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Malignant tumors seriously threaten human life and health. Radiotherapy and chemotherapy are the conventional methods for the clinical treatment of advanced tumors. The prognosis and efficacy are still far from satisfactory due to the radiotherapy has serious adverse effects on the body and the chemotherapy often causes problems such as tumor resistance and cell proliferationinhibition. Therefore， the search for new， safe， and effective anti-tumor drugs and the elucidation of their molecular mechanisms are effective measures for clinical treatment of tumors and improvement of patients' quality of life. Active ingredients derived from Chinese herbal medicines and natural products have gradually become a hot spot in the research and development of anti-tumor drugs due to their multi-target and multi-channel anti-tumor pharmacological activity characteristics and their advantages such as less adverse reaction on the body. Bruceine D is a class of tetracyclic triterpenoids extracted from the fruit of the Chinese herbal medicine Bruceae Fructus， with anti-inflammatory， anti-malarial， anti-parasitic， and other pharmacological activities， and its anti-tumor activity is particularly significant. Pharmacological studies have found that bruceine D can regulate various cellular physiological activities such as proliferation， apoptosis， invasion， and migration of lung cancer， liver cancer， pancreatic cancer， intestinal cancer， and other cancer cells by targeting different signaling pathways. Bruceine D can be used in combination with other chemotherapeutic drugs to improve the sensitivity of tumor cells to chemotherapeutic drugs， thereby reducing the adverse effect of chemotherapy. Clinical application practice has shown that Bruceae Fructus oil emulsion injection containing bruceine D has significant advantages in the efficacy and safety of tumor treatment. Although there are many studies on the antitumor pharmacological activity of bruceine D and its clinical efficacy is significant， the specific antitumor molecular mechanism of bruceine D is still unclear， and there is a lack of systematic review on the existing antitumor mechanism of bruceine D. Therefore， based on the research on bruceine D in China and abroad in recent years， this paper reviewed the anti-tumor effect and related molecular mechanisms of bruceine D from six aspects， namely， tumor cell proliferation， apoptosis， metastasis and invasion， glucose metabolism process， autophagy， and chemotherapy sensitivity. This paper is expected to provide a pharmacological basis and scientific reference for the antitumor drug development and clinical application of bruceine D.
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Objective To explore the effect of KCNQ1OT1 gene knockout combined with bruceine D on the proliferation, migration, and invasion of breast cancer MDA-MB-231 cells. Methods Cell Counting Kit-8, wound healing, and Transwell invasion assay were used to detect the effects of bruceine D and siKCNQ1OT1 on the viability, migration, and invasion of MDA-MB-231 cells. Effect of bruceine D and siKCNQ1OT1 on the expression of KCNQ1OT1 in MDA-MB-231 cells was detected by qRT-PCR. Western blot was used to detect the effect of bruceine D and siKCNQ1OT1 on the expression of EMT-related proteins and CDC42, p-MKK7, MKK7 proteins in MDA-MB-231 cells. Results Bruceine D and siKCNQ1OT1 could significantly inhibit the viability, migration, and invasion of MDA-MB-231 cells, and the inhibitory effect was enhanced when they were combined (all P < 0.05); bruceine D downregulated the expression of KCNQ1OT1 in MDA-MB-231 cells (all P < 0.05); bruceine D combined with siKCNQ1OT1 significantly decreased CDC42, p-MKK7, N-cadherin, and Vimentin expression in MDA-MB-231 cells and increased the expression of E-cadherin (all P < 0.05). Conclusion Bruceine D combined with siKCNQ1OT1 significantly inhibit the proliferation, migration, invasion, and EMT of human breast cancer MDA-MB-231 cells, and its molecular mechanism may be related to the blocking of CDC42/MKK7 signaling pathway.
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Acute kidney injury after cardiac surgery(CSA-AKI) is the most common complication after cardiac surgery. Monitoring, early diagnosis of CSA-AKI and timely intervention are of the great significance to reduce the incidence of CSA-AKI and improve the prognosis of patients. This article mainly reviews the diagnostic criteria of CSA-AKI, new biomarkers of renal injury and the application value of non-invasive renal blood flow and oxygen metabolism monitoring in the early diagnosis of CSA-AKI, in order to provide a basis for early clinical prediction and diagnosis of CSA-AKI through the understanding of early diagnosis and related non-invasive monitoring of CSA-AKI, so as to carry out effective intervention and improve the prognosis of patients undergoing cardiac surgery.
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Objective:To explore the factors affecting the antiviral treatment efficacy of acquired immunodeficiency syndrome (AIDS) patients.Methods:A total of 107 patients diagnosed with human immunodeficiency virus (HIV) infection in the clinic of Beihai People′s Hospital from January 2016 to June 2018 were selected.The patients were divided into two groups according to whether they voluntarily accepted traditional Chinese medicine treatment, including treatment group who received highly active anti-retroviral therapy (HAART) and traditional Chinese medicine prescription of Ping Gan Jie Du (42 cases), and control group who were only treated with HAART (65 cases). The virological and immunological responses were compared between the two groups at 48 weeks of treatment. The interleukin-28B (IL-28B) rs12979860 genotypes were measured by using the direct sequencing of polymerase chain reaction products. Logistic regression was used to analyze the influencing factors of antiviral efficacy in AIDS patients.Comparison between groups was performed by independent sample t test、matched sample t test or chi-square test. Results:At week 48 of treatment, 41 (97.62%) of the 42 patients in the HAART plus Ping Gan Jie Du group obtained virological response, while 58 (89.23%) of the 65 patients in the HAART group alone acquired virological response, which was not significantly different ( χ2=0.100, P>0.05). The numbers of CD4 + T lymphocytes increased at week 48 of treatment in the HAART plus Ping Gan Jie Du group and HAART group were (244.32±101.83)/μL and (211.56±112.50)/μL, respectively. The was no statistically significant difference ( t=1.522, P>0.05). Among the 92 patients with IL-28B CC genotype, 88 (95.65%) acquired virological response, while 11 of the 15 patients with non-IL-28B CC genotype acquired virological response, which was not significantly different ( χ2=0.394, P>0.05). And CD4 + T lymphocytes in patients with IL-28B CC genotype increased ((229.72±101.17)/μL), which was higher than that without IL-28B CC genotype ((173.40±89.64)/μL), with statistically significant difference ( t=2.028, P=0.045). Multivariate logistic regression analysis showed that baseline CD4 + T lymphocyte count≤200/μL, IL-28B CC genotype, and treatment plan including protease inhibitor were helpful to improve the antiviral efficacy. Conclusion:Baseline CD4 + T lymphocyte count ≤200/μL, IL-28B CC genotype, and protease inhibitor in HAART regimen are the influencing factors of antiviral efficacy in AIDS patients.
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Background@#African swine fever virus (ASFV), classical swine fever virus (CSFV), and porcine reproductive and respiratory syndrome virus (PRRSV) are still prevalent in many regions of China. Co-infections make it difficult to distinguish their clinical symptoms and pathological changes. Therefore, a rapid and specific method is needed for the differential detection of these pathogens. @*Objectives@#The aim of this study was to develop a multiplex real-time quantitative reverse transcription polymerase chain reaction (multiplex qRT-PCR) for the simultaneous differential detection of ASFV, CSFV, and PRRSV. @*Methods@#Three pairs of primers and TaqMan probes targeting the ASFV p72 gene, CSFV 5′untranslated region, and PRRSV ORF7 gene were designed. After optimizing the reaction conditions, including the annealing temperature, primer concentration, and probe concentration, multiplex qRT-PCR for simultaneous and differential detection of ASFV, CSFV, and PRRSV was developed. Subsequently, 1,143 clinical samples were detected to verify the practicality of the assay. @*Results@#The multiplex qRT-PCR assay could specifically and simultaneously detect the ASFV, CSFV, and PRRSV with a detection limit of 1.78 × 10 0 copies for the ASFV, CSFV, and PRRSV, but could not amplify the other major porcine viruses, such as pseudorabies virus, porcine circovirus type 1 (PCV1), PCV2, PCV3, foot-and-mouth disease virus, porcine parvovirus, atypical porcine pestivirus, and Senecavirus A. The assay had good repeatability with coefficients of variation of intra- and inter-assay of less than 1.2%. Finally, the assay was used to detect 1,143 clinical samples to evaluate its practicality in the field. The positive rates of ASFV, CSFV, and PRRSV were 25.63%, 9.36%, and 17.50%, respectively. The co-infection rates of ASFV+CSFV, ASFV+PRRSV, CSFV+PRRSV, and ASFV+CSFV+PRRSV were 2.45%, 2.36%, 1.57%, and 0.17%, respectively. @*Conclusions@#The multiplex qRT-PCR developed in this study could provide a rapid, sensitive, specific diagnostic tool for the simultaneous and differential detection of ASFV, CSFV, and PRRSV.
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Angelicae Sinensis Radix， derived from a medicinal and edible plant Angelica sinensis， is one of the traditional bulk Chinese medicines. In addition to gynecological blood stagnation and deficiency， its indications also include dysmenorrhea， deficiency and cold-induced abdominal pain， and rheumatoid arthritis. With the in-depth study of Angelicae Sinensis Radix， its anti-inflammatory and analgesic activities have attracted widespread attention. However， there has been no systemic report. The present study comprehensively reviewed the anti-inflammatory and analgesic activities of Angelicae Sinensis Radix （including its compositions， extracts， and different processed products） and mechanisms published in recent 30 years. The anti-inflammatory effect of Angelicae Sinensis Radix was achieved mainly by blocking the expression of proteins and genes in nuclear factor-κB （NF-κB）， mitogen-activated protein kinases （MAPK）， and Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathways， inhibiting the release of inflammatory mediators including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， nitric oxide （NO）， prostaglandin E2 （PGE2） and IL-1β， and maintaining the high sensitivity of immune cells in the host to external stimuli. The mechanism of analgesic effect may be related to the suppression of the production of algesic substances （such as inflammatory factors and chemokines） or blocking of the amplification and transmission of pain perception in cascade reaction. Furthermore， the study also pointed out some problems in modern research and proposed suggestions on its future research to provide references for investigation and clinical applications of Angelicae Sinensis Radix.
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@#Diabetic retinopathy(DR)has always been considered as microangiopathy. However, a large number of studies have confirmed that DR can not only cause retinal angiopathy, but also cause retinal neurodegeneration. Recently, more and more evidence also shows that retinal neurodegeneration occurred before retinal angiopathy in the early stage of DR, and retinal neurodegeneration may be involved in the occurrence and development of microvascular abnormalities. At present, the mechanism of diabetic retinal neurodegeneration is not very clear. This paper reviews the research progress on the mechanism of diabetic retinal neurodegeneration in recent years.
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Objective:To analyze the dynamic changes of T lymphocytes in patients with COVID-19.Methods:Blood samples were collected from 40 COVID-19 cases and 40 healthy controls in Beihai People′s Hospital from January to February, 2020. The counts of CD4 + T and CD8 + T lymphocytes were detected by flow cytometry. Moreover, the T lymphocyte counts in 24 convalescent patients with two consecutive negative nucleic acid test results were also detected. Results:The leukocytes and lymphocytes in the patients with acute COVID-19 were significantly lower than those in the healthy controls [(4.71±1.54)×10 9 cell/L vs (6.26±1.44)×10 9 cell/L, (1.13±0.41)×10 9 cell/L vs (1.51±0.39)×10 9 cell/L; both P<0.05]. The counts of CD4 + T and CD8 + T lymphocytes in the patients with acute COVID-19 were significantly lower than those in the healthy controls [(447.15±144.42) cell/μl vs (592.83±146.76) cell/μl, (309.35±173.05) cell/μl vs (397.20±136.94) cell/μl; both P<0.05], while no significant difference was observed in the CD4 + /CD8 + T cell ratio ( P>0.05). In the 24 convalescent COVID-19 patients, the counts of CD4 + T and CD8 + T lymphocytes were higher during convalescence than in the acute phase [(598.08±138.71) cell/μl vs (420.67±147.38) cell/μl, (439.08±166.94) cell/μl vs (296.67±151.06) cell/μl; both P<0.05], but there was no significant difference in the T lymphocyte counts between the convalescent patients and the healthy controls ( P>0.05). Conclusions:A transient immune deficiency occurred in patients with acute COVID-19, but the impaired immune function could restore to normal level during recovery.
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Objective: To observe the inhibitory effect of astragalus polysaccharides (APS) on growth of human breast cancer MDA-MB-231 xenograft tumor in nude mice and its effect on the apoptosis of tumor cells, in order to study the effect of APS on growth and induction of apoptosis of triple negative breast cancer MDA-MB-231 and its possible molecular mechanism. Method: Human breast cancer cell MDA-MB-231 was inoculated into the right axillary subcutaneous of BALB/c-nu female nude mice to establish the transplanted tumor model of breast cancer. Eighteen nude mice were randomly divided into 3 groups:model group (saline per day), low-dose APS group (200 mg·kg-1 APS per day), and high-dose APS group (400 mg·kg-1 APS per day), with 6 rats in each group. The drug was administered by gavage (200 μL) daily for 21 days. In the experiment, the length and diameter of breast cancer transplanted tumor were measured every two days, and the tumor volume was recorded and calculated. At the end of the experiment, the changes of tumor mass and tumor volume of the low and high-dose APS groups and the model group were observed and compared, and the tumor inhibition rate was calculated. The cell morphology in tumor tissue was observed by hematoxylin-eosin (HE) staining, and Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) was used to verify the apoptosis of breast cancer tissues. The expressions of apoptosis-related proteins, such as B-cell lymphoma/leukemia-2 protein (Bcl-2), Bcl-2 associated X protein (Bax), Caspase in tumor tissues was detected by Western blot. Result: The tumor volume of breast cancer decreased in the low and high-dose APS groups, and the tumor inhibition rates were 37.9%and 57.57%, respectively, with statistically significant differences from the model group (PP0.01). HE of tumor tissue cells showed that APS led to obvious morphological changes, with apoptosis in the tissue cells. TUNEL staining showed that the apoptosis rate of tumor cells in APS intervention groups was higher than that in control group. Western blot showed that expression of Bcl-2 protein decreased(PPPPConclusion: APS can effectively inhibit the growth of MDA-MB-231 breast cancer xenografts in nude mice and induce apoptosis in human breast cancer MDA-MB-231 cells. The mechanism may be related to the effect of APS on expressions of apoptosis-related proteins Bcl-2, Bax, Caspase-9 and Caspase-7 in breast cancer cells.
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Measurement of corpse temperature is mainly used for estimation of early postmortem interval, and rectal temperature is often used as a representative of body's core temperature in actual work because it is simple, quick and non-invasive. At present, the rectal temperature postmortem interval estimation method internationally accepted and widely used is HENSSGE's nomogram method, while many domestic scholars also deduced their own regression equations through a large number of case data. Estimation of postmortem interval based on rectal temperature still needs further study. The nomogram method needs to be optimized and extended, and quantification of its influencing factors needs to be dealt with more scientifically. There is still a lack of consensus on the probability and duration of the temperature plateau. There is no clear understanding of the probability and extent of the change in initial temperature caused by various causes. New methods and ideas enrich methodological research, but it still lacks systemicity and practicality. This article reviews the researches on estimation of postmortem interval based on rectal temperature in order to summarize the current situation of previous researches and seek new breakthrough points. Because the decline of body temperature can be easily influenced by many factors in vitro and vivo, and the influencing factors in different regions vary greatly, regionalization research and application may be a practical exploration to improve the accuracy of postmortem interval determination.
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Humans , Autopsy , Body Temperature , Cadaver , Postmortem Changes , Probability , Temperature , Time FactorsABSTRACT
BACKGROUND AND OBJECTIVE: The diagnosis and evaluation of inflammatory bowel disease is quite complex. An ideal, noninvasive marker for this disease is quite urgently needed. Fecal S100A12 is a member of the S100 protein family and is secreted by activated neutrophils. We aim to evaluate it as a biomarker for inflammatory bowel disease patients in China. METHODS: Fecal S100A12 was measured in 18 Crohn's disease, 21 ulcerative colitis, and 17 healthy controls. Diagnostic value was evaluated by receiver operating characteristic (ROC) analysis in comparison with C-reactive protein and erythrocyte sedimentation rate. The correlation between fecal S100A12 and clinical characteristics was also evaluated. RESULTS: We found significant increases (p<0.01) in the diagnostic value of S100A12 in both Ulcerative Colitis and Crohn's Disease when compared to healthy controls. In ulcerative colitis, fecal S100A12 correlated with fecal occult blood (p=0.02, r=0.55); in Crohn's disease, it correlated with disease duration, albumin and platelet levels (p=0.01, r=-0.53; p<0.01, r=-0.65; p=0.04, r=0.45. respectively). No correlation occurred between fecal S100A12 and other clinical conditions. CONCLUSION: Fecal S100A12 is valuable in distinguishing inflammatory bowel disease patients versus healthy controls. However, the sensitivity and specificity are limited when compared with that described in western countries. The correlation between S100A12 and clinical characteristics is limited as well. More research is need to better explore this interaction in Chinese patients.
JUSTIFICATIVA E OBJETIVO: O diagnóstico e avaliação da doença inflamatória intestinal é bastante complexo. Um marcador ideal, não invasivo para esta doença é urgentemente necessário. O S100A12 fecal é um membro da família de proteínas S100 e é secretado por neutrófilos ativados. Pretendemos avaliá-lo como biomarcador para pacientes com doença inflamatória intestinal na China. MÉTODOS: a proteína fecal S100A12 foi medida em 18 pacientes com Moléstia de Crohn, 21 pacientes com Colite Ulcerativa e 17 voluntários saudáveis (controles). O valor diagnóstico foi avaliado através da análise da característica de operação do receptor (ROC) em comparação com a proteína C reativa e com a taxa sedimentação eritrocitária. A correlação entre S100A12 fecal e características clínicas também foi avaliada. RESULTADOS: Observamos aumentos significativos (p < 0.01) no valor diagnóstico de S100A12 tanto na Colite Ulcerativa quanto na Doença de Crohn quando comparados aos controles saudáveis. Na colite ulcerativa, a proteína S100A12 fecal correlacionou com sangue oculto fecal (p = 0,02, r = 0,55); Na doença de Crohn, correlacionou com a duração da doença, albumina e níveis de plaquetas (p = 0,01, r = -0,53; p <0,01, r = -0,65; p = 0,04, r = 0,45, respectivamente). Não houve correlação entre S100A12 fecal e outras condições clínicas. CONCLUSÃO: O S100A12 fecal é valioso para distinguir pacientes com doença inflamatória intestinal versus controles saudáveis. No entanto, a sensibilidade e especificidade é limitada quando comparada com a descrita nos países ocidentais. A correlação entre S100A12 e características clínicas é limitada. Mais pesquisas são necessárias para explorar melhor essa interação em pacientes chineses.
Subject(s)
Humans , Colitis, Ulcerative/diagnosis , Crohn Disease/diagnosis , S100A12 Protein/analysis , Occult Blood , Biomarkers/analysis , ChinaABSTRACT
Objective To investigate the characteristics of the serum creatinine change patterns and its clinical signifi cance in patients with acute myocardial infarction(AMI)undergoing emergent percutaneous coronary intervention(PCI). Methods Two hundred and ninety-three consecutive ST elevation myocardial infarction(STEMI) patients who underwent emergent PCI were retrospectively grouped into the descending type,increasing type,stable type,U curve type and converse U curve type according to the dynamic changes serum creatinine in within 72h after PCI. The characteristics of diff erent patterns relationship of the respective pattern to the Mehran risk score,the serum creatinine changes between admission to 1 month after PCI,and the incidence of adverse events were analyzed.Results The proportion of the 5 pattern groups was 9.9%(decending type),17.7(increasing type),47.1%(stable type),4.1%(U curve type)and 21.2%(converse U curve type),respectively. The incidence of adverse events was higher in the increasing type,stable type and converse U curve type compared to the other 2 types in 1 month after PCI. Hypotension before admission and volume expansion therapy were more common in the groups of descending type and U curve type while diuretics were more frequently used in converse U curve type than descending type. The decline of creatinine from admission to 1 month after PCI were 57.9% in descending type and 27.3% in U curve type. Conclusions The dynamic change of serum creatinine presents with multiple patterns in patients undergoing emergent PCI. Hypotension before admission,volume expansion therapy,and the use of diuretics may aff ect the value of serum creatinine. The serum creatinine level at admission seems not suitable for baseline assessment to evaluate the risk of contrast-induced acute kidney injury in some patients.
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Objective To compare the incidence of contrast-induced acute kidney injury(CI-AKI) following iso-osmolar iodixanol or low-osmolar iohexol administration in patients with acute myocardial infarction(AMI)undergoing emergent percutaneous coronary intervention(PCI). Methods The study was a prospectiverandomized controlled study.Consecutive patients with AMI were assigned to either the iodixanol group or the iohexol group randomly after they were categorized in different group according to the infarcted walls(inferior and anterior infarction)indicated by electrocardiogram. The primary end point was the incidence of CI-AKI,which is defined as serum creatinine(sCr)increase>25% or>0.5 mg/dl(44 μmol/L)from baseline witin 72 hours. Results Two hundred ninety-seven patients were enrolled and allocated to the iodixanol group(n=149)or the iohexol group(n=148),and CI-AKI occurred in 22.1% of patients in the iodixanol group and 16.9% of patients in the iohexol group (95% confidence interval –14.2% to 3.8%,P for noninferiority<0.002). The incidence of CI-AKI was higher in the anterior infarction group than in the inferior infarction group(21.4% vs. 11.6%,P<0.01). Conclusions In patients with AMI who underwent emergent PCI,iohexol was not inferior to iodixanol on the incidence of CI-AKI,and it is reasonable to avoid selection bias for assigning patients into inferior and anterior infarction group according to the infarcted walls for the future CI-AKI related clinical study.
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Objective To compare the incidence of contrast-induced acute kidney injury(CI-AKI) following iso-osmolar iodixanol or low-osmolar iohexol administration in patients with acute myocardial infarction(AMI)undergoing emergent percutaneous coronary intervention(PCI). Methods The study was a prospectiverandomized controlled study.Consecutive patients with AMI were assigned to either the iodixanol group or the iohexol group randomly after they were categorized in different group according to the infarcted walls(inferior and anterior infarction)indicated by electrocardiogram. The primary end point was the incidence of CI-AKI,which is defined as serum creatinine(sCr)increase>25% or>0.5 mg/dl(44 μmol/L)from baseline witin 72 hours. Results Two hundred ninety-seven patients were enrolled and allocated to the iodixanol group(n=149)or the iohexol group(n=148),and CI-AKI occurred in 22.1% of patients in the iodixanol group and 16.9% of patients in the iohexol group (95% confidence interval –14.2% to 3.8%,P for noninferiority<0.002). The incidence of CI-AKI was higher in the anterior infarction group than in the inferior infarction group(21.4% vs. 11.6%,P<0.01). Conclusions In patients with AMI who underwent emergent PCI,iohexol was not inferior to iodixanol on the incidence of CI-AKI,and it is reasonable to avoid selection bias for assigning patients into inferior and anterior infarction group according to the infarcted walls for the future CI-AKI related clinical study.
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<p><b>BACKGROUND</b>Myocardial infarction (MI) is a major disease burden. Wild-type p53-induced phosphatase 1 (Wip1) has been studied extensively in the context of cancer and the regulation of different types of stem cells, but the role of Wip1 in cardiac adaptation to MI is unknown. We investigated the significance of Wip1 in a mouse model of MI.</p><p><b>METHODS</b>The study began in June 2014 and was completed in July 2016. We compared Wip1-knockout (Wip1-KO) mice and wild-type (WT) mice to determine changes in cardiac function and survival in response to MI. The heart weight/body weight (HW/BW) ratio and cardiac function were measured before MI. Mouse MI was established by ligating the left anterior descending (LAD) coronary artery under 1.5% isoflurane anesthesia. After MI, survival of the mice was observed for 4 weeks. Cardiac function was examined by echocardiography. The HW/BW ratio was analyzed, and cardiac hypertrophy was measured by wheat germ agglutinin staining. Hematoxylin and eosin (H&E) staining was used to determine the infarct size. Gene expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) was assessed by quantitative real-time polymerase chain reaction (qPCR), and the levels of signal transducers and activators of transcription 3 (stat3) and phosphor-stat3 (p-stat3) were also analyzed by Western blotting. Kaplan-Meier survival analysis, log-rank test, unpaired t-test, and one-way analysis of variance (ANOVA) were used for statistical analyses.</p><p><b>RESULTS</b>Wip1-KO mice had a marginally increased HW/BW ratio and slightly impaired cardiac function before LAD ligation. After MI, Wip1-deficient mice exhibited increased mortality (57.14% vs. 29.17%; n = 24 [WT], n = 35 [Wip1-KO], P< 0.05), increased cardiac hypertrophy (HW/BW ratio: 7 days: 7.25 ± 0.36 vs. 5.84 ± 0.18, n = 10, P< 0.01, and 4 weeks: 6.05 ± 0.17 vs. 5.87 ± 0.24, n = 10, P > 0.05; cross-sectional area: 7 days: 311.80 ± 8.29 vs. 268.90 ± 11.15, n = 6, P< 0.05, and 4 weeks: 308.80 ± 11.26 vs. 317.00 ± 13.55, n = 6, P > 0.05), and reduced cardiac function (ejection fraction: 7 days: 29.37 ± 1.38 vs. 34.72 ± 1.81, P< 0.05, and 4 weeks: 19.06 ± 2.07 vs. 26.37 ± 2.95, P< 0.05; fractional shortening: 7 days: 13.72 ± 0.71 vs. 16.50 ± 0.94, P< 0.05, and 4 weeks: 8.79 ± 1.00 vs. 12.48 ± 1.48, P< 0.05; n = 10 [WT], n = 15 [Wip1-KO]). H&E staining revealed a larger infarct size in Wip1-KO mice than in WT mice (34.79% ± 2.44% vs. 19.55% ± 1.48%, n = 6, P< 0.01). The expression of IL-6 and p-stat3 was downregulated in Wip1-KO mice (IL-6: 1.71 ± 0.27 vs. 4.46 ± 0.79, n = 6, P< 0.01; and p-stat3/stat3: 1.15 ± 0.15 vs. 1.97 ± 0.23, n = 6, P< 0.05).</p><p><b>CONCLUSION</b>The results suggest that Wip1 could protect the heart from MI-induced ischemic injury.</p>
Subject(s)
Animals , Male , Mice , Echocardiography , Interleukin-1beta , Metabolism , Interleukin-6 , Metabolism , Mice, Knockout , Myocardial Infarction , Genetics , Metabolism , Pathology , Myocytes, Cardiac , Metabolism , Protein Phosphatase 2C , Genetics , Metabolism , Real-Time Polymerase Chain Reaction , Tumor Necrosis Factor-alpha , Metabolism , Ventricular RemodelingABSTRACT
The present study investigated the chemical composition of ethylacetate extracts from an endophytic actinomycete Streptomyces sp. A0916 and its host Polygonum cuspidatum. A comparative analysis of the antimicrobial and antioxidant properties of the extracts was also conducted. 32 compounds of P. cuspidatum and 23 compounds of Streptomyces sp. A0916 were isolated and identified by GC/MS. Antimicrobial activities of the extracts were evaluated using eight microbial strains (3 Gram-positive bacteria, 3 Gram-negative bacteria, and 2 fungi). The Streptomyces sp. A0916 extracts showed a wide range of antimicrobial activities and presented greater antimicrobial effectiveness than the P. cuspidatum extracts. The minimum inhibitory concentration (MIC) of Streptomyces sp. A0916 extracts against the ampicillin-resistant strain Enterococcus faecium SIIA843 was 32 μg·mL(-1). Furthermore, the extracts had greater antimicrobial effect against Gram-positive bacteria than Gram-negative bacteria. Finally, the antioxidant activity of the Streptomyces sp. A0916 extracts was equal to that of the P. cuspidatum extracts. In conclusion, our results suggest that the endophytic actinomycetes of the medicinal plants are an important source of bioactive substances.
Subject(s)
Anti-Infective Agents , Chemistry , Pharmacology , Antioxidants , Chemistry , Pharmacology , Bacteria , Fallopia japonica , Chemistry , Microbiology , Fungi , Plant Extracts , Chemistry , Pharmacology , Streptomyces , Chemistry , Classification , GeneticsABSTRACT
Objective: To access the risk for smoking on morbidity of acute ST-segment elevation myocardial infarction (STEMI) at different gender and age population. Methods: A case-control study was conducted in 2026 STEMI patients and 2026 control subjects with matched gender and age (±2 years) in our hospital from 2010-01-14 to 2016-02-27. The relationship between smoking and STEMI morbidity was analyzed. Results: Smoking was an important risk factor for STEMI morbidity in male gender and it was negatively related to age, as STEMI in young male smokers (≤45 years): adjusted OR=7.000, 95% CI 4.235-11.570; in middle age male smokers (46-59 years):adjusted OR=5.296, 95% CI 3.904-7.185 and in elder male smokers (≥60 years): adjusted OR=4.686, 95% CI 2.860-4.751. Conclusion: Smoking is a major risk factor for STEMI morbidity, while it is different from age and gender; the young male smokers have the highest risk to suffer from STEMI.
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<p><b>BACKGROUND</b>The effect of selective and non-selective cyclooxygenase (COX) inhibitors on tendon healing was variable. The purpose of the study was to evaluate the influence of non-selective COX inhibitor, ibuprofen and flurbiprofen axetil and selective COX-2 inhibitor, celecoxib on the tendon healing process in a rabbit model.</p><p><b>METHODS</b>Ninety-six New Zealand rabbits were used as rotator cuff repair models. After surgery, they were divided randomly into four groups: ibuprofen (10 mg·kg-1·d-1), celecoxib (8 mg·kg-1·d-1), flurbiprofen axetil (2 mg·kg-1·d-1), and control group (blank group). All drugs were provided for 7 days. Rabbits in each group were sacrificed at 3, 6, and 12 weeks after tendon repair. Tendon biomechanical load failure tests were performed. The percentage of type I collagen on the bone tendon insertion was calculated by Picric acid Sirius red staining and image analysis. All data were compared among the four groups at the same time point. All data in each group were also compared across the different time points. Qualitative histological evaluation of the bone tendon insertion was also performed among groups.</p><p><b>RESULTS</b>The load to failure increased significantly with time in each group. There were significantly lower failure loads in the celecoxib group than in the control group at 3 weeks (0.533 vs. 0.700, P = 0.002), 6 weeks (0.607 vs. 0.763, P = 0.01), and 12 weeks (0.660 vs. 0.803, P = 0.002), and significantly lower percentage of type I collagen at 3 weeks (11.5% vs. 27.6%, P = 0.001), 6 weeks (40.5% vs. 66.3%, P = 0.005), and 12 weeks (59.5% vs. 86.3%, P = 0.001). Flurbiprofen axetil showed significant differences at 3 weeks (failure load: 0.600 vs. 0.700, P = 0.024; percentage of type I collagen: 15.6% vs. 27.6%, P = 0.001), but no significant differences at 6 and 12 weeks comparing with control group, whereas the ibuprofen groups did not show any significant difference at each time point.</p><p><b>CONCLUSIONS</b>Nonsteroidal anti-inflammatory drugs can delay tendon healing in the early stage after rotator cuff repair. Compared with nonselective COX inhibitors, selective COX-2 inhibitors significantly impact tendon healing.</p>
Subject(s)
Animals , Male , Rabbits , Anti-Inflammatory Agents, Non-Steroidal , Pharmacology , Biomechanical Phenomena , Celecoxib , Pharmacology , Cyclooxygenase 2 Inhibitors , Pharmacology , Flurbiprofen , Pharmacology , Ibuprofen , Pharmacology , Rotator Cuff , Pathology , Tendon Injuries , Drug Therapy , Wound HealingABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of component I from agkistrodon acutus venomon (AAVC-I) the migration of human umbilical vein endothelial cells (HUVECs), and to elucidate the possible anti-angiogenic mechanism of AAVC-I.</p><p><b>METHODS</b>The effect of AAVC-I on the migration of HUVECs which was cultivated in vitro and treated with AAVC-1 at four concentrations: 0, 20, 40, 80 microg/ml, was observed by methods of scratch wound-healing and Transwell assay. The expression level of mRNA and protein of P-selectin and intercellular cell adhension molecule-I (ICAM-1) were examined by RT-PCR and Western blot assay.</p><p><b>RESULTS</b>Compared with the blank group, the migration ability of HUVECs in each AAVE-I treated group was reduced in a dose-dependent manner, and the expression level of the mRNA and protein of P-selectin and ICAM-1 were decreased.</p><p><b>CONCLUSION</b>AAVC-I inhibits the migration of endothelial cell, which is acted by down-regulation of the expression content of mRNA and protein of P-selectin and ICAM-1.</p>
Subject(s)
Humans , Cell Movement , Cells, Cultured , Crotalid Venoms , Pharmacology , Down-Regulation , Human Umbilical Vein Endothelial Cells , Intercellular Adhesion Molecule-1 , Metabolism , P-Selectin , Metabolism , RNA, MessengerABSTRACT
Aims: The principle aim of this study was to obtain high quality metagenomic DNA from the high humus-containing, alkaline soils of the chinampas, an artificial sustainable agroecosystem. Study Design: Different protocols reported previously were tested and were modified to extract the metagenomic DNA. Quality of the DNA samples was evaluated by amplification of 16S rRNA gene with PCR and T-RFLP (Terminal Restriction Fragment Length Polymorphism) analysis. Place and Duration of Study: This study was performed in Department of Microbiology, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional during 2011-2012. Methodology: Four soil samples were collected from two chinampas at the depth of 0-30 cm and 30-60cm. A protocol started with repeated prewashing before the direct cell lysis with lysozyme followed by SDS treatments, frozen and melting cycling was developed which combined the DNA isolation and purification procedures. The 16SrRNA genes were amplified from the extracted metagenomic DNAs and were used for T-RFLP fingerprinting analysis. Results: The 16SrRNA genes were amplified from all the DNA extracts corresponding to the four soil samples and were successfully used in the T-RFLP analysis, which generated 25 to 109T-RFs in the four soil samples digested separately with the restriction endonucleases HaeIII, HhaI and MspI. Conclusion: The protocol developed in the present study could generate high molecular weight and high quality metagenomic DNA from soils with high content of humic materials, for which the other reported protocols were not functioned. This soil harboured very diverse and unique bacterial communities belonging to at least nine phyla that might contribute to the high soil fertility.