Irisin-loaded electrospun core-shell nanofibers as calvarial periosteum accelerate vascularized bone regeneration by activating the mitochondrial SIRT3 pathway DOI Creative Commons
Xi Hua,

Mingzhuang Hou,

Lei Deng

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Июль 26, 2023

Abstract The scarcity of native periosteum poses a significant clinical barrier in the repair critical-sized bone defects. challenge enhancing regenerative potential healing is further compounded by oxidative stress at fracture site. However, introduction artificial has demonstrated its ability to promote regeneration through provision appropriate mechanical support and controlled release pro-osteogenic factors. In this study, polylactic acid (PLLA)/hyaluronic (HA)-based nanofibrous membrane was fabricated using coaxial electrospinning technique. incorporation irisin into core-shell structure PLLA/HA nanofibers (PLLA/HA@Irisin) achieved sustained release. vitro experiments that PLLA/HA@Irisin membranes exhibited favorable biocompatibility. osteogenic differentiation marrow mesenchymal stem cells (BMMSCs) improved PLLA/HA@Irisin, as evidenced increase alkaline phosphatase (ALP) activity matrix mineralization. Mechanistically, significantly enhanced mitochondrial function BMMSCs via activation sirtuin 3 antioxidant pathway. To assess therapeutic effectiveness, were implanted situ calvarial defects rats. results four eight weeks post-surgery indicated implantation superior efficacy promoting vascularized formation, enhancement synthesis development new blood vessels. our study indicate electrospun possess characteristics biomimetic periosteum, showing for effectively treating improving maintaining redox homeostasis BMMSCs.

Язык: Английский

Irisin alleviates hepatic steatosis by activating the autophagic SIRT3 pathway DOI Creative Commons
Ying Zhao, Jia Li,

Anran Ma

и другие.

Chinese Medical Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 18, 2025

Abstract Background: Disruption of hepatic lipid homeostasis leads to excessive triglyceride accumulation and the development metabolic dysfunction-associated steatotic liver disease (MASLD). Autophagy, a critical process in metabolism, is impaired MASLD pathogenesis. Irisin, skeletal muscle-driven myokine, regulates but its impact on metabolism not well understood. Here, we aimed explore role irisin steatosis underlying mechanisms involved. Methods: A high-fat diet (HFD)-induced mouse model was used, recombinant protein, herein referred as “Irisin”, intraperitoneally administered for 4 weeks evaluate effects accumulation. Liver tissues were stained with Oil red O (ORO), (TG) total cholesterol (TC) contents measured serum homogenates. The expression autophagosome marker microtubule-associated protein 1 light chain 3 (LC3), autophagy receptor sequestosome-1 (SQSTM1/p62), initiation complex unc-51-like kinase (ULK1) lysosomal functional cathepsin B via Western blotting, transcription factor EB (TFEB) analyzed immunofluorescence autophagic changes. effect flux further evaluated palmitic acid-induced HepG2 cells by measuring degradation chloroquine (CQ), analyzing colocalization LC3 lysosome-associated (LAMP1). possible mechanism examined sirtuin (SIRT3) pathway validated using overexpression SIRT3 plasmid transfection or siRNA-mediated knockdown. Student’s t -test utilized statistical analysis. Results: Irisin significantly reduces mice fed HFD, accompanied enhanced hepatocyte upregulation pathway. In cells, attenuated accumulation, which partially dependent levels. Mechanistically, treatment upregulated phosphorylated AMP-activated (AMPK), inhibited mammalian target rapamycin (mTOR) activity, promoted TFEB nucleus translocation, increased expression, degradation, alleviated steatosis. No significant changes phosphorylation ULK1 hepatocytes observed. However, when siRNA used knock down , those reversed, exacerbated. Conclusions: Our findings highlight potential therapeutic modulating potentially providing novel management MASLD. Further research needed elucidate clinical applications this approach

Язык: Английский

Процитировано

1

The Role of the Myokine Irisin in the Protection and Carcinogenesis of the Gastrointestinal Tract DOI Creative Commons
Monika Pinkas, Tomasz Brzozowski

Antioxidants, Год журнала: 2024, Номер 13(4), С. 413 - 413

Опубликована: Март 28, 2024

Recently discovered irisin, a member of the myokines family, is potential mediator exercise-induced energy metabolism and factor promoting browning white adipose tissue. Recent evidence indicates that this myokine, released from contracting muscles, can mediate beneficial effects exercise on health. Irisin may be therapeutic agent against obesity has been shown to play an important role in protection various cells, tissues, organs due its anti-inflammatory, antioxidative, anti-cancer properties. Our aim was review recent experimental clinical studies irisin expression, release into bloodstream, tissue targets, contribution protective gastrointestinal tract. Particular emphasis placed inflammatory bowel disease, intestinal ischemia/reperfusion injury, periodontitis, other digestive tract disorders, including carcinogenesis. Overall, holds significant as novel target molecule, offering safe approach treating diseases.

Язык: Английский

Процитировано

5

Eternal Youth: A Comprehensive Exploration of Gene, Cellular, and Pharmacological Anti-Aging Strategies DOI Open Access
Kristina V. Kitaeva, Valeriya V. Solovyeva, Nataliya L. Blatt

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(1), С. 643 - 643

Опубликована: Янв. 4, 2024

The improvement of human living conditions has led to an increase in average life expectancy, creating a new social and medical problem—aging, which diminishes the overall quality life. aging process body begins with activation effector signaling pathways cells, resulting loss their normal functions deleterious effects on microenvironment. This, turn, leads chronic inflammation similar transformations neighboring cells. cumulative retention these senescent cells over prolonged period results deterioration tissues organs, ultimately leading reduced elevated risk mortality. Among most promising methods for addressing age-related illnesses are pharmacological, genetic, cellular therapies. Elevating activity aging-suppressing genes, employing specific groups native genetically modified utilizing senolytic medications may offer potential delay ailments long term. This review explores strategies advancements field anti-aging therapies currently under investigation, particular emphasis gene therapy involving adeno-associated vectors cell-based therapeutic approaches.

Язык: Английский

Процитировано

4

Sirt3 Rescues Porphyromonas gingivalis‐Impaired Cementogenesis via SOD2 Deacetylation DOI Creative Commons

Xin Huang,

Huiqing Gou,

Jirong Xie

и другие.

Cell Proliferation, Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

ABSTRACT The keystone pathogen Porphyromonas gingivalis (P.g.) is responsible for cementum resorption in periodontitis; however, the mechanism involved it remains unclear. Sirtuin 3 (Sirt3) a NAD + ‐dependent protein deacetylase contributing to mitochondrial homeostasis and various cell functions. In this study, expression of Sirt3 cementoblasts was found be increased during cementoblast mineralisation development, while decreased gradually under P.g. infection multiplicity infection‐dependent manner. Compared with wild type mice, knockout mice showed less cellular lower capacity Runx2 OCN cementoblasts. inhibition by 3‐TYP or silencing lentivirus both confirmed impaired cementogenesis. Conversely, honokiol (HKL) simulated bind applied activate HKL‐mediated activation facilitated rescued P.g.‐suppressed markedly. Superoxide dismutase 2 (SOD2), downstream molecule Sirt3, similar pattern different conditions. Silencing SOD2 demonstrated restrain mineralisation. pan acetylation detected decrease Sirt3‐upregulating conditions increase Sirt3‐downregulating binding also verified. Furthermore, specific SOD2‐K68 were upregulated downregulated HKL stimulation. Moreover, K68Q mutation simulating mineralisation, K68R deacetylation it. Altogether, deacetylates via K68 orchestrate P.g.‐perturbed cementogenesis, Sirt3‐targeted treatment candidate.

Язык: Английский

Процитировано

0

Poly(lactide acid)-based microneedles enhanced by tunicate cellulose nanocrystals for potential diabetic periodontitis treatment DOI
Yang Yang,

Guoyuan Zhou,

Yang Chen

и другие.

Carbohydrate Polymers, Год журнала: 2025, Номер unknown, С. 123629 - 123629

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0

Irisin-loaded electrospun core-shell nanofibers as calvarial periosteum accelerate vascularized bone regeneration by activating the mitochondrial SIRT3 pathway DOI Creative Commons
Xi Hua,

Mingzhuang Hou,

Lei Deng

и другие.

Regenerative Biomaterials, Год журнала: 2023, Номер 11

Опубликована: Окт. 31, 2023

Abstract The scarcity of native periosteum poses a significant clinical barrier in the repair critical-sized bone defects. challenge enhancing regenerative potential healing is further compounded by oxidative stress at fracture site. However, introduction artificial has demonstrated its ability to promote regeneration through provision appropriate mechanical support and controlled release pro-osteogenic factors. In this study, poly (l-lactic acid) (PLLA)/hyaluronic acid (HA)-based nanofibrous membrane was fabricated using coaxial electrospinning technique. incorporation irisin into core-shell structure PLLA/HA nanofibers (PLLA/HA@Irisin) achieved sustained release. vitro experiments that PLLA/HA@Irisin membranes exhibited favorable biocompatibility. osteogenic differentiation marrow mesenchymal stem cells (BMMSCs) improved PLLA/HA@Irisin, as evidenced increase alkaline phosphatase activity matrix mineralization. Mechanistically, significantly enhanced mitochondrial function BMMSCs via activation sirtuin 3 antioxidant pathway. To assess therapeutic effectiveness, were implanted situ calvarial defects rats. results 4 8 weeks post-surgery indicated implantation superior efficacy promoting vascularized formation, enhancement synthesis development new blood vessels. our study indicate electrospun possess characteristics biomimetic periosteum, showing for effectively treating improving maintaining redox homeostasis BMMSCs.

Язык: Английский

Процитировано

6

Causal Relationship between Mitochondrial Biological Function and Periodontitis: Evidence from a Mendelian Randomization Study DOI Open Access
Huan Zhou,

Yan-Xin Qi,

Ruoyan Cao

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(14), С. 7955 - 7955

Опубликована: Июль 21, 2024

A growing number of studies indicate that mitochondrial dysfunction serves as a pathological mechanism for periodontitis. Therefore, this two-sample Mendelian randomization (MR) study was carried out to explore the causal associations between biological function and periodontitis, because specific nature relationship remains inconclusive in existing MR studies. Inverse variance weighting, randomization-Egger, weighted mode, simple median analyses were performed assess relationships exposure factors The results present revealed association periodontitis medium-chain acyl-CoA dehydrogenase (MCAD), malonyl-CoA decarboxylase (MLYCD), glutaredoxin 2 (Grx2), oligoribonuclease (ORN), pyruvate carboxylase (PC). Notably, MCAD MLYCD are causally linked serve protective factors. However, Grx2, ORN, PC risk Our established such insights may provide promising approach treating via regulation.

Язык: Английский

Процитировано

1

The interconnection between periodontitis and HIV-1 latency: Molecular mechanisms and therapeutic insights DOI
Tengyi Zheng, Fangguo Lu, Tiange Cai

и другие.

International Immunopharmacology, Год журнала: 2024, Номер 143, С. 113402 - 113402

Опубликована: Окт. 21, 2024

Язык: Английский

Процитировано

1

Attenuated NIX in impaired mitophagy contributes to exacerbating cellular senescence in experimental periodontitis under hyperglycemic conditions DOI Open Access

Danni Song,

Beibei Chen, Tianfan Cheng

и другие.

FEBS Journal, Год журнала: 2024, Номер unknown

Опубликована: Дек. 24, 2024

Premature accumulation of senescent cells results in tissue destruction, and it is one the potential primary mechanisms underlying accelerated progression diabetes periodontitis. However, whether this characterized phenomenon could account for periodontal pathogenesis under hyperglycemic conditions remains unclear. In study, we assessed phenotypic changes experimental periodontitis conditions. Next, investigated mitochondrial function mitophagy pathways cellular senescence vitro vivo. Our findings showed that significant occurred gingival tissues diabetic mice with increased expression senescence-related protein p21

Язык: Английский

Процитировано

1

MiR-29a-5p engages in the mechanism of diabetic retinopathy by specifically targeting SIRT3 DOI Creative Commons
J. He,

Shuai Chao Wei,

qing Liang

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Апрель 3, 2024

Abstract Whether miR-29a-5p is associated with diabetic retinopathy (DR) still a subject of ongoing discussion. The current research examines the involvement in regulating apoptosis, oxidative stress, and inflammation retinal ganglion cells (RGCs) generated by high glucose (HG). Additionally, we are interested analyzing contribution developing DR. We obtained peripheral blood samples from 7 people DR 14 individuals without Subsequently, conducted biochemical indices analyses qRT-PCR. randomly divided RGCs into low groups, HG + inhibitor negative control groups. SIRT3 siRNA was transfected through lipofectamine 3000 reagent. Cell vitality detected MTT; qRT-PCR applied to identify expression; Detection ROS, SOD, MDA levels quantified using DCFH-DA, WST-1, colorimetric methods, respectively; IL-6 TNF-α contents were analyzed utilizing ELISA; Dual-luciferase gene reporter experiment used examine if specific target miR-29a-5p; Flow cytometry evaluated apoptosis RGCs; technique Western blotting identified expression Caspase-3, Bax Bcl-2 proteins. markedly elevated DR, it had positive correlations total cholesterol (TC) fasting (FBG). combination miR-29a-5p, cholesterol, triglycerides (TG) exhibits significant diagnostic value for demonstrating both sensitivity specificity. High stimulated worsened cellular inflammatory response, apoptotic levels. Transfection protected against HG-induced injury, inflammation, apoptosis. Furthermore, dual-luciferase provided confirmation that as negatively regulated expression. Notably, knockdown abolished protection inhibition on RGCs. Suppression safeguards injury caused via boosting signaling, which might provide new prevention treatment strategy

Язык: Английский

Процитировано

0