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PubMed | The First Affiliated Hospital Of China Medical University
Type: | Journal: European journal of pharmacology | Year: 2016

Nowadays, drugs protecting ischemia/reperfusion (I/R) myocardium become more suitable for clinic. It has been confirmed lycopene has various protections, but lacking the observation of its effect on endoplasmic reticulum stress (ERS)-mediated apoptosis caused by hypoxia/reoxygenation (H/R). This study aims to clarify the protective effect of lycopene on ERS induced by H/R in H9C2 cardiomyocytes. Detect the survival rate, lactic dehydrogenase (LDH) activity, apoptosis ratio, glucose-regulated proteins 78 (GRP78), C/EBP homologous protein (CHOP), c-Jun-N-terminal protein Kinase (JNK) and Caspase-12 mRNA and protein expression and phosphorylation of JNK (p-JNK) protein expression. LDH activity, apoptosis ratio and GRP78 protein expression increase in the H/R group, reduced by lycopene. The survival rate reduces in the H/R and thapsigargin (TG) groups; lycopene and 4-phenyl butyric acid (4-PBA) can improve it caused by H/R, lycopene also can improve it caused by TG. The apoptosis ratio, the expression of GRP78, CHOP and Caspase-12 mRNA and protein and p-JNK protein increase in the H/R and TG groups, weaken in the lycopene+H/R, 4-PBA+H/R and lycopene+TG groups. There is no obvious change in the expression of JNK mRNA or protein. Hence, our results provide the evidence that 10 M lycopene plays an obviously protective effect on H/R H9C2 cardiomyocytes, realized through reducing ERS and apoptosis. The possible mechanism may be related to CHOP, p-JNK and Caspase-12 pathways.


Lv M.,The First Affiliated Hospital of China Medical University | Li B.,Liaoning Medical University | Li Y.,The First Affiliated Hospital of China Medical University | Mao X.,The First Affiliated Hospital of China Medical University | And 2 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2011

Introduction: Breast cancer is increasingly regarded as a heterogeneous disease which can be classified into distinct molecular subtypes with prognostic significance. Materials and methods: ER, PR, HER2 and ki-67 were used to divided 102 breast cancers treated with neoadjuvant chemotherapy (NCT) into 4 subtypes: luminal A (ER+, PR+, HER2-, and ki-67 ≤14%), luminal B (ER+, PR+, HER2- and ki-67>14%; ER+ and/or PR+, HER2+), HER2-overexpression (ER-, PR- and HER2+) and triple-negative (ER-, PR-,and HER2 Results: Among 102 patients, a pCR was seen in 16 (15.7%) patients. The pathologic complete remission (pC) rates according to different subtypes are as follows: luminal A, 0 of 20 (0.0%), luminal B, 2 of 23 (8.7%), HER2-overexpression 4 of 18 (22.2%), and triple-negative, 10 of 41 (24.4%) (p=0.041). In triple-negative subtype patients, the rates of pCR differed significantly among the 3 chemotherapy regimens with 5.6% (1/18) for CEF (cyclophosphamide, epirubicin and flurouracil), 20.0% (1/5) for TE (docetaxel and epirubicin) and 44.4% (8/18) for TCb (docetaxel and carboplatin) (p=0.024). In locally advanced breast cancer patients, the rates of pCR seem to differ among the 3 chemotherapy regimens with 6.7% (2/30) for CEF, 0.0% (0/8) for TE and 23.1% (6/26) for TCb, but this did not attain statistical significance (p>0.05). Conclusions: Molecular subtypes are good predictors for response to NCT in breast cancer patients in Northeast China. Compared with luminal A tumors, HER2-overexpression and triple-negative subtypes are more sensitive to NCT. For triple-negative breast cancer, we concluded that the TCb combination is a promising NCT regimen. Our results also indicated that the TCb combination is promising for the treatment of locally advanced breast cancer.


Shao C.,The First Affiliated Hospital of China Medical University | Gu J.,The First Affiliated Hospital of China Medical University | Meng X.,The First Affiliated Hospital of China Medical University | Zheng H.,The First Affiliated Hospital of China Medical University | Wang D.,The First Affiliated Hospital of China Medical University
International Journal of Clinical and Experimental Medicine | Year: 2015

Objectives: Glucose fluctuation is suggested to be the leading cause of beta-cell damages. To determine how it induces beta-cell dysfunction, we systematically evaluated the effects of intermittent high glucose (IHG) in INS-1 rat pancreatic beta-cells on their proliferation activity, apoptosis, insulin secretion, reactive oxygen species (ROS), intracellular concentration of Ca2+ ([Ca2+]i), and the PTEN expression as well as AKT phosphorylation. Methods: Prior to the examinations, INS-1 cells were treated with normal glucose (NG, 11.1 mmol/L), sustained high glucose (SHG, 33 mmol/L), IHG (switching per 12 h in 11.1 mmol/l or 33 mmol/L), NG+α-lipoic acid (LA, pretreated with LA 12 h before exposure to NG), SHG+LA (pretreated with LA 12 h before being exposed to 33.3 mmol/L glucose) and IHG+LA (pretreated with LA 12 h before being cultured with IHG). The cells in each group were cultured with indicated concentrations of glucose for 3 days. The evaluations were carried out on the cell viability, apoptosis rate, insulin secretion, [Ca2+]i, ROS and the expressions of PTEN and p-AKT. Results: The current study determined that IHG induces more apoptosis and significant increases of [Ca2+]i and intracellular ROS levels, compared to SHG and NG treatments to INS-1 cells. Moreover, IHG leads to more than 20% decrease on cell viability and over 50% reduction on insulin secretion (from 5.48±0.79 mIU/L to 2.51±0.58 mIU/L). The negative regulation of IHG on insulin signaling in beta-cells is identified via western blot analysis with results of the elevated expression of PTEN and lowered phosphorylation levels of AKT post IHG treatment. While the pretreatment of the antioxidant LA can significantly suppress the above responses induced by high glucose treatment. Conclusions: This study demonstrated that IHG plays a detrimental role in the viability, expansion, and function of beta-cells. IHG could be more harmful to the INS-1 cells than the SHG treatment. The rate increase of apoptosis in beta-cells could be caused by the suppressed insulin signaling, which is resulted from the raised ROS level by abnormal glucose treatments. Undergoing oxidative stress induced by high glucose treatments, including SHG and IHG, might be an important player in mediating the injury process to beta-cells, concluded from the beneficial rescue by the antioxidant LA treatment. © 2015, E-Century Publishing Corporation. All rights reserved.


Wang B.,The First Affiliated Hospital of China Medical University | Liu L.,The First Affiliated Hospital of China Medical University
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology | Year: 2016

Along with the aging process, the spectrum of liver disease changes greatly. Nonalcoholic fatty liver disease (NAFLD) in elderly people lead to low liver function and is also the major cause of extrahepatic diseases, such as cardiovascular disease and malignant tumor. This review provides an overview of the morphological structure and function of the liver in aged people, and discusses the characteristics of weakness, malnutrition and limited movement in the elderly, as well as the current status of multiple diseases and multiple drug use. Finally, this article puts forward some appropriate regimens for the diagnosis and treatment of NAFLD in elderly people to provide a reference for clinical practice.


Yin Y.,The First Affiliated Hospital of China Medical University | Hou G.,The First Affiliated Hospital of China Medical University | Li E.,The First Affiliated Hospital of China Medical University | Wang Q.,The First Affiliated Hospital of China Medical University | Kang J.,The First Affiliated Hospital of China Medical University
Respiratory Research | Year: 2014

Background: Peroxisome proliferator-activated receptor-gamma (PPARγ) is a ligand-activated transcription factor that exerts multiple biological effects. Growing evidence suggests that PPARγ plays an important role in inflammation; however, the effects of this transcription factor on the inflammation caused by smoking are unclear.Methods: We measured the expression of inflammatory cytokines (leukotriene B4, LTB4 and interleukin 8, IL-8), PPARγ and toll-like receptors (TLR2 and TLR4) in alveolar macrophages (AMs) harvested from rats exposed to cigarette smoke (CS) for 3 months in vivo. Some of the rats were pre-treated with rosiglitazone (PPARγ agonist, 3 mg/kg/day, ip), rosiglitazone (3 mg/kg/day, ip) + BADGE (bisphenol A diglycidyl ether, a PPARγ antagonist, 30 mg/kg/day, ig), or BADGE alone (30 mg/kg/day, ig). We also measured the expression of PPARγ, TLR2, TLR4 and nuclear factor-kappaB (NF-κB) in AMs gained from normal rats, which exposed to 5% CSE (cigarette smoke extract) for 12hrs, respectively pretreated with PBS, rosiglitazone (30 uM), rosiglitazone (30 uM) + BADGE (100 uM), 15d-PGJ2 (PPARγ agonist, 5 uM), 15d-PGJ2 (5 uM) + BADGE (100 uM), or BADGE (100 uM) alone for 30 min in vitro.Results: In vivo, rosiglitazone counteracted CS-induced LTB4 and IL-8 release and PPARγ downregulation, markedly lowering the expression of TLR4 and TLR2. In vitro, both rosiglitazone and 15d-PGJ2 inhibited CS-induced inflammation through the TLR4 signaling pathway.Conclusions: These results suggest that PPARγ agonists regulate inflammation in alveolar macrophages and may play a role in inflammatory diseases such as COPD. © 2014 Yin et al.; licensee BioMed Central Ltd.


PubMed | The First Affiliated Hospital of China Medical University and Dalian Medical University
Type: | Journal: Postgraduate medicine | Year: 2017

Immunoglobulin A nephropathy (IgAN) is the most frequent cause of primary renal disease, and clarifying the pathogenesis of IgAN is of great importance for its diagnosis and treatment. It is well known that Mycobacterium tuberculosis (MTB) can infect the urinary tract and result in the typical symptoms of cystitis. However, MTB can also affect the kidney more insidiously. Patients may present with glomerular disease, and sometimes with advanced renal failure. This study was to investigate the association between MTB infection and IgA nephropathy (IgAN), and the early diagnosis of MTB-mediated IgAN by means of early secreted antigenic target 6 (ESAT-6) detection in renal biopsies.One hundred and twenty patients were divided into 3 groups: a renal tuberculosis (RTB) group, a glomerulonephritis without MTB infection (GN-TBI) group and a glomerulonephritis with MTB infection (GN+TBI) group. Morning urine samples were collected for MTB culture. Immunohistochemistry for ESAT-6 expression in renal tissues was performed.The incidence rate of IgAN in the GN+TBI group was 66.7%, which was significantly higher than that of the GN-TBI group. In the GN+TBI group, the ESAT-6 expression was positively associated with IgAN incidence. There was a statistical association between the positive expression of ESAT-6 and the incidence of IgAN. The sensitivity and specificity of urine MTB culture in diagnosing renal MTB infection was 23.3% and 100% respectively, while the sensitivity and specificity of ESAT-6 detection was 100% and 91.1% respectively. Compared with urine MTB culture, the sensitivity of ESAT-6 detection was significantly increased.MTB infection might be associated with the occurrence of IgAN, and ESAT-6 detection in renal tissues may be helpful for the early diagnosis of MTB-mediated IgAN.


PubMed | the First Affiliated Hospital of China Medical University
Type: Journal Article | Journal: American journal of physical medicine & rehabilitation | Year: 2016

This case report describes the first patient with avascular necrosis of the femoral head of Association Research Circulation Osseous stage IV, treated with radial extracorporeal shock wave therapy. By contrast, previous studies demonstrated the efficacy of a single treatment of focused extracorporeal shock wave therapy in improving pain and Harris Hip Scale in patients with avascular necrosis of the femoral head of Association Research Circulation Osseous stage I to III. The affected hip was treated with 6000 impulses of radial extracorporeal shock wave therapy at 10 Hz and an intensity ranging from 2.5 to 4.0 bar at 7-day intervals for 24 mos. The Harris Hip Scale values were 33, 43, 56, 77, 81, 88, and 92 at baseline and 1, 3, 6, 12, 18, and 24 mos, respectively. The radiographs showed that the subluxation of the right hip was slightly aggravated. Joint effusion was reduced, bone marrow edema disappeared, the density became more uniform, and the gluteal muscles were more developed based on magnetic resonance imaging. Increased tracer uptake was evident along the joint margin and superolateral aspect of the head both before and after radial extracorporeal shock wave therapy. This case report demonstrates the feasibility of long-term radial extracorporeal shock wave therapy in Association Research Circulation Osseous stage IV patients.


PubMed | The First Affiliated Hospital of China Medical University
Type: Journal Article | Journal: Pain physician | Year: 2016

Postherpetic neuralgia (PHN) is often refractory to existing treatments. Treatment of the dorsal root ganglion (DRG) using monopolar pulsed radiofrequency (PRF), which is a non- or minimally neurodestructive technique, is not efficacious in all patients.This study aimed to determine the safety and clinical efficacy of bipolar high-voltage, long-duration PRF on the DRG in PHN patients.Self before-after controlled clinical trial.Department of Pain Medicine, the First Affiliated Hospital of China Medical University.Ninety patients diagnosed with PHN for > 3months were included. Bipolar high-voltage, long-duration PRF at 42C for 900 seconds was applied after the induction of paresthesias covered the regions of hyperalgesic skin. The therapeutic effects were evaluated using a visual analog scale (VAS) and the 36-item Short Form health survey (SF-36) before treatment and one, 4, 8, and 12 weeks after PRF.The VAS scores at one, 4, 8, and 12 weeks after PRF treatment were significantly lower than before treatment (P < 0.001). The SF-36 scores, which included physical functioning, physical role, bodily pain, general health perceptions, vitality, social function, emotional role, and the mental health index, were significantly improved up to 12 weeks after PRF treatment (P < 0.001). No serious adverse effects were identified following treatment. The main adverse reactions included pain, tachycardia, and high blood pressure (especially when the field strength was enhanced).Single center study, relatively small number of patients, lack of a control group.Bipolar high-voltage, long-duration PRF on the DRG is an effective and safe therapeutic alternative for PHN patients. This treatment could improve the quality of life of PHN patients.NO ChiCTR-OCS-14005461.


PubMed | The First Affiliated Hospital of China Medical University
Type: | Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie | Year: 2016

Lysine-specific demethylase 1(LSD1), the first identified histone demethylase, plays an important role in the epigenetic regulation of gene activation and repression. Up-regulated LSD1expression has been reported in several malignant tumors.Our aim, therefore, was to better understand the mechanisms underlying the upregulation of LSD1 in gastric cancer.We used lentiviral shRNA to knockdown LSD1 in the gastric cancer MKN-28 cell line. Cell proliferation was measured by MTT assay while cell apoptosis was assessed by Annexin V-FITC/PI double staining flow cytometry. The invasive potential of gastric cancer cells was determined by matrigel invasion assay. Protein expression was detected by Western blot. In vivo, the effect of knocking down LSD1 on tumor growth and protein expression in gastric cancer cells in nude mice was investigated.LSD1 knockdown in MKN-28 cell lines resulted in increasing the activity of cisplatin in vitro and the inhibition of cancer cell proliferation and invasion, and induced cell apoptosis. The expression of TGF-1, VEGF, Bcl-2, -catenin, p-ERK and p-Smad 2/3 proteins was inhibited in LSD1 knockdown cells. Moreover, in an in vivo model of gastric cancer, LSD1 knockdown suppressed tumor growth and protein expression.LSD1 knockdown affected the fuction of gastric cancer MKN-28 cell line. LSD1 may be a latent target in the diagnosis and therapy of gastric cancer.


PubMed | The First Affiliated Hospital of China Medical University
Type: Journal Article | Journal: Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology | Year: 2016

Along with the aging process, the spectrum of liver disease changes greatly. Nonalcoholic fatty liver disease (NAFLD) in elderly people lead to low liver function and is also the major cause of extrahepatic diseases, such as cardiovascular disease and malignant tumor. This review provides an overview of the morphological structure and function of the liver in aged people, and discusses the characteristics of weakness, malnutrition and limited movement in the elderly, as well as the current status of multiple diseases and multiple drug use. Finally, this article puts forward some appropriate regimens for the diagnosis and treatment of NAFLD in elderly people to provide a reference for clinical practice.

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