scholarly journals Terazosin Stimulates Pgk1 to Remedy Gastrointestinal Disorders

2021 ◽  
Vol 23 (1) ◽  
pp. 416
Author(s):  
Jingjing Liu ◽  
Wenyang Zhao ◽  
Chun Li ◽  
Tongyu Wu ◽  
Liang Han ◽  
...  
Keyword(s):  
Gastrointestinal Disease ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
Health Concern ◽  
Disease Treatment ◽  
Atp Production ◽  
Anti Inflammation ◽  
Clinical Drug

Gastrointestinal disease is the most common health concern that occurs due to environmental, infectious, immunological, psychological, and genetic stress. Among them, the most frequent diseases are gastric ulcer (GU) and ulcerative colitis (UC). DSS-induced UC and ethanol-stimulated GU models resemble the pathophysiology of human gastrointestinal disease. The current study was designed to explore the anti-oxidation, anti-inflammation, anti-cell death properties of terazosin, an α-adrenergic receptor antagonist, in vivo and in vitro. Our results indicate that terazosin dramatically activates Pgk1, and upregulates glycose metabolism, evidenced by the enhanced ATP production and higher LDH enzymatic activity. Also, terazosin significantly enhances p-AKT expression and inhibits NF-κB p65 activation through abrogating the phosphorylation of IKBα, as well as lowers Caspase-1 and GSDMD expression. The findings in this study demonstrate that terazosin exhibits anti-inflammatory effects by downregulating NF-κB-GSDMD signal pathway, along with enhancing glycolysis for gastrointestinal disease treatment. Meanwhile, we also find terazosin ameliorates ethanol-induced gastric mucosal damage in mice. Collectively, as a clinical drug, terazosin should be translated into therapeutics for gastrointestinal disease soon.

Methylmercury-induced pro-inflammatory cytokines activation and its preventive strategy using anti-inflammation N-acetyl-l-cysteine: a mini-review

2020 ◽  
Vol 35 (3) ◽  
pp. 233-238
Author(s):  
Muflihatul Muniroh
Keyword(s):  
Inflammatory Cytokines ◽  
Health Concern ◽  
Brain Cells ◽  
Preventive Strategy ◽  
Hearing Impairments ◽  
Sensory Disturbances ◽  
Anti Inflammation ◽  
Pro Inflammatory Cytokines

AbstractThe exposure of methylmercury (MeHg) has become a public health concern because of its neurotoxic effect. Various neurological symptoms were detected in Minamata disease patients, who got intoxicated by MeHg, including paresthesia, ataxia, gait disturbance, sensory disturbances, tremors, visual, and hearing impairments, indicating that MeHg could pass the blood-brain barrier (BBB) and cause impairment of neurons and other brain cells. Previous studies have reported some expected mechanisms of MeHg-induced neurotoxicity including the neuroinflammation pathway. It was characterized by the up-regulation of numerous pro-inflammatory cytokines expression. Therefore, the use of anti-inflammatories such as N-acetyl-l-cysteine (NAC) may act as a preventive compound to protect the brain from MeHg harmful effects. This mini-review will explain detailed information on MeHg-induced pro-inflammatory cytokines activation as well as possible preventive strategies using anti-inflammation NAC to protect brain cells, particularly in in vivo and in vitro studies.

scholarly journals Effects of KB-5492, a New Anti-Ulcer Agent, on Ethanol- and Acidified Aspirin-Induced Gastric Mucosal Damage In Vivo and In Vitro

1994 ◽  
Vol 64 (1) ◽  
pp. 41-48 ◽  
Author(s):  
Yasuo Morimoto ◽  
Shinya Oshima ◽  
Hideaki Hara ◽  
Takayuki Sukamoto
Keyword(s):  
Mucosal Damage ◽  
Gastric Mucosal Damage

scholarly journals Gastroprotective effects of Nelumbinis Rhizomatis Nodus carbonisata-derived carbon dots on ethanol-induced gastric ulcers in rats

2020 ◽  
Author(s):  
Juan Luo ◽  
Jie Hu ◽  
Meiling Zhang ◽  
Yue Zhang ◽  
Jiashu Wu ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Average Diameter ◽  
Mucosal Damage ◽  
In Vitro Cytotoxicity ◽  
Gastric Mucosal Damage ◽  
Gastric Ulcers ◽  
Necrosis Factor Alpha ◽  
In Vivo Experiments

Abstract BackgroundGastric ulcers is a common gastrointestinal digestive system disease. Considering the frequency of human gastric ulcers, the side effects and cost of some existing synthetic drugs, the use of natural products is an important choice for many people. The aim of present study was to explore gastroprotective effects of nelumbinis rhizomatis nodus carbonisata carbon dots (NRNC-CDs) on ethanol-induced gastric ulcers in rats.MethodsThe NRNC-CDs were synthesized via high temperature calcinations treatment at 350 ℃ for 1 h were characterized by various spectroscopic and electron microscopy techniques for their structural, morphological, and optical properties. In vitro cytotoxicity of CDs for the human gastric epithelial cells line (GES-1 cells) was assessed by the CCK-8 assay. Furthermore, the study evaluated gastroprotective effects of NRNC-CDs on ethanol-induced gastric ulcers in rats, followed by a preliminary study on the possible mechanisms of gastroprotection.ResultesNRNC-CDs with a quantum yield of 1.38% have an average diameter of 2.89±0.82nm and the lattice spacing of 0.29 nm , and exerted low toxicity to GES-1 cells by CCK-8 test. In vivo experiments showed that NRNC-CDs remarkably reduced gastric mucosal damage and significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GSH-Px). In addition, NRNC-CDs also significantly inhibited tumor necrosis factor-alpha (TNF-a) and pro-inflammatory interleukin-6 (IL-6) level in gastric tissues. Histological findings demonstrated that NRNC-CDs exhibited a protective effect against tissue alterations in response to the ethanol-induced ulcer.ConclussionThe potent gastroprotective effect of NRNC-CDs were thus attributed to its anti-inflammatory and antioxidant effects. This discovery provides guidance for further research the effect of CDs in gastrointestinal digestive diseases.

scholarly journals Curcumin: A Potent Protectant against Esophageal and Gastric Disorders

2019 ◽  
Vol 20 (6) ◽  
pp. 1477 ◽  
Author(s):  
Slawomir Kwiecien ◽  
Marcin Magierowski ◽  
Jolanta Majka ◽  
Agata Ptak-Belowska ◽  
Dagmara Wojcik ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Curcuma Longa ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
Gastric Cancer Cells ◽  
Wide Range ◽  
Anti Inflammatory ◽  
Pleiotropic Properties

Turmeric obtained from the rhizomes of Curcuma longa has been used in the prevention and treatment of many diseases since the ancient times. Curcumin is the principal polyphenol isolated from turmeric, which exhibits anti-inflammatory, antioxidant, antiapoptotic, antitumor, and antimetastatic activities. The existing evidence indicates that curcumin can exert a wide range of beneficial pleiotropic properties in the gastrointestinal tract, such as protection against reflux esophagitis, Barrett’s esophagus, and gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs (NSAIDs) and necrotizing agents. The role of curcumin as an adjuvant in the treatment of a Helicobacter pylori infection in experimental animals and humans has recently been proposed. The evidence that this turmeric derivative inhibits the invasion and proliferation of gastric cancer cells is encouraging and warrants further experimental and clinical studies with newer formulations to support the inclusion of curcumin in cancer therapy regimens. This review was designed to analyze the existing data from in vitro and in vivo animal and human studies in order to highlight the mechanisms of therapeutic efficacy of curcumin in the protection and ulcer healing of the upper gastrointestinal tract, with a major focus on addressing the protection of the esophagus and stomach by this emerging compound.

Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity

2019 ◽  
Vol 26 (7) ◽  
pp. 494-501 ◽  
Author(s):  
Sameer Suresh Bhagyawant ◽  
Dakshita Tanaji Narvekar ◽  
Neha Gupta ◽  
Amita Bhadkaria ◽  
Ajay Kumar Gautam ◽  
...  
Keyword(s):  
Biological Effects ◽  
Exchange Chromatography ◽  
Health Concern ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ic50 Values ◽  
Chickpea Lectin

Background: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. Methods: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. Results: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. Conclusion: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.

scholarly journals Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3651
Author(s):  
Alexandru Blidisel ◽  
Iasmina Marcovici ◽  
Dorina Coricovac ◽  
Florin Hut ◽  
Cristina Adriana Dehelean ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Prediction Models ◽  
3D Models ◽  
Experimental Models ◽  
Health Concern ◽  
Liver Carcinoma ◽  
Tumor Type

Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.

Nonprotein sulfhydryl compounds in canine gastric mucosa: effects of PGE2 and ethanol

1985 ◽  
Vol 249 (1) ◽  
pp. G137-G144 ◽  
Author(s):  
T. A. Miller ◽  
D. Li ◽  
Y. J. Kuo ◽  
K. L. Schmidt ◽  
L. L. Shanbour
Keyword(s):  
Gastric Mucosa ◽  
Low Dose ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
High Dose ◽  
Mucosal Protection ◽  
Gastric Mucosal Protection ◽  
Sulfhydryl Compounds ◽  
Mild Irritants

By use of an in vivo canine chambered stomach preparation in which the gastric mucosa was partitioned into two equal halves, the effect of topical 16,16-dimethyl PGE2 (DMPGE2) (1 microgram/ml of perfusate) and 8% and 40% ethanol on tissue levels of nonprotein sulfhydryl compounds was assessed. Both DMPGE2 and 8% ethanol significantly increased (P less than 0.005) mucosal levels of nonprotein sulfhydryls when compared with corresponding mucosa bathed with saline alone. In contrast, mucosa bathed with 40% ethanol showed significantly decreased levels. If mucosa was bathed with DMPGE2 or 8% ethanol prior to exposing the stomach to 40% ethanol, this depletion in sulfhydryl compounds was not observed. Since other experimental observations have shown that exogenously administered prostaglandins and mild irritants (such as low-dose alcohol) can prevent gastric mucosal damage by necrotizing agents (such as high-dose alcohol), our findings are consistent with the hypothesis that nonprotein sulfhydryls may play a role in mediating gastric mucosal protection.

scholarly journals The Role of Herbal Bioactive Components in Mitochondria Function and Cancer Therapy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Fangfang Tao ◽  
Yanrong Zhang ◽  
Zhiqian Zhang
Keyword(s):  
Cancer Therapy ◽  
Cancer Cell ◽  
Apoptotic Cell ◽  
Redox Status ◽  
Cancer Therapies ◽  
Bioactive Components ◽  
Atp Production

Mitochondria are highly dynamic double-membrane organelles which play a well-recognized role in ATP production, calcium homeostasis, oxidation-reduction (redox) status, apoptotic cell death, and inflammation. Dysfunction of mitochondria has long been observed in a number of human diseases, including cancer. Targeting mitochondria metabolism in tumors as a cancer therapeutic strategy has attracted much attention for researchers in recent years due to the essential role of mitochondria in cancer cell growth, apoptosis, and progression. On the other hand, a series of studies have indicated that traditional medicinal herbs, including traditional Chinese medicines (TCM), exert their potential anticancer effects as an effective adjunct treatment for alleviating the systemic side effects of conventional cancer therapies, for reducing the risk of recurrence and cancer mortality and for improving the quality of patients’ life. An amazing feature of these structurally diverse bioactive components is that majority of them target mitochondria to provoke cancer cell-specific death program. The aim of this review is to summarize the in vitro and in vivo studies about the role of these herbs, especially their bioactive compounds in the modulation of the disturbed mitochondrial function for cancer therapy.

scholarly journals NIK promotes metabolic adaptation of glioblastoma cells to bioenergetic stress

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Michael L. Kamradt ◽  
Ji-Ung Jung ◽  
Kathryn M. Pflug ◽  
Dong W. Lee ◽  
Victor Fanniel ◽  
...  
Keyword(s):  
Stress Responses ◽  
Glucose Deprivation ◽  
Metabolic Adaptation ◽  
Mitochondrial Morphology ◽  
Atp Production ◽  
Tumor Microenvironments ◽  
Iκb Kinase ◽  
Critical Measure

AbstractCancers, including glioblastoma multiforme (GBM), undergo coordinated reprogramming of metabolic pathways that control glycolysis and oxidative phosphorylation (OXPHOS) to promote tumor growth in diverse tumor microenvironments. Adaptation to limited nutrient availability in the microenvironment is associated with remodeling of mitochondrial morphology and bioenergetic capacity. We recently demonstrated that NF-κB-inducing kinase (NIK) regulates mitochondrial morphology to promote GBM cell invasion. Here, we show that NIK is recruited to the outer membrane of dividing mitochondria with the master fission regulator, Dynamin-related protein1 (DRP1). Moreover, glucose deprivation-mediated metabolic shift to OXPHOS increases fission and mitochondrial localization of both NIK and DRP1. NIK deficiency results in decreased mitochondrial respiration, ATP production, and spare respiratory capacity (SRC), a critical measure of mitochondrial fitness. Although IκB kinase α and β (IKKα/β) and NIK are required for OXPHOS in high glucose media, only NIK is required to increase SRC under glucose deprivation. Consistent with an IKK-independent role for NIK in regulating metabolism, we show that NIK phosphorylates DRP1-S616 in vitro and in vivo. Notably, a constitutively active DRP1-S616E mutant rescues oxidative metabolism, invasiveness, and tumorigenic potential in NIK−/− cells without inducing IKK. Thus, we establish that NIK is critical for bioenergetic stress responses to promote GBM cell pathogenesis independently of IKK. Our data suggest that targeting NIK may be used to exploit metabolic vulnerabilities and improve therapeutic strategies for GBM.

A new in vitro model for ethanol-induced gastric mucosal damage

1999 ◽  
Vol 41 (4) ◽  
pp. 167-172 ◽  
Author(s):  
Yassir M.Al-Mulla Hummadi ◽  
Rafid A Najim ◽  
Imad B Farjou
Keyword(s):  
In Vitro Model ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
Vitro Model
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