Gut Hormones as Potential Therapeutic Targets or Biomarkers of Response in Depression: The Case of Motilin

Mapping Intimacies ◽

10.20944/preprints202108.0369.v1 ◽

2021 ◽

Author(s):

Ravi Philip Rajkumar

Keyword(s):

Antidepressant Drug ◽

Gut Hormones ◽

Peptide Hormone ◽

Specific Reference ◽

Gut Peptides ◽

Mechanistic Pathway ◽

Predictors Of Response ◽

Treatment Of Depression ◽

Prevalence Of Depression

Recent research has identified the gut-brain axis as a key mechanistic pathway and potential therapeutic target in depression. In this paper, the potential role of gut hormones as potential treatments or predictors of response in depression is examined, with specific reference to the peptide hormone motilin. This possibility is explored through two methods: (a) a conceptual review of the possible links between motilin and depression, including evidence from animal and human research as well as clinical trials, and (b) an analysis of the relationship between a functional polymorphism (rs2281820) of the motilin (MLN) gene and cross-national variations in the prevalence of depression. It was observed that (a) there are several plausible mechanisms, including interactions with diet, monoamine, and neuroendocrine pathways, to suggest that motilin may be relevant to the pathophysiology and treatment of depression, and (b) there was a significant correlation between rs2281820 allele frequencies and the prevalence of depression after correcting for multiple confounding factors. These results suggest that further evaluation of the utility of motilin and related gut peptides as markers of antidepressant response is required, and that these molecular pathways represent potential future mechanisms for antidepressant drug development.

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Gut Hormones as Potential Therapeutic Targets or Biomarkers of Response in Depression: The Case of Motilin

Life ◽

10.3390/life11090892 ◽

2021 ◽

Vol 11 (9) ◽

pp. 892

Author(s):

Ravi Philip Rajkumar

Keyword(s):

Antidepressant Drug ◽

Gut Hormones ◽

Peptide Hormone ◽

Specific Reference ◽

Gut Peptides ◽

Scientific Databases ◽

Mechanistic Pathway ◽

Predictors Of Response ◽

Treatment Of Depression ◽

Prevalence Of Depression

Recent research has identified the gut–brain axis as a key mechanistic pathway and potential therapeutic target in depression. In this paper, the potential role of gut hormones as potential treatments or predictors of response in depression is examined, with specific reference to the peptide hormone motilin. This possibility is explored through two methods: (1) a conceptual review of the possible links between motilin and depression, including evidence from animal and human research as well as clinical trials, based on a literature search of three scientific databases, and (2) an analysis of the relationship between a functional polymorphism (rs2281820) of the motilin (MLN) gene and cross-national variations in the prevalence of depression based on allele frequency data after correction for potential confounders. It was observed that (1) there are several plausible mechanisms, including interactions with diet, monoamine, and neuroendocrine pathways, to suggest that motilin may be relevant to the pathophysiology and treatment of depression, and (2) there was a significant correlation between rs2281820 allele frequencies and the prevalence of depression after correcting for multiple confounding factors. These results suggest that further evaluation of the utility of motilin and related gut peptides as markers of antidepressant response is required and that these molecular pathways represent potential future mechanisms for antidepressant drug development.

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Glucocorticoids in the Physiological and Transcriptional Regulation of 5-HT1A Receptor and the Pathogenesis of Depression

The Neuroscientist ◽

10.1177/1073858420975711 ◽

2020 ◽

pp. 107385842097571

Author(s):

Darakhshan Jabeen Haleem

Keyword(s):

Transcriptional Regulation ◽

Critical Role ◽

Treatment Strategies ◽

Therapeutic Agents ◽

Stressful Events ◽

Antagonist Activity ◽

Treatment Of Depression ◽

Prevalence Of Depression ◽

Circulating Levels

There is growing increase in the global prevalence of depression, but treatment outcome of this highly disabling disease is not satisfactory. Many patients are not benefitted by the currently prescribed antidepressants—together with this partial remission is very common. Improving treatment strategies and developing better therapeutic agents for treating depression is therefore highly needed. Stress-related epigenetic changes play a critical role in the pathogenesis as well as treatment of depression. Stressful events activate hypothalamic-pituitary-adrenal axis to increase circulating levels of glucocorticoids (GCs), and a greater sensitivity to this fright and flight response increases risk of depression. A role of serotonin (5-hydroxytryptamine; 5-HT) in responses to stress and in the pathogenesis and treatment of depression is well established. Substantial evidence supports a critical role of 5-HT1A receptors in these effects of 5-HT. The present article targets stress-induced higher and sustained increases of GCs and mediated influences on the physiological as well transcriptional regulation of 5-HT1A receptors to evaluate their causal role in the pathogenesis of depression. It is suggested that synthetic compounds with antagonist activity for GC receptors and agonist activity for 5-HT1A receptors may prove better therapeutic agents for treating depression.

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The Role of Gasotransmitters in Gut Peptide Actions

Frontiers in Pharmacology ◽

10.3389/fphar.2021.720703 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wout Verbeure ◽

Harry van Goor ◽

Hideki Mori ◽

André P. van Beek ◽

Jan Tack ◽

...

Keyword(s):

Smooth Muscles ◽

Gut Hormones ◽

Gut Peptides ◽

Physiological Processes ◽

Physiological Alterations ◽

Stomach Acid ◽

Low Concentrations ◽

Peptide Release ◽

Glucagon Like Peptide 1

Although gasotransmitters nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) receive a bad connotation; in low concentrations these play a major governing role in local and systemic blood flow, stomach acid release, smooth muscles relaxations, anti-inflammatory behavior, protective effect and more. Many of these physiological processes are upstream regulated by gut peptides, for instance gastrin, cholecystokinin, secretin, motilin, ghrelin, glucagon-like peptide 1 and 2. The relationship between gasotransmitters and gut hormones is poorly understood. In this review, we discuss the role of NO, CO and H2S on gut peptide release and functioning, and whether manipulation by gasotransmitter substrates or specific blockers leads to physiological alterations.

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Role of Self Help Groups A Study with Specific Reference to Vellore District

GIS Business ◽

10.26643/gis.v14i6.11704 ◽

2019 ◽

Vol 14 (6) ◽

pp. 243-252

Author(s):

Dr. M.A. Bilal Ahmed ◽

Dr. S. Thameemul Ansari

Keyword(s):

Leadership Role ◽

Three Dimensions ◽

Specific Reference ◽

Government Organizations ◽

Research Article ◽

Self Help ◽

The People ◽

The World ◽

Self Help Groups

SHG is a movement which came to being in the early 1969. Prof. Muhammed Younus, a great economist of Bangladesh took initiative in setting up Self Help Groups and these SHGs were gradually spread all over the world. This social movement unites the people hailing from poor background. Those who are joining this group feel socially and economically responsible to one another. In India, there are some likeminded bodies and stakeholders of some government organizations play pivotal role towards the formation of SHG In this research article, role of SHGs in Vellore district is studies under the three dimensions of Cognitive role, leadership role and role towards entrepreneurship.

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The Role of Neuropeptide Y and Peptide YY in the Development of Obesity via Gut-brain Axis

Current Protein and Peptide Science ◽

10.2174/1389203720666190125105401 ◽

2019 ◽

Vol 20 (7) ◽

pp. 750-758 ◽

Cited By ~ 7

Author(s):

Yi Wu ◽

Hengxun He ◽

Zhibin Cheng ◽

Yueyu Bai ◽

Xi Ma

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neuropeptide Y ◽

Metabolic Diseases ◽

Peptide Yy ◽

Vital Role ◽

Gut Peptides ◽

Nonalcoholic Fatty Liver ◽

The Central Nervous System

Obesity is one of the main challenges of public health in the 21st century. Obesity can induce a series of chronic metabolic diseases, such as diabetes, dyslipidemia, hypertension and nonalcoholic fatty liver, which seriously affect human health. Gut-brain axis, the two-direction pathway formed between enteric nervous system and central nervous system, plays a vital role in the occurrence and development of obesity. Gastrointestinal signals are projected through the gut-brain axis to nervous system, and respond to various gastrointestinal stimulation. The central nervous system regulates visceral activity through the gut-brain axis. Brain-gut peptides have important regulatory roles in the gut-brain axis. The brain-gut peptides of the gastrointestinal system and the nervous system regulate the gastrointestinal movement, feeling, secretion, absorption and other complex functions through endocrine, neurosecretion and paracrine to secrete peptides. Both neuropeptide Y and peptide YY belong to the pancreatic polypeptide family and are important brain-gut peptides. Neuropeptide Y and peptide YY have functions that are closely related to appetite regulation and obesity formation. This review describes the role of the gutbrain axis in regulating appetite and maintaining energy balance, and the functions of brain-gut peptides neuropeptide Y and peptide YY in obesity. The relationship between NPY and PYY and the interaction between the NPY-PYY signaling with the gut microbiota are also described in this review.

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Efficacy of Phytocannabinoids in Epilepsy Treatment: Novel Approaches and Recent Advances

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18083993 ◽

2021 ◽

Vol 18 (8) ◽

pp. 3993

Author(s):

Aaron M. Farrelly ◽

Styliani Vlachou ◽

Konstantinos Grintzalis

Keyword(s):

Therapeutic Potential ◽

Significant Proportion ◽

Future Research ◽

Specific Reference ◽

Undesirable Side Effect ◽

Treatment Resistant ◽

Current Review ◽

Epilepsy Treatment ◽

Clinical Environments

Epilepsy is a neurological disorder mainly characterised by recurrent seizures that affect the entire population diagnosed with the condition. Currently, there is no cure for the disease and a significant proportion of patients have been deemed to have treatment-resistant epilepsy (TRE). A patient is deemed to have TRE if two or more antiepileptic drugs (AEDs) fail to bring about seizure remission. This inefficacy of traditional AEDs, coupled with their undesirable side effect profile, has led to researchers considering alternative forms of treatment. Phytocannabinoids have long served as therapeutics with delta-9-THC (Δ9-THC) receiving extensive focus to determine its therapeutic potential. This focus on Δ9-THC has been to the detriment of analysing the plethora of other phytocannabinoids found in the cannabis plant. The overall aim of this review is to explore other novel phytocannabinoids and their place in epilepsy treatment. The current review intends to achieve this aim via an exploration of the molecular targets underlying the anticonvulsant capabilities of cannabidiol (CBD), cannabidavarin (CBDV), delta-9-tetrahydrocannabivarin (Δ9-THCV) and cannabigerol (CBG). Further, this review will provide an exploration of current pre-clinical and clinical data as it relates to the aforementioned phytocannabinoids and the treatment of epilepsy symptoms. With specific reference to epilepsy in young adult and adolescent populations, the exploration of CBD, CBDV, Δ9-THCV and CBG in both preclinical and clinical environments can guide future research and aid in the further understanding of the role of phytocannabinoids in epilepsy treatment. Currently, much more research is warranted in this area to be conclusive.

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The Emerging Role of Polyphenols in the Management of Type 2 Diabetes

Molecules ◽

10.3390/molecules26030703 ◽

2021 ◽

Vol 26 (3) ◽

pp. 703

Author(s):

Yao Wang ◽

Hana Alkhalidy ◽

Dongmin Liu

Keyword(s):

Type 2 Diabetes ◽

Glucose Homeostasis ◽

Gut Hormones ◽

Nutritional Regulation ◽

Gi Tract ◽

Cell Dysfunction ◽

Glucagon Like Peptide 1 ◽

Metabolic Action

Type 2 diabetes (T2D) is a fast-increasing health problem globally, and it results from insulin resistance and pancreatic β-cell dysfunction. The gastrointestinal (GI) tract is recognized as one of the major regulatory organs of glucose homeostasis that involves multiple gut hormones and microbiota. Notably, the incretin hormone glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L-cells plays a pivotal role in maintaining glucose homeostasis via eliciting pleiotropic effects, which are largely mediated via its receptor. Thus, targeting the GLP-1 signaling system is a highly attractive therapeutic strategy to treatment T2D. Polyphenols, the secondary metabolites from plants, have drawn considerable attention because of their numerous health benefits, including potential anti-diabetic effects. Although the major targets and locations for the polyphenolic compounds to exert the anti-diabetic action are still unclear, the first organ that is exposed to these compounds is the GI tract in which polyphenols could modulate enzymes and hormones. Indeed, emerging evidence has shown that polyphenols can stimulate GLP-1 secretion, indicating that these natural compounds might exert metabolic action at least partially mediated by GLP-1. This review provides an overview of nutritional regulation of GLP-1 secretion and summarizes recent studies on the roles of polyphenols in GLP-1 secretion and degradation as it relates to metabolic homeostasis. In addition, the effects of polyphenols on microbiota and microbial metabolites that could indirectly modulate GLP-1 secretion are also discussed.

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Emerging Silk Material Trends: Repurposing, Phase Separation and Solution-Based Designs

Materials ◽

10.3390/ma14051160 ◽

2021 ◽

Vol 14 (5) ◽

pp. 1160

Author(s):

F. Philipp Seib

Keyword(s):

Phase Separation ◽

Recent Progress ◽

Fiber Formation ◽

Live Cells ◽

Specific Reference ◽

New Developments ◽

Silk Fabrics ◽

Induced Crystallization ◽

Liquid Liquid Phase Separation

Silk continues to amaze. This review unravels the most recent progress in silk science, spanning from fundamental insights to medical silks. Key advances in silk flow are examined, with specific reference to the role of metal ions in switching silk from a storage to a spinning state. Orthogonal thermoplastic silk molding is described, as is the transfer of silk flow principles for the triggering of flow-induced crystallization in other non-silk polymers. Other exciting new developments include silk-inspired liquid–liquid phase separation for non-canonical fiber formation and the creation of “silk organelles” in live cells. This review closes by examining the role of silk fabrics in fashioning facemasks in response to the SARS-CoV-2 pandemic.

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Immunotherapy in Adrenocortical Carcinoma: Predictors of Response, Efficacy, Safety, and Mechanisms of Resistance

Biomedicines ◽

10.3390/biomedicines9030304 ◽

2021 ◽

Vol 9 (3) ◽

pp. 304

Author(s):

Marta Araujo-Castro ◽

Eider Pascual-Corrales ◽

Javier Molina-Cerrillo ◽

Teresa Alonso-Gordoa

Keyword(s):

Adrenocortical Carcinoma ◽

Checkpoint Inhibitors ◽

Treatment Options ◽

Progression Free Survival ◽

Mechanisms Of Resistance ◽

Response Efficacy ◽

Predictors Of Response ◽

Primary Endpoints ◽

Tumor Mutational Burden

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options in the advanced stages. Immunotherapy offers hope for altering the orthodox management of cancer, and its role in advanced ACC has been investigated in different studies. With the aim clarifying the role of immunotherapy in ACC we performed a comprehensive review about this topic focusing on the predictors of response, efficacy, safety, and the mechanisms of resistance. Five clinical trials with four immune checkpoint inhibitors (pembrolizumab, avelumab, nivolumab, and ipilimumab) have investigated the role of immunotherapy in advanced ACC. Despite, the different primary endpoints used in these studies, the reported rates of overall response rate and progression free survival were generally poor. Three main potential markers of response to immunotherapy in ACC have been described: Expression of PD-1 and PD-L1, microsatellite instability and tumor mutational burden. However, none of them has been validated in prospective studies. Several mechanisms of ACC immunoevasion may be responsible of immunotherapy failure, and a greater knowledge of these mechanisms might lead to the development of new strategies to overcome the immunotherapy resistance. In conclusion, although currently the role of immunotherapy is limited, the identification of immunological markers of response and the implementation of strategies to avoid immunotherapy resistance could improve the efficacy of this therapy.

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