibure induces an anti-gonadotropic effect in the newly hatched hatchlings probably by quenching the pituitary gonadotropins.
在脊椎动物中,促性腺激素在脊椎动物卵巢发育及其内分泌功能中起着至关重要的作用。目前的研究设想确定甲基化是如何影响10日龄雌性花斑斑蝶幼雏发育中的卵巢的组织解剖结构和类固醇生成能力的。在繁殖季节从怀孕的雌虫身上采集卵,在31.5±0.5℃的产卵温度下孵育直至孵化。用活白蚁喂养幼仔。10日龄雌雏鸟腹腔注射甲醇6μg,加入0.05ml 0.7%生理盐水,隔日注射,连续注射21 d。用适当的盐水处理过的幼龟作为对照。结果显示,与基线对照组相比,甲基沙脲显著减少卵母细胞数量(P<0.02)和原始卵泡数量(P<0.001),降低原始卵泡直径,增加卵泡前闭锁卵泡数量(P<0.001),同时抑制卵巢发育进程。发现三种类型的闭锁卵泡。卵泡卵浆及间质区Δ5-3β-hydroxysteroid脱氢酶组织酶活性降低。激素生成下调可能是由于性腺激素分泌被剥夺,药物作用于下丘脑-垂体-卵巢轴,扰乱了负反馈机制。本研究揭示了甲基甲醚作为一种抗促性腺激素药物改变垂体促性腺激素的合成和分泌。推测甲基甲醚可能通过抑制垂体促性腺激素而对初生雏鸟产生抗促性腺激素作用。
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引用次数: 0
Maternal Di-(2-Ethylhexyl) Phthalate (DEHP) Exposure Impairs Insulin Signal in the Liver and Gastrocnemius Muscles of Female Offspring Rats 母体暴露于二-(2-乙基己基)邻苯二甲酸酯(DEHP)对雌性后代大鼠肝脏和腓肠肌胰岛素信号的影响
Pub Date : 2023-08-17 DOI: 10.18311/jer/2023/32523
Divyaa Srinivasan, Gokulapriya Rajagopal, Balasubramanian Karundevi, Kamakshi Arjunan Leela, R. S. Bhaskaran
Di-(2-Ethylhexyl) Phthalate (DEHP) is a potent endocrine disruptor that is commonly present in consumer products and cosmetics. Exposure to DEHP during gestational and lactational periods can adversely affect glucoregulation and lead to the onset of diabetes in progeny. The liver and gastrocnemius muscles play an important role in regulating glucose metabolism and insulin action. This study was designed to investigate the effect of maternal DEHP exposure on insulin signaling molecules in the liver and gastrocnemius muscles of adult female offspring rats. Rat dams were given DEHP (10 and 100 mg/kg b.wt./day) by oral gavage from gestation day 9 (GD 9) to the end of the lactation period Postnatal Day (PND) 21. On PND 80, female offspring rats in diestrus were euthanized and found reduced body weight, organ (liver and gastrocnemius) weight, and hyperglycemia in DEHP-exposed rats. Western blots revealed a dose-dependent reduction in the expression of Insulin Receptor - (IR), IRS, Akt, and GSK-3β proteins as well as their phosphorylated forms in the liver and gastrocnemius muscles of DEHP-exposed offspring rats. Maternal DEHP exposure reduced the levels of GLUT2 and GLUT4 level in the liver and gastrocnemius muscles, respectively. Liver and renal function markers were dose-dependently increased in the serum of offspring female rats born to DEHP exposed mother during gestation and lactation. Thus, the study revealed that maternal DEHP exposure impaired the expression of insulin signaling molecules in the two important tissues involved in glucose metabolism, the liver and gastrocnemius muscles, suggesting that phthalates exposure during development may contribute to the onset of diabetes in female offspring.
邻苯二甲酸二(2-乙基己基)酯(DEHP)是一种强效的内分泌干扰物,通常存在于消费品和化妆品中。妊娠期和哺乳期暴露于DEHP可对血糖调节产生不利影响,并导致后代发生糖尿病。肝脏和腓肠肌在调节葡萄糖代谢和胰岛素作用中起重要作用。本研究旨在探讨母体DEHP暴露对成年雌性子代大鼠肝脏和腓肠肌胰岛素信号分子的影响。从妊娠第9天(GD 9)至产后第21天(PND 21)哺乳期结束,分别给予DEHP(10和100 mg/kg b.w.t. /天)灌胃。在PND 80中,对雌鼠仔鼠实施安乐死,发现dehp暴露大鼠体重减轻,器官(肝脏和腓肠肌)重量减轻,血糖升高。Western blot结果显示,暴露dehp的后代大鼠肝脏和腓肠肌中胰岛素受体- (IR)、IRS、Akt和GSK-3β蛋白及其磷酸化形式的表达呈剂量依赖性降低。母体DEHP暴露分别降低肝脏和腓肠肌中GLUT2和GLUT4水平。妊娠期和哺乳期DEHP暴露母鼠所生子代大鼠血清中肝肾功能指标呈剂量依赖性升高。因此,本研究揭示母体暴露于DEHP会损害参与葡萄糖代谢的两个重要组织——肝脏和腓肠肌中胰岛素信号分子的表达,提示发育过程中暴露于邻苯二甲酸盐可能导致雌性后代发生糖尿病。
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引用次数: 0
A Crosstalk Between Pineal and Major Extra-Pineal Sources of Melatonin and its Role in Ovarian Growth and Maturation in Fish 松果体和主要松果体外褪黑素来源的串扰及其在鱼类卵巢生长和成熟中的作用
Pub Date : 2023-08-17 DOI: 10.18311/jer/2023/33014
Sona Sutradhar, Farha Yasmin, A. Roy, Russel Sarkar, S. Mukherjee
Pinealocytes of the pineal gland in vertebrates mainly synthesize melatonin (5-methoxy-N-acetyl-tryptamine). Moreover, melatonin is synthesized in several extra-pineal cells, including the photoreceptor cells of the retina, the cells of the gut, and the hepatocytes of the liver in different vertebrates, including fish species. One of the remarkable features of pineal and retinal melatonin is that it is produced rhythmically in synchronization with the environmental Light-Dark (LD) cycle, with a daily nighttime peak. However, the melatonin synthesis in tissue/cells from the extra-pineal and extra-retinal origin(s) may not always undergo photoperiod-regulated daily variations but is also dependent on the environmental food entrainment factors (in the gut), acting as the most reliable synchronizer(s) in its daily rhythm features. Moreover, the regulation of the liver and ovary (important for fish reproduction) is unclear. In this review, we attempt a comparative account of the nature and regulation of endogenous melatonin synthesis between a source like the pineal gland and many other nonpineal origins, which have gained serious attention in the last ten years. We also review the functions of melatonin in regulating fish ovarian growth and maturation. The physiological melatonin levels, manipulated either endogenously (by photoperiodic modulations) or exogenously (by injections or by feeds), have tremendous effects on reproductive events in fish at the age of its first maturity, as revealed in recent findings. Characterization and identification of the importance of pineal gland melatonin in the growth of the oocytes via the hypothalamic-pituitary-gonadal axis have been explored several years back. The identification of melatonin receptors about fourteen years back on the wall of developing oocyte spurt the breakthrough, which introduced the concept of direct control of melatonin on developing oocytes. Thus, this review gains uniqueness by addressing the latest developments recorded in the field of melatonin and fish reproduction, particularly in improving oocyte maturation. Nonetheless, an attempt has been made to underline approaches that need to be developed to apply the molecule in large-scale aquaculture.
脊椎动物松果体的松果体细胞主要合成褪黑素(5-甲氧基- n -乙酰基-色胺)。此外,褪黑素在几种松果体外细胞中合成,包括视网膜的感光细胞、肠道细胞和不同脊椎动物(包括鱼类)的肝脏肝细胞。松果体和视网膜褪黑素的一个显著特征是,它的产生与环境的光-暗(LD)周期有节律性同步,每天夜间达到峰值。然而,来自松果体外和视网膜外来源的组织/细胞中的褪黑激素合成可能并不总是经历光周期调节的日常变化,但也依赖于环境食物干扰因素(在肠道中),在其日常节律特征中充当最可靠的同步器。此外,对肝脏和卵巢(对鱼类繁殖很重要)的调节尚不清楚。在这篇综述中,我们试图比较松果体和许多其他非松果体来源的内源性褪黑激素合成的性质和调控,这在过去的十年中得到了严重的关注。本文还对褪黑素在调节鱼类卵巢生长和成熟中的作用进行了综述。最近的研究表明,生理褪黑素水平,无论是内源性(通过光周期调节)还是外源性(通过注射或饲料),都对鱼类首次成熟时的生殖事件产生巨大影响。松果体褪黑素通过下丘脑-垂体-性腺轴在卵母细胞生长中的重要性的表征和鉴定已经在几年前进行了探索。大约14年前,在发育中的卵母细胞壁上发现褪黑激素受体,这一突破引入了褪黑激素直接控制发育中的卵母细胞的概念。因此,本文对褪黑素与鱼类生殖,特别是促进卵母细胞成熟的最新研究进展进行了综述。尽管如此,人们还是试图强调需要开发的方法,以便将这种分子应用于大规模水产养殖。
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引用次数: 0
Glucocorticoid-Induced Dose-Dependent Reproductive Impairments in Male Albino Rat 糖皮质激素诱导的雄性白化大鼠剂量依赖性生殖损伤
Pub Date : 2023-08-17 DOI: 10.18311/jer/2023/34312
Sunita Patel, S. Rai
The present study is aimed at elucidating the effect of different doses of Dexamethasone (DEX) on testis and epididymis of male Wistar rats. Thirty-six rats were divided into six groups, each containing six rats: one control (CON), and five groups of rats treated with five (30 μg, 40 μg, 50 μg, 60 μg, 70 μg/100 g body weight) doses of dexamethasone intraperitoneally (i.p.) for twenty-one days. The results revealed a dose-dependent decrease in testes and epididymis weight. DEX-treated rats evidenced significant increase in TBARS levels, this being the highest in 70 μg/100 g body weight (bw) which could be a consequence of the highest level of free radical generation. The activity level of antioxidative enzymes Superoxide Dismutase (SOD), Catalase (CAT), Glutathione (GSH), and protein content significantly declined in dexamethasone-treated rats in a dose-dependent manner. Histological observation revealed different degrees of germ cell degeneration/alterations in testis and epididymis The present finding suggests that exposure to dexamethasone (70 μg/100 g bw) can potentially lead to severe impairments in male reproductive tissues (testis and epididymis) structure and function, which may consequently lead to male infertility.
本研究旨在探讨不同剂量地塞米松对雄性Wistar大鼠睾丸和附睾的影响。36只大鼠分为6组,每组6只:对照组1只(CON), 5组大鼠分别腹腔注射5种剂量(30、40、50、60、70 μg/100 g体重)地塞米松21 d。结果显示睾丸和附睾重量呈剂量依赖性下降。dex处理大鼠的TBARS水平显著增加,在70 μg/100 g体重(bw)时最高,这可能是自由基生成水平最高的结果。地塞米松处理大鼠抗氧化酶超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽(GSH)活性水平和蛋白质含量呈剂量依赖性显著下降。本研究提示,地塞米松暴露(70 μg/100 g bw)可能导致男性生殖组织(睾丸和附睾)结构和功能的严重损伤,从而导致男性不育。
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引用次数: 0
Sexual Biology and Mating Behaviour in Decapod Crustaceans: A Case Study with Coral Reef Dwelling Caridean Shrimps 十足甲壳类动物的性生物学和交配行为:以珊瑚礁栖虾为例
Pub Date : 2023-05-19 DOI: 10.18311/jer/2023/31247
T. Subramoniam
Crustaceans have diversified sexual systems, incorporating various reproductive modalities such as gonochorism and a wide variety of hermaphroditism. In particular, the coral reef- dwelling caridean shrimps, living in symbiosis with other marine invertebrates, have developed unusual sexual systems that have given origin to a range of social systems, including the highly advanced eusociality. Protandric hermaphroditism, common among the caridean shrimps, has also reached a unique sexual condition, known as protandric simultaneous hermaphroditism, in the genus, Lysmata. Similarly, mating systems in the caridean shrimps are highly diverse and divergent. In addition, their occurrence in the coral reef shrimps is correlated to their life style adaptations such as their commensal association with other invertebrates. Other ecological factors like the predation risk from outside of the host animals and differences in the host characteristics may also be the driving forces in determining mating associations. Furthermore, the transition from sexual monogamy to social monogamy under conditions of their symbiotic life led to complex community living in several synalpheid shrimps. Understandably, the existence of various sexual and mating systems in these caridean shrimps has a dependence on the eco- social conditions prevalent in the coral reef biota.
甲壳类动物具有多样化的性系统,包括各种生殖方式,如雌雄同体和各种各样的雌雄同体。特别是与其他海洋无脊椎动物共生的生活在珊瑚礁上的栉齿虾,已经发展出了不同寻常的性系统,从而产生了一系列社会系统,包括高度发达的群居性。原雄蕊雌雄同体在caridean虾中很常见,在Lysmata属中也达到了一种独特的性条件,称为原雄蕊同时雌雄同体。同样,caridean虾的交配系统也是高度多样化和分化的。此外,它们在珊瑚礁虾中的出现与它们的生活方式适应有关,例如它们与其他无脊椎动物的共生关系。其他生态因素,如来自宿主动物外部的捕食风险和宿主特征的差异,也可能是决定交配关联的驱动力。此外,在共生生活条件下,从性一夫一妻制向社会性一夫一妻制的转变导致了多对虾复杂的群落生活。可以理解的是,这些鲤鱼虾的各种性和交配系统的存在依赖于珊瑚礁生物群中普遍存在的生态社会条件。
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引用次数: 0
Epididymis of the Lizard Eutropis carinata: A Light Microscopic and Ultrastructural Seasonal Study 棘尾蜥蜴附睾:光镜和超微结构的季节性研究
Pub Date : 2023-05-16 DOI: 10.18311/jer/2023/31257
Ivan Aranha, M. Bhagya, B. Sagar
The epididymis of the lizard Eutropis carinata can be divided into four regions viz., an initial segment (extra testicular) Efferent ductules (Eds) and three regions, the anterior region, a broad middle, and a narrow posterior, comparable to the caput, corpus, and cauda epididymidis of mammals. The anterior region of the epididymis is closely associated with a whitish initial segment (extra testicular), the Efferent ductules (Eds). The epididymal wall consists of an epithelial layer lining the lumen resting on a basement membrane surrounded by four to five layers of smooth circular muscles, a layer of connective tissue, and a layer of serosa. The ultrastructure study of the initial segment of epididymis the Eds during breeding season discloses four cell types in its epithelium viz., ciliated, non-ciliated, Apical-Mitochondria Rich Cells (AMRC), and basal cells. The anterior, middle, and posterior regions of the epididymis show five different cell types namely principal, basal, AMRC, narrow, and clear cells. Ciliated and non-ciliated cells are limited to the initial segment of the epididymis while, principal, narrow, and clear cells are found in the rest of the three regions of the epididymis. Basal and AMRC are found in all four regions. AMRCs are the most abundant cell type in the initial segment while principal cells are the major components of the epithelial lining of the remaining regions of the epididymis. During the non-breeding season, all the cell types are present but with regression and altered cytology of the cells without any sign of cellular activity in the different regions of the epididymis. During the breeding season, even the circulating testosterone levels are significantly higher compared to the non-breeding season. This is the first report describing different cell types in the initial segment and three different regions of the epididymis with ultrastructural seasonal variations in the Keeled Indian Mabuya, Eutropis carinata (Scincidae).
蜥蜴的附睾可分为四个区域,即初始段(睾丸外)传出小管(ed)和三个区域,即前区、宽中部和窄后部,可与哺乳动物的附睾头、体和尾相媲美。附睾的前部与白色的初始部分(睾丸外),传出小管(ed)密切相关。附睾壁由一层上皮组成,该上皮位于基底膜上,由四到五层光滑的圆形肌肉、一层结缔组织和一层浆膜包围。对繁殖期附睾起始段的超微结构进行了研究,发现其上皮细胞有纤毛细胞、非纤毛细胞、顶端富线粒体细胞(AMRC)和基底细胞四种类型。附睾的前、中、后区域显示五种不同的细胞类型,即主细胞、基底细胞、AMRC细胞、窄细胞和透明细胞。纤毛细胞和非纤毛细胞局限于附睾的起始部分,而主要的、狭窄的和透明的细胞则存在于附睾的其余三个区域。在所有四个区域均发现基底和AMRC。amrc是初始段中最丰富的细胞类型,而主细胞是附睾其余区域上皮衬里的主要成分。在非繁殖季节,所有类型的细胞都存在,但细胞的退化和细胞学改变,在附睾的不同区域没有任何细胞活动的迹象。在繁殖季节,甚至循环睾酮水平也明显高于非繁殖季节。本文首次报道了龙骨印度马布雅(龙骨印度马布雅)附睾初始节和三个不同区域的细胞类型及其超微结构的季节性变化。
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引用次数: 0
Inhibition of Cholesterol Biosynthesis Modulates Epithelial-Mesenchymal Transition in Primary Cicatricial Alopecia Through TGFβ and Angiotensin Receptors 抑制胆固醇生物合成通过TGFβ和血管紧张素受体调节原发性瘢痕性脱发的上皮-间质转化
Pub Date : 2023-05-12 DOI: 10.18311/jer/2023/33509
Leemon Nikhila, Suresh Surya, Shahul Hameed Najeeb, T. M. Binumon, P. P. Sreejith
Introduction: Primary Cicatricial Alopecia (PCA) is an autoimmune condition that affects the skin and causes hair loss in patients. In PCA the hair follicles of the patients are irreversibly damaged and replaced with fibrous tissue. This diseased condition lends relevance to our work since the fibrosis raises the potential that PCA may be affected in some way by the Epithelial Mesenchymal Transition (EMT). We used small interfering RNAs (siRNA) of TGFβ, AGTR and their regulators to identify the EMT modulation. Because these molecules mediate the induction of EMT. This study explores the idea of lowering PCA fibrosis by modifying EMT markers. Methods: We chose 7 DHC and BM15766 to investigate the function of cholesterol biosynthesis inhibition. We employed the HFORS in vitro and the mouse in vivo model system to examine EMT regulation PCA. Quantitative real-time PCR was utilised to examine the expression of genes in PCA scalp samples, compound-treated HFORS, and mouse tissues; immunohistochemistry was used to confirm the protein estimate in the scalp samples; and small interfering RNA (siRNA) transfection was used to identify the functional analysis of TGFβ and AGTR. Results: Reduced cholesterol production in PCA patients leads to permanent hair follicle damage. The in vitro and in vivo study using 7DHC and BM15766 revealed cells were positive for the EMT markers. PPARγ, AhR, and AGTR together can act as vital EMT regulators. As a result, the PPARγ agonist, AhR, and AGTR antagonist significantly downregulate the expression of CDH1, SNAIL1, and SMA. The markers of EMT are likewise deregulated by the transfection of siRNA for TGFβ and AGTR. Conclusion: We clarify how EMT is regulated in hair loss circumstances by suppressing cholesterol biosynthesis. We further confirm that EMT modulators (PPARγ, AhR, AGTR, and TGFβ) and siRNA can be employed as potentially effective strategies to slow the advancement of EMT. As a result, we propose these cholesterol and EMT modulators as potential inhibitors in PCA etiology.
简介:原发性瘢痕性脱发(PCA)是一种影响皮肤并导致患者脱发的自身免疫性疾病。在PCA中,患者的毛囊不可逆转地受损并被纤维组织所取代。这种疾病与我们的工作相关,因为纤维化增加了PCA可能在某种程度上受到上皮间充质转化(EMT)影响的可能性。我们使用TGFβ, AGTR及其调节因子的小干扰rna (siRNA)来鉴定EMT调制。因为这些分子介导了EMT的诱导。本研究探讨了通过修改EMT标记物来降低PCA纤维化的想法。方法:选择7 DHC和BM15766,研究其抑制胆固醇生物合成的功能。我们采用体外HFORS和小鼠体内模型系统检测EMT调控PCA。采用实时荧光定量PCR检测PCA头皮样品、复合处理HFORS和小鼠组织中基因的表达;采用免疫组化方法对头皮样品进行蛋白估计;采用小干扰RNA (siRNA)转染对TGFβ和AGTR进行功能鉴定分析。结果:PCA患者胆固醇含量降低导致永久性毛囊损伤。用7DHC和BM15766进行体外和体内研究,发现细胞对EMT标志物呈阳性。PPARγ、AhR和AGTR一起可以作为重要的EMT调节因子。结果,PPARγ激动剂、AhR和AGTR拮抗剂显著下调CDH1、SNAIL1和SMA的表达。EMT的标记物同样通过转染TGFβ和AGTR的siRNA而解除调控。结论:我们阐明了EMT是如何通过抑制胆固醇生物合成来调节脱发的。我们进一步证实,EMT调节剂(PPARγ、AhR、AGTR和TGFβ)和siRNA可以作为减缓EMT进展的潜在有效策略。因此,我们提出这些胆固醇和EMT调节剂作为PCA病因学的潜在抑制剂。
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引用次数: 0
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Journal of Endocrinology and Reproduction
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