American Journal of Translational Research
·
2025
·Vol. 17
·期 10
·7749
·
IF 1.6
Xiaowen Li,Ruikang Guo,Lingling Liang,Hao Liang,Guangqi Zhou,Qinglan Lu,Yonghui Huang,Zhen Qi,Xiaojie Li
Objective: Periodontitis, a prevalent oral disease leading to alveolar bone defects, remains a primary cause of tooth loss in adults. The biologic mechanisms driving bone loss in periodontitis are still poorly understood, limiting the development of genetic treatment. This study investigates potential therapeutic targets for alveolar bone loss by analyzing transcriptomic data related to the osteogenic differentiation of induced pluripotent stem cells (iPSCs). Methods: Using in vitro and in vivo models, we examined the role of neuropeptide Y receptor Y1 (NPY1R) and the PI3K-AKT-mTOR (PAM) signaling pathway in osteogenic differentiation and bone loss. A combination of bioinformatics, molecular biology, and histologic techniques was employed to pinpoint key signaling events that influence bone remodeling in periodontitis and to identify potential intervention points. Results: Transcriptomic profiling during iPSC osteogenic differentiation revealed significant upregulation of neuropeptide Y (NPY) and NPY1R. Suppression of NPY1R reduced the osteogenic capacity of iPSCs. Activation of the PAM pathway was observed during osteogenesis, and treatment with LY294002, a PAM pathway inhibitor, led to decreased osteogenic activity. In vivo experiments using a rat periodontitis model confirmed increased expression of NPY1R and activation of the PAM pathway, suggesting a role in bone repair processes. Conclusion: The NPY/NPY1R axis and the PAM signaling pathway appear to regulate bone regeneration and may be involved in preventing alveolar bone loss in periodontitis. These findings provide a new direction for therapy targeting bone defects associated with periodontal disease.
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Frontiers in Microbiology
·
2026
·
IF 4.5
Jiawei Huang,Qianqian Wang,Xiaowen Guo,Yuanyuan Niu,Junhong Huang,Boyi Zhang,Zixuan Guo,Zilong Wang,Shuying Feng
Background: Mulberry leaf (Morus alba L.) is an edible plant that has been found to have medicinal effects in the treatment of hyperuricemia (HUA). The bioactive compounds of mulberry leaf and their mechanisms of action have not been determined yet.Methods: In-silico methodologies were used to identify bioactive compounds and to determine the underlying mechanisms of mulberry leaf. In order to verify the biochemical mechanism and intestinal microbiota, in vivo experiments were conducted.Results: Kaempferol was identified as the principal bioactive compound, while the key targets were AKT1 and TNF. Molecular docking and dynamics simulations revealed that AKT1-kaempferol and TNF-kaempferol complexes showed strong and stable binding pattern after a 100 ns simulation. In vivo studies demonstrated that kaempferol exerted significant anti-HUA effects. Specifically, kaempferol reduces AKT expression and phosphorylation, which may in turn reduces the oxidative stress and inflammatory pathways and signal transmission of the kidneys. Meanwhile, the application of kaempferol attenuated gut microbiota dysbiosis caused by HUA.Conclusion: Kaempferol may regulate UA metabolism and inflammatory injury by modulating the AKT signaling pathway, and exert its effects on the gut-kidney axis and restoring gut microbiota composition.
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Materials Today Bio
·
2026
·
IF 10.2
Haohua Lai,Li Dong,Dongdong Jiang,Chen Shi,Wenbo Zhong,Chengxiang Sha,Junwei Yan,Xiao Wang,Jing Zhang,Ziyi Yu,Zhaowei Yin,Bin Liang
Osteochondral defects (OCDs) remain challenging to repair due to the complex structural and biological heterogeneity of the cartilage–bone interface. Here, we developed a bilayer microsphere–scaffolds composite by integrating melt electrowriting (MEW) scaffolds with two types of functionalized hydrogel microspheres (HMPs). The upper layer consisted of disulfide-containing poly ethylene glycol diacrylate (HB-PBHE)/thiolated hyaluronic acid (SH-HA) microspheres encapsulating kartogenin (KGN) liposomes (HM@PHK) to promote chondrogenesis, while the lower layer was formed by GelMA/nano-hydroxyapatite (nHAP) microspheres loaded with curcumin (Cur) liposomes (HM@GMAC) to provide osteoinductive, antioxidative, and anti-inflammatory cues. This bilayer construct exhibited uniform architecture, favorable mechanics, and controlled drug release. In vitro, the system promoted bone marrow–derived mesenchymal stem cells (BMSCs) migration, chondrogenic and osteogenic differentiation, and attenuated oxidative stress–induced apoptosis while modulating macrophage polarization. Transcriptomic analysis revealed that both layers activated the PI3K-AKT pathway, with the upper phase regulating the PI3K-AKT-SOX9 axis for chondrogenesis and the lower phase promoting osteogenesis and cytoprotection via PI3K-AKT-RUNX2/BAX signaling. In vivo implantation in rat femoral condyle defects demonstrated superior cartilage–bone reconstruction. Collectively, this multifunctional bilayer microsphere–scaffolds system provides stratified regulation of osteochondral repair through coordinated structural support, bioactive delivery, and immunomodulation, offering a clinically translatable approach to osteochondral defect regeneration.
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BIOMARKERS
·
2026
·
IF 1.9
Yang Jiang,Xiaosheng Jin
Background PM2.5-induced COPD lacks effective therapies due to unclear pathogenesis. This study explores the role of miR-122 and PTEN in PM2.5-related COPD.Methods Using a combination of in vitro and in vivo assays, including cigarette smoke extract (CSE)-induced NR8383 cells and a rat smoke model, combined with MTT, qPCR, flow cytometry, WB, HE staining, Masson staining, HIC, and TUNEL assays, we investigated the role of microRNA-122 (miR-122) and phosphatase and tensin homolog (PTEN) in the molecular mechanisms underlying PM2.5-induced COPD.Results Our findings demonstrate that CSE-induced the down-regulated expression of miR-122 leads to the activation of PTEN, which in turn regulates the AKT signaling pathway in NR8383 cells. This modulation results in decreased expression of B-cell lymphoma 2 (BCL2), promoting cell apoptosis. Besides, the result from a rat model of COPD exposed to smoke also confirms this molecular axis which ultimately exacerbating COPD. Specifically, compared with the control, there is significant pulmonary structural damage in model rats exposed to PM2.5, including enlarged alveolar intervals, increased alveolar cavity size, pulmonary fibrosis, and evidence of alveolar destruction with concomitant parabronchial inflammation.Conclusion Our research reveals novel insights of PM2.5-induced COPD and proposes the miR-122/PTEN pathway as a potential therapeutic target.
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Journal of Ginseng Research
·
2026
·
IF 7.5
Qianru Yang,Xiaoxue Chen,Jintong Cai,Zhengwen Xie,Yuhan Nie,Jinghui Sun,He Li,Chunmei Wang
Background Ginseng - Schisandra herb pair is a classic representative one of the "combination of tonification and astringency" in traditional Chinese medicine. Ginseng tonifies lung Qi and benefits heart Qi, while Schisandra restrains the lung, nourishes the kidney, calms the mind, and soothes the spirit. When they are used in combination, one can play a tonifying role and another can serve as an astringency, with tonification but without stagnation and with astringency but without depression, so the combination can not only enhance the efficacy of replenishing Qi and nourishing Yin but also strengthen the effect of astringing and consolidating. However, the underlying mechanism and action of its combined use in the prevention and treatment of asthma remain unclear. Methods An asthma model in mice was established by using ovalbumin (OVA) combined with aluminum hydroxide (Al(OH) 3 ), so as to evaluate the anti-asthmatic effect of Ginseng - Schisandra herb pair and determine its optimal compatibility ratio. For further validation, an in vitro asthma model was developed by stimulating human bronchial epithelial cells (BEAS-2B) with interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α). The chemical profile of the herb pair extract was comprehensively analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Potential bioactive components and anti-asthma mechanisms were predicted through network pharmacology analysis and subsequently verified by Western blot and immunofluorescence assays. Results Ginseng - Schisandra herb pair could improve the behavior of asthmatic mice, alleviate the pathological damage of lung tissue, reduce the levels of inflammatory factors in the serum of asthmatic mice and the asthma model BEAS-2B cells, increase the activity of superoxide dismutase (SOD), and decrease the levels of malondialdehyde (MDA) and reactive oxygen species (ROS). A total of 72 bioactive components were identified from the Ginseng - Schisandra herb pair extract, and the herb pair could inhibit the expression of PI3K-AKT pathway-related proteins in the lung tissue of asthmatic mice and BEAS-2B cells. Conclusion Ginseng - Schisandra herb pair can effectively alleviate the airway inflammatory response and oxidative stress injury by regulating the PI3K-AKT signaling pathway in mice to exert an anti-asthmatic effect. Among different compatibility ratios and compared with single herbs, the 2:1 ratio of the herb pair exhibits the optimal therapeutic efficacy.
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Stem Cell Reports
·
2026
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IF 5.6
Zhe Yang,Xin Li,Niujian Wu,Ling Wang,Zhanjin Lu,Lingling Wang,Shisong Han,Hongyun Lu
Bone marrow mesenchymal stem cell (BMSC) lineage commitment contributes to metabolic bone diseases, but whether glucagon-like peptide-1 (GLP-1) regulates osteo-adipogenic fate remains unclear. Here, RNA sequencing was performed to identify potential pathways regulated by GLP-1 in BMSCs, followed by gain- and loss-of-function experiments. Furthermore, BMSC-specific Hif-2α knockout mice with glucocorticoid-induced osteoporosis were treated with semaglutide to evaluate skeletal effects. GLP-1 suppressed adipogenesis and promoted osteogenesis of BMSCs in a dose-dependent manner. Transcriptomic analysis identified PI3K-AKT and hypoxia signaling as major GLP-1-regulated pathways. Mechanistically, GLP-1 inhibited AKT activation during adipogenesis and reshaped AKT signaling dynamics during osteogenesis. Loss of HIF-2α largely abolished GLP-1-mediated regulation of AKT activity. In vivo , semaglutide improved trabecular bone mass in osteoporotic mice, whereas this bone-protective effect was markedly diminished in Hif-2α -knockout mice. Our findings suggest that GLP-1 modulates BMSC lineage commitment by inhibiting adipogenesis and enhancing osteogenesis through HIF-2α-associated regulation of AKT signaling.
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Materials Today Bio
·
2026
·
IF 11
Xin Sui,Ling-Feng Li,Bing-Wen Zhong,Zhan-Hua Cao,De-Feng Yang,Yuan Zhuang,Jia-Mu Ren,Tong-tong Yan,Bing Han,Zhi-Hui Liu
Mechanical tensile forces play a crucial role in modulating bone tissue behavior and the response of surrounding cells in vivo. During orthodontic tooth movement, tensile stresses within the periodontal ligament on the tension side stimulate bone deposition. Drawing inspiration from this biological process, our work introduces a strategy using mechanically active materials to enhance bone defect healing. We utilize liquid crystal elastomers (LCEs), a class of soft active materials known for excellent actuation performance. LCEs apply stable mechanical forces to target bone tissue, mimicking the traction of the periodontal ligament and actively promoting bone regeneration. By employing a sequential thiol-Michael/thiol-ene click reaction, optimizing component ratios, and utilizing low-temperature crosslinking, the driving temperature of LCE was significantly reduced to 27.3°C. This advancement eliminates limitations on its medical applications in tissue regeneration. Moreover, both in vitro and in vivo experiments confirm that LCE-induced tensile forces enhance bone regeneration. The LAMB1-ITGB4 signaling axis mediates the process via the PI3K-AKT pathway. This mechanobiological approach opens new avenues for bone defect healing and provides mechanistic insights into how mechanical tensile forces promote bone regeneration.
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Chinese Medicine
·
2026
·Vol. 21
·期 1
·129
·
IF 7.4
Dong Jinwang,Cao Yang,Chen Xiujin,Xie Tao,Zhang Xiaobo,Zhao Qingpeng,Shi Cunhu,Miao Qiangqiang,Xu Zhengwei,Yan Liang,Dong Liang
Background Spinal cord injury (SCI) induces gut microbiota dysbiosis, which significantly affects recovery. Buyang Huanwu Decoction (BHD), a traditional Chinese medicine formula, has shown therapeutic effects on SCI. Although BHD is known to modulate gut microbiota, whether its benefits are mediated through the gut–spinal cord axis remains unclear. Methods A rat SCI model was established. BHD was administered orally, and fecal microbiota transplantation (FMT) from BHD-treated rats (BHD-FMT) was performed to assess neuroprotective and gut-protective effects. Behavioral testing, histology, and immunofluorescence evaluated motor recovery, inflammation, and neuroregeneration. Gut microbiota profiling was performed using 16S rDNA sequencing and metagenomics, while targeted metabolomics quantified tryptophan metabolites. Transcriptomics validated key pathways, and a microbiota–metabolite–signaling network was constructed. Results BHD significantly improved motor function, reduced spinal inflammation, and promoted neuronal survival and axonal regeneration. It restored gut function, reduced colonic inflammation, and enhanced ZO-1 and Occludin expression, which were further confirmed by FMT. BHD-FMT reshaped the gut microbiota and enriched Lactobacillus johnsonii , which correlated positively with recovery. Metabolomics showed increased tryptophan metabolites, including indole-3-lactic acid (ILA) and indole-3-propionic acid (IPA), with ILA strongly associated with functional improvement. Transcriptomic analysis and Western blot validation demonstrated that BHD-FMT activated the AhR–PI3K/Akt pathway, which was suppressed by an AhR antagonist. Conclusion BHD promotes neuroregeneration after SCI by reshaping gut microbiota and enhancing tryptophan metabolism, potentially exerting its effects through the L. johnsonii –ILA–AhR–PI3K/Akt network. These findings reveal a gut–spinal cord axis–mediated mechanism of BHD and highlight microecological targets for SCI therapy. Graphical
The alternative text for this image may have been generated using AI.
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International Journal of Nanomedicine
·
2026
·
IF 8.7
Yan Yan,Ke Wang,Li Ren,Jun-jie Ma,Xing-chun Zhu,Hao-feng Ding,Jia-xin Chu,Zhi-gao Zhu,Jing-yi Xia,Yi Xia,Yuan Xu,Meng-han He,Wen-rui Wang,Cong-li Zhang
Purpose This study aims to address the issues that limit the clinical application of Dl-3-n-butylphthalide (NBP) due to its poor water solubility and low bioavailability, and to explore its therapeutic potential in renal ischemia-reperfusion (I/R) injury. We attempted to utilize layered double hydroxide (LDH) to construct a novel nano-drug delivery system to enhance the stability and efficacy of NBP, and to deeply investigate its potential mechanism of action.Methods By loading NBP onto LDH, LDHs-NBP nanocomplexes were successfully constructed. Subsequently, the effects of LDHs-NBP on renal function, tissue pathology, cell apoptosis, oxidative stress and mitochondrial function were systematically evaluated in rat renal ischemia-reperfusion injury models and HK-2 cell hypoxia/reoxygenation models. The molecular mechanism of the PI3K-AKT-Nrf2 signaling pathway was analyzed through immunohistochemistry and Western Blot.Results The experimental results show that the drug loading capacity of LDHs-NBP nanocomplexes is 24.26%. Compared with pure NBP, LDHs-NBP more effectively improve renal function in rats, reduces serum creatinine (SCr) and blood urea nitrogen (BUN), decreases inflammatory infiltration and structural damage in renal tissues, and exhibits stronger antioxidant capacity—evidenced by decreased malondialdehyde (MDA) levels and increased superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities. At the cellular level, LDHs-NBP significantly inhibits apoptosis and ROS production in HK-2 cells, alleviates mitochondrial dysfunction, and its protective effect is closely associated with activation of the PI3K-AKT-Nrf2 signaling pathway.Conclusion This study successfully constructed an NBP nano-complex based on LDH, and confirmed that LDHs-NBP has significant therapeutic advantages in renal ischemia-reperfusion injury. The mechanism may be related to the activation of the PI3K-AKT-Nrf2 pathway. This study provides experimental evidence for the application of LDHs-NBP in the treatment of renal ischemia-reperfusion injury, and shows a promising translational prospect and clinical value.
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MOLECULES
·
2026
·Vol. 31
·期 12
·2158
·
IF 5.1
Jingran Cui,Xuting Song,Heran Liu,Zhenhai Cui,Mengmeng Sun,Min He,Meiying Jin
Background: Glucocorticoid-induced osteoporosis (GIOP) is marked by impaired osteogenesis and reduced bone formation. Isobavachin (IBA), a flavonoid from Psoralea corylifolia, shows multiple potentials in anti-inflammatory and bone metabolism regulations, but its effects against GIOP remain unclear. This study investigated the osteoprotective effects and potential mechanism of IBA using zebrafish GIOP model. Methods: osteoprotective effects of IBA was assessed by fluorescence imaging in a prednisolone-induced zebrafish model, following with osteogenic gene expressions measured by RT-qPCR. Potential targets and pathways of IBA was filtered and predicted by network pharmacology, molecular docking, and molecular dynamics (MD) simulations, and finally validated with a pharmacological rescue experiment using a PI3K-specific inhibitor. Results: IBA improved bone mineralization and upregulated osteogenesis-related genes. Network pharmacology identified the PI3K-Akt pathway as a key pathway, with ESR1, GSK3B, MTOR, and CCND1 as core targets. PI3K inhibition attenuated the osteoprotective effects of IBA and suppressed downstream osteogenic gene expression. Conclusions: IBA alleviates GIOP by modulating the ESR1-associated PI3K-Akt signaling pathway and may serve as a multi-target therapeutic candidate for osteoporosis.
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Stem Cell Research & Therapy
·
2026
·
IF 7.8
Li Xiao-huan,Lian Fu-wei,Lv Feng,Luo Xiao-Ling,Hu Bang-li,Zhang Li-tu,Ning Shu-fang
Background Mesenchymal stem cells (MSCs)-derived exosomes present great potential as nanocarriers for targeted drug delivery. Moreover, the therapeutic efficacy of exosomes can be substantially enhanced through functional modifications and the incorporation of bioactive molecules. Methods In this study, the MSCs were cultured under two-dimensional (2D) and three-dimensional (3D) cell culture conditions. The culture supernatants were collected for isolating exosomes. The characteristics and yields of exosomes from 2D and 3D cultures were detected by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), western blot analysis, and bicinchoninic acid (BCA) assay. Subsequently, 3D exosomes were loaded with miR-99b-5p and modified with iRGD peptide were formed into a new engineered exosome, designated as iRGD-Exo-miR-99b-5p. The effects of these engineered exosomes on the progression of colorectal cancer (CRC) were assessed through a series of in vivo and in vitro experiments. Results The 3D-cultured MSCs exhibited a higher yield of exosomes and enhanced uptake by CRC cells. Further in vitro experiments demonstrated that 3D-exosomes loaded with miR-99b-5p effectively inhibit the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of CRC cells. Results from a xenograft tumor model indicate that iRGD-modified exosomes were significantly enriched at tumor sites. Furthermore, exosomes modified with iRGD and loaded with miR-99b-5p were employed for CRC treatment, resulting in substantial tumor growth inhibition and enhanced the chemotherapy efficacy of 5-fluorouracil (5-FU) in vivo, without inducing notable toxicity or side effects. Mechanistically, exosome-mediated delivery of miR-99b-5p downregulated FGFR3 expression, thereby inhibiting the activation of the PI3K/AKt signaling pathway and promoting ferroptosis, ultimately attenuating CRC progression. Conclusions Collectively, iRGD-modified 3D exosomes loaded with miR-99b-5p were able to specifically target tumor sites, thereby significantly suppressing CRC growth through the induction of ferroptosis via regulating the FGFR3/PI3K/AKt signaling pathway. These findings suggest that functional engineering and bioactive loading of 3D-exosomes derived from MSCs represent a promising strategy for targeted cancer therapy. Graphical
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2026
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IF 6.7
Jirui Wei,Xiaozheng He,Tingting Shi,Xiayu Jin,Jun Huang,Qingyao Du,Junda Huang,Tao Li,Xunjie Xie,Yuxin Huang,Chengtao Nie,Yiqi Fan,Xixiao Yang,Luyao Song,Waijiao Tang
Epidemiological studies indicate that Metabolic Associated Fatty Liver Disease (MAFLD) has become the most prevalent chronic liver disease globally. Identifying bioactive molecules from natural plants that can prevent and ameliorate MAFLD is an effective approach to discovering new MAFLD therapeutics. Liupao tea possesses antioxidant and metabolic regulatory properties. This study aimed to identify the active components of Liupao tea polyphenol extract (PLE), and its potential targets and mechanisms of action in the prevention of MAFLD. We performed experiments on MAFLD mice to establish the prevention efficacy of PLE against MAFLD and determine its optimal dosage. Furthermore, network pharmacology, molecular docking, and SPR were performed to predict that PLE’s targets for preventing MAFLD concentrate on the hepatic EGFR target. Knockout of EGFR in hepatocytes attenuated the effects of PLE. These findings indicate that PLE inhibits lipid accumulation by downregulating the EGFR/pEGFR-AKT/pAKT-SREBP-1-ACC1 pathway through binding to the EGFR receptor, thereby preventing MAFLD.
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