BIOLOGICAL TRACE ELEMENT RESEARCH
·
2025
·
IF 3.6
Liang Chen,Chen Mingyang,Mu Zhidan,Tian Xinyan,Zhao Wenzhen,Hu Yarong,Su Juan
The aim of this study was to explore the role of the ZnT9 protein in obesity-induced sperm maturation disorders in men. We generated a mouse model of obesity-induced weak spermatogenesis via a high-fat diet (HFD) for 10 weeks. In addition to the HFD, a 5-week intervention of salubrinal (SAL) (an inhibitor of endoplasmic reticulum stress) (1 mg/kg/day), ZnSO 4 (15 mg/kg/day), and their combination was started at week 6, after which sperm viability and epididymal tissue damage were assessed. To investigate the role of the ZnT9 protein in spermatogenesis, the expression levels of the ZnT9 protein, endoplasmic reticulum stress (ERS)–related protein, Wnt pathway protein, and apoptosis-related protein in epididymal tissue were measured. Compared with those in the normal (N) group, the mice in the HFD group presented decreased sperm motility, damaged epididymal tissue, epididymal tissue showed decreased expression of ZnT9, β-catenin, LEF protein and mRNA, and increased expression of total cholesterol (TC) and triglycerides (TG), GRP78, Caspase-3, BAX protein and mRNA, as well as increased apoptosis as shown by TUNEL staining. Compared with the HFD group, HFD + ZnSO 4 group, HFD + SAL group, and HFD + ZnSO 4 + SAL groups resulted in reduced epididymal damage, improved decreased total cholesterol (TC) and triglycerides (TG), sperm viability, increased expression of ZnT9, β-catenin, LEF protein and mRNA, and decreased expression of GRP78, Caspase-3, and BAX protein and mRNA, as well as decreased apoptosis as shown by TUNEL staining in epididymal tissues. According to this study, obesity leads to elevated ERS and affects ZnT9 protein synthesis. Inhibition of the Wnt pathway ultimately leads to cell death and damage in epididymal tissue and decreased sperm viability.
研究领域:
生殖生物学
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分子生物学
·
营养学
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产品关联
DOI
PubMed
高影响因子
CANCER SCIENCE
·
2023
·
IF 5.7
Bo‐Wen Zuo,Wan‐Xin Yao,Meng‐Die Fang,Juan Ren,Ling‐Lan Tu,Run‐Jie Fan,Yan‐Mei Zhang
The Brother of Regulator of Imprinted Sites (BORIS, gene symbol CTCFL) has previously been shown to promote colorectal cancer cell proliferation, inhibit cancer cell apoptosis, and resist chemotherapy. However, it is unknown whether Boris plays a role in the progression of in situ colorectal cancer. Here Boris knockout (KO) mice were constructed. The function loss of the cloned Boris mutation that was retained in KO mice was verified by testing its activities in colorectal cell lines compared with the Boris wild‐type gene. Boris knockout reduced the incidence and severity of azoxymethane/dextran sulfate‐sodium (AOM/DSS)‐induced colon cancer. The importance of Boris is emphasized in the progression of in situ colorectal cancer. Boris knockout significantly promoted the phosphorylation of γH2AX and the DNA damage in colorectal cancer tissues and suppressed Wnt and MAPK pathways that are responsible for the callback of DNA damage repair. This indicates the strong inhibition of colorectal cancer in Boris KO mice. By considering that the DSS‐promoted inflammation contributes to tumorigenesis, Boris KO mice were also studied in DSS‐induced colitis. Our data showed that Boris knockout alleviated DSS‐induced colitis and that Boris knockdown inhibited the NF‐κB signaling pathway in RAW264.7 cells. Therefore Boris knockout eliminates colorectal cancer generation by inhibiting DNA damage repair in cancer cells and relieving inflammation in macrophages. Our findings demonstrate the importance of Boris in the development of in situ colorectal cancer and provide evidence for the feasibility of colorectal cancer therapy on Boris.
研究领域:
癌症生物学
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分子生物学
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免疫学
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遗传学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2022
·
IF 14.224
Wenqi Diao,Jin Yan,Xuedong Wang,Qiuhui Qian,Huili Wang
Although triclosan (TCS) is ubiquitously detected in environmental media and organisms, little information is available on its cardiotoxicity and underlying mechanisms. Herein, acute TCS exposure (0.69–1.73 μM) to zebrafish from embryos (6 hpf) to larvae (72 hpf) resulted in cardiac development defects, including increased angle between atrium and ventricle, prolonged SV-BA distance, linearized heart and pericardial cyst in 72-hpf larvae. These malformations resulted from interfered oxidative-stress pathways, reflecting in accumulated ROS and MDA and inhibited SOD and CAT activities. By RT-qPCR, the transcription levels of four cardiac development-related marker genes were significantly up-regulated except for gata4 . Besides, miR-144 was identified as a regulatory molecule of TCS-induced cardiac defects by integrating analyses of artificial intervene expression and RNA-Seq data. Interestingly, the target genes of miR-144 were found and interacted with the above marker genes through constructing protein-protein interaction networks. After intervening the expression of miR-144 by microinjecting and activating Wnt pathway by an agonist BML-284, we confirmed that up-regulated miR-144 suppressed the expression of angiogenesis-related genes and negatively regulated Wnt pathway, further triggering angiogenesis disorders and cardiac phenotypic malformation. These findings unravel the underlying molecular mechanisms regarding TCS-induced cardiac development toxicity, and contribute to early warning and risk management of TCS.
研究领域:
毒理学
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分子生物学
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发育生物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Hao Tang,Yameng Yu,Xinxin Zhan,Feilong Wang,Dong Xiang,Yufeng Zheng,Hong Lin,Dandan Xia
Periodontitis is a prolonged inflammatory disease caused by bacterial infection. Oxidative stress induced by inflammation leads to excessive production of reactive oxygen species (ROS) and difficulties in bone tissue regeneration. ROS-scavenging agents regulate the periodontal tissue microenvironment, which is of great significance in the treatment of periodontitis. In this study, a zinc-cobalt bimetallic organic framework (Zn/Co-MOF) is constructed to alleviate local tissue inflammation and bone resorption in periodontitis by cascading antioxidant activity. In vitro experimental results show that the Zn/Co-MOF not only provides effective cellular protection against ROS attack in human bone marrow mesenchymal stem cells and osteoblast precursor cells (MC3T3-E1), but also promotes osteogenic differentiation. In vivo experiments in rat periodontitis models confirm that Zn/Co-MOFs can reduce local periodontal tissue inflammation, reduce osteoclasts, and promote the recovery of alveolar bone height defects, which is beneficial for the treatment of periodontitis. RNA sequencing results show that the Zn/Co-MOF promotes bone tissue regeneration mainly through activated Wnt pathways, which accelerate osteogenic differentiation. Overall, the Zn/Co-MOF exhibits antioxidant capacity and promotes bone regeneration, making it a promising strategy for the treatment of periodontitis.
研究领域:
牙科学
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材料科学
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再生医学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Oncologie
·
2023
·Vol. 25
·期 3
·233-243
·
IF 0.9
Simin Deng,Yuan Xu,Binbin Gao,Tingting Yu,Lun Kuang,Bo’ang Han,Shaolun Feng,Haodong Chi,Qing Cao,Shen Yue,Chen Liu
Objectives
The Sonic hedgehog (SHH) signaling is essential in animal development and tissue homeostasis. Aberrant activation of SHH pathway has been implicated in tumorigenesis and progression of several cancers, including ovarian cancer. Therefore, targeting SHH pathway may pave the way for successful ovarian cancer treatment.
Methods
To identify the potential SHH inhibitors from traditional Chinese medicines, we herein employed two in vitro cell models. In addition, western blotting and quantitative real-time PCR were performed to evaluate the inhibitory activity of Anemarrhenasaponin I (An-I) on SHH signaling in ovarian cancer cells. Cell proliferation assay and transwell assay were used to assess the effect of An-I on tumorigenicity. We also applied RNA-seq to examine the potential mechanism of An-I against ovarian cancer.
Results
Drug screening results showed that An-I drastically inhibited SHH signaling. More importantly, An-I effectively suppressed ovarian cancer cell proliferation and aggressiveness. RNA-seq-based transcriptome data showed that An-I affected ovarian cancer cells by suppressing SHH-WNT-Matrix metalloproteinases (MMPs) pathway.
Conclusions
An-I suppressed ovarian cancer progression by inhibiting SHH-WNT-MMP signaling transduction, providing a new treatment strategy for ovarian cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xinqing Shi,Jiaman Liu,Wanqin Zhang,Shinian Zeng,Fan Lin,Haining Wang,Bo Teng
After winemaking, tannins with high polymerization remain in the pomace. Utilizing these tannin fractions is a concern for the wine industry. While tannins show potential in treating hyperpigmentation, their mechanisms in vivo and at the cellular level are unclear. Herein, pomace tannin fractions (PTFs) were isolated post-winemaking. Nuclear magnetic resonance spectroscopy and mass spectrometry analysis showed PTFs were composed of ( epi )catechin gallate and (epi)catechin as terminal and extensional units, with polymerization degrees of 10, 16, and 35. In vivo studies demonstrated that PTFs removed ∼76 % of skin melanin, comparable to hydroquinone. The inhibition by PTFs is due to: (1) Inhibition of the Wnt and melanogenesis pathways, downregulating key melanin synthesis proteins (TYR, TYRP1, TYRP2); (2) Inducing cell cycle arrest at the G1/S checkpoint, disrupting DNA, decreasing mitochondrial membrane potential and integrity, and slowing melanocyte proliferation; (3) Superior tyrosinase inhibitory activity by binding to tyrosinase, chelating copper ions, and demonstrating antioxidant properties. These findings suggest that PTFs inhibit melanin synthesis by the combination of the above mentioned ways, supporting the medical use of winemaking tannins.
研究领域:
药理学
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皮肤病学
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生物化学
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化妆品科学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Tangfei Guan,Xin Yang,Canhui Hong,Jiali Zhu,Peiyun Xiao,Yongshou Yang,Chenggui Zhang,Zhengchun He
Introduction: Alopecia areata (AA), an autoimmune hair-loss disease due to follicular inflammatory cell infiltration, lacks an ideal cure. The Periplaneta Americana (PA) extract (PA-011), a traditional Chinese medicine with anti-inflammatory, antioxidant, tissue-repair-promoting, and immune-regulating properties, was studied for its AA-treating effects.Methods: Guided by network pharmacology, AA model mice were treated with PA-011. Hair growth, skin tissue, inflammatory factors, and Wnt protein levels were examined. Transcriptomics, metabolomics, and 16S rRNA sequencing explored the hair-growth-promoting mechanisms.Results: Network pharmacology showed PA-011 could regulate AA-related targets and pathways. PA-011 intervention promoted hair follicle cell proliferation and hair growth in AA mice, reduced skin TNF-α, IL-23, and VCAM-1 expression. Transcriptomics and WB analysis indicated PA-011 downregulated inflammatory genes, activated Wnt3a, and modulated the TGF-β pathway. Metabolomics found PA-011 regulated metabolic pathways. 16S rRNA analysis showed it reversed AA-induced skin microbiota changes, inhibiting pathogens and promoting probiotics. Multi-omics analysis revealed PA-011 regulated skin microbiota and metabolic balance for hair growth.Discussion: In conclusion, PA-011 alleviates AA by reducing skin inflammation and modulating skin microbiota, suggesting its potential as an AA therapeutic.
研究领域:
药理学
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皮肤病学
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免疫学
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微生物学
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中医药学
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系统生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·
IF 6.6
Xin Jin,Zelin Ou,Guowei Zhang,Rong Shi,Jumin Yang,Wenguang Liu,Gaoxing Luo,Jun Deng,Wei Wang
With an increasing proportion of drug-resistant bacteria, photothermal therapy (PTT) is a promising alternative to antibiotic treatment for infected diabetic skin ulcers. However, the inevitable thermal damage to the tissues restricts its clinical practice. Carbon monoxide (CO), as a bioactive gas molecule, can selectively inhibit bacterial growth and promote tissue regeneration, which may be coordinated with PTT for drug-resistant bacteria killing and tissue protection. Herein, a CO-mediated PTT agent (CO@mPDA) was engineered by loading manganese carbonyl groups into mesoporous polydopamine (mPDA) nanoparticles via coordination interactions between the metal center and a catechol group. Compared to the traditional PTT, the CO-mediated PTT increases the inhibition ratio of the drug-resistant bacteria both in vitro and in diabetic wound beds by selectively inhibiting the co-chaperone of the heat shock protein 90 kDa (Hsp90), and lowers the heat resistance of the bacteria rather than the mammalian tissues. Meanwhile, the tissue-protective proteins, such as Hsp90 and vimentin (Vim), are upregulated via the WNT and PI3K-Akt pathways to reduce thermal injury, especially with a laser with a high-power density. The CO-mediated PTT unified the bacterial killing with tissue protection, which offers a promising concept to improve PTT efficiency and minimize the side-effects of PTT when treating infected skin wounds.
研究领域:
生物医学工程
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纳米技术
·
药学
·
伤口愈合
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产品关联
DOI
PubMed
高影响因子
Food Frontiers
·
2024
·
IF 7.4
Xiaxia Fan,Mangmang Feng,Dan Guo,Songtao Li,Yuxuan An,Jinmiao Tian,Zhuoyu Li
Chemoresistance is a major cause of breast cancer (BC) recurrence and metastasis, and chemotherapy resistance comes from tumor stemness. Our previous study showed that quinoa bran terpenoids (QBT) exhibited significant antitumor activity. In this study, we found that QBT increased the sensitivity of drug-resistant BC cells to the chemotherapeutic drugs adriamycin (ADR) and taxol (TAX). A novel lncRNA 667012 was identified along with QBT treatment. Moreover, overexpression of lncRNA 667012 promoted drug resistance, and the reduction of 667012 restored the drug sensitivity of resistant BC cells. More importantly, the findings revealed that lncRNA 667012 promoted stemness maintenance via the stemness-related Wnt pathway. Furthermore, the result showed that QBT reduced 667012 expression and inhibited the activation of β-catenin, thereby attenuating the stemness characteristics of BC and enhancing chemosensitivity. Consistently, the data were confirmed in the xenograft mice model. These results suggest that QBT could reverse chemoresistance by inhibiting stemness. It has the potential to be developed as a novel chemotherapeutic agent or chemosensitizer for BC treatment.
研究领域:
肿瘤学
·
分子生物学
·
药理学
·
植物科学
✓ 已验证
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2019
·
IF 4.527
Gaofeng Cui,Haiqi Yuan,Zhiyan Jiang,Jing Zhang,Zhipeng Sun,Guohua Zhong
The widely distributed β-carboline alkaloids exhibit promising psychopharmacological and biochemical effects. Harmine, a natural β-carboline, can inhibit insect growth and development with unclear mechanisms. In this study, harmine (at 0-200 mg/L) showed a dose-dependent inhibitory effect on the pupal weight, length, height, pupation rate and eclosion rate of fruit flies Drosophila melanogaster , which was similar to the inhibition induced by the well-known botanical insect growth regulator azadirachtin . Moreover, the expression levels of major regulators from the developmental signaling network were down-regulated during the pupal stage except Numb , Fringe , Yorkie and Pten . The Notch, Wnt, Hedgehog and TGF-β pathways mainly played vital roles in coping with harmine exposure in pupae stage, while the Hippo, Hedgehog and TGF-β elements were involved in the sex differences. Notch , Hippo , Hedgehog , Dpp and Armadillo were proved to be suppressed in the developmental inhibition with fly mutants, while Numb and Punt were increased by harmine. In conclusion, harmine significantly inhibited the development of Drosophila by negatively affecting their developmental signaling network during different stages. Our results establish a preliminary understanding of the developmental signaling network subjected to botanical component-induced growth inhibition and lay the groundwork for further application.
研究领域:
昆虫学
·
分子生物学
·
发育生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomolecules and Biomedicine
·
2024
·
IF 0
Huaxian Chen,Xingyang Wan,Qiulan He,Guozhong Xiao,Yihui Zheng,Minyi Luo,Chaoxin Yang,Donglin Ren,Li Lu,Hui Peng,Hongcheng Lin
The cellular characteristics of intestinal cells involved in the therapeutic effects of astragaloside IV (AS-IV) for treating slow transit constipation (STC) remain unclear. This study aimed to determine the dynamics of colon tissue cells in the STC model and investigate the effects of AS-IV treatment by single-cell RNA sequencing (scRNA-seq). STC mouse models were developed using loperamide, with subsequent treatment using AS-IV. Colon tissues and feces were collected for scRNA-seq and targeted short-chain fatty acid quantification. We integrated scRNA-seq data with network pharmacology to analyze the effect of AS-IV on constipation. AS-IV showed improvement in defecation for STC mice induced by loperamide. Notably, in STC mice, epithelial cells, T cells, B cells, and fibroblasts demonstrated alterations in cell proportions and aberrant functions, which AS-IV partially rectified. AS-IV has the potential to modulate the metabolic pathway of epithelial cells through its interaction with peroxisome proliferator-activated receptor gamma (PPARγ). AS-IV reinstated fecal butyrate levels and improved energy metabolism in epithelial cells. The proportion of naïve CD4+T cells is elevated in STC, and the differentiation of these cells into regulatory T cells (Treg) is regulated by B cells and fibroblasts through the interaction of ligand-receptor pairs. AS-IV treatment can partially alleviate this trend. The status of fibroblasts in STC undergoes alterations, and the FB_C4_Adamdec1 subset, associated with angiogenesis and the Wingless-related integration (Wnt) pathway, emerges. Our comprehensive analysis identifies perturbations of epithelial cells and tissue microenvironment cells in STC and elucidates mechanisms underlying the therapeutic efficacy of AS-IV.
研究领域:
药理学
·
胃肠病学
·
分子生物学
·
网络药理学
✓ 已验证
产品关联
DOI
PubMed
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2018
·
IF 2.559
Zhigang Nie,Sen Chen,Shuang Deng,Linsheng Long,Puji Peng,Mingyong Gao,Shile Cheng,Jiarui Cao,Hao Peng
Objective Glucocorticoids (GCs)-induced osteoblast apoptosis has been identified as an important cause of GCs related osteonecrosis of the femoral head (ONFH). Glycogen synthase kinase 3β (GSK3β) has been proved to mediate dexamethasone (Dex)-induced osteoblast apoptosis. This study aimed to investigate the underlying mechanism of GSK3β in Dex-induced osteoblast apoptosis. Methods Osteoblast cells were transfected with lentivirus expressing GSK3β-shRNA, and a DNA microarray was performed to analyze gene expression after Dex treatment with or without GSK3β-shRNA. Some differentially expressed genes were further validated by quantitative real-time-PCR (qRT-PCR). Results 460 genes were up-regulated (at least 2-fold) with Dex treatment but down-regulated (at least 2-fold) with GSK3β-shRNA treatment. In addition, 315 genes were down-regulated (at least 2-fold) with Dex treatment but up-regulated (at least 2-fold) with GSK3β-shRNA treatment. Among these genes, the apoptosis-related genes Hoxb8 , Kif18a , Dock8, Dlk1, Tnfsf14 , Casq2 , Bcl2l14 and mechanosensation-related gene Piezo2 were selected for further qRT-PCR analysis. 7 of 8 genes (Piezo2, Hoxb8, Kif18a, Dlk1, Tnfsf14, Casq2, Bcl2l14) showed the same tendency between gene chip results and qRT-PCR results. The microarray data also showed that apoptotic pathway, MAPK pathway, TGFβ pathway and Wnt pathway might be related to the mechanism of GSK3β in Dex-induced osteoblast apoptosis. Conclusion Our findings indicate that GSK3β-shRNA treatment can alter various genes expression levels and change diverse signaling pathways involved in Dex-induced osteoblast apoptosis. Furthermore, Piezo2, Hoxb8, Kif18a, Dlk1, Tnfsf14, Casq2 and Bcl2l14 genes may play an important role in the GSK3β-mediated osteoblast apoptosis process.
研究领域:
药理学
·
细胞生物学
·
分子生物学
·
基因组学
✓ 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）