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Objective: To study therapeutic effect of metoprolol combined trimetazidine on ischemic heart failure (IHF) and its influence on inflammatory factors. Methods: A total of 172 IHF patients treated in our hospital were collected. They were randomly and equally divided into trimetazidine group and combined treatment group (received metoprolol combined trimetazidine), and both groups were treated for 30d. Cardiac function, levels of inflammatory factors, N terminal pro brain natriuretic peptide (NT-proBNP), heart type fatty acid-binding protein (H-FABP) and quality of life (QOL) before and after treatment, and cerebral infarction rate after one-year treatment were compared between two groups. Results: Compared with trimetazidine group after treatment, there were significant rise in left ventricular ejection fraction [(44. 68±4. 51) ％ vs. (49. 79±4. 99) ％], significant reductions in left ventricular end-diastolic dimension [(50. 41± 5. 06) mm vs. (47. 28±4. 83) mm], left ventricular end-systolic dimension [(41. 57±4. 22) mm vs. (36. 72±3. 71) mm], levels of NT-proBNP [(3. 48±0. 35) ng/L vs. (3. 06±0. 32) ng/L], H-FABP [(11. 41±1. 26) μg/L vs. (8. 55±0. 86) μg/L], interleukin 6 [(53. 21±5. 36) ng/L vs. (43. 58±4. 44) ng/L], tumor necrosis factorα [(161. 97±16. 28) ng/L vs. (108. 27±10. 11) ng/L]and C reactive protein [(15. 72±1. 59) ng/L vs. (11. 10±1. 12) ng/L]and QOL score [(48. 75±4. 89) scores vs. (43. 15±4. 33) scores]in combined treatment group, P＜0. 05 or＜0. 01. Total effective rate of combined treatment group was significantly higher than that of trimetazidine group (90. 70％ vs. 72. 09％, P=0. 002); after one-year treatment, incidence rate of cerebral infarction in combined treatment group was significantly lower than that of trimetazidine group (2. 33％ vs. 10. 47％, P=0. 029). Conclusion: Metoprolol combined trimetazidine can significantly improve myocardial blood supply, correct immune imbalance, improve cardiac function and quality of life in IHF patients. The therapeutic effect is significant, and it can prevent cerebral infraction, which is worth extending.
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Objective To investigate the effects of ZNF331 overexpression on proliferation and apoptosis of human colon cancer cell HCT116, and the relevant apoptotic mechanism.Methods The lentivirus vector of overexpressed ZNF331,Flag-pLV-Neo-ZNF331,was constructed and packaged.HCT116/p53 +/+(wild type p53)and HCT116/p53 -/-(deficient p53)cells were infected.Clones with ZNF331 overexpression were identified by Western blotting.Cell proliferation assay,colony formation assay and flow cytometry analysis were used to examine the effects of ZNF 331 on cell proliferation and apoptosis.Immunoprecipitation,luciferase reporter gene assay and real-time PCR were performed to detect interactions between ZNF331 and p53, p53 transcriptional activity and the expression of p 53 apoptotic target genes, respectively.Results The lentivirus vector of overexpressed ZNF 331 was successfully generated.Stable clones of ZNF331 overexpression were established.ZNF331 showed no significant effect on cell proliferation of HCT 116/p53 +/+, but inhibited cell proliferation of HCT116/p53 -/-(P<0.01).ZNF331 could interact with p53,dose-dependently inhibit the transcriptional activity of p53 and downregulate the mRNA levels of pro-apoptotic p53 target genes, Puma and p53AIP1 (P<0.05).ZNF331 could suppress p53-induced apoptosis(P <0.01).Conclusion The influence of ZNF331 overexpression on colon cancer cell proliferation is dependent on p 53 status.ZNF331 overexpression can suppress colon cancer cell apoptosis by interacting with p 53 and inhibiting the transcriptional activity of p 53.
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The aim of this paper is to study the effect of astragaloside Ⅳ on renal fibrosis mice with ischemia-reperfusion injury (IRI) and discuss the mechanism. Male C57BL/6 50 mice were randomly divided into four groups, namely Sham-operated group, model group, AS-Ⅳ prevention group and AS-Ⅳ treatment group. Since the day of surgery, the mice in astragaloside Ⅳ prevention group were treated with astragaloside Ⅳ by gavage for 30 days at the dose of 30 mg·kg⁻¹·d⁻¹. At the 60th day after surgery, the mice in astragaloside Ⅳ treatment group were treated with astragaloside Ⅳ 100 by gavage for 30 days at the dose of 30 mg·kg⁻¹·d⁻¹. The mice in Sham-operated group and model group were treated with double distilled water containing 0.1% ethanol instead of astragaloside Ⅳ. Serum creatinine and blood urea nitrogen were detected by chemical methods. Histopathological changes and collagen deposition of affected kidneys were observed under optical microscope by HE and Masson staining. The expression levels of Toll like receptor pathway related molecules (TLR4,MyD88,TRAF6,TRAM,TRIF,NF-κB,TNF-α,IL-6, IFN-) in affected kidneys were observed by immunohistochemistry, Western blot methods and reverse transcription-PCR atprotein and mRNA levels in each group. The results showed that the degrees of fibrosis and histopathological damage of affected kidneys of mice in model group were the most obvious. And the expression levels of TLR4/MyD88 dependent signaling pathway-related molecules (TLR4 and MyD88, TRAF6 and NF-κB) in affected kidneys of mice in model group were the highest. At the same time, there was no difference in the expression levels of TLR4/MyD88 independent signaling pathway-related molecules（TRAM, TRIF）among sham-operated group, model group, astragaloside IV prevention group and astragaloside Ⅳ treatment group. In astragaloside Ⅳ prevention group and astragaloside Ⅳ treatment group, the injury of affected kidney was obviously reduced, and the protein expression levels of TLR4/MyD88 dependent signaling pathway-related molecules were also correspondingly reduced; at the same time, the expressions of terminal inflammatory cytokines (TNF-α,IL-6, IFN-) were suppressed. Therefore, astragaloside Ⅳ may improve renal interstitial fibrosis in mice after IRI by inhibiting the expression of TLR4/MyD88 dependent signaling pathway and the release of inflammatory cytokines (TNF-α,IL-6, IFN-), while the TLR4/MyD88 independent signaling pathway may not be involved in the process of renal fibrosis after ischemia-reperfusion injury.
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PURPOSE: We investigated whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) could promote the development of preinvasive and invasive breast cancer in mouse mammary tumor virus (MMTV-erbB2) mice with estrogen receptor-positive tumors. METHODS: MMTV-erbB2 mice were randomly divided into three experimental groups with 20 mice in each group. MMTV-erbB2 mice were treated with daily subcutaneous injections of vehicle or rhG-CSF (low-rhG-CSF group, rhG-CSF 0.125 microg; vehicle-rhG-CSF group, normal saline 0.25 microg; and high-rhG-CSF group, rhG-CSF 0.25 microg) at 3 months of age. Cellular and molecular mechanisms of G-CSF action in mammary glands were investigated via immunohistochemistry and reverse transcription polymerase chain reaction. RESULTS: Low, but not high, rhG-CSF doses significantly accelerated mammary tumorigenesis in MMTV-erbB2 mice. Short-term treatment with rhG-CSF could significantly promote the development of preinvasive mammary lesions. The cancer prevention effect was associated with reduced expression of proliferating cell nuclear antigen, cluster of differentiation 34, and signal transducers and activators of transcription 3 in mammary glands by >80%. CONCLUSION: We found that G-CSF was regulated by rhG-CSF both in vitro and in vivo. Identification of G-CSF genes helped us further understand the mechanism by which G-CSF promotes cancer. Low doses of rhG-CSF could significantly increase tumor latency and increase tumor multiplicity and burden. Moreover, rhG-CSF effectively promotes development of both malignant and premalignant mammary lesions in MMTV-erbB2 mice.
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Animais , Humanos , Camundongos , Neoplasias da Mama , Carcinogênese , Proliferação de Células , Estrogênios , Fator Estimulador de Colônias de Granulócitos , Imuno-Histoquímica , Injeções Subcutâneas , Glândulas Mamárias Humanas , Vírus do Tumor Mamário do Camundongo , Reação em Cadeia da Polimerase , Antígeno Nuclear de Célula em Proliferação , Transcrição Reversa , TransdutoresRESUMO
<p><b>OBJECTIVE</b>To investigate the relation between the progressive effects of chronic intermittent hypoxia (CIH) on cognitive function and the change of cholinergic neuron.</p><p><b>METHODS</b>Forty adult male Sprague-Dawley rats were randomly averagely divided into four groups: control group, CIH 1 week group, CIH 3 week group and CIH 5 week group. The cognitive function was assessed by the Morris Water Maze. The necrosis neurons in prefrontal cortex and hippocampus were observed and counted. The cholin acetyltransferase (ChAT) immunostained cells in prefrontal cortex and hippocampus were identified and quantitated.</p><p><b>RESULTS</b>The spatial learning and memory impairments progressed from 1 to 5 5 weeks in rats. Compared with the control group, the cognitive impairments in CIH5w group were significant (P < 0.05). The degeneration or necrosis neurons in prefrontal cortex and hippocampus were significantly increased in CIH rats, and worsen gradually along with the hypoxia. The ChAT immunostained cells in prefrontal cortex and hippocampus were gradually reduced. The ChAT immunostained cells of prefrontal cortex and hippocampus in CIH3w group and CIH5w group were less than that in control group (P < 0.05).</p><p><b>CONCLUSION</b>Chronic intermittent hypoxia induced slowly progressive spatial learning and memory impairments in rats, which maybe associated with the damage of neurons and the reduction of ChAT in prefrontal cortex and hippocampus.</p>