scholarly journals Integrated Pharmacogenetics Analysis of the Three Fangjis Decoctions for Treating Arrhythmias Based on Molecular Network Patterns

2021 ◽  
Vol 8 ◽  
Author(s):  
Penglu Wei ◽  
Dehuai Long ◽  
Yupei Tan ◽  
Wenlong Xing ◽  
Xiang Li ◽  
...  

Aim: To explore the diverse target distribution and variable mechanisms of different fangjis prescriptions when treating arrhythmias based on the systems pharmacology.Methods: The active ingredients and their corresponding targets were acquired from the three fangjis [Zhigancao Tang (ZT), Guizhigancao Longgumuli Tang (GLT), and Huanglian E'jiao Tang (HET)] and the arrhythmia-related genes were identified based on comprehensive database screening. Networks were constructed between the fangjis and arrhythmia and used to define arrhythmia modules. Common and differential gene targets were identified within the arrhythmia network modules and the cover rate (CR) matrix was applied to compare the contributions of the fangjis to the network and modules. Comparative pharmacogenetics analyses were then conducted to define the arrhythmia-related signaling pathways regulated by the fangjis prescriptions. Finally, the divergence and convergence points of the arrhythmia pathways were deciphered based on databases and the published literature.Results: A total of 187, 105, and 68 active ingredients and 1,139, 1,195, and 811 corresponding gene targets of the three fangjis were obtained and 102 arrhythmia-related genes were acquired. An arrhythmia network was constructed and subdivided into 4 modules. For the target distribution analysis, 65.4% of genes were regulated by the three fangjis within the arrhythmia network. ZT and GLT were more similar to each other, mainly regulated by module two, whereas HET was divided among all the modules. From the perspective of signal transduction, calcium-related pathways [calcium, cyclic guanosine 3′,5′-monophosphate (cGMP)-PKG, and cyclic adenosine 3′,5′-monophosphate (cAMP)] and endocrine system-related pathways (oxytocin signaling pathway and renin secretion pathways) were associated with all the three fangjis prescriptions. Nevertheless, heterogeneity existed between the biological processes and pathway distribution among the three prescriptions. GLT and HET were particularly inclined toward the conditions involving abnormal hormone secretion, whereas ZT tended toward renin-angiotensin-aldosterone system (RAAS) disorders. However, calcium signaling-related pathways prominently feature in the pharmacological activities of the decoctions. Experimental validation indicated that ZT, GLT, and HET significantly shortened the duration of ventricular arrhythmia (VA) and downregulated the expression of CALM2 and interleukin-6 (IL-6) messenger RNAs (mRNAs); GLT and HET downregulated the expression of CALM1 and NOS3 mRNAs; HET downregulated the expression of CRP mRNA.Conclusion: Comparing the various distributions of the three fangjis, pathways provide evidence with respect to precise applications toward individualized arrhythmia treatments.

2021 ◽  
Vol 12 ◽  
Author(s):  
Lingyu Cui ◽  
Bo Wang ◽  
Changjing Ren ◽  
Ailan Wang ◽  
Hong An ◽  
...  

Single-cell sequencing technology can not only view the heterogeneity of cells from a molecular perspective, but also discover new cell types. Although there are many effective methods on dropout imputation, cell clustering, and lineage reconstruction based on single cell RNA sequencing (RNA-seq) data, there is no systemic pipeline on how to compare two single cell clusters at the molecular level. In the study, we present a novel pipeline on comparing two single cell clusters, including calling differential gene expression, coexpression network modules, and so on. The pipeline could reveal mechanisms behind the biological difference between cell clusters and cell types, and identify cell type specific molecular mechanisms. We applied the pipeline to two famous single-cell databases, Usoskin from mouse brain and Xin from human pancreas, which contained 622 and 1,600 cells, respectively, both of which were composed of four types of cells. As a result, we identified many significant differential genes, differential gene coexpression and network modules among the cell clusters, which confirmed that different cell clusters might perform different functions.


Author(s):  
John Newell-Price ◽  
Alia Munir ◽  
Miguel Debono

Endocrinology is the study of hormones (and their glands of origin), their receptors, the intracellular signalling pathways they invoke, and their associated diseases. The clinical specialty of endocrinology focuses specifically on the endocrine organs, that is, the organs whose primary function is hormone secretion, including the hypothalamus, the pituitary, the thyroid, the parathyroid, the adrenal glands, the pancreas, and the reproductive organs.


Author(s):  
Maha Sellami ◽  
Nicola Luigi Bragazzi ◽  
Maamer Slimani ◽  
Lawrence Hayes ◽  
Georges Jabbour ◽  
...  

Hormones are secreted in a circadian rhythm, but also follow larger-scale timetables, such as monthly (hormones of the menstrual cycle), seasonal (i.e., winter, summer), and, ultimately, lifespan-related patterns. Several contexts modulate their secretion, such as genetics, lifestyle, environment, diet, and exercise. They play significant roles in human physiology, influencing growth of muscle, bone, and regulating metabolism. Exercise training alters hormone secretion, depending on the frequency, duration, intensity, and mode of training which has an impact on the magnitude of the secretion. However, there remains ambiguity over the effects of exercise training on certain hormones such as glucoregulatory hormones in aging adults. With advancing age, there are many alterations with the endocrine system, which may ultimately alter human physiology. Some recent studies have reported an anti-aging effect of exercise training on the endocrine system and especially cortisol, growth hormone and insulin. As such, this review examines the effects of endurance, interval, resistance and combined training on hormones (i.e., at rest and after) exercise in older individuals. We summarize the influence of age on glucoregulatory hormones, the influence of exercise training, and where possible, examine masters’ athletes’ endocrinological profile.


1988 ◽  
Vol 119 (2) ◽  
pp. 283-290 ◽  
Author(s):  
Marie Simard ◽  
Carol J. Mirell ◽  
A. Eugene Pekary ◽  
Jerry Drexler ◽  
Kalman Kovacs ◽  
...  

Abstract. Pituitary thyrotrope tumours are a rare cause of hyperthyroidism. Prior in vitro studies of these tumours have revealed various patterns of differentiation and secretory activity. We have characterized the histological, biochemical, molecular and physiological features of a thyrotrope adenoma in order to define its origin and autonomy. Histochemical and electron micrograph findings confirmed the diagnosis of a thyrotrope cell adenoma. Immunostaining was positive for TSH and GH in the cytoplasm of the adenoma cells. Tissue extracts contained TSH-IR which co-eluted with authentic hTSH when analysed by gel filtration. Tumour fragments studied in a tissue culture system secreted TSH, α-subunit and GH. TRH (30 nmol/l) stimulated TSH and GH secretion. T3 (1.5 nmol/l) inhibited GH release and had no effect on TSH secretion. GnRH (50 nmol/l), dexamethasone (10−4 mol/l), SRIH (1 μmol/l) and TRH-glycine, a tetrapeptide precursor of TRH, stimulated TSH release. Dexamethasone inhibited GH and α-subunit secretion. Stable transcripts for α- and β-subunits of TSH and GH messenger RNAs were detected by molecular hybridization in cytosolic fractions. Immunohistochemistry, in vitro secretory function, and mRNA analysis suggest multidirectional differentiation of the tumour cells. TRH-glycine may have a direct stimulatory effect upon pituitary thyrotropes.


1987 ◽  
Vol 35 (11) ◽  
pp. 1347-1351 ◽  
Author(s):  
R A DeLellis ◽  
H J Wolfe

Histochemistry has played a major role in the development and implementation of new methods for analysis of gene expression at the cellular level. With the techniques of immunocytochemistry and in situ hybridization, the products of RNA translation as well as specific messenger RNAs and genomic DNAs can be demonstrated and can provide highly dynamic analyses of gene transcription and translation in individual cells. In endocrine pathology, these approaches have been particularly effective for correlation of functional abnormalities with the varying manifestations of disease at the cellular level. In addition, these methods have been valuable in the formulation of novel clinical and pathological concepts, and will continue to provide important tools for diagnostic and prognostic assessment of neoplastic and non-neoplastic disorders of the endocrine system.


1990 ◽  
Vol 2 (1) ◽  
pp. 11 ◽  
Author(s):  
MR Luck ◽  
RJ Rodgers ◽  
JK Findlay

Bovine granulosa cells were cultured under defined conditions to examine (1) their secretion of immunoreactive inhibin, oxytocin, progesterone and oestradiol during differentiation in vitro; (2) their expression, by Northern analysis, of specific mRNAs for inhibin and oxytocin as compared with uncultured cells; (3) possible interrelationships between the four secreted hormones; and (4) the hypothesis that androgens and steroidogenesis influence the secretion of inhibin. The secretion of inhibin and oestradiol fell rapidly over the first few days of culture but remained at detectable levels for at least 7 days. Conversely, the secretion of oxytocin and progesterone rose steadily as culture progressed. These changes occurred spontaneously (i.e. without gonadotrophin treatment) and were not dependent on the addition of serum to the culture medium. Messenger RNAs for the inhibin alpha- and beta A-subunits were present in uncultured cells but barely detectable or undetectable in cells cultured for 4 days. Conversely, the mRNA for oxytocin, which was not detectable in uncultured cells, was present in cultured cells and increased in quantity as culture progressed. Treatment of cells with testosterone (5 nM-5 microM), in the presence or absence of serum (10% FCS), had no effect on the secretion of inhibin but stimulated the declining oestradiol secretion. Treatment with ascorbic acid (0.5 mM) increased the secretion of oxytocin and progesterone, as previously described, but not that of inhibin. Treatment with aminoglutethimide (0.5 mM), an inhibitor of steroidogenesis, substantially inhibited progesterone secretion and the response of oestradiol secretion to testosterone, but had no effect on the secretion of either inhibin or oxytocin. We conclude that bovine granulosa cells differentiate spontaneously in defined culture in a manner that, as defined by the secretion of steroid and peptide hormones, closely resembles their luteinization in vivo. The switch in protein hormone secretion from inhibin to oxytocin is accompanied by a corresponding change in mRNA expression. The changes in steroid and peptide hormone secretions that take place in culture appear to occur independently of one another although their absolute cause remains to be determined. In contrast to previous studies, we could find no evidence for the regulation of inhibin secretion by either androgens or steroidogenesis.


2002 ◽  
Vol 74 (6) ◽  
pp. 881-890
Author(s):  
Thongchai Dumrongpokaphan ◽  
Yongwimon Lenbury

Many endocrine systems have been found to incorporate some form of cascade mechanism into their operation. Such a mechanism involves an amplification system where an initial reaction gives rise to the generation of multiple second reactions, each of which sets off multiple third reactions, and so on. Examples will be presented, with special attention paid to the hypothalamus­pituitary­testicular axis. The production and secretion of luteinizing hormone (LH) is governed by the medial-basal region of the hypothalamus. It is well known that the release of LH is a highly regulated process determined by negative and positive feedback, as well as neural components. The presence of gonadatropin-releasing hormone (GnRH) on specific adenohypophyseal cell membrane receptors results in the release of LH, which is then transported systemically to the Leydig cells of the testes. All the factors governing the release of these hormones, as well as a biochemical description of their actions, have not been completely elucidated, nor is the mechanism behind the pulsatile fashion in which the decapeptide GnRH and LH are released clearly explained. We describe how such a cascade mechanism in a self-regulatory system may be modeled and analyzed by a singular perturbation approach, identifying conditions that give rise to episodic hormone secretion or activity. Insightful and valuable interpretations can be made from such analysis of the cascade system.


Animals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 239
Author(s):  
Xiaosheng Zhang ◽  
Chunxiao Dong ◽  
Jing Yang ◽  
Yihai Li ◽  
Jing Feng ◽  
...  

Juvenile superovulation can provide a wealth of oocyte material for embryo production, animal cloning, and genetic modification research, but embryos derived from juvenile oocytes show poor efficiency in subsequent developmental capacity. In order to reveal the formation mechanism of large numbers of follicles and poor oocyte quality in juvenile ovaries under superovulation treatment, differentially expressed microRNAs (miRNAs) and messenger RNAs (mRNAs) were characterized and investigated in the ovaries of lambs and adult sheep using high-throughput sequencing technology. The majority of differentially expressed miRNAs (337/358) were upregulated in lamb libraries. The expression levels of mRNAs related to hormone receptors (follicle-stimulating hormone receptor, FSHR; luteinizing hormone/choriogonadotropin receptor, LHCGR; estrogen receptor 1, ESR1), steroid hormone secretion (cytochrome P450 family 11 subfamily A member 1, CYP11A1; cytochrome P450 family 17 subfamily A member 1, CYP17A1; cytochrome P450 family 19 subfamily A member 1, CYP19A1), and oocyte quality (pentraxin 3, PTX3; BCL2 apoptosis regulator, BCL2; caspase 3, CASP3) were significantly different between the lamb and adult libraries. The miRNA aor-miR-143, which targets FSHR, was highly and differentially expressed, and PTX3 was predicted to be targeted by oar-miR-485-3p and oar-miR-377-3p in the ovine ovary. A considerable number of miRNAs were predicted to inhibit ESR1 expression in lamb ovaries. In conclusion, oar-miR-143 and FSHR molecules, among others, might regulate follicle formation, and oar-miR-485-3p, oar-miR-377-3p, and PTX3, among others, may be associated with oocyte quality. These identified miRNAs and mRNAs will be beneficial for the prediction of ovarian superovulation potential and screening of oocytes.


Author(s):  
Helen E. Turner ◽  
Richard Eastell ◽  
Ashley Grossman

This chapter discusses oncological disorders of the endocrine system, including markers for diagnosis, such as chromogranin A, serum neuron-specific enolase, and pancreatic polypeptide (PP). It also describes imaging techniques such as CT and endoscopy, which are matched to neuroendocrine tumour (NET) type. The chapter outlines pathogenesis, symptoms, and management options for NETs such as gastro-entero-pancreatic tumours, insulinomas, gastinomas, glucagonomas, vasoactive intestinal polypeptide (VIP)-secreting tumours or ‘VIPomas’, and somatostatinomas. Ectopic hormone production is described along with disorders such as syndrome of inappropriate anti-diuretic hormone secretion (SIADH), parathyroid hormone-related protein (PTHrP) tumours, ectopic adrenocorticotropic hormone tumours, and human chorionic gonadotrophin (hCG) tumours, as well as their pathophysiology and respective medical management strategies. The chapter details endocrine function following chemotherapy and radiotherapy, listing associated anatomical structures and the biochemical effects of such treatments.


Author(s):  
Jaak Jürimäe

Physical exercise regulates energy balance and is important to growth and maturation. These processes are regulated by the endocrine system. Endocrine mechanisms in the response to sport training include growth hormone-insulin-like growth factor-1 (GH-IGF-1), hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes, and peripheral markers of energy homeostasis. Physical performance is associated with anabolic adaptations of the GH-IGF-1 system in child athletes alongside spontaneous growth, while heavy training does not affect basal testosterone levels. In female adolescent athletes, the major factor altering reproductive hormone secretion is energy deficiency, rather than exercise stress or increase in exercise energy expenditure. Ghrelin is another indicator of energy imbalance across the menstrual cycle. Pubertal onset decreases ghrelin, and leptin levels are reduced and may remain unchanged between prepuberty and maturation in athletes. To better understand the influence of high training load on hormonal markers responsible for overall growth and energy homeostasis, growing athletes should be monitored often.


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