JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
·
IF 5.7
Tong Liu,Siqing Fan,Pengfei Meng,Mingxia Ma,Yanxin Wang,Jiaojiao Han,Yufei Wu,Xiao Li,Xiurong Su,Chenyang Lu
Gut microbiota provides an important insight into clarifying the mechanism of active substances with low bioavailability, but its specific action mechanism varied case by case and remained unclear. Dihydroquercetin (DHQ) is a bioactive flavonoid with low bioavailability, which showed beneficial effects on colitis alleviation and gut microbiota modulation. Herein, we aimed to explore the microbiota-dependent anticolitis mechanism of DHQ in sight of gut microbiota metabolites and their interactions with microRNAs (miRNAs). Dietary supplementation of DHQ alleviated dextran sulfate sodium-induced colitis phenotypes and improved gut microbiota dysbiosis. Fecal microbiota transplantation further revealed that the anticolitis activity of DHQ was mediated by gut microbiota. To clarify how the modulated gut microbiota alleviated colitis in mice, the tandem analyses of the microbiome and targeted metabolome were performed, and altered profiles of metabolite short-chain fatty acids (SCFAs) and bile acids and their producers were observed in DHQ-treated mice. In addition, SCFA treatment showed anticolitis activity compared to that of bile acids, along with the specific inhibition on the phosphoinositide-3-kinase (PI3K)-protein kinase B (Akt) pathway. Subsequently, the colonic miRNA profile of mice receiving SCFA treatment was sequenced, and a differentially expressed miR-10a-5p was identified. Both prediction analysis and dual-luciferase reporter assay indicated that miR-10a-5p directly bind to the 3′-untranslated regions of gene pik3ca, inhibit the PI3K-Akt pathway activation, and lead to colitis alleviation. Together, we proposed that gut microbiota mediated the anticolitis activity of DHQ through the SCFAs/miR-10a-5p/PI3K-Akt axis, and it provided a novel insight into clarifying the microbiota-dependent mechanism via the interaction between metabolites and miRNAs.
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JOURNAL OF CELLULAR BIOCHEMISTRY
·
2023
·Vol. 124
·期 4
·557-572
·
IF 4
Juan Gu,Xu Chu,Yujia Huo,Chaoyi Liu,Qingge Chen,Shengnan Hu,Yanyan Pei,Pu Ding,Sen Pang,Ming Wang
Gastric cancer (GC) with pulmonary metastasis is one of the deadliest diseases in the world; however, the underlying pathological mechanisms and potential therapeutic targets remain to be elucidated. As exosomes play indispensable roles in the formation of premetastatic niches (PMN) and cancer metastasis. Therefore, investigating the underlying mechanisms of exosome-mediated pulmonary metastasis of GC may shed new light on identifying novel therapeutic targets for GC treatment. GC-derived exosomes were isolated from the conditioned medium of mouse forestomach carcinoma (MFC) cell line. The effects of MFC-derived exosomes on pulmonary macrophage polarization were analyzed by reverse- transcription polymerase chain reaction and flow cytometry. Expression of PD-L1 and other proteins was evaluated by Western blot. Exosomal microRNAs (miRNAs) were analyzed by microarray. GC-derived exosomes (GC-exo) accumulated in high numbers in the lungs and were ingested by macrophages. The extracellular-signal-regulated kinase (ERK) signaling pathway was activated by GC-exo, inducing macrophage immunosuppressive-phenotype differentiation and increased PD-L1 expression. miRNA-sequencing identified 130 enriched miRNAs in GC-exo. Among the enriched miRNAs, miR-92a-3p plays a major role in activating ERK signaling via inhibition of PTEN expression. In addition, inhibiting ERK signaling with PD98059 significantly reduced the expression of PD-L1 in macrophages and, therefore, reversed the immunosuppressive PMN and inhibited the colonization of GC cells in the lungs. This study identified a novel mechanism of GC-exo mediated PD-L1 expression in lung macrophages that facilitates lung PMN formation and GC pulmonary metastasis, which also provided a potential therapeutic target for GC with pulmonary metastasis treatment.
研究领域:
肿瘤学
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免疫学
·
分子生物学
·
癌症生物学
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Journal of Radiation Research and Applied Sciences
·
2025
·
IF 2.5
Yu Zhang,Hongbo Lv,Chao Chen,Zixu Li,Zhaoyu Xie,Miaomiao Wu,Zhixu Zhu,Ying Fan,Jing Li,Qiang Gao,Jun Han,Hui Che,Lan Ma
Background Ischemic stroke (IS) is a major global cause of mortality and long-term disability, and effective therapies are urgently needed. Hydrogen sulfide (H 2 S) has shown neuroprotective effects in various neurological disorders, but its mechanisms in IS remain unclear. This study aims to explore the role and mechanism of H 2 S in IS treatment. Methods IS models were established in vivo using middle-cerebral-artery occlusion (MCAO) in rats and in vitro using oxygen-glucose deprivation/reoxygenation (OGD/R) in PC12 cells. These models were treated with H 2 S donors NaHS or GYY4137. Pathological features were evaluated using TTC, FJC, H&E, and Nissl staining. Cell viability was assessed with live/dead staining and CCK-8 assay. RNA sequencing identified gene expression changes after H 2 S treatment under OGD/R conditions. Ferroptosis-related markers, lipid peroxidation (GSH, SOD, MDA), ROS levels, and the expression of SLC7A11 and GPX4 were measured by flow cytometry, Western blot, and immunofluorescence. MiR-27a levels were quantified by qRT-PCR. Results NaHS administration in MCAO rats reduced infarct volume, increased Nissl body density, and decreased degenerating neurons. GYY4137 exhibited similar neuroprotective effects in vitro. RNA sequencing revealed that GYY4137 reversed ferroptosis-related gene changes, including SLC7A11. H 2 S supplementation inhibited neuronal ferroptosis, shown by increased SLC7A11 and GPX4 expression, elevated GSH and SOD levels, and reduced MDA content. Additionally, MCAO or OGD/R induced miR-27a expression, which negatively regulated SLC7A11. H 2 S reversed this induction, and miR-27a overexpression partially blocked the anti-ferroptotic effect of H 2 S. Conclusion H 2 S alleviated IS-induced brain injury by suppressing ferroptosis, partially through miR-27a-dependent regulation of SLC7A11. These findings suggest H 2 S as a promising therapeutic agent for IS, warranting further clinical exploration.
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JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Mingju Shui,Yi Chen,Miao Guo,Guofeng Zhong,Hongyi Li,Yaqin Xiao,Qin Yuan,Beixin Yuan,Xiaoying Liu,Hefeng Zhou,Zhejie Chen,Shengpeng Wang
Ulcerative Colitis (UC) is a chronic intestinal disease with limited treatment options, where current therapies often suffer from inadequate efficacy and substantial side effects. While polyphenol-based nanocarriers show promise for nucleic acid delivery, a systematic screening approach to identify optimal polyphenols for this purpose remains unexplored. Therefore, we conducted a systematic screening of 110 natural polyphenols to develop an efficient miRNA delivery system for UC intervention. Sinapic acid (SA) was identified as the lead candidate and complexed with miR-124 mimics, followed by sequential encapsulation with a poly(amidoamine) (PAMAM) dendrimer and hyaluronic acid (HA) coating to form HPPR NPs. As expected, HPPR mediated efficient intracellular delivery of miR-124, leading to significant downregulation of the expression of IL-6R , CCL-2 , STAT3 , and their downstream genes in a murine model of dextran sulfate sodium (DSS)-induced acute colitis. HPPR also markedly suppressed the production of pro-inflammatory cytokines and facilitated intestinal mucosal regeneration. Moreover, the system effectively modulated gut microbiota homeostasis by enriching beneficial bacteria ( Akkermansia and norank_f__Muribaculaceae ) while simultaneously suppressing pathogenic bacteria ( Escherichia-Shigella and Helicobacter ). Collectively, this study not only establishes a polyphenol-based strategy for optimizing nucleic acid delivery but also presents a promising nanotherapeutic platform for UC treatment.
研究领域:
纳米医学
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分子生物学
·
胃肠病学
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药物递送
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免疫学
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Stem Cells International
·
2025
·Vol. 2025
·期 1
·5243270
·
IF 3.3
Bei Li,Qiongni Wang,Linru Shi,Qifeng Liu,Hui Qian,Lixia Yu,Cheng Ji
Diabetic kidney disease (DKD) is characterized by a continuous decline in renal function and progressive fibrosis, making it a leading cause of end-stage kidney disease with limited therapeutic options. Recently, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown great potential in tissue regeneration and repair, offering a new avenue for the treatment of DKD. The purpose of this study is to explore the function and mechanism of action of EVs derived from human umbilical cord MSCs (hucMSC-EVs) in the development of DKD. Our findings show that under high-glucose (HG) conditions, miR-146b-5p is highly expressed in glomerular mesangial cells, downregulating the target protein Merlin, which promotes the activation of the YAP signaling pathway and induces mesangial cell fibrotic-like changes, leading to a significant deposition of collagen and interstitial fibrosis in the kidney. In vivo and in vitro experimental findings reveal that hucMSC-EVs can significantly inhibit miR-146b-5p, upregulate Merlin expression, prevent the nuclear translocation of YAP, improve renal function, and reduce collagen deposition, demonstrating a significant antifibrotic effect. The findings of this study emphasize the central role of the miR-146b-5p/Merlin/YAP axis in hucMSC-EVs-mediated inhibition of renal fibrosis and highlight the potential of MSC-EVs as a targeted nanotherapeutic strategy for DKD.
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Signal Transduction and Targeted Therapy
·
2018
·Vol. 3
·期 1
·1-10
·
IF 0
Zhao Yang,Chen Jing,Wei Wenxin,Qi Xinming,Li Chunzhu,Ren Jin
Chemotherapeutic treatments against hepatocellular carcinoma (HCC) are necessary for both inoperable patients to improve prospects for survival and surgery patients to improve the outcome after surgical resection. However, multidrug resistance (MDR) is a major obstacle to obtaining desirable results. Currently, increasing the chemotherapy sensitivity of tumor cells or discovering novel tumor inhibitors is an effective therapeutic strategy to solve this issue. In the present study, we uncovered the dual-inhibitory effect of miR-338-5p: on the one hand, it could downregulate ABCB1 expression and sensitize HCC cells to doxorubicin and vinblastine by directly targeting the 3′-untranslated region (3′-UTR) of ABCB1, while, on the other hand, it could suppress the proliferation of HCC cells by directly targeting the 3′-UTR of EGFR and reducing EGFR expression. Since EGFR regulates ABCB1 levels, the indirect action of miR-338-5p in ABCB1 modulation was revealed, in which miR-338-5p inhibits ABCB1 expression by targeting the EGFR/ERK1/2 signaling pathway. These data indicate that the miR-338-5p/EGFR/ABCB1 regulatory loop plays a critical role in HCC, and a negative correlation between miR-338-5p and EGFR or ABCB1 was also detected in HCC clinical samples. In conclusion, these findings reveal a critical role for miR-338-5p in the regulation of MDR and proliferation of HCC, suggesting the potential therapeutic implications of miR-338-5p in HCC treatment.
研究领域:
肿瘤学
·
分子生物学
·
药理学
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Journal of Biomedical Nanotechnology
·
2022
·Vol. 18
·期 12
·2708-2720
·
IF 3.641
Duan Ping,Cheng Jing,Mao Ruotong,Wang Ruina,Jin Yueqi,Li Chunyang
MicroRNAs, one type of non-coding RNA, and Icariin have attracted tremendous attention concerning various diseases, especially cancers. Also, the function of Icariin on malignant behaviors by targeting miR-875-5p/MDM4 axis in cervical cancer remains unknown. MiR-875-5p analogs combined
with MDM4 or Icariin were used to explore autophagy and epithelial-mesenchymal transition in cancer cells. Xenograft mice were highlighted to elucidate the influences of Icariin and miR-875-5p in vivo. As a result, miR-875-5p was cut down in cervical cancer cells, which promoted malignant
phenotype, autophagy, and limited apoptosis in cervical cancer cells. Contrarily,miR-875-5p overexpression had a contrary performance in cervical cancer cells. miR-875-5p was validated as a sponge of MDM4. Enhanced expression of MDM4 weakened the performance of miR-875-5p mimic on autophagy
and epithelial-mesenchymal transition. Moreover, Icariin reversed the stimulative action of the inhibitor on autophagy and xenograft tumor growth. Generally, These findings imply that Icariin could be identified as a curative avenue for cervical cancer via miR-875-5p/MDM4 axis.
研究领域:
肿瘤学
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分子生物学
·
药理学
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Clinical Interventions in Aging
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2022
·
IF 3.829
Bao Hai,Yunlong Ma,Xiaoyu Pan,Lei Yong,Chen Liang,Guanping He,Chenlong Yang,Bin Zhu,Xiaoguang Liu
Background Disc degeneration (DD) is one of the common diseases worldwide, which deeply influences normal life and leads to excruciating pain. However, an effective treatment for DD is still not identified.Method The present study systemically examined the effect of melatonin on annulus fibrosus (AF) cells of patients with DD.Results Melatonin had the effect of promoting proliferation, inducing autophagy, and suppressing apoptosis on AF cells of patients with DD. Moreover, melatonin contributed to the translation and transcription of autophagy-related protein ATG7 and inhibited the function of miR-106a-5p in AF cells. In addition, the results suggested that miR-106a-5p mediated the expression of ATG7 by directly binding to its 3′UTR in AF cells.Conclusion This research not only gained a deep insight of melatonin mode of action, but also indicated its potential target signaling pathway in AF cells.
研究领域:
神经病学
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细胞生物学
·
分子生物学
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Virulence
·
2026
·
IF 6.8
Xinxian Wang,Shurui Yang,Lichun Xie,Shanshan Qi,Libo Gao,Yongmei Li,Qian Li,Junlong Bi,Jianping Liu,Yongneng Li,Gefen Yin
Classical swine fever virus (CSFV) remains a major threat to the global swine industry, yet the involvement of host miRNAs in its pathogenic mechanisms is not fully understood. In this study, we demonstrate for the first time that miR-17-5p inhibits CSFV replication through an autophagy-dependent mechanism by targeting polycystin-2 (PKD2), a key calcium channel protein that regulates the AMPK/mTOR signaling pathway. Using the PK-15 cell model, we found that CSFV infection significantly upregulates miR-17-5p expression. Functional assays revealed that miR-17-5p exerts antiviral effects by directly binding to the 3’-UTR of PKD2, as confirmed by bioinformatics prediction and dual-luciferase reporter assays. Silencing of PKD2 recapitulated the antiviral effect of miR-17-5p overexpression, while PKD2 reconstitution restored viral replication by activating AMPK signaling and suppressing mTOR activity, thereby significantly enhancing autophagic flux – as evidenced by increased LC3-II/I ratio and decreased p62 levels. Mechanistically, PKD2 regulates intracellular calcium dynamics, modulating the AMPK/mTOR-autophagy axis to promote CSFV proliferation. This work uncovers a novel host antiviral mechanism in which a miRNA controls virus-induced autophagy via calcium signaling. To our knowledge, this is the first report to establish the pivotal role of miRNA-mediated calcium signaling modulation in flavivirus-host interactions. These findings provide a mechanistic framework and potential therapeutic targets for anti-CSFV interventions focused on PKD2 or autophagy regulation.
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JOURNAL OF MOLECULAR HISTOLOGY
·
2026
·Vol. 57
·期 1
·30
·
IF 2.2
Xiang Shouyu,Liu Wei,Tang Cheng,Xie Chuhai,Hu Hailan,Zhou Jianhui,Cao Yanming,Ling Long
Bone marrow mesenchymal stem cells (BMSCs) play a significant role in bone defect repair. Currently, the limited survival and function of transplanted BMSCs pose major obstacles to tissue repair mediated by these cells. Therefore, the exploration of BMSCs transplantation activity has become an urgent clinical problem. In this experiment, we constructed lentiviral vectors with overexpression and silencing of miR-19b-3p and utilized a rat fracture model. The effects of BMSCs proliferation were examined using CCK-8, the Annexin V-FITC apoptosis kit and TUNEL assay, the effects of BMSCs osteogenic differentiation were detected using ALP and Alizarin red staining. Furthermore, Western blotting and qRT-PCR were employed to examine the expression of key proteins in the PTEN/Akt/mTOR signaling pathway and autophagy-related proteins. Moreover, the impact of miR-19b-3p on bone microstructure was assessed using Micro CT, HE, Safranin O/Fast Green, as well as Masson staining, and Immunohistochemistry analysis examined PTEN, p62 and Runx2 expression levels on fracture site. By constructing lentiviral vectors with overexpression and silencing of miR-19b-3p, we found that silencing miR-19b-3p significantly promoted the proliferation as well as the osteogenic differentiation of BMSCs under hypoxia. Western blotting and qRT-PCR results showed that silencing miR-19b-3p significantly increased PTEN, LC3, and Beclin1 expression while decreasing p-Akt, p-mTOR, and p62 expression. Furthermore, by constructing the fracture rats and administering hypoxia-treated BMSCs transfected with miR-19b-3p via tail vein injection, we found that silencing miR-19b-3p obviously increased the formation of trabecular and promoted the healing of the fractures. Immunohistochemistry analysis showed that silencing miR-19b-3p upregulated PTEN and Runx2 expression levels and suppressed p62 expression with statistical significance. In summary, these findings suggest that miR-19b-3p may regulate BMSCs’ autophagy and osteogenic differentiation under hypoxia via the PTEN/Akt/mTOR signaling pathway, thereby promoting fracture healing and providing a potential target for the treatment of fractures.
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2026
·Vol. 30
·期 17
·e71359
·
IF 4.7
Xuesong Xu,Shichong Qiao
Apoptosis and functional loss of articular chondrocytes serve as initiating events in temporomandibular joint osteoarthritis (TMJOA), and FoxO3 represents a critical molecule for sustaining chondrocyte homeostasis. This study investigates the regulatory mechanism of the lncRNA‐OIP5‐AS1/hsa‐miRNA‐223‐3p/FoxO3 axis in TMJOA, aiming to identify potential therapeutic targets for this disease. Single‐cell database analysis first revealed markedly reduced FoxO3 expression in TMJOA‐derived chondrocytes. A rat TMJOA model was then constructed and assigned to control, model, and FoxO3 overexpression groups; micro‐CT and histological staining, including HE and Safranin O‐fast green staining, were applied to assess articular cartilage injury, while immunohistochemistry was used to detect cartilage‐associated proteins Col2a1, MMP‐13, Aggrecan, and ADAMTS‐5. Further in vitro experiments validated the chondroprotective function of FoxO3 as well as the binding interaction between FoxO3 and rno‐miRNA‐223‐3p. Database screening confirmed significant down‐regulation of FoxO3 in TMJOA cartilage. Animal experiments demonstrated that FoxO3 overexpression mitigated chondrocyte injury in rat TMJOA lesions, increased Col2a1 and Aggrecan levels, and suppressed MMP‐13 and ADAMTS‐5 expression. Cellular assays showed that FoxO3 overexpression enhanced chondrocyte proliferation and matrix synthesis and preserved chondrocyte function. Sequencing and cellular evidence indicated that rno‐miRNA‐223‐3p directly targets FoxO3 mRNA to repress its transcription and negatively modulate FoxO3 abundance, consequently aggravating chondrocyte apoptosis. Collectively, rno‐miRNA‐223‐3p suppresses FoxO3 activity to facilitate TMJOA pathogenesis, and the lncRNA‐OIP5‐AS1/rno‐miRNA‐223‐3p/FoxO3 regulatory cascade may act as a promising molecular target for TMJOA clinical intervention.
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2026
·
IF 4.8
Tingting Guo,Chang Zuo,Ping Bai,Lingjing Hu
A novel multi-functional DNA tetrahedron-based target-induced cascaded cyclic catalytic amplification (TICA) assay was developed for the sensitive detection of microRNA-21 (miR-21) in prostate cancer. This strategy ingeniously integrates two distinct DNA tetrahedron with specific functions (catalytic tetrahedron (Cat-DT) and signal DNA tetrahedron (Sig-DT)) to create a self-sustaining amplification circuit. The process is initiated when miR-21 triggers the release of a DNAzyme enzymatic strand (E-DNA), which converts Cat-DT into tri-branched DNA nanostructures (TB-DNA). Critically, each TB-DNA acts as a cascaded amplifier, bearing three E-DNA units that drive the exponential generation of more catalytic sites. Furthermore, the system employs an ingenious feedback loop: the TB-DNA/Sig-DT interaction produces a fluorescent signal while regenerating a miR-21-mimetic strand to perpetuate the catalytic cycle. This “target → catalyst → new target” paradigm enables ultra-efficient amplification, achieving a wide linear range from 600 fM to 100 nM and a low detection limit of 400 fM for miR-21. Notably, the TICA strategy significantly shortens the total reaction time to 80 min, demonstrating great potential for rapid and sensitive clinical diagnostics.
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