Diabetes mellitus: Classification, mediators, and complications; A gate to identify potential targets for the development of new effective treatments

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115734 - 115734

Published: Oct. 17, 2023

Nowadays, diabetes mellitus has emerged as a significant global public health concern with remarkable increase in its prevalence. This review article focuses on the definition of and classification into different types, including type 1 (idiopathic fulminant), 2 diabetes, gestational hybrid forms, slowly evolving immune-mediated ketosis-prone other special types. Diagnostic criteria for are also discussed. The role inflammation both is explored, along mediators potential anti-inflammatory treatments. Furthermore, involvement various organs highlighted, such adipose tissue obesity, gut microbiota, pancreatic β-cells. manifestation Langerhans β-cell islet inflammation, oxidative stress, impaired insulin production secretion addressed. Additionally, impact liver cirrhosis, acute kidney injury, immune system complications, diabetic complications like retinopathy neuropathy examined. Therefore, further research required to enhance diagnosis, prevent chronic identify therapeutic targets management associated dysfunctions.

Language: Английский

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The Intestinal Barrier Dysfunction as Driving Factor of Inflammaging

Nutrients, Journal Year: 2022, Volume and Issue: 14(5), P. 949 - 949

Published: Feb. 23, 2022

The intestinal barrier, composed of the luminal microbiota, mucus layer, and physical barrier consisting epithelial cells immune cells, latter residing underneath within plays a special role in health disease. While there is growing knowledge on changes to different layers associated with disease development, function also an important during aging. Besides composition cellular junctions, entire gastrointestinal physiology contributes essential age-related changes. This reflected by substantial differences microbial throughout life span. Even though it remains difficult define physiological distinguish them from early signs pathologies, studies centenarians provide insights into features longevity. reviewed this narrative review article might contribute definition strategies prevent development diseases elderly. Thus, targeted interventions improve overall will be prevention for healthy aging future.

Language: Английский

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Lactic acid bacteria modulate the CncC pathway to enhance resistance to β-cypermethrin in the oriental fruit fly

The ISME Journal, Journal Year: 2024, Volume and Issue: 18(1)

Published: Jan. 1, 2024

Abstract The gut microbiota of insects has been shown to regulate host detoxification enzymes. However, the potential regulatory mechanisms involved remain unknown. Here, we report that bacteria increase insecticide resistance by activating cap “n” collar isoform-C (CncC) pathway through enzymatically generated reactive oxygen species (ROS) in Bactrocera dorsalis. We demonstrated Enterococcus casseliflavus and Lactococcus lactis, two lactic acid-producing bacteria, B. dorsalis β-cypermethrin regulating cytochrome P450 (P450) enzymes α-glutathione S-transferase (GST) activities. These symbionts also induced expression CncC muscle aponeurosis fibromatosis. BdCncC knockdown led a decrease caused bacteria. Ingestion ROS scavenger vitamin C resistant strain affected BdCncC/BdKeap1/BdMafK, resulting reduced GST activity. Furthermore, feeding with E. or L. lactis showed BdNOX5 increased production, BdCncC/BdMafK genes. Moreover, acid activated ROS-associated regulation Collectively, our findings indicate symbiotic modulate intestinal pathways affecting physiological biochemistry, thus providing new insights into involvement insect microbes development resistance.

Language: Английский

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Short Chain Fatty Acids: Essential Weapons of Traditional Medicine in Treating Inflammatory Bowel Disease

Molecules, Journal Year: 2024, Volume and Issue: 29(2), P. 379 - 379

Published: Jan. 12, 2024

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal inflammatory disease, mainly including Crohn's (CD) ulcerative colitis (UC). In recent years, the incidence prevalence of IBD have been on rise worldwide become significant concern health huge economic burden patients. The occurrence development involve variety pathogenic factors. changes in short-chain fatty acids (SCFAs) are considered to be an important mechanism this disease. SCFAs metabolites microbial environment, which closely involved regulating immune, anti-tumor, anti-inflammatory activities. Changes metabolite levels can reflect homeostasis microflora. Recent studies shown that provide energy for host cells microflora, shape regulate immune system, thereby physiology. effectively reduce enteritis, cardiovascular colon cancer, obesity, diabetes, also play role maintaining balance metabolism (mainly glucose metabolism) improving insulin tolerance. many numerous decoctions natural compounds traditional Chinese medicine promising therapeutic activities multiple animal models thus attracted increasing attention from scientists study treatment. Some these medicines or alleviate colonic inflammation clinical symptoms by generation SCFAs. This reviews effects various bioactive substances production their potential impacts severity inflammation. On basis, we discussed IBD-associated inflammation, as well related regulatory factors signaling pathways. addition, our understanding limitations current research prospects future new therapies targeting review may widen effect view alleviating models, contributing researchers.

Language: Английский

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Host-microbiota interaction in intestinal stem cell homeostasis

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: May 17, 2024

Intestinal stem cells (ISCs) play a pivotal role in gut physiology by governing intestinal epithelium renewal through the precise regulation of proliferation and differentiation. The microbiota interacts closely with myriad actions, including immune metabolic interactions, which translate into tight connections between microbial activity ISC function. Given diverse functions affecting metabolism macronutrients micronutrients, dietary nutrients exert pronounced effects on host-microbiota interactions and, consequently, fate. Therefore, understanding intricate interaction regulating homeostasis is imperative for improving health. Here, we review recent advances that shape function, such as pattern-recognition receptors metabolites, lactate indole metabolites. Additionally, regulatory nutrients, proteins, carbohydrates, vitamins, minerals (e.g. iron zinc), are thoroughly explored relation to their impact ISCs. Thus, highlight multifaceted mechanisms homeostasis. Insights gained from this provide strategies development or microbiota-based interventions foster

Language: Английский

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The Role of Reactive Oxygen Species in Colorectal Cancer Initiation and Progression: Perspectives on Theranostic Approaches

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 752 - 752

Published: Feb. 22, 2025

Altered levels of reactive oxygen species (ROS) are recognized as one the key factors in mediating tumor cell survival tissue microenvironment, where they play a role initiation, progression and recurrence/relapse colorectal cancer (CRC). Tumor cells can adapt to oxidative stress (OS) using genetic or metabolic reprogramming long short term. In addition, defend themselves through positive regulation antioxidant molecules, enhancing ROS-driven proliferation. Balanced eustress influence chemotherapy resistance, allowing survive treatment. Secondary effects include increased ROS production redox stress, which kill eliminate drug resistance. Anticancer treatments based on manipulating could represent gold standard CRC therapy. Therefore, exploring modulation response OS deregulated signaling pathways may lead development new personalized overcome therapy this review, we explore initiation their diagnostic implications biomarkers disease. Furthermore, focused involvement different therapeutic options, such surgery, radiotherapy, theranostic imaging, immunotherapy other precision medicine approaches.

Language: Английский

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Oral administration of aripiprazole to Drosophila causes intestinal toxicity

Disease Models & Mechanisms, Journal Year: 2025, Volume and Issue: 18(3)

Published: March 1, 2025

ABSTRACT Aripiprazole is a third-generation antipsychotic medication that was introduced to mitigate the poor tolerability of older antipsychotics. In contrast drugs act as dopamine receptor antagonists in brain, aripiprazole functions partial agonist. has been identified an off-target inhibitor mitochondrial respiratory complex I. We observed patients prescribed often report gastrointestinal disturbances, but mechanism underlying these side effects not clear. modelled potential toxicity system using fruit fly (Drosophila melanogaster). consumption impaired Drosophila gut function and faecal output. It also reduced membrane increased reactive oxygen species (ROS) levels intestinal cells. ROS activate c-Jun N-terminal kinase (JNK) pathway, which induces cellular stress cell death. JNK activation cells flies, resulting death, suppressed by antioxidants. conclude activates pathway death via production. Using antioxidant supplements may help reduce aripiprazole-induced toxicity.

Language: Английский

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Short-chain fatty acids reprogram metabolic profiles with the induction of reactive oxygen species production in human colorectal adenocarcinoma cells

Computational and Structural Biotechnology Journal, Journal Year: 2023, Volume and Issue: 21, P. 1606 - 1620

Published: Jan. 1, 2023

Short-chain fatty acids (SCFAs) exhibit anticancer activity in cellular and animal models of colon cancer. Acetate, propionate, butyrate are the three major SCFAs produced from dietary fiber by gut microbiota fermentation have beneficial effects on human health. Most previous studies antitumor mechanisms focused specific metabolites or genes involved pathways, such as reactive oxygen species (ROS) biosynthesis. In this study, we performed a systematic unbiased analysis acetate, ROS levels metabolic transcriptomic signatures at physiological concentrations colorectal adenocarcinoma cells. We observed significantly elevated treated Furthermore, regulated were overlapping pathways levels, including response metabolism, acid transport glucose mitochondrial respiratory chain complex, one-carbon amino glutaminolysis, which directly indirectly linked to production. Additionally, regulation occurred types-dependent manner, with an increasing degree acetate propionate then butyrate. This study provides comprehensive how induce production modulate cancer cells, is vital for understanding

Language: Английский

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NADPH Oxidases: Redox Regulators of Stem Cell Fate and Function

Antioxidants, Journal Year: 2021, Volume and Issue: 10(6), P. 973 - 973

Published: June 17, 2021

One of the major sources reactive oxygen species (ROS) generated within stem cells is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family enzymes (NOXs), which are critical determinants redox state beside antioxidant defense mechanisms. This balance involved in another one that regulates cell fate: indeed, self-renewal, proliferation, and differentiation decisive steps for during embryo development, adult tissue renovation, therapy application. Ex vivo culture-expanded being investigated repair immune modulation, but events such as aging, senescence, oxidative stress reduce their ex crucial clinical applications. Here, we review role NOX-derived ROS biology functions, focusing on positive negative effects triggered by activity different NOX isoforms. We report recent findings downstream molecular targets NOX-ROS signaling can modulate homeostasis lineage commitment discuss implications expansion engraftment, function, longevity. highlights a pivotal regulator several populations, conclude these aspects have important utility cells, further studies pharmacological modulation human imperative.

Language: Английский

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Ursolic Acid Protects Sodium Dodecyl Sulfate-Induced Drosophila Ulcerative Colitis Model by Inhibiting the JNK Signaling

Antioxidants, Journal Year: 2022, Volume and Issue: 11(2), P. 426 - 426

Published: Feb. 21, 2022

Ursolic acid (UA) is a bioactive molecule widely distributed in various fruits and vegetables, which was reported to play therapeutic role ulcerative colitis (UC) induced by toxic chemicals. However, the underlying mechanism has not been well clarified vivo. Here, using Drosophila UC model sodium dodecyl sulfate (SDS), we investigated defensive effect of UA on intestinal damage. The results showed that could significantly protect from damage caused SDS exposure. Further, alleviated accumulation reactive oxygen species (ROS) malondialdehyde (MDA) upregulated activities total superoxide dismutase (T-SOD) catalase (CAT). Moreover, proliferation differentiation intestine stem cells (ISCs) as excessive activation c-Jun N-terminal kinase (JNK)-dependent JAK/STAT signaling pathway were restored UA. In conclusion, prevents injury compounds reducing JNK/JAK/STAT pathway. may provide theoretical basis for functional food or natural medicine development.

Language: Английский

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