INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
·
IF 4.7
Wenyao Yang,Juanzhu Han,Liping Zhang,Yunsong Sun,Yuchen Zhu,Yiyu Liu,Jingyu Chen,Xiaoyao Liao,Hui Liao,Weizhuo Xu,Yongbo Song
Skeletal muscle inflammation associated with sepsis has been identified as a critical pathological process contributing to metabolic dysfunction and poor clinical outcomes. Voltage-gated sodium channels (VGSCs) have been implicated in immune modulation; however, their specific roles in skeletal muscle inflammation remain poorly understood. In this study, the VGSC subtype Nav1.5 was investigated as a potential regulator of inflammation, and the therapeutic efficacy of a novel recombinant scorpion peptide, DKK678, was evaluated. An in vitro model using lipopolysaccharide (LPS)-stimulated C2C12 cells and an in vivo cecal ligation and puncture (CLP) model in septic mice were established. In both models, Nav1.5 expression was significantly upregulated in response to inflammatory stimuli, while Nav1.4 expression remained unchanged. The nuclear factor kappa B (NF-κB) signaling pathway was found to be activated, contributing to increased expression of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), adhesion molecules (VCAM-1), and gap junction proteins (Cx43). Suppression of VGSC activity using lidocaine resulted in the inhibition of NF-κB phosphorylation and downregulation of inflammatory markers, while the expression of interleukin-10 (IL-10) and interleukin-4 (IL-4) were restored. Tetrodotoxin (TTX) treatment did not replicate these effects, suggesting Nav1.5-specific involvement. DKK678 was developed through bioinformatic design and molecular docking simulations, which predicted a stronger binding affinity and structural stability with Nav1.5 compared to Nav1.4. These predictions were validated through functional experiments. In vitro, DKK678 treatment dose-dependently inhibited LPS-induced NF-κB pathway activation and reversed abnormal expression of VCAM-1 and Cx43. In vivo, DKK678 significantly ameliorated CLP-induced skeletal muscle damage, suppressed inflammatory cytokine production, and improved tissue histopathology. Furthermore, the structural integrity of immune organs such as the thymus and spleen was preserved in DKK678-treated septic mice, with partial restoration of lymphocyte populations and organ indices. Notably, Nav1.5 expression was downregulated by DKK678, while Nav1.4 expression remained unaffected. These results demonstrate that Nav1.5 serves as a critical inflammatory modulator in skeletal muscle and immune tissues. Its upregulation was shown to drive NF-κB pathway activation and inflammatory cytokine production. By targeting Nav1.5, DKK678 was able to exert dual protective effects on both skeletal muscle and immune organs under septic conditions. The therapeutic potential of DKK678 was found to be comparable to that of dexamethasone (DEX) at high doses, without altering Nav1.4 expression. In conclusion, the present study provides new mechanistic insight into the role of Nav1.5 in skeletal muscle inflammation and identifies DKK678 as a promising peptide therapeutic that targets Nav1.5 to suppress NF-κB-mediated inflammatory injury. These findings suggest that Nav1.5 inhibition represents a viable strategy for the treatment of sepsis-associated myositis and related inflammatory disorders.
研究领域:
免疫学
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药理学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-18
·
IF 12.6
Wang Yingqian,Ma Zeqiang,Jiang Lehua,Bojan Nataraj,Sha Yiwen,Huang Boyu,Ming Lianxi,Shen Junnan,Pang Weijun
Background Skeletal muscle lipid deposition is a key manifestation of obesity, often accompanied by decreased exercise capacity and muscle atrophy. Skeletal muscle as the largest organ in the body, makes it challenges for designing targeted drug delivery systems. Lipid nanoparticles (LNPs) are widely used as a safe and efficient delivery carrier, there is limited research on LNPs that specifically target skeletal muscle. Results A LNP designed with five specific receptor complements on its surface, which specifically targets skeletal muscle in vivo in mice, without off-target effects on other tissues and organs. MiR-130a, a regulator of PPARG, which is a key factor in skeletal muscle lipid deposition, was encapsulated with LNP (LNP@miR-130a). In high-fat diet (HFD) mice, LNP@miR-130a effectively reduced skeletal muscle lipid deposition, increased exercise activity and enhanced muscle mass. Interestingly, the myokines in skeletal muscle have also changed which may leading to reduce the adipose tissue weight and liver lipid deposition in HFD mice. Conclusions These results indicated LNP@miR-130a is a promising inhibitor of skeletal muscle lipid deposition and may help alleviate obesity. This study provides new insights for obesity treatment and lays foundation for the development of targeted skeletal muscle therapeutics. Graphical
研究领域:
生物医学
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分子生物学
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药剂学
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DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION
·
2021
·Vol. 336
·期 4
·364-375
·
IF 2.656
Alida M. Bailleul,Jing Lu,Zhiheng Li
Iodine-based contrasting agents for computed tomography (CT) have been used for decades in medicine. Agents like Lugol's iodine enhance the contrasts between soft tissues and mineralized (skeletal) tissues. Because a recent study on extant avian heads showed that iodine–ethanol (I 2 E) is a better contrast enhancer overall than the standard Lugol's iodine, here, we tested if I 2 E could also enhance the CT contrasts of two fossilized skeletal tissues: bone and calcified cartilage. For this, we used a partial ankle joint from an extinct pheasant from the Late Miocene of Northwest China (Linxia Basin). The pre-staining CT scans showed no microstructural details of the sample. After being immersed into a solution of 1% I 2 E for 8 days and scanned a second time, the contrasts were drastically enhanced between the mineralized tissues (bony trabeculae and calcified cartilage) and the sediments and minerals inside vascular spaces. After three other staining-scanning cycles in 2%, 3%, and 6% I 2 E solutions, the best contrasts were obtained after immersion in 6% I 2 E for 7 days. Energy Dispersive Spectroscopy showed that iodine was preferentially absorbed by the mineralized tissues and the minerals in the vascular spaces, but not by the sediments. This method not only effectively increased the contrasts of two different fossilized skeletal tissues, it was also non-destructive and reversible because part of the fossil was successfully de-stained after a few days in pure ethanol. These preliminary results indicate that iodine-ethanol has the potential to be used widely in vertebrate paleontology to improve CT imaging of fossilized tissues. Research Highlights We immersed the partial ankle joint of a fossil bird from the Miocene of China into solutions of iodine-ethanol. The CT contrasts of the fossilized bony trabeculae and the calcified cartilage were positively enhanced; in a reversible and non-destructive manner.
研究领域:
古生物学
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医学影像学
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DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
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IF 4.7
Shuo Zhang,Shuang Guo,Pengyu Wang,Yan Song,Leiming Yang,Qiyu Sun,Qi Huang,Youzhi Zhang
Background Skeletal muscle atrophy is a clinical concern in diabetic nephropathy, and without effective therapeutic approaches. Massive evidence has demonstrated that dapagliflozin, a sodium-glucose co-transporter 2 inhibitor can relieve diabetic nephropathy by inhibiting glucose re-absorption or podocyte pyroptosis. Nevertheless, whether dapagliflozin could treat skeletal muscle atrophy or the potential protection mechanism in diabetic nephropathy mice is unclear. Methods The variety of approaches were used to assess the particular histology-associated characteristics, mRNA, and protein expression. These included examing the morphology of renal and skeletal muscle tissues through H&E staining, detecting mRNA and protein expression through real-time PCR and Western blot analysis, and monitoring fasting blood glucose levels by using Blood Glucose Monitor Test Kits. Results Dapagliflozin mitigated renal tissue injury with podocyte protein-nephrin and skeletal muscle atrophy effectively with mitochondrial-related proteins. Meanwhile, our research revealed that Casp3 was the target gene and dapagliflozin could decrease the expressions. Subsequently, we verified that dapagliflozin can effectively decrease canonical pyroptosis pathway proteins, which include Gasdermin D, NLRP3, Casp1, and ASC. Meanwhile, Palmitic acid (PA) induced Gasdermin E-N fragment (non-canonical pyroptosis protein) in C2C12 cells, and then released the inflammatory molecules such as IL-1β, IL-18, and NF-kappaB, which were suppressed by dapagliflozin treatment. Aside from that, dapagliflozin demonstrated a good binding affinity to the Casp3 and Gasdermin D protein, whereas it had a less binding affinity with NLRP3, Casp1, ASC, and Gasdermin E. At last, the Gasdermin D inhibitor can reverse the therapeutic effect of dapagliflozin. Conclusion Dapagliflozin alleviates skeletal muscle atrophy in diabetic nephropathy mice, which is through the Gasdermin D-mediated canonical pyroptosis pathway.
研究领域:
医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Neurophotonics
·
2020
·
IF 2.537
Yusha Li,Jianyi Xu,Jingtan Zhu,Tingting Yu,Dan Zhu
Three-dimensional visualization of the innervation in skeletal muscles is helpful for understanding the morphological structure and function. iDISCO, a whole-mount immunolabeling and clearing technique, provides a valuable tool for volume imaging of intramuscular nerve fibers but suffers from the nonspecific staining caused by the anti-mouse secondary antibody when using the murine primary antibody. We developed a modified iDISCO method by introducing pretreatment of ScaleCUBIC-1 reagent, termed m-iDISCO. The m-iDISCO method could eliminate the nonspecific staining and achieve uniform and complete labeling of nerve fibers in various muscles with mouse anti-neurofilament primary antibody. Combining the m-iDISCO method with light-sheet microscopy enabled us to visualize the innervation of adult mouse tibialis anterior and trace the nerve fibers from extramuscular branches to intramuscular terminal branches. This method represents an effective alternative for studying the innervation of intact skeletal muscles in health and disease.
研究领域:
神经生物学
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肌肉生理学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry C
·
2021
·Vol. 9
·期 31
·10005-10012
·
IF 7.393
Lili Li,Xiaoshuang Yu,Abdur Raheem Aleem,Xiaolin Zhang,Yue Zhao,Xinzhi Wang,Yanying Zhang,Yao Wang,Wenfei Shen,Olle Inganäs,Jianguo Tang
In this article, a natural biological porous material, from living diatoms, is used to prepare new UV-protection hybrid materials with an Eu3+-complex. By removing the organic protoplasm of living diatoms, the exoskeleton with a regular pore structure arrangement was obtained. The Eu3+-complex was chemically bonded to the exoskeleton modified by the silane coupling agent (3-aminopropyl)trimethoxy silane (APTMS). Compared with pure Eu3+-complexes, the fluorescence intensity of this hybrid material was increased by approximately 10 times. For illustrating its applications in the field of UV-protection, we mixed the USDU with polyacrylonitrile to produce flexible and transparent polymer films. The hybrid composite film (USDU@PAN) achieved partial absorption of ultraviolet light between 200 and 400 nm. At the same time, it also emits visible fluorescence and the intensity of the fluorescence is greatly increased. Therefore, the USDU@PAN film has wide application prospects in areas such as photoelectric sensors and UV-protection devices. More importantly, we transform natural organisms into materials with excellent optical properties. Therefore, it can be used in the field of UV-protection.
研究领域:
材料科学
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生物学
✓ 已验证
DOI
高影响因子
Foods
·
2023
·Vol. 12
·期 13
·2471
·
IF 5.2
Jinjie Li,Yi Li,Xiangying Suo,Jiangtao Li,Da Huang,Guangning Kou
Bayberry is known to be a rich source of natural flavonoids and has been reported to have various health-promoting abilities. However, its function on regulating skeletal muscle fiber type remains unclear. This study examined whether bayberry extract affects skeletal muscle fiber type by promoting fast myofiber formation, as well as the potential molecular mechanism. After eight weeks, the “Biqi” bayberry extract (BBE) groups mice displayed markedly enhanced grip strength and improved metabolic rate compared to the control group mice. BBE also significantly increased myofibers size, LDH activity, MyHC-IIb (fast-twitch mRNA) expression, and the percentage of fast-twitch myofibers, while decreasing SDH activity, MyHC-I (slow-twitch mRNA) expression, and slow-twitch myofibers percentage in the skeletal muscle of the mice. The effect of BBE on regulating skeletal muscle fiber type remodeling is likely attributed to its activation of the Akt-FoxO1 pathway. Our findings indicated that BBE can effectively regulate the expression and proportion of fast-twitch fibers, making it a potential therapy for improving glucose homeostasis of skeletal muscle.Keywords:bayberry extract;skeletal muscle;fast-twitch fibers;myofiber type;FoxO1
研究领域:
药理学
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分子生物学
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运动生理学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2025
·
IF 19
Yeying Lin,Xudan Xing,Xinchang Kang,Mingjie Liu,Tianhua Xiao,Yangengchen Zhong,Chuyang Xiang,Chengyun Ning,Yuhe Jiang,Guoxin Tan,Lei Zhou
Although hydrogel-based therapies have demonstrated promising results in treating volumetric muscle loss (VML), addressing diabetic skeletal muscle defects remains a major challenge due to the interplay of chronic inflammation and impaired regenerative capacity associated with diabetes mellitus. This study presents a novel multifunctional hydrogel bioelectronic conductor designed specifically for diabetic VML repair. The hydrogel, which self-assembles from mannose receptor-binding glucomannan, polydopamine-functionalized conductive polypyrrole, and gelatin, mimics the mechanical properties of native muscle tissue while providing immunomodulatory and electrocoupling effects. Multiple crosslinking mechanisms, involving both dynamic covalent and noncovalent interactions, endow the hydrogel with enhanced tissue adhesion (adhesion strength of 69.41 kPa to soft tissue), elasticity (100% self-recovery), and rapid self-healing ability (less than 1 min). The electrically conductive hydrogel-based elastic bioelectronics can reestablish effective electrical coupling with electroactive muscle tissue, while its intrinsic immunomodulatory properties induce M2-type macrophage polarization to alleviate chronic inflammatory response. In a diabetic rat VML defect model, the hydrogel bioelectronic conductor facilitated effective immunomodulation, muscle regeneration, and functional recovery of injured VML. These results suggest that the integration of tissue-mimicking mechanics with both immunomodulatory and conductive properties offers a promising therapeutic approach for diabetic skeletal muscle repair.
研究领域:
生物医学工程
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再生医学
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材料科学
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产品关联
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
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IF 6.1
Yuanzhao Wu,Ye'anlun Zhu,An Cheng,Weixuan Yao,Binjie Wang,Ruonan Zheng,Jiye Wang
Tefluthrin, a pyrethroid insecticide commonly used in soil, has raised concerns due to its widespread use and residual presence in aquatic environments. Nevertheless, studies on the toxicological mechanisms of tefluthrin at relevant concentrations during the early life stages of aquatic species remain limited. In this study, we assessed the developmental effects of tefluthrin exposure at concentrations of 1, 10, and 100 μg/L over 8 days on zebrafish embryos/larvae. Exposure to 100 μg/L of tefluthrin significantly reduced hatchability and survival rates, leading to cardiac edema and skeletal deformities. Alizarin Red and Alcian Blue staining showed reduced skeletal mineralization and disrupted craniofacial morphology. Importantly, tefluthrin exposure resulted in the dysregulation of important genes involved in heart and skeletal development, including nppa , vmhc , sox9b , gata4 , runx2a , shha , sp7 , and bmp2b . Mechanistically, tefluthrin exposure increased reactive oxygen species (ROS), decreased antioxidant enzyme activities (SOD, CAT), and elevated malondialdehyde (MDA). Furthermore, exposure to tefluthrin caused significant cell apoptosis in larvae, accompanied by dysregulation in the transcriptional expression of apoptotic genes ( bcl2 , bax , p53 , and caspase-3 ). Treatment with the antioxidant astaxanthin alleviated tefluthrin-induced oxidative stress and provided protection against heart and skeletal toxicity. In conclusion, this study demonstrated that tefluthrin's developmental toxicity affected heart and skeletal development, with mechanisms involving changes in gene expression, oxidative stress, and apoptosis, providing valuable insights for assessing environmental and food contamination risks.
研究领域:
毒理学
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环境科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Autophagy
·
2024
·
IF 14.6
Qingyuan Zhang,Chunhui Chen,Ye Ma,Xinyi Yan,Nianhong Lai,Hao Wang,Baogui Gao,Anna Meilin Gu,Qinrui Han,Qingling Zhang,Lei La,Xuegang Sun
Regressing the accelerated degradation of skeletal muscle protein is a significant goal for cancer cachexia management. Here, we show that genetic deletion of Pgam5 ameliorates skeletal muscle atrophy in various tumor-bearing mice. pgam5 ablation represses excessive myoblast mitophagy and effectively suppresses mitochondria meltdown and muscle wastage. Next, we define BNIP3 as a mitophagy receptor constitutively associating with PGAM5. bnip3 deletion restricts body weight loss and enhances the gastrocnemius mass index in the age- and tumor size-matched experiments. The NH2-terminal region of PGAM5 binds to the PEST motif-containing region of BNIP3 to dampen the ubiquitination and degradation of BNIP3 to maintain continuous mitophagy. Finally, we identify S100A9 as a pro-cachectic chemokine via activating AGER/RAGE. AGER deficiency or S100A9 inhibition restrains skeletal muscle loss by weakening the interaction between PGAM5 and BNIP3. In conclusion, the AGER-PGAM5-BNIP3 axis is a novel but common pathway in cancer-associated muscle wasting that can be targetable. Abbreviation: AGER/RAGE: advanced glycation end-product specific receptor; BA1: bafilomycin A1; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; Ckm-Cre: creatinine kinase, muscle-specific Cre; CM: conditioned medium; CON/CTRL: control; CRC: colorectal cancer; FUNDC1: FUN14 domain containing 1; MAP1LC3A/LC3A: microtubule associated protein 1 light chain 3 alpha; PGAM5: PGAM family member 5, mitochondrial serine/threonine protein phosphatase; S100A9: S100 calcium binding protein A9; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20; TIMM23: translocase of inner mitochondrial membrane 23; TSKO: tissue-specific knockout; VDAC1: voltage dependent anion channel 1.
研究领域:
肿瘤学
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细胞生物学
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肌肉生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
·
2018
·
IF 3.247
Na Zhang,Yahui zhou,Qingxin Yuan,Yao Gao,Yan Wang,Xingyun Wang,Xianwei Cui,Pengfei Xu,Chenbo Ji,Xirong Guo,Lianghui You,Nan Gu,Yu Zeng
T2DM is a global health problem that seriously lowers the quality of life and insulin resistance makes a considerable contribution to the pathophysiology of T2DM. Long noncoding RNAs (lncRNAs) have emerged as important regulators in glucose and lipid metabolism. However, comprehensive analysis of lncRNAs in db/db mice skeletal muscle and their potential roles involved in skeletal muscle insulin resistance (IR) remains poorly characterized. Here, we identified 331 lncRNAs, 172 upregulated and 159 downregulated (|fold change|>2, q<0.05), differentially expressed in db/db mice skeletal muscle. Gene Ontology analysis, Pathway analysis and Gene Set Enrichment Analysis of network gene expression revealed the potential functions of dysregulated lncRNAs may involve skeletal muscle function, fatty acid metabolism and the PPAR signaling pathway. In addition, differentially expressed lncRNAs were verified in skeletal muscle from the widely known IR mouse models ( db/db and ob/ob mice). Further validation of lncRNAs in C2C12 myotubes exposed with various concentrations of palmitate uncovered that lncRNAs were responsive to palmitate exposure at the high concentrations (0.5mM and 0.75mM). Coexpression analysis revealed the key lncRNA-mRNA interactions and indicated a potential regulatory role of lncRNAs. Moreover, we characterized two candidate lncRNAs Gm15441 and 3110045C21Rik by a comprehensive examination of their genomic context and validated their expression with neighboring genes (Txnip and Ddr2) by the Spearman correlation analysis. Collectively, these findings improve our understanding of lncRNAs that mediate skeletal muscle insulin resistance in diabetes and represent potential molecular therapeutic targets to improve insulin sensitivity and associated metabolic diseases.
研究领域:
分子生物学
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代谢疾病
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遗传学
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2025
·
IF 8.1
Xia Hangbin,Yang Chen,Li Huili,Huang Lingwei,Zeng Zhen,Chi Runrun,Yang Ziwei,Wang Yuzen,Chang Jiang,Jiao Yiren,Li Wenzhong
Muscle satellite cells (MuSCs) play a vital role in skeletal muscle regeneration. However, in intractable muscle diseases such as volumetric muscle loss (VML), the quantity and function of MuSCs are significantly reduced, severely limiting the body's inherent muscle regeneration capability. In this study, we propose a novel strategy to modulate the fate of MuSCs using a combination of bioactive magnesium (Mg) and silicon (Si) ions, sustainably delivered through magnesium silicate (MgSiO3, MS) bioceramic-based scaffolds. In vitro, Mg and Si ions synergistically promote the proliferation and differentiation of MuSCs. Similarly, Mg and Si ions derived from MS/poly (L-lactic acid) (MS/PLLA) composite scaffold also increases the proliferation and differentiation ability of MuSCs. Furthermore, MS/PLLA composite scaffolds facilitate the activation of MuSCs, regeneration of muscle fiber, and neovascularization, while inhibiting fibrosis, thereby effectively restoring muscle function and promoting tibialis anterior muscle functional regeneration in a VML mouse model. Mechanistically, the combination of Mg and Si ions promotes the activation and proliferation of MuSCs by activating the Notch1-Hes1 pathway. Besides, the combination of Mg and Si ions also improves the differentiation of MuSCs by up-regulating Myod and Myog, and enhances fusion by up-regulating Mymk and Mymx expression. The outcomes of our research introduce a promising approach to the treatment of skeletal muscle injuries and related diseases.
研究领域:
再生医学
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生物材料学
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分子生物学
✓ 已验证
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）