BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2023
·
IF 3.1
Ling Chen,Zhongwen Li,Wumei Wei,Bin An,Yao Tian,Wenjing Liu,Shuaishuai Niu,Yukai Wang,Liu Wang,Wei Li,Jie Hao,Jun Wu
Acute liver failure (ALF) is a clinical syndrome characterized by the accelerated development of hepatocyte necrosis and significant mortality. Given that liver transplantation is now the only curative treatment available for ALF, there is an urgent need to explore innovative therapies. Mesenchymal stem cells (MSCs) have been applied in preclinical studies for ALF. It had been demonstrated that human embryonic stem cell-derived immunity-and-matrix regulatory cells (IMRCs) met the properties of MSCs and had been employed in a wide range of conditions. In this study, we conducted a preclinical evaluation of IMRCs in the treatment of ALF and investigated the mechanism involved. ALF was induced in C57BL/6 mice via intraperitoneal administration of 50% CCl 4 (6 mL/kg) mixed with corn oil, followed by intravenous injection of IMRCs (3 × 10 6 cells/each). IMRCs improved histopathological changes in the liver and reduced alanine transaminase (ALT) or aspartate transaminase (AST) levels in serum. IMRCs also promoted cell renewal in the liver and protected it from CCl 4 damage. Furthermore, our data indicated that IMRCs protected against CCl 4 -induced ALF by regulating the IGFBP2-mTOR-PTEN signaling pathway, which is associated with the repopulation of intrahepatic cells. Overall, IMRCs offered protection against CCl 4 -induced ALF and were capable of preventing apoptosis and necrosis in hepatocytes, which provided a new perspective for treating and improving the prognosis of ALF.
研究领域:
肝病学
·
干细胞生物学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2018
·
IF 2.559
Qing Shu,Song Lai,Xiao-Mei Wang,Yun-Long Zhang,Xiao-Lei Yang,Hai-Lian Bi,Hui-Hua Li
Pathological cardiac hypertrophy is the main risk factor for heart diseases. The ubiquitin-proteasome system (UPS) is the major intracellular protein degradation system involved in the development of cardiac hypertrophic remodeling. Ubiquitin-activating enzyme E1, a key component of the UPS, catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation via proteasome . However, the functional role of E1 (UBA1) in regulation of hypertrophic remodeling in angiotensin II (Ang II)-infused mice remains unknown. In this study, male wild-type mice were treated with UBA1 inhibitor PYR-41 at two doses of 5 and 10 mg and infused with Ang II (1000 ng/kg/min) for 14 days. Systolic blood pressure was detected by using tail-cuff system. Cardiac function was assessed by echocardiography. Hypertrophic remodeling was analyzed examined by histological examinations. The expressions of genes and proteins were detected by quantitative real-time PCR and immunoblotting analysis. After 14 days, Ang II infusion significantly increased UBA1 expression at both mRNA and protein levels in the hearts. Furthermore, Ang II-infused mice showed a significant increase in systolic blood pressure compensatory cardiac function, hypertrophy, interstitial fibrosis, inflammation and oxidative stress compared with saline-treated controls, whereas these effects were dose-dependently attenuated in PYR-41-treated mice. These beneficial actions were associated mainly with inhibition of PTEN degradation and multiple downstream mediators (AKT, ERK1/2, STAT3 , TGF-β/Smad2/3 and NF-kB(p65)). In conclusion, these results indicate that inhibition of UBA1 suppresses Ang II-induced hypertrophic remodeling, and suggest that administration of low dose PYR-41 may be a new potential therapeutic approach for treating hypertensive heart diseases.
研究领域:
心脏病学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 19
·6528-6541
·
IF 6.843
Jiefei Peng,Ranran Wang,Wanru Sun,Minhua Huang,Rong Wang,Youjie Li,Pingyu Wang,Guangbin Sun,Shuyang Xie
Lung cancer is the second most common tumor and has the highest mortality rate. Both novel therapeutic targets and approaches are needed to improve the overall survival of patients with lung cancer. MicroRNA-320a-3p belongs to the miR-320a family and has been reported as a tumor suppressor in multiple cancers. However, its definitive role and precise mechanism in the progression of lung cancer remain unclear. In this study, we developed a new type of gold nanorod modified with polyethyleneimine that targets cancer-specific nanoparticles by RGD peptide, which could condense miRNA to self-assemble supramolecular nanoparticles. The designed nanoparticles can achieve integrin αvβ3-targeted cancer therapy, realize photosensitive therapy by laser irradiation and attain gene-targeted therapy by miRNAs. These nanoparticles could deliver miR-320a into lung cancer cells specifically and efficiently. Moreover, we demonstrated that Au-RGD-miR-320a nanoparticles combined with laser irradiation dramatically inhibited the proliferation and metastasis, and enhanced the apoptosis of lung cancer, both in vitro and in vivo. In terms of the mechanism, miR-320a inhibits Sp1 expression by directly binding to the 3′UTR of Sp1, and it eventually enhanced the expression of PTEN and inhibited the expression of matrix metallopeptidase 9 (MMP9). These findings provide a new and promising anticancer strategy via the use of Au-RGD-miR-320a nanoparticles, and identify miR-320a/Sp1 as a potential target for future systemic therapy against lung cancer.
研究领域:
肿瘤学
·
纳米技术
·
分子生物学
·
治疗学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Yuling Tong,Ruilin Wang,Xia Liu,Miao Tian,Yanling Wang,Yanfei Cui,Wenjun Zou,Yanling Zhao
Ethnopharmacological relevance Zuojin Pill (ZJP) is a classic prescription composed of Coptis chinensis and Tetradium ruticarpum (A.Juss.) T.G.Hartley, which is often used in the treatment of digestive system diseases . Aim of this study The purpose of this study was to explore the therapeutic effect and potential mechanism of ZJP on chronic atrophic gastritis (CAG) induced by MNNG . Materials and methods The GES-1 and rat model of CAG was established by MNNG. Detection of cell viability, morphological changes and proliferation of GES-1 by CCK-8 and high content screening (HCS) assay. G-17, IL-8 and TNF-α in rat serum were detected by ELISA kit. The expression of related mRNA and protein on TGF-β1/PI3K/Akt signal axis were detected by RT-PCR and Western blot . Results The results showed that ZJP could significantly improve the GES-1 damage induced by MNNG and improve the gastric histomorphology of CAG rats. The intervention of ZJP could significantly reduce the content of G-17 and inflammatory factors IL-8, TNF- α, IL-6 and IL-1β, inhibit the expression of TGF-β1, PI3K and their downstream signals p-Akt, p-mTOR, P70S6K, and promote the expression level of PTEN, LC3-II and Beclin-1. Conclusion ZJP has a good therapeutic effect on CAG induced by MNNG, which may be closely related to the inhibition of TGF-β1/PI3K/Akt signal pathway.
研究领域:
药理学
·
民族药理学
·
胃肠病学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2016
·Vol. 41
·期 8
·2110-2118
·
IF 2.472
Zhu Mingming,Li Bingfei,Ma Xiao,Huang Cong,Wu Rui,Zhu Weiwei,Li Xiaoting,Liang Zhaofeng,Deng Feifei,Zhu Jianyun,Xie Wei,Yang Xue,Jiang Ye,Wang Shijia,Wu Jieshu,Geng Shanshan,Xie Chunfeng,Zhong Caiyun,Liu Haiyan
Aluminum (Al)-induced apoptosis is considered as the major cause of its neurotoxicity. Folic acid possesses neuroprotective function by preventing neural cell apoptosis. microRNAs (miRNAs) are important regulators of gene expression participating in cellular processes. As a key component of the miR-17-92 cluster, miR-19 is implicated in regulating apoptotic process, while its role in the neuroprotective effect of folic acid has not been investigated. The present study aimed to investigate the potential involvement and function of miR-19 in the protective action of folic acid against Al-induced neural cell apoptosis. Human SH-SY5Y cells were treated with Al-maltolate (Al-malt) in the presence or absence of folic acid. Results showed that Al-malt-induced apoptosis of SH-SY5Y cells was effectively prevented by folic acid. Al-malt suppressed the expression of miR-19a/19b, along with alterations of miR-19 related apoptotic proteins including PTEN, p-AKT, p53, Bax, Bcl-2, caspase 9 and caspase 3; and these effects were ameliorated by folic acid. miR-19 inhibitor alone induced apoptosis of SH-SY5Y cells. Combination treatment of folic acid and miR-19 inhibitor diminished the neuroprotective effect of folic acid. These findings demonstrated that folic acid protected neuronal cells against Al-malt-induced apoptosis by preventing the downregulation of miR-19 and modulation of miR-19 related downstream PTEN/AKT/p53 pathway.
研究领域:
神经科学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 23
·期 1
·1-10
·
IF 2.447
Tian Zhang,Tan Wang,Xinxu Chen,Zhenqiang Zhao,Zhibin Chen
The composition of the intestinal flora of patients with Parkinson's disease (PD) can change. However, whether reshaping the gut microbial composition can treat PD remains to be seen. The present study evaluated the effect of intestinal flora in the treatment of PD in a C57BL/6 mouse PD model induced by 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP). Chronic, low‑dose, MPTP‑treated mice exhibited upregulated gene expression levels of TNF‑α and IL‑1β in the substantia nigra (SN) of the mice, and induced intestinal microbial disorders. This indicated that the chronic low‑dose MPTP model could be used to evaluate the progress of early intestinal pathology and intestinal flora imbalance in PD. After transplantation of faecal bacteria to MPTP‑induced PD mice, the level of inflammation in the SN of the mice was reduced, and motor dysfunction was alleviated. Notably, faecal microbiota transplantation (FMT) upregulated the abundance of Blautia but downregulated Anaerostipes, Bifidobacterium, ASF356 and Ruminococcus in the gut of PD mice. In addition, FMT reduced the activation of microglia and astrocytes in the SN and reduced the expression levels of GSK3β, IL‑1β, inducible nitric oxide synthase and phosphorylated PTEN in the SN. Overall, the present study demonstrated that gut microbial dysfunction is associated with the pathogenesis of PD, and that FMT can protect PD mice by inhibiting neuroinflammation.
研究领域:
神经科学
·
微生物学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2020
·
IF 5.115
Lingling Ou,Ting Sun,Minyi Liu,Ye Zhang,Zhiying Zhou,Xiaozhen Zhan,Lihong Lu,Qingtong Zhao,Renfa Lai,Longquan Shao
Background MicroRNAs (miRNAs) are widely believed to be promising targets for oral squamous cell carcinoma (OSCC) gene therapy. miR-214 has been identified as a promoter of OSCC aggression and metastasis. Methods Graphene oxide-polyethylenimine (GO-PEI) complexes were prepared and loaded with a miRNA inhibitor at different N/P ratios. The transfection efficiency of GO-PEI-inhibitor was tested in Cal27 and SCC9 cells. Moreover, the tumor inhibition ability of GO-PEI-inhibitor was measured in an OSCC xenograft mouse model by intratumoral injection. Results Here, we show that a GO-PEI complex efficiently delivers a miR-214 inhibitor into OSCC cells and controls the intracellular release of the miR-214 inhibitor. These results indicate that the GO-PEI-miR-214 inhibitor complex efficiently inhibited cellular miR-214, resulting in a decrease in OSCC cell invasion and migration and an increase in cell apoptosis by targeting PTEN and p53. In the xenograft mouse model, the GO-PEI-miR-214 inhibitor complex significantly prevented tumor volume growth. Conclusion This study indicates that functionalized GO-PEI with low toxicity has promising potential for miRNA delivery for the treatment of OSCC.
研究领域:
肿瘤学
·
分子生物学
·
基因治疗
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Yimin Wang,Yanan Zhang,Zhihui Yang,Lei Zhang,Xiangping Chen,Guliang Yang,Jianfeng Zhan,Shiming Li,Feng He,Guanwei Fan
Psoriasis is an inflammatory skin disease accompanied with chronic papulosquamous lesions and multiple comorbidities that considerably affect patients’ quality of life. In order to develop an enhanced therapeutic strategy for psoriasis, 5-demethylnobiletin (5-DN), a kind of polymethoxyflavones (PMFs) with high anti-inflammatory activity, was delivered in vitro and in vivo by the nanocarrier of mesoporous silica nanoparticles (MSNs) both in the human keratinocytes HaCaT cell line and the mouse model with psoriasis-like lesions. The drug-loaded nanocarrier system (MSNs@5-DN) significantly improved the biocompatibility and bioavailability of 5-DN. Investigations at cell biological, histopathological, and molecular levels revealed the pharmacological mechanism of the drug delivery system, including the inhibition of inflammatory responses by downregulating the proinflammatory cytokine levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6). The upregulation of anti‑inflammatory cytokine of transforming growth factor-β1 (TGF-β1) and microRNA-17-5p, a critical regulator of the PTEN/AKT pathway, was also observed. The psoriasis-like lesions were markedly ameliorated in the mouse models treated with MSNs@5-DN. The designed drug-loading system shows an enhanced therapeutic outcome for psoriasis-like lesion compared with free 5-DN. This study revealed the synergistic effect of functionalized MSNs loaded with PMFs on the clinical treatment of human psoriasis.
研究领域:
药学
·
纳米技术
·
皮肤科
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Polymer Chemistry
·
2016
·Vol. 7
·期 26
·4352-4366
·
IF 5.687
Changyu He,Zhen Zhang,Qinglai Yang,Qing Chang,Zhifeng Shao,Bing Gong,Yu-Mei Shen,Bingya Liu,Zhenggang Zhu
A reductive tri-block copolymer PEG-SS-PLA-SS-PEI with a double disulphide linkage in the backbone directed by H-bonding association was synthesized and self-assembled into cationic polymeric nanomicellar particles for in vivo antimiRNA delivery with an average diameter of 68 nm and a zeta potential of approximately 39 mV. The chemical structure of the copolymer was well characterized by 1H NMR and GPC. The cationic polymeric nanomicellar particles could be unpacked in an intracellular reductive environment (GSH) leading to the release of encapsulated antimiRNA. MTT assays in vitro showed no significant cytotoxicity of SGC7901 gastric cancer cells incubated with PEG-SS-PLA-SS-PEI micelles. The in vitro study indicated that the micelle-based antimiR-21 delivery system could effectively facilitate cellular uptake and greatly down-regulate the expression level of miR-21 in SGC7901 cell lines, which was comparable to Lipofectamine™ 2000. The down regulation of miR-21 remarkably induced apoptosis, suppressed the tumor cell migration and invasion, and increased the expression of target genes such as phosphatase and tensin homolog deleted on chromosome ten (PTEN) and Programmed Cell Death Protein 4 (PDCD4). More importantly, the in vivo systemic administration of the micelles/antimiR-21 complex in a gastric cancer model significantly inhibited tumor growth and increased the expression of target genes. The nanoparticle based on the PEG-SS-PLA-SS-PEI copolymer would be a safe and efficient carrier for delivery of therapeutic antimiRNA, which shows a prospective therapy method in gastric cancer.
研究领域:
纳米技术
·
药学
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2024
·
IF 14.3
Xiang Gao,Haolin Zhao,Jiao Liu,Min Wang,Zhihong Dai,Wenjun Hao,Yanlong Wang,Xiang Wang,Min Zhang,Pixu Liu,Hailing Cheng,Zhiyu Liu
Despite the initial efficacy of enzalutamide in castration-resistant prostate cancer (CRPC), inevitable resistance remains a significant challenge. Here, the synergistic induction of copper-dependent cell death (cuproptosis) in CRPC cells is reported by enzalutamide and copper ionophores (elesclomol/disulfiram). Mechanistically, enzalutamide treatment increases mitochondrial dependence in CRPC cells, rendering them susceptible to cuproptosis, as evidenced by specific reversal with the copper chelator tetrathiomolybdate. This susceptibility is characterized by hallmarks of cuproptosis, including lipoylated protein aggregation and iron-sulfur cluster protein instability. Interestingly, the mitochondrial matrix reductase, FDX1, specifically correlates with elesclomol sensitivity, suggesting a potential mechanistic divergence between the two copper ionophores. Notably, this synergistic effect extends beyond in vitro models, demonstrating efficacy in 22Rv1 xenografts, mouse Pten p53 knockout organoids. Importantly, enzalutamide significantly enhances copper ionophore-mediated cytotoxicity in enzalutamide-resistant cells. Collectively, these findings indicate that enzalutamide and copper ionophores synergistically induce cuproptosis, offering a promising therapeutic avenue for CRPC, potentially including enzalutamide-resistant cases.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
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）