Scientific Reports
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2025
·Vol. 15
·期 1
·1-13
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IF 3.9
Yang Le,Wang Jie,Li Peng,Guo Yuxi,Li Siyuan,Liu Shuangyu,Lou Yingying,Qi Jinlong,Yang Qian
Gastric cancer (GC) is a severe malignancy characterized by late diagnosis, poor prognosis, and low survival rates. Its progression is often linked to chronic non-atrophic gastritis (CNAG) and chronic atrophic gastritis (CAG), which show atypical symptoms. Identifying biomarkers for CNAG, CAG, and GC progression is crucial for earlier diagnosis and prevention. This study conducted non-targeted metabolomics on 81 clinical samples (17 controls; 23, 23, and 18 from CNAG, CAG, and GC patients, respectively) using ultra-high-performance Liquid chromatography and high-resolution mass spectrometry. A total of 763 metabolites were identified, of which eight metabolic pathways were in dysregulation at different disease stages. Disease progression showed pronounced disruptions in amino acid, Lipid, and microbial metabolism. Targeted metabolomics identified 56 metabolites, with significant differences in O-(4,8-dimethylnonanoyl) carnitine and dehydroepiandrosterone sulfate (DHEAS). DHEAS and L-threonic acid (L-TA) were validated as biomarkers, with detection methods developed and applied to confirm their clinical significance. These findings enhance understanding of CNAG, CAG, and GC progression and provide validated biomarkers for potential clinical application in GC diagnosis and treatment.
研究领域:
肿瘤学
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消化病学
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代谢组学
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分子生物学
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转化医学
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疾病 biomarker 发现
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2019
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IF 3.414
Nur Amanina Syariff Tan,Nelli Giribabu,Kamarulzaman Karim,Shaik Nyamathulla,Naguib Salleh
Ethnopharmacological relevance Marantodes pumilum (MP) (Kacip Fatimah) is used to maintain the well-being of post-menopausal women. However, its role in ameliorating post menopause-related vaginal atrophy (VA) is unknown. Aims To investigate the ability of intravaginal MP gel treatment to ameliorate VA in sex-steroid deficient condition, mimicking post-menopause. Methods Ovariectomized female Sprague-Dawley rats received MP (100 μg/ml, 250 μg/ml and 500 μg/ml) and estriol (E) gels intravaginally for seven consecutive days. Rats were then euthanized and vagina was harvested and subjected for histological and protein expression and distribution analyses. Vaginal ultrastructure was observed by transmission electron microscopy (TEM). Results Thickness of vaginal epithelium increased with increasing intravaginal MP doses. Additionally, increased in expression and distribution of proliferative protein i.e. PCNA, tight junction protein i.e. occludin , water channel proteins i.e. AQP-1 and AQP-2 and proton extruder protein i.e. V-ATPase A1 were observed in the vagina following intravaginal MP and E gels treatment. Intravaginal MP and E gels also induced desmosome formation and approximation of the intercellular spaces between the vaginal epithelium. Conclusions Intravaginal MP was able to ameliorate features associated with VA; thus, it has potential to be used as an agent to treat this condition.
研究领域:
药理学
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妇科学
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分子生物学
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DOI
PubMed
高影响因子
ACS Nano
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2024
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IF 15.8
Cewen Hu,Bin Liu,Xinyue Huang,Zhilong Wang,Kaiqi Qin,Luyi Sun,Zengjie Fan
Muscle atrophy resulting from peripheral nerve injury (PNI) poses a threat to a patient’s mobility and sensitivity. However, an effective method to inhibit muscle atrophy following PNI remains elusive. Drawing inspiration from the sea cucumber, we have integrated microneedles (MNs) and microchannel technology into nerve guidance conduits (NGCs) to develop bionic microneedle NGCs (MNGCs) that emulate the structure and piezoelectric function of sea cucumbers. Morphologically, MNGCs feature an outer surface with outward-pointing needle tips capable of applying electrical stimulation to denervated muscles. Simultaneously, the interior contains microchannels designed to guide the migration of Schwann cells (SCs). Physiologically, the incorporation of conductive reduced graphene oxide and piezoelectric zinc oxide nanoparticles into the polycaprolactone scaffold enhances conductivity and piezoelectric properties, facilitating SCs’ migration, myelin regeneration, axon growth, and the restoration of neuromuscular function. These combined effects ultimately lead to the inhibition of muscle atrophy and the restoration of nerve function. Consequently, the concept of the synergistic effect of inhibiting muscle atrophy and promoting nerve regeneration has the capacity to transform the traditional approach to PNI repair and find broad applications in PNI repair.
研究领域:
生物医学工程
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神经科学
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材料科学
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DOI
PubMed
高影响因子
ACS Omega
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2025
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IF 4.3
Bin Wang,Peng He,Xiaowei Liu,Shunjie Wu,Xinlin Lu,Bin Xu
Muscles and bones are adjacent in spatial position and closely related in function. Exosomes can achieve communication between donor and receptor cells by carrying molecules, such as miRNAs. Therefore, the purpose of this study is to use exosome-miRNA as a bridge, explore the correlation between clinical manifestations, and use bioinformatics and machine learning to cluster and screen exosome-miRNA sequencing data. In vitro and in vivo experiments were conducted to validate the screened molecules. Three parts were explored to identify miRNAs that play a key regulatory role in the muscle–exosome–bone system. Ultimately, it was found that miR-92a-1-5p may play a crucial role in this system; that is, atrophic muscle cells can inhibit osteogenic differentiation by releasing exosomes carrying miR-92a-1-5p into osteoblasts and targeting Col1a1.
研究领域:
生物信息学
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分子生物学
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医学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2025
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IF 8.3
Yu Liu,Honglin Chen,Kun Chen,Qi Shang,Feng Lin,Peng Zhang,You Zhang,Weicheng Qin,Huiwen Liu,Weiyu Qiu,Xingda Chen,Yan Gong,Yixuan Jiang,Yuzhuo Zhang,Jiahui He,Wenhua Zhao,Hui Ren,Gengyang Shen,Xiaobing Jiang
Background Skeletal muscle atrophy, which is a debilitating condition exacerbated by estrogen deficiency, lacks effective therapeutic interventions. Although ferroptosis (an iron-dependent form of cell death driven by lipid peroxidation) has emerged as a contributor to muscle degeneration, its regulatory mechanisms remain poorly defined. In this study, we identified luteolin, which is a natural flavonoid, as a potent inhibitor of ferroptosis that mitigates estrogen deficiency-induced muscle atrophy by targeting SLC7A11. Purpose The aim of this study was to investigate the role of ferroptosis in the anti-muscle atrophy effects of luteolin. Methods Via database screening, luteolin was identified as a potential drug for improving muscle atrophy, and the promotion of C2C12 myogenic differentiation by luteolin was detected by using immunofluorescence (IF), quantitative reverse transcription PCR (RT-qPCR) and western blot (WB). The mechanism of luteolin-mediated ferroptosis in muscle atrophy was confirmed by RNA-seq, transmission electron microscopy (TEM), and GSH, MDA, SOD and Fe 2+ assays. Molecular docking, molecular dynamics simulation, surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) and siRNA-mediated gene knockout were applied to validate the notion that the mechanism of luteolin treatment of muscle atrophy involves target binding to SLC7A11. In addition, this study confirmed the role of luteolin in ameliorating muscle atrophy via the modulation of the SLC7A11-mediated ferroptosis pathway in vivo . Finally, the effect of luteolin on the myogenic differentiation of HsKMCs was investigated. Results Luteolin promotes myogenic differentiation and significantly inhibits myotube atrophy, with the main mechanism of these effects involving the direct binding of luteolin to the SLC7A11 protein to inhibit the occurrence of ferroptosis. We confirmed that luteolin can inhibit ferroptosis in muscle tissue and improve the loss of muscle mass and strength due to muscle atrophy in vivo . In addition, luteolin significantly inhibited myotube atrophy in HsKMCs and promoted their myogenic differentiation by modulating the SLC7A11-mediated ferroptosis. Conclusions Our findings demonstrate that luteolin regulates myogenesis and prevents muscle atrophy through binding to SLC7A11 and subsequently inhibiting ferroptosis. This study elucidates the critical role of the SLC7A11-ferroptosis axis in preserving muscle physiology during atrophy, while identifying luteolin as a therapeutic agent capable of targeting SLC7A11 to suppress ferroptosis and alleviate muscle atrophy.
研究领域:
医学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Materials
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2025
·Vol. 18
·期 6
·1351
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IF 3.2
Ming Liu,Zhicun Liu,Xiangkai Qiao,Cheng Chen,Hongtu Guo,Hao Gu,Junbo Li,Tiedong Sun
Nanomotors driven by endogenous enzymes are favored in biology and pharmacy due to their spontaneous driving and efficient biocatalytic activity, and have potential applications in the treatment of clinical diseases that are highly dependent on targeted effects. For diseases such as muscle atrophy, using energy molecules such as ATP to improve cellular metabolism is a relatively efficient treatment method. However, traditional adenosine triphosphate (ATP) therapies for muscle atrophy face limitations due to instability under physiological conditions and poor targeting efficiency. To address these challenges, we developed an endogenous proton-gradient-driven ATP transport motor (ATM), a nanomotor integrating chloroplast-derived FoF1-ATPase with a biocompatible flask-shaped organic shell (FOS). The ATM is synthesized by vacuum-injecting phospholipid-embedded FoF1-ATPase nanothylakoids into ribose-based FOS, enabling autonomous propulsion in acidic microenvironments through proton-driven negative chemotaxis (directional movement away from regions of higher proton concentration). This nanomotor converts proton gradients into ATP synthesis, directly replenishing cellular energy deficits in atrophic tissues. In vitro studies demonstrated high biocompatibility (>90% cell viability at 150 μg/mL) and pH-responsive motility, achieving speeds up to 4.32 μm/s under physiological gradients (ΔpH = 3). In vivo experiments using dexamethasone-induced muscle atrophy mice revealed that ATM treatment accelerated weight recovery and restored normal muscle morphology, with treated mice exhibiting cell sizes comparable to healthy controls (30–40 μm vs. 15–25 μm in untreated). These results highlight the ATM’s potential as a precision therapeutic platform for metabolic disorders, leveraging the natural enzyme functionality and synthetic material design to enhance efficacy while minimizing systemic toxicity.
研究领域:
生物医学工程
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药理学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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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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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Jiaying Liu,Yuanfan Chen,Jing Zhang,Yun Zheng,Yun An,Chenglai Xia,Yonger Chen,Song Huang,Shaozhen Hou,Dong Deng
Ethnopharmacological relevance The dried fruit of Crataegus pinnatifida Bunge (Hawthorn in Chinese) is a traditional medicine used in China, Japan and Korea for thousands of years. Hawthorn is documented in the Chinese Pharmacopoeia , as a folk medicine that is used to eliminate food, strengthen the stomach, move qi and dissipate blood stasis, treat stagnation of meat and food, gastric distention and fullness, and has anti-inflammatory effects. Vitexin, a flavonoid glycoside, is an important biologically active compound derived from Hawthorn, with significant antioxidant and anti-inflammatory properties. The pharmacological effects of Hawthorn are highly correlated with the antioxidant and anti-inflammatory effects of vitexin. Aim of the study The aim of the present study was to investigate the effect of vitexin on the alleviation of chronic atrophic gastritis (CAG) induced by 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) in a rat model, as well as to elucidate the underlying mechanisms involved. Materials and methods CAG was administered at a concentration of 170 μg/mL MNNG in the drinking water of rats, and the effects of vitexin (30 mg/kg, once daily for 6 weeks) on gastric tissues were subsequently analyzed. Pathological damage was assessed using H&E and AB-PAS staining. Gastrointestinal hormone levels, specifically motilin (MTL) and gastrin (GAS), were quantified using biochemical index determination kits. To evaluate the levels of cytokines, specifically IL-1β and IL-18, in gastric tissue, an enzyme-linked immunosorbent assay (ELISA) was performed. Additionally, to investigate the effects of vitexin on the NLRP3 inflammasome, GES-1 cells were subjected to treatment with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). The targeting of NLRP3 by vitexin was assessed in vitro using CESTA, DARTS, and a synthesized biotin-labeled vitexin probe (biotin-vitexin) in conjunction with dual immunofluorescence. RT-PCR, Western blotting and immunofluorescence were used to evaluate the ameliorative effect of oysterin on LPS + ATP-induced GES-1 cells in vitro. Results Administration of vitexin significantly alleviated the symptoms of chronic atrophic gastritis (CAG) by reducing weight loss and minimizing gastric tissue damage. Treatment with vitexin in CAG rats effectively reduces the production of pro-inflammatory cytokines. Furthermore, vitexin attenuated the activation of the NLRP3 inflammasome in CAG induced by MNNG. Mechanistic experiments showed that NLRP3 is a direct cellular target of vitexin, while vitexin inhibited rat NLRP3 inflammasome. Conclusion Vitexin mitigates MNNG-induced CAG, and its protective effect is linked to the inhibition of NLRP3 inflammasome activation.
研究领域:
药理学
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民族药理学
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胃肠病学
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·Vol. 12
·期 24
·2202707
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IF 10
Kai Li,Yuting Zhu,Qiang Zhang,Yahong Shi,Tun Yan,Xi Lu,Huizhen Sun,Tingting Li,Zhongxian Li,Xiaoli Shi,Dong Han
Injectable hydrogels have been extensively used in tissue engineering where high mechanical properties are key for their functionality at sites of high physiological stress. In this study, an injectable, conductive hydrogel is developed exhibiting remarkable mechanical strength that can withstand a pressure of 500 kPa (85% deformation rate) and display good fatigue resistance, electrical conductivity, and tissue adhesion. A stable covalent cross-linked network with a slip-ring structure by threading amino β -cyclodextrin is formed onto the chain of a four-armed (polyethylene glycol) amino group, and then reacted with the four-armed (polyethylene glycol) maleimide under physiological conditions. The addition of silver nanowires enhances the hydrogel's electrical conductivity, enabling it to act as a good conductor in vivo. The hydrogel is injected into the fascial space, and the results show that the weight and muscle tone of the atrophied gastrocnemius muscle improve, subsequently alleviating muscle atrophy. Overall, this study provides a simple method for the preparation of a conductive hydrogel with high mechanical properties. In addition, the interstitial injection provides a strategy for the use of hydrogels in vivo.
研究领域:
生物医学工程
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组织工程
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DOI
PubMed
高影响因子
ACS Nano
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2023
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IF 17.1
Renjie Tan,Ke Zhang,Yifan Si,Shuai Zhang,Jieqiong Yang,Jinlian Hu
Long-term immobilization of joints can lead to disuse atrophy of the muscles in the joints. Oral nutrients are used clinically for rehabilitation and therapeutic purposes, but bioavailability and targeting are limited. Here, we report tea polyphenols (dietary polyphenols), sustained-release nanofilms that release tea polyphenols through slow local degradation of core–shell nanofibers in muscles. This dietary polyphenol does not require gastrointestinal consumption and multiple doses and can directly remove inflammatory factors and superoxide generated in muscle tissue during joint fixation. The quality of muscles is increased by 30%, and muscle movement function is effectively improved. Although nanofibers need to be implanted into muscles, they can improve bacterial infections after joint surgery. To investigate the biological mechanism of this core–shell nanomembrane prevention, we conducted further transcriptomic studies on muscle, confirming that in addition to achieving antioxidation and anti-inflammation by inhibiting TNF-α and NF-κB signaling pathways, tea polyphenol core–shell nanofibers can also promote muscle formation by activating the p-Akt signaling pathway.
研究领域:
生物医学工程
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2021
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IF 2.63
Yuling Tong,Manyi Jing,Xu Zhao,Honghong Liu,Shizhang Wei,Ruisheng Li,Xia Liu,Min Wang,Hongtao Song,Yanling Zhao
The classic prescription Zuojin Pill (ZJP) shows a good therapeutic effect on chronic atrophic gastritis (CAG); it is of great significance to clarify its specific mechanism. Therefore, we explore the mechanism of ZJP on MNNG-induced CAG by integrating approaches. First of all, through the pathological changes of gastric tissue and the expression level of PGI and PGI/II in serum, the expression of inflammation-related factors was determined by RT-PCR to determine the efficacy. Then, UPLC-Q-TOF/MS was used for plasma and urine metabolomic analysis to screen the specific potential biomarkers and metabolic pathway of ZJP in ameliorating CAG and to explore its possible mechanism. ZJP significantly ameliorate the pathological injury of gastric tissue, increase levels of PGI and PGI/II, and reduce the expression level of proinflammatory factors. Through metabolomic analysis, 9 potential metabolic differences were identified and 6 related metabolic pathways were enriched. These findings indicate for the first time the potential mechanism of ZJP in improving CAG induced by MNNG and are of great significance to the clinical development and application of ZJP-related drugs.
研究领域:
中药学
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代谢组学
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病理学
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DOI
高影响因子
Autophagy
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2024
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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
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）