Overexpression of IL-10 in Adipose Mesenchymal Stem Cells Promotes Wound Healing in Diabetic Mice DOI Creative Commons
Hui Zhao,

Feng Song,

Xiao Shi

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Abstract Background: Diabetic ulcer is a serious chronic non-healing wound, which often leads to amputation or even death, causing great damage the patients and their families. In recent years, stem cells are increasingly studied for tissue repair. Adipose tissue-derived mesenchymal (Adipose-derived cells, ADSCs) have advantages of wide source easy access. ADSCs can accelerate wound healing reduce scar hyperplasia, especially wounds, cannot heal with traditional treatments, bring hope these patients. Our study intends overexpress IL-L 10 in by genetic engineering technology, transplant ADSC-IL diabetic mouse use role IL-10 promoting M2 macrophages transformation, combined achieve rapid wounds. Methods: The expression protein supernatant ADSC-IL10 was assessed using an ELISA kit. Flow cytometry employed analyze surface cell markers (CD44, CD73, CD90, CD105) ADSC-IL10. Additionally, migration proliferation were evaluated through scratch assays MTT assays. lipogenic marker PPARγ osteogenic RUNX2 detected fluorescent real-time quantitative PCR. Conditioned media from (ADSC-IL10-CM) ADSC-PCDH (ADSC-CM) culture peritoneal (Raw 264.7). Following 12-hour incubation period, Raw 264.7 harvested mRNA extraction. types identified qPCR, M1 phenotype determined CD86 Arg-1 CD206. levels inflammatory factors, including IL-1β, IL-6, IL-10, MCP-1, growth factors such as EGF, VEGF, TGFβ-1, quantified qPCR. transwell method utilized assess impact ADSC-IL10-CM ADSC-CM on normal skin fibroblasts. scribing applied examine effect human immortalized epidermal cells. A model induced high-fat, high-sugar diet streptozocin. group, 1×10^6 transplanted onto 1.5cm×1.5cm surface, similarly, group. control group received equal volume 0.9% saline. process mice observed documented at various time points. Tissue samples wounds days 3 7 subjected histological staining qPCR analysis. HE used monitor progress, while immunofluorescence (CD206, Arg-1) quantify presence M2-type skin. CD206 genes measured ascertain macrophage phenotypes within tissues. Levels MCP-1 evaluate status TGFβ-1 tissues assessed. Conclusion: overexpression does not alter biological characteristics ADSCs. When into mice, more effectively than alone. mechanism enhances may encompass several aspects: it stimulates macrophages, suppresses secretion pro-inflammatory promotes production like VEGF. encourages fibroblasts sites mice.

Language: Английский

Regulation of cellular and systemic sphingolipid homeostasis DOI
Andrew Kuo, Timothy Hla

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(10), P. 802 - 821

Published: June 18, 2024

Language: Английский

Citations

22
Nonenzymatic lysine d-lactylation induced by glyoxalase II substrate SLG dampens inflammatory immune responses DOI Creative Commons

Qihang Zhao,

Qiang Wang, Qinghua Yao

et al.

Cell Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Abstract Immunometabolism is critical in the regulation of immunity and inflammation; however, mechanism preventing aberrant activation-induced immunopathology remains largely unclear. Here, we report that glyoxalase II (GLO2) glycolysis branching pathway specifically downregulated by NF-κB signaling during innate immune activation via tristetraprolin (TTP)-mediated mRNA decay. As a result, its substrate S -D-lactoylglutathione (SLG) accumulates cytosol directly induces d -lactyllysine modification proteins. This nonenzymatic lactylation SLG greatly facilitated nearby cysteine residue, as it initially reacts with to form reversible -lactylated thiol intermediate, followed SN -transfer lactyl moiety proximal lysine. Lactylome profiling identifies 2255 sites mostly cytosolic proteins activated macrophages, global protein structure analysis suggests proximity residue determines susceptibility lysine SLG-mediated -lactylation. Furthermore, preferentially enriched involved inflammatory pathways, -lactylation at 310 (K310) RelA attenuates transcriptional activity restore homeostasis. Accordingly, TTP-binding site mutation or overexpression GLO2 vivo blocks this feedback cells promotes inflammation, whereas genetic deficiency pharmacological inhibition restricts both vitro vivo. Importantly, dysregulation GLO2/SLG/ regulatory axis closely associated human phenotypes. Overall, our findings uncover an immunometabolic loop SLG-induced implicate promising target for combating clinical disorders.

Language: Английский

Citations

6
Recent advances in epidemiology, pathogenesis, diagnosis, and treatment of inflammatory bowel disease: Insights from the past two years DOI Creative Commons
Jian Wan, Jiaming Zhou, Zhuo Wang

et al.

Chinese Medical Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Abstract Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a chronic inflammation of the gastrointestinal tract with unknown etiology. The cause IBD widely considered multifactorial, prevailing hypotheses suggesting that microbiome various environmental factors contribute to inappropriate activation mucosal immune system in genetically susceptible individuals. Although incidence has stabilized Western countries, it rapidly increasing newly industrialized particularly China, making global disease. Significant changes multiple biomarkers before diagnosis during preclinical phase provide opportunities for earlier intervention. Advances technology have driven development telemonitoring tools, such as home-testing kits fecal calprotectin, serum cytokines, therapeutic drug concentrations, well wearable devices testing sweat cytokines heart rate variability. These tools enable real-time activity assessment timely treatment strategy adjustments. A wide range novel drugs IBD, interleukin-23 inhibitors (mirikizumab, risankizumab, guselkumab) small-molecule (etrasimod upadacitinib), been introduced past few years. Despite these advancements, approximately one-third patients remain primary non-responders initial treatment, half eventually lose response over time. Precision medicine integrating multi-omics data, advanced combination therapy, complementary approaches, stem cell transplantation, psychological therapies, neuromodulation, gut modulation may offer solutions break through ceiling.

Language: Английский

Citations

3
Complex Role of Regulatory T Cells (Tregs) in the Tumor Microenvironment: Their Molecular Mechanisms and Bidirectional Effects on Cancer Progression DOI Open Access
Yu Wang, Jiazhou Li, Shingo Nakahata

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7346 - 7346

Published: July 4, 2024

Regulatory T cells (Tregs) possess unique immunosuppressive activity among CD4-positive cells. Tregs are ubiquitously present in mammals and function to calm excessive immune responses, thereby suppressing allergies or autoimmune diseases. On the other hand, due their function, thought promote cancer progression. The tumor microenvironment (TME) is a multicellular system composed of many cell types, including cells, infiltrating cancer-associated fibroblasts (CAFs). Within this environment, recruited by chemokines metabolic factors impede effective anti-tumor responses. However, some cases, presence can also improve patient's survival rates. Their functional consequences may vary across locations, stages. An in-depth understanding precise roles mechanisms actions Treg crucial for developing treatments, emphasizing need further investigation validation. This review aims provide comprehensive overview complex multifaceted within TME, elucidating cellular communications, signaling pathways, impacts on progression highlighting potential through interactions with molecules.

Language: Английский

Citations

13
Synthesis and Application of Selenium Nanoparticles for the Modulation of Inflammatory Diseases DOI Creative Commons
Xueli Bai, Tianfei Zhou, Xiaowen Wu

et al.

Nano Biomedicine and Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

2
Ferroptosis meets inflammation: a new frontier in cancer therapy DOI
Hu Liu,

Hui Xue,

Qian Guo

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217696 - 217696

Published: April 1, 2025

Language: Английский

Citations

2
Bioactive sphingolipids as emerging targets for signal transduction in cancer development DOI
Wentao Jia,

Jiaying Yuan,

Jinbo Zhang

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(5), P. 189176 - 189176

Published: Sept. 1, 2024

Language: Английский

Citations

8
Theoretical Framework and Emerging Challenges of Lipid Metabolism in Cancer DOI Creative Commons
Qiuying Gu, Yuan Wang, Ping Yi

et al.

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Elevated lipid metabolism is one of hallmarks malignant tumors. Lipids not only serve as essential structural components biological membranes but also provide energy and substrates for the proliferation cancer cells tumor growth. Cancer meet their needs by coordinating processes absorption, synthesis, transport, storage, catabolism. As research in this area continues to deepen, numerous new discoveries have emerged, making it crucial scientists stay informed about developments metabolism. In review, we first discuss relevant concepts theories or assumptions that help us understand -based therapies. We then systematically summarize latest advancements including mechanisms, novel targets, up-to-date pre-clinical clinical investigations anti-cancer treatment with targeted drugs. Finally, emphasize emerging directions therapeutic strategies, future prospective challenges. This review aims insights guidance field

Language: Английский

Citations

8
Targeting ACSLs to modulate ferroptosis and cancer immunity DOI
Junhong Lin,

Yongfeng Lai,

Fujia Lu

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

7
Interleukin-10 exhibit dose-dependent effects on macrophage phenotypes and cardiac remodeling after myocardial infarction DOI Creative Commons

Jing J. Zhang,

Rodrigue Rizk, Xiaoping Li

et al.

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 15, 2025

Interleukin-10 (IL-10) is a potent immunomodulatory cytokine widely explored as therapeutic agent for diseases, including myocardial infarction (MI). High-dose IL-10 treatment may not achieve expected outcomes, raising the question of whether has dose-dependency, or even uncharted side-effects from overdosing. We hypothesized that dose-dependent effects on macrophage (Mφ) phenotypic transition and cardiac remodeling after MI. Using RAW264.7 monocyte models, we examined administering differential doses exogenous (0-1,000 ng/mL) perturbs classic M1 (pro-inflammatory) M2 (anti-inflammatory) phenotypes polarized Mφ alters prospective polarization. then investigated impact single intramyocardial administration function, structure, inflammation post-MI, using mouse MI model. Compared with 0-ng/mL control, 250-ng/mL had strongest overall in decreasing increasing while ≥500-ng/mL dampened polarization augmented native secretion more effectively than low vitro. Echocardiography revealed 250-ng group consistently higher contractile function lower left ventricular (LV) dilatation saline control over 6 weeks ≥1,000-ng groups exhibited transient LV ejection fraction at 5 days post-MI vivo. Moreover, different differentially modulated gene expression, phagocytic cell infiltration infarct, fibrosis, revascularization some, but all, exerting beneficial effects. Our study suggested an effective dose range phenotypes, trigger cardioprotective unwanted manner.

Language: Английский

Citations

1