Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Март 2, 2023

Abstract Epigenetics regulates gene expression and has been confirmed to play a critical role in variety of metabolic diseases, such as diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), osteoporosis, gout, hyperthyroidism, hypothyroidism others. The term ‘epigenetics’ was firstly proposed 1942 with the development technologies, exploration epigenetics made great progresses. There are four main epigenetic mechanisms, including DNA methylation, histone modification, chromatin remodelling, noncoding RNA (ncRNA), which exert different effects on diseases. Genetic non-genetic factors, ageing, diet, exercise, interact jointly affect formation phenotype. Understanding could be applied diagnosing treating diseases clinic, biomarkers, drugs, editing. In this review, we introduce brief history well milestone events since proposal ‘epigenetics’. Moreover, summarise research methods general mechanisms modulation. Furthermore, interaction between genetic or factors. Finally, clinical trials applications

Язык: Английский

---

Insights and implications of sexual dimorphism in osteoporosis

Bone Research, Год журнала: 2024, Номер 12(1)

Опубликована: Фев. 18, 2024

Osteoporosis, a metabolic bone disease characterized by low mineral density and deterioration of microarchitecture, has led to high risk fatal osteoporotic fractures worldwide. Accumulating evidence revealed that sexual dimorphism is notable feature osteoporosis, with sex-specific differences in epidemiology pathogenesis. Specifically, females are more susceptible than males while prone disability or death from the disease. To date, sex chromosome abnormalities steroid hormones have been proven contribute greatly osteoporosis regulating functions cells. Understanding its related complications essential for improving treatment strategies tailored women men. This literature review focuses on mechanisms underlying mainly population aging patients, chronic glucocorticoid administration, diabetes. Moreover, we highlight implications developing therapeutics preventive screening approaches Additionally, challenges translating bench research bedside treatments future directions overcome these obstacles will be discussed.

Язык: Английский

---

Luteolin rescues postmenopausal osteoporosis elicited by OVX through alleviating osteoblast pyroptosis via activating PI3K-AKT signaling

Phytomedicine, Год журнала: 2024, Номер 128, С. 155516 - 155516

Опубликована: Март 16, 2024

Recently, osteoblast pyroptosis has been proposed as a potential pathogenic mechanism underlying osteoporosis, although this remains to be confirmed. Luteolin (Lut), flavonoid phytochemical, plays critical role in the anti-osteoporosis effects of many traditional Chinese medicine prescriptions. However, its protective impact on osteoblasts postmenopausal osteoporosis (PMOP) not elucidated. This research aimed determine effect Lut ameliorating PMOP by alleviating and sustaining osteogenesis. was designed investigate novel both cell animal models. Ovariectomy-induced models were established mice with/without daily gavaged 10 or 20 mg/kg body weight Lut. The bone microstructure, metabolism oxidative stress evaluated with 0.104 Estradiol Valerate Tablets positive control. Network pharmacological analysis molecular docking employed mechanisms treatment. Subsequently, impacts PI3K/AKT axis, stress, mitochondria, assessed. In vitro, cultured (MC3T3-E1(14) cells exposed H2O2 examine signaling pathway, osteogenic differentiation, mitochondrial function, pyroptosis. Our findings demonstrated that Lut, similar control drug, effectively reduced systemic loss enhanced induced ovariectomy. indicated axis target, response nuclear membrane function being key mechanisms. Consequently, investigated. vivo data revealed deactivated following ovariectomy, restored phosphorylation proteins, thereby reactivating axis. Additionally, alleviated abnormalities intervention mitigated inhibition osteogenesis, well H2O2-induced Furthermore, attenuated ROS accumulation dysfunction. including osteogenesis restoration, anti-pyroptosis, maintenance, all reversed LY294002 (a pathway inhibitor). summary, could improve dysfunction, alleviate GSDME-mediated maintain via activating PI3K/Akt offering new therapeutic strategy for PMOP.

Язык: Английский

---

Adropin’s Role in Energy Homeostasis and Metabolic Disorders

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(15), С. 8318 - 8318

Опубликована: Июль 28, 2022

Adropin is a novel 76-amino acid-peptide that expressed in different tissues and cells including the liver, pancreas, heart vascular tissues, kidney, milk, serum, plasma many parts of brain. Adropin, encoded by Enho gene, plays crucial role energy homeostasis. The literature review indicates adropin alleviates degree insulin resistance reducing endogenous hepatic glucose production. improves metabolism enhancing utilization mice, sensitization signaling pathways such as Akt phosphorylation activation transporter 4 receptor. Several studies have also demonstrated cardiac function, efficiency coronary blood flow mice. can reduce levels serum triglycerides, total cholesterol low-density lipoprotein cholesterol. In contrast, it increases level high-density cholesterol, often referred to beneficial inhibits inflammation tissue pro-inflammatory cytokines tumor necrosis factor alpha interleukin-6. protective effect on endothelium through an increase expression endothelial nitric oxide synthase. This article provides overview existing about pathological conditions.

Язык: Английский

---

Tetrahedral Framework Nucleic Acids Based Small Interfering RNA Targeting Receptor for Advanced Glycation End Products for Diabetic Complications Treatment

ACS Nano, Год журнала: 2023, Номер 17(22), С. 22668 - 22683

Опубликована: Сен. 26, 2023

Complications arising from diabetes can threaten multiple organs. Advanced glycation end products (AGEs) play a significant role in inducing these complications. Highly processed diets and hyperglycemia facilitate the accumulation of AGEs body. Interaction between their main receptor (RAGE) initiates transmission intracellular inflammatory cell death signals, which ultimately lead to To counter AGEs-induced damage, we developed an siRNA-binding tetrahedral framework nucleic acids (TDN) system, termed Tsi, combines potent membrane penetrability serum stability TDN with gene-targeting specificity siRNA-RAGE. Tsi effectively persistently downregulates expression RAGE, thereby suppressing inflammation by blocking NF-κB pathway as well exhibiting antioxidant functions. Furthermore, regulates pyroptosis state macrophages via NLRP3/caspase-1 axis, inhibits spread signals maintains homeostasis. This is great significance for synergistic treatment strategy systemic complications patients refractory hyperglycemia. In summary, this study describes nanomedicine that targets RAGE suppresses AGE-induced inflammation. acid drug holds long-lasting efficacy independent lowering hyperglycemia, provides diabetic age-related diseases.

Язык: Английский

---

Activation of NLRP3 signaling contributes to cadmium-induced bone defects, associated with autophagic flux obstruction

The Science of The Total Environment, Год журнала: 2023, Номер 893, С. 164787 - 164787

Опубликована: Июнь 13, 2023

Язык: Английский

---

Irisin as an agent for protecting against osteoporosis: A review of the current mechanisms and pathways

Journal of Advanced Research, Год журнала: 2023, Номер 62, С. 175 - 186

Опубликована: Сен. 3, 2023

Osteoporosis is recognized as a skeletal disorder characterized by diminished bone tissue quality and density. Regular physical exercise widely acknowledged to preserve enhance health, but the detailed molecular mechanisms involved remain unclear. Irisin, factor derived from muscle during exercise, influences muscle. Since its discovery in 2012, irisin has been found promote growth reduce resorption, establishing tangible link between exertion health. Consequently, mechanism which prevents osteoporosis have attracted significant scientific interest.

Язык: Английский

---

Development of D–A–D‐Type NIR‐II Photothermal Agents for Synergistic Eradication of Multidrug‐Resistant Bacteria and Promoting Diabetic Wound Healing

Advanced Functional Materials, Год журнала: 2024, Номер unknown

Опубликована: Авг. 29, 2024

Abstract The challenge in treating diabetic foot infections caused by drug‐resistant bacteria is rapidly eradicating and accelerating wound healing. NIR‐II‐induced photothermal therapy (PTT) offers notable advantages over conventional treatments, such as broad‐spectrum bactericidal efficacy, better penetration depth biological tissues, higher skin tolerance thresholds, making it particularly suitable for addressing infections. Herein, found that NIR‐II dye IR26 exhibited good effects but poor stability. By modifying with methoxy triphenylamine groups, a novel D–A–D‐type small molecule agent (IRC) developed, high stability conversion efficiency (44.3%). IRC maximum absorption wavelength of 1166 nm emission 1238 nm. However, PTT alone cannot effectively promote Therefore, nanoplatforms (Cur‐IRC@PCM) are developed coloading curcumin, natural wound–healing compound, into thermosensitive liposomes to treat MRSA‐infected wounds. Under 980 laser irradiation, Cur‐IRC@PCM provided controlled the precise release synergizing eradicate accelerate closure. intelligent antibacterial also exhibits excellent biocompatibility, rendering promising therapeutic tool biomedical fields combating bacterial

Язык: Английский

---

Irisin improves diabetic cardiomyopathy-induced cardiac remodeling by regulating GSDMD-mediated pyroptosis through MITOL/STING signaling

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 171, С. 116007 - 116007

Опубликована: Янв. 3, 2024

Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM). However, the mechanisms underlying DCM-induced cardiac injury remain unclear. Recently, role cyclic GMP-AMP synthase/stimulator interferon gene (cGAS/STING) signaling and pyroptosis in DCM has been investigated. Based on our previous results, this study was designed to examine impact irisin, mitochondrial ubiquitin ligase (MITOL/MARCH5), cGAS/STING dysfunction effect gasdermin D (GSDMD)-dependent pyroptosis. High-fat diet-induced mice H9c2 cells were used for geometry function or pyroptosis-related biomarker assessment at end experiments. Here, we show that impairs by increasing fibrosis GSDMD-dependent pyroptosis, including activation MITOL signaling. Our results confirmed protective irisin partially offset We also demonstrated plays pivotal pathological process pathogenesis. indicate treatment protects against injury, homeostasis, through upregulation.

Язык: Английский

---

FNDC5/irisin ameliorates bone loss of type 1 diabetes by suppressing endoplasmic reticulum stress‑mediated ferroptosis

Journal of Orthopaedic Surgery and Research, Год журнала: 2024, Номер 19(1)

Опубликована: Март 30, 2024

Язык: Английский

---