improved-rodent-model-of-myocardial-ischemia-and-reperfusion-injury

Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury

Myocardial ischemia and reperfusion injury (MIRI), induced by coronary heart disease (CHD), causes damage to the cardiomyocytes. Furthermore, evidence ...

Nanjing University of Chinese Medicine

To investigate the effects of Liangxue Tongyu Formula (LXTYF), a compound traditional Chinese herbal medicine, on brain edema in rats with intracerebral hemorrhage and to explore the mechanism.

[Effects of Liangxue Tongyu Formula on brain edema and expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rats with intracerebral hemorrhage].

To investigate the effects of Liangxuehuayu Recipe on hemorheology in rats with blood stasis syndrome induced by mutifactor stimuli.

Effect of Liangxuehuayu Recipe on hemorheology in rats with blood stasis syndrome.

To explore the mechanism of Xiaoai Jiedu Recipe (XJR) for fighting against tumors by detecting tumor gene expression profiles of H22 tumor-bearing mice.

[Effect of xiaoai jiedu recipe on gene expression profiles in H22 tumor-bearing mice].

Here we evaluated the anti-cancer activity of aqueous Oldenlandia diffusa (OD) extracts (ODE) in colorectal cancer (CRC) cells. We showed that ODE exerted potent anti-proliferative, cytotoxic and pro-apoptotic activities against a panel of established CRC lines (HCT-116, DLD-1, HT-29 and Lovo) and primary (patient-derived) human CRC cells. ODE activated AMP-activated protein kinase (AMPK) signaling, which led to subsequent mTORC1 inhibition and Bcl-2/HIF-1α downregulation in CRC cells. In ODE-treated CRC cells, AMPKα1 formed a complex with p53. This might be important for p53 activation and subsequent cancer cell apoptosis. Inhibition of AMPK signaling, though dominant negative (dn) mutation or shRNA/siRNA knockdown of AMPKα1 attenuated ODE-exerted CRC cytotoxicity. In vivo, i.p. administration of ODE inhibited HCT-116 xenograft tumor growth in SCID mice. In addition, AMPK activation, mTORC1 inhibition and p53 activation were observed in ODE-treated HCT-116 xenograft tumors. These results suggest that ODE inhibits CRC cells in vitro and in vivo, possibly via activation of AMPK-dependent signalings.

Aqueous Oldenlandia diffusa extracts inhibits colorectal cancer cells via activating AMP-activated protein kinase signalings.

Luteolin (LTL) exerts remarkable tumor suppressive activity on various types of cancers, including non-small cell lung cancer (NSCLC). However, it is not completely understood whether the mechanism of its action against NSCLC is related to microRNAs (miRNAs). In the present study, we investigated the anti-tumor effects of LTL on NSCLC in vitro and in vivo. The results revealed that LTL could inhibit cell proliferation and induce apoptosis in both A549 and H460 cells. In a H460 xenograft tumor model of nude mice, LTL significantly suppressed tumor growth, inhibited cell proliferation, and induced apoptosis. miRNA microarray and quantitative PCR (qPCR) analysis indicated that miR-34a-5p was dramatically upregulated upon LTL treatment in tumor tissues. Furthermore, MDM4 was proved to be a direct target of miR-34a-5p by luciferase reporter gene assay. LTL treatment was associated with increased p53 and p21 protein expressions and decreased MDM4 protein expression in both NSCLC cells and tumor tissues. When miR-34a-5p was inhibited in vitro, the protein expressions of Bcl-2 and MDM4 were recovered, while that of p53, p21, and Bax were attenuated. Moreover, caspase-3 and caspase-9 activation induced by LHL treatment in vitro were also suppressed by miR-34a-5p inhibition. Overall, LTL could inhibit tumorigenesis and induce apoptosis of NSCLC cells by upregulation of miR-34a-5p via targeting MDM4. These findings provide novel insight into the molecular functions of LTL that suggest its potential as a therapeutic agent for human NSCLC.

Luteolin Inhibits Tumorigenesis and Induces Apoptosis of Non-Small Cell Lung Cancer Cells via Regulation of MicroRNA-34a-5p.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer. Early detection and management of HNSCC may prevent progression of the disease. Long non-coding RNAs (lncRNAs) may serve as prognostic biomarkers for various cancer types. The current study downloaded an RNA-Seq dataset containing 43 tumor-normal pairs. An independent t-test identified that the expression level of lncRNA LOC541471 was significantly increased in tumor tissues compared with healthy tissues. Additionally, the current study demonstrated that high lncRNA LOC541471 expression was significantly associated with increasing lymph node metastasis classification and perineural invasion. A multivariate Cox regression analysis revealed that high lncRNA LOC541471 expression levels were an independent predictor for reduced overall survival (n=487) and relapse-free survival (n=355). According to the anatomic neoplasm subdivision, HNSCC samples were classified as oropharyngeal carcinoma (n=297), oral carcinoma (n=80), laryngeal carcinoma and hypopharyngeal carcinoma (n=123). A negative association was revealed between lncRNA LOC541471 expression and overall survival in all subtypes of HNSCC. Therefore, lncRNA LOC541471 is significantly negatively associated with overall survival and relapse-free survival of patients with HNSCC and may be considered a potential prognostic factor for HNSCC.

Long non-coding RNA LOC541471: A novel prognostic biomarker for head and neck squamous cell carcinoma.

With high incidence and mortality, gastric cancer seriously threatened human's life. It is arduous and necessary to investigate its pathogenesis and dig effective drugs. In this study, we explored the role of 6-Gingerol (GI), a natural active ingredient, in treating gastric cancer cells. MTT assay and colony formation assay were utilized to confirmed that GI can control the proliferation of gastric cancer cells, which is time and concentration-dependent to some extent. The Annexin V-FITC/PI staining results by flow cytometry reveal that GI induces the apoptosis of gastric cancer cells. And a study on further pathways by western blot shows that GI brings about cell apoptosis by inhibiting the activation of STAT3. GI therefore may be a good candidate for treating gastric cancer.

6-Gingerol inhibits proliferation in gastric cancer via the STAT3 pathway in vitro.

2-hydroxy-3-methylanthraquinone (HMA), an anthraquinone monomer in traditional Chinese medicine Hedyotis diffusa, has been reported to inhibit the growth of several types of cancer, but its effect on lung cancer has not been adequately investigated.

2-Hydroxy-3-methylanthraquinone inhibits lung carcinoma cells through modulation of IL-6-induced JAK2/STAT3 pathway.

Quercetin (QCT) has been shown to have anticancer activities associated with apoptosis and autophagy induction. However, whether autophagy is functionally responsible for the inhibitory effect of QCT on hepatocellular carcinoma (HCC) remains elusive. This study aims to investigate if QCT inhibits HCC growth via autophagy induction. The in vitro experiments showed that QCT inhibited the growth of human HCC cells in dose- and time-dependent manners and had minimal cytotoxicity to normal hepatocytes. QCT increased both autophagosomes and autolysosomes in HCC cells, as determined by electron microscopy, GFP-RFP-LC3 fluorescence confocal microscopy and Western blot analysis of autophagy-related biomarkers. Functional assays using pathway-specific inhibitors, activators or siRNAs indicated that QCT stimulated autophagy in part via inhibiting the AKT/mTOR pathway and activating the MAPK pathways. Further functional experiments using autophagy inhibitors demonstrated that QCT induced apoptosis of HCC cells in part via stimulating autophagy. The in vivo studies showed that QCT significantly inhibited tumor growth associated with apoptosis induction and autophagy stimulation, and that inhibition of autophagy significantly alleviated the QCT effect on tumor growth inhibition and apoptosis induction. To the best of our knowledge, this is the first in vivo report to demonstrate that QCT inhibits HCC tumor growth and induces apoptosis in part via stimulation of autophagy. Our results provide strong experimental evidence to support that autophagy stimulation may be an important mechanism by which QCT induces cancer cell apoptosis, and pave the way for further clinical investigations by applying QCT or QCT-rich foods for HCC intervention.

Quercetin inhibits growth of hepatocellular carcinoma by apoptosis induction in part via autophagy stimulation in mice.

To investigate the efficacy of celastrol treatment of hepatocellular carcinoma (HCC) cells in vitro and in vivo and to propose a mechanism of action.

Celastrol induces caspase-dependent apoptosis of hepatocellular carcinoma cells by suppression of mammalian target of rapamycin.

[This retracts the article DOI: 10.21037/tcr.2017.06.18.].

Article	Year
[Effects of Liangxue Tongyu Formula on brain edema and expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rats with intracerebral hemorrhage]. Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine\| PubMed ID: 20388475	2010
Effect of Liangxuehuayu Recipe on hemorheology in rats with blood stasis syndrome. Asian Pacific journal of tropical medicine\| PubMed ID: 23199709	2012
[Effect of xiaoai jiedu recipe on gene expression profiles in H22 tumor-bearing mice]. Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine\| PubMed ID: 24273980	2013
Aqueous Oldenlandia diffusa extracts inhibits colorectal cancer cells via activating AMP-activated protein kinase signalings. Oncotarget\| PubMed ID: 27322552	2016
Luteolin Inhibits Tumorigenesis and Induces Apoptosis of Non-Small Cell Lung Cancer Cells via Regulation of MicroRNA-34a-5p. International journal of molecular sciences\| PubMed ID: 29393891	2018
Long non-coding RNA LOC541471: A novel prognostic biomarker for head and neck squamous cell carcinoma. Oncology letters\| PubMed ID: 30675311	2019
6-Gingerol inhibits proliferation in gastric cancer via the STAT3 pathway in vitro. Cellular and molecular biology (Noisy-le-Grand, France)\| PubMed ID: 30942163	2019
2-Hydroxy-3-methylanthraquinone inhibits lung carcinoma cells through modulation of IL-6-induced JAK2/STAT3 pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology\| PubMed ID: 31035048	2019
Quercetin inhibits growth of hepatocellular carcinoma by apoptosis induction in part via autophagy stimulation in mice. The Journal of nutritional biochemistry\| PubMed ID: 31078904	2019
Celastrol induces caspase-dependent apoptosis of hepatocellular carcinoma cells by suppression of mammalian target of rapamycin. Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan\| PubMed ID: 34114395	2021
Retraction: Cyclooxygenase-2 mediates puerarin to inhibit the invasion and metastasis of lung cancer A549 cells. Translational cancer research\| PubMed ID: 35130335	2019

Mian-Hua Wu

Biography

JoVE Journal Publications

Other Publications