NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2024
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IF 3.1
Sun Hui,Wang ZiTong,Tu BingHua,Shao ZiChen,Li YiDan,Han Di,Jiang YinJie,Zhang Peng,Zhang WeiChang,Wu YunYan,Wu XiaoMing,Liu Chi-Ming
Type 2 diabetes mellitus (T2DM) is a metabolic disease. Diabetes increases the risk of benign prostatic hyperplasia (BPH). Capsaicin is extracted from chili peppers and possesses many pharmacological properties, including anti-diabetic, pain-relieving, and anti-cancer properties. This study aimed to investigate the effects of capsaicin on glucose metabolism and prostate growth in T2DM mice and uncover the related mechanisms. Mice model of diabetes was established by administering a high-fat diet and streptozotocin. Oral administration of capsaicin for 2 weeks inhibited prostate growth in testosterone propionate (TP)-treated mice. Furthermore, oral administration of capsaicin (5 mg/kg) for 2 weeks decreased fasting blood glucose, prostate weight, and prostate index in diabetic and TP-DM mice. Histopathological alterations were measured using hematoxylin & eosin (H&E) staining. The protein expression of 5α-reductase type II, androgen receptor (AR), and prostate-specific antigen (PSA) were upregulated in diabetic and TP-DM mice, but capsaicin reversed these effects. Capsaicin decreased the protein expression of p-AKT, insulin-like growth factor-1 (IGF-1), IGF-1R, and the receptor for advanced glycation end products (RAGE) in diabetic and TP-DM mice. Capsaicin also regulated epithelial-mesenchymal transition (EMT) and modulated the expression of fibrosis-related proteins, including E-cadherin, N-cadherin, vimentin, fibronectin, α-SMA, TGFBR2, TGF-β1, and p-Smad in TP-DM mice. In this study, capsaicin alleviated diabetic prostate growth by attenuating EMT. Mechanistically, capsaicin affected EMT by regulating RAGE/IGF-1/AKT, AR, and TGF-β/Smad signalling pathways. These results provide with new therapeutic approach for treating T2DM or T2DM-induced prostate growth.
研究领域:
药理学
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内分泌学
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糖尿病
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前列腺健康
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信号转导
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DOI
PubMed
高影响因子
JOURNAL OF SURGICAL RESEARCH
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2021
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IF 2.192
Shaohang Cheng,Runxiao Lv,Jing Xu,Abdul Razaq Hirman,Lili Du
ABSTRACT Background Stem cell-based regenerative therapy is a novel approach to severe damaged skin. Perinatal tissues such as placenta are considered as promising alternatives. The present study aimed to investigate the effect of insulin-like growth factor-1 (IGF-1)-expressing placenta-derived mesenchymal stem cells (hPMSCs) on healing of burn wounds. Materials and methods hPMSCs were isolated from human placenta, and IGF-1 was transducted into hPMSCs via lentivirus . Flow cytometry and MTT assay were performed to assess cell apoptosis and viability, respectively. Immunostaining of CK19 and ki67 was for evaluating epithelial differentiation ability and cell proliferation . For in vivo studies, we established a mouse model of scalding and performed local administration of IGF-1-expressing hPMSCs via subcutaneous injection . Wound histology was analyzed with H&E staining. The expression of fibrogenic cytokines was detected by western blot. The production of pro-inflammatory factors was measured by ELISA. Results Overexpression of IGF-1 promoted cell proliferation and epithelial differentiation of hPMSCs in vitro and in vivo . Mice with burn injury displayed increased wound contraction and healing rates following treatment with IGF-1-expressing hPMSCs. There was less inflammatory infiltration and reduced collagen disposition in the presence of IGF-1 at the wound site. Administration of IGF-1-expressing hPMSCs suppressed inflammation by decreasing the levels of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6. Besides, IGF-1 increased VEGF expression, and decreased TGF-β1, collagen I and collagen III expressions in vivo . Conclusions IGF-1-expressing PMSCs promotes cell proliferation and epithelial differentiation, inhibits inflammation and collagen deposition, and thus contributes to wound healing.
研究领域:
干细胞生物学
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再生医学
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伤口愈合
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免疫学
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DOI
PubMed
高影响因子
Regenerative Therapy
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2026
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IF 4
Yi Zhang,Qi Fang,Xiao Yang
Introduction 3D-printing implants have attracted increasing attention for enhancing the regeneration of various wound types. The rigidity of traditional 3D printing materials limits their applicability in skin wound repair. In addition, improving the bioactivity of polymeric materials remains an urgent challenge to be addressed. Insulin-like growth factor-1 (IGF-1) is widely recognized for its efficacy in skin wound repair. However, the potency of IGF-1 in wound regeneration is limited by its unstable binding to the implants. Methods In this study, A phase inversion-based deposition modeling 3D printing technique was employed to construct flexible poly(lactic-co-glycolic acid) (PLGA) scaffold. Additionally, a novel 3D-printing flexible skin implantation functionalized with bioorthogonal IGF-1 (DA-IGF-1) was fabricated. The adhesion, proliferation and relative mRNA expression of cells on PLGA scaffold were assessed. Meanwhile, a full-thickness skin defect regeneration model was established on the rat back to evaluate the wound repair efficacy of the implanted scaffolds. Results The DA-IGF-1 exhibited outstanding binding ability on the scaffold. The resulting PLGA flexible scaffold modified with DA-IGF-1 showed significantly enhanced hydrophilicity and biocompatibility compared with the control group materials ( p < 0.05). The expression of wound regeneration related genes was also upregulated significantly in the DA-IGF-1 group ( p < 0.05). In vivo study indicated that bioactive implants effectively promoted healing and neovascularization of full-thickness skin defects in rats. Conclusion These results demonstrated that the 3D-printing flexible PLGA scaffold modified with bioorthogonal IGF-1 holds great potential for application as a novel therapeutic strategy for wound regeneration.
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高影响因子
Frontiers in Physiology
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2024
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IF 3.2
Li Xi-Tong,Qian Xiu-Juan,Chen Hong,Wang Xing-Duo,Wu Xia
Glycerophosphocholine (GPC) is a water-soluble small molecule found naturally in humans and foods such as milk and soybeans. It can activate the IIS pathway by regulating the expression of daf-2, ins-18 and daf-16 genes, sek-1 and skn-1 genes of MAPK pathway, sod-3, ctl-1, gst-4 and other antioxidant genes. GPC can relieve symptoms related to aging in organisms. The aim of this study was to probe the effects of GPC on the longevity and stress resistance of the entomopathogenic nematode (EPN) Steinernema kraussei 0657L strain. The results showed that the lifespan of S. kraussei 0657L was significantly prolonged by 50 mM GPC treatment, which was 54.55% longer than that of the control (0 mM GPC). GPC significantly inhibited reactive oxygen species (ROS) and lipofuscin accumulation, but the body size and fecundity of S. kraussei 0657L had little changed. At the same time, the longevity of S. kraussei 0657L exposed to heat shock and UV-B radiation was significantly prolonged than that with no external stress. GPC supplementation increased the activity of antioxidant enzymes and corresponding gene expression. Under treatment with 50 mM GPC, the activities of superoxide dismutase and catalase were increased by 1.90- and 4.13-fold, respectively, the expression of the sod-3 and ctl-1 genes was increased by 3.60- and 0.60-fold, respectively, and harmful reactive oxygen species were removed. In addition, the expression levels of the ins-18, skn-1, sek-1 and gst-4 genes related to the insulin/IGF-1 signaling pathway were upregulated 1.04-, 1.84-, 2.21- and 1.24-fold, respectively. These results indicate that GPC is mainly involved in the lifespan regulation of S. kraussei 0657L and plays an important role in resistance to external stress by activating the insulin/IGF-1 signaling pathway and downstream PI3K/MAPK kinase, creating a new idea for improving the commercial efficacy of S. kraussei. It also laid a theoretical foundation for its further efficient development and utilization in the field of biological control.
研究领域:
分子生物学
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生物控制
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遗传学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
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2026
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IF 5.2
Liangyong Shao,Xiaohan Zhang,Jiamei Xin,Baorui Li,Huiyong Lian,Jiao Xie,Kai Yu,Ye Zhang,Hao Wang
Silibinin had both anti-obesity and anti-aging effects. • The effects of Silibinin on obesity and aging were linked to the IIS pathway. • Network pharmacology and molecular docking verified Silibinin 's anti-obesity mechanism. Although silibinin (SIL), from milk thistle, has been reported to promise health promotion and disease treatment, the potential mechanism of SIL in improving obesity is still unknown. The fat accumulation was decreased by 78% and 49% in cellular and high glucose-induced (HGI) Caenorhabditis elegans ( C.elegans ) models. The decreased lipid droplets in both average size and quantity in the cytoplasm of the liver and EWATs were obtained by histology (hematoxylin & eosin) experiments. The promoted health effects in lifespan, stress ability, antioxidant ability, changed lipofuscin accumulation, pharyngeal pumping rate, and aging-related indexes of exercise were also confirmed. The increased expressions of daf-2, akt-1, daf-16, and skn-1 , combined with the downstream target genes of IIS-mediated mTOR signaling factors ( pha-4, hlh-30, lgg-1, and unc-51 ) and adipose-related factors ( nhr-49, fat-5, fat-6, and fat-7 ) in C. elegans were verified through the insulin/insulin-like growth factor-1 signaling pathway. SIL was proposed as a potential adjuvant remedy or nutraceutical for improving obesity and promoting health. Download: Download high-res image (146KB) Download: Download full-size image
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Danyang Liu,Yiming Song,Bing Zheng,Jianhua Xie,Yi Chen,Jiayan Xie,Xinyi Chen,Qiang Yu
This study aimed to investigate the mitigation effect of epigallocatechin gallate (EGCG) on aging induced by 3-monochloropropane-1,2-diol (3-MCPD) in Caenorhabditis elegans, evaluate health indicators during the process, and reveal the underlying mechanism through transcriptomics and identification of mutants. The results showed that EGCG alleviated the declined fertility, shortened lifespan, reduced body size, weakened movement, increased reactive oxygen species and lipofuscin, and damaged antioxidative stress response and excessive heat shock proteins caused by 3-MCPD. Transcriptomics study indicated that treatment with 3-MCPD and EGCG altered gene expression, and gene mutants confirmed the involvement of insulin/IGF-1 signaling pathway in mediating the process that EGCG alleviated the aging toxicity induced by 3-MCPD. The study showed that EGCG alleviated the aging toxicity induced by 3-MCPD.
研究领域:
分子生物学
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毒理学
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遗传学
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DOI
PubMed
高影响因子
NATURE CELL BIOLOGY
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2025
·Vol. 27
·期 8
·1357-1366
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IF 19.1
Du Xian,Li Wenyan,Li Guiying,Guo Chenyue,Tang Xuyi,Bao Rujuan,Li Runchang,Huang Haiyan,Xu Shuiyu,Yu Xiaoyan,Han Qiaoqiao,Wan Jie,Li Song,Sun Jiayuan,Zhao Ren,Ye Youqiong,Gao Qiang,Ni Zhi-Yu,Cui Xingang,Zou Qiang
Dietary nutrients are inextricably linked to antitumour immune responses. However, the effect of diet-derived galactose on antitumour immunity remains unclear. Here we show that dietary galactose augments CD8 + T cell immunity to suppress tumour progression. High-galactose feeding drives hepatocyte-derived insulin-like growth factor binding protein 1 (IGFBP-1) production, thus restraining IGF-1 signalling-dependent T cell exhaustion. IGF-1 receptor (IGF-1R) deficiency in T cells potentiates antitumour CD8 + T cell responses and phenocopies high-galactose feeding by preventing T cell exhaustion. Circulating galactose reprograms hepatocyte metabolism to inactivate mTORC1, thereby inducing the production of IGFBP-1 to boost CD8 + T cell function. Furthermore, patients with cancer who have high plasma IGFBP-1 levels exhibit blocked T cell exhaustion and enhanced T cell responses in tumour tissues. These findings reveal that dietary galactose specifically elicits potent antitumour CD8 + T cell responses by facilitating hepatocyte-derived IGFBP-1 production, providing insights into the development of more effective immunotherapies against cancers.
研究领域:
免疫学
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肿瘤学
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分子生物学
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转化医学
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代谢调控
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DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
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2025
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IF 4.3
Li Ting,Zhou Sheng-Yang,Quan Wei,Zhou Yu,Wu Jian,Zhao Li-Ping,Qiao Chen-Meng,Zhao Wei-Jiang,Cui Chun,Shen Yan-Qin
More than 80% of patients with Parkinson’s disease (PD) exhibit severe gastrointestinal symptoms, which seriously affect life quality of life. Several large-scale epidemiological studies have confirmed that exercise can improve motor symptoms of PD patients, but the influence on gastrointestinal symptoms has not been reported. To clarify whether exercise can enhance intestinal barrier and ameliorate intestinal inflammation in PD mice, we examined whether moderate-intensity treadmill exercise for 6 weeks could alleviate gastrointestinal symptoms in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute PD mice. Our results demonstrated that 6 weeks moderate-intensity treadmill exercise enhanced the expression of Muc-2 and tight junction proteins, while reducing the expression of cytokines and chemokines, in the distal colon. Moreover, 6 weeks of treadmill exercise reduced the concentrations of short-chain fatty acids (SCFAs) and the expression of G protein-coupled receptor 43 (GPR43) to maintain the intestinal barrier and alleviate intestinal inflammation. Further data showed that 6 weeks of moderate-intensity treadmill exercise enhanced insulin-like growth factor 1 (IGF-1) expression and activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Taken as a whole, these results revealed that 6 weeks of moderate-intensity treadmill exercise enhanced intestinal barrier function, reduced intestinal inflammation and corrected abnormal concentrations of SCFAs by activating IGF-1/PI3K/Akt pathway in MPTP-induced subacute PD mice.
研究领域:
神经生物学
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运动医学
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胃肠病学
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DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
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2026
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IF 4.7
Gao Xiaobo,Lei Bocheng,Zhao Xiaomin,Zhang Ying
Many active ingredients from traditional Chinese medicine (TCM) have been applied in bone tissue engineering. However, the fuzzy mechanism of these ingredients limits their application. In this study, a novel biomimetic bone scaffold functionalized with two TCM ingredients, nano deer bone meals (nBM) and neferine (Nef), as well as collagen-binding IGF-1 (CBD-IGF-1) was fabricated via a combination of phase inversion and particle leaching methods. The biomimetic CIGF1&Nef@PLGA/nBM scaffold mimicked cancellous bone in terms of its porous structure and bone matrix composition rich in collagen. Both Nef contained in the scaffold and CBD-IGF-1 bound to collagen matrix could be slowly released from the scaffold, exerting long-term and safe bioactivity. In vitro tests showed that the CIGF1&Nef@PLGA/nBM composite significantly enhanced the adhesion, proliferation and osteogenic differentiation of MC3T3-E1 cells on the material. Nef and IGF-1 in CIGF1&Nef@PLGA/nBM scaffold exerted a synergistic effect on IGF-1-mediated osteogenic differentiation via IGF-1R axis to ensure the osteogenic activity of the biomimetic scaffold. In vivo skull defect repair experiment confirmed that CIGF1&Nef@PLGA/nBM could promote the neocortical bone formation and osseous maturation, further accelerating the bone defect repair. The findings of this research demonstrated that the biomimetic CIGF1&Nef@PLGA/nBM scaffold is a promising implantation in bone defect therapy.
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Zheng Xing,Wenhao Yang,Chen Zhao,Yuhui Wang,Xiaolian Jiang,Song Qian,Yun Chu,Jiang Xia,Cheng Wang,Jianhao Wang
Androgenetic alopecia (AGA), the preeminent form of clinical hair loss, poses a significant challenge to patients. Growth factors (GFs) have been investigated for the treatment of hair loss. However, the issue of their optimal intra-dermal delivery remains a formidable obstacle. Type XVII collagen (COL17), which plays a crucial role in regulating the hair follicle aging process, has emerged as a highly promising candidate for hair loss treatment. Considering these constraints, we developed an I GF-1 loaded borate- m odified rh C OL 17 MN platform (I-mCOL17 MNs) for the treatment of AGA. The mCOL17 MNs are engineered to precisely control the release of bioactive payloads in response to dynamic changes in the microenvironment. A comprehensive investigation was conducted to verify the physicochemical characteristics, as well as the in vitro and in vivo biological activities of the MNs. Our findings demonstrate that, when contrasted with the clinically utilized drug minoxidil, our MN exhibits a remarkable capacity to enhance neovascularization, alleviate tissue-based inflammatory responses, and promote hair regeneration in murine models of AGA. Overall, this MN represents a novel, safer, and more efficient strategy for the treatment of AGA, offering new hope for patients suffering from this prevalent condition.
研究领域:
生物医学工程
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皮肤病学
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药剂学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
·
IF 6.2
Wenmiao He,Zhiwei Liu,Hongchao Zhang,Qian Liu,Zhenkun Weng,Dongmei Wang,Wenhui Guo,Jin Xu,Dayong Wang,Zhaoyan Jiang,Aihua Gu
Bisphenol S (BPS) is widely presented and affects aging with unclear mechanisms. Here, we applied C. elegans to evaluate the effects of BPS on lifespan and healthspan and to investigate the underlying mechanisms. Both early-life and whole-life exposure to BPS at environmentally relevant doses (0.6, 6, 60 μg/L) significantly decreased lifespan, and healthspan (body bend, pharyngeal pumping, and lipofuscin accumulation). BPS exposure impaired mitochondrial structure and function, which promoted ROS production to induce oxidative stress. Furthermore, BPS increased expressions of the insulin/IGF-like signaling (IIS). Also, BPS inhibited expression of the IIS transcription factor daf-16 and its downstream anti-oxidative genes. Quercetin effectively improved BPS-induced oxidative stress byreversing BPS-regulated IIS/ daf-16 pathway and anti-oxidative gene expressions. In daf-2 and daf-16 mutants, the effects of BPS and quercetin on lifespan, healthspan, oxidative stress, and anti-oxidative genes expressions were reversed, demonstrating the requirement of IIS/ daf-16 for aging regulation. Molecular docking and molecular dynamics simulations confirmed the stable interaction between DAF-2 and BPS mainly via three residues (VAL1260, GLU1329, and MET1395), which was attenuated by quercetin. Our results highlighted that adverse effects of BPS on impairing lifespan and healthspan by affecting IIS/ daf-16 function against mitochondrial stress, which could be inhibited by quercetin treatment. Thus, we first revealed the underlying mechanisms of BPS-induced aging and the potential treatment.
研究领域:
毒理学
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老年学
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分子生物学
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DOI
PubMed
高影响因子
Regenerative Therapy
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2024
·
IF 3.4
Min Ge,Li Sun,Defeng Wang,Chunchao Hei,Tingjuan Huang,Zhongxin Xu,Qizhi Shuai
The use of stem cell-based treatment systems is prevalent in regenerative medicine. To enhance the regenerative capabilities of stem cells, growth factors are typically incorporated into the treatment system. Nonetheless, traditional hydrogel-encapsulated or heparinized scaffolds that bind factors have limitations. In this study, we prepared a biomaterial strategy using uniform poly(lactic-co-glycolic) acid (PLGA) microspheres (uPLGA-Ms) fabricated by microfluidic to sustain delivery of insulin-like growth factor 1 (IGF-1), a critical protein for hMSCs biological functions. The uPLGA-Ms loaded IGF-1 were highly monodispersed through precise manipulation of the flow rate of the two-phase of the flow-focusing microchannle. The results showed that the uPLGA-Ms stabilize IGF-1 and provide a more efficient sustained delivery and cost-effective of growth factor. Gene expression analysis demonstrated the uPLGA delivery of IGF-1 results in a (enhanced) supported hMSCs expansion, survival, stemness, and secretion abilities comparable with the conventional soluble IGF-1 group. In summary, this material-based strategy to stabilize and sustain delivery of growth factor has broad potential to regeneration of various tissues and organs.
研究领域:
再生医学
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生物材料
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干细胞治疗
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组织工程
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）