doxorubicin induces chronic heart failure in rats by regulating mitochondrial dynamics via drp1/fundc1 pathway / 中国药理学通报

Aim To investigate the damage degree of doxorubicin hydrochloride( DOX )on cardiac function in rats, and to explore its possible mechanism. Methods Experiment 1: SD rats( n=48 )were randomly divided into control group( normal saline ), DOX 1 group( DOX cumulative dose 12 mg·kg-1 ;intraperitoneal injection ), DOX 2 group( 15 mg·kg-1 ;)and DOX 3 group( 18 mg·kg-1 ;). Cardiac structure and cardiac function were detected by echocardiography. B-type natriuretic peptide( BNP )was detected by ELISA. The morphological changes of myocardium were observed by Hematoxylin-eosin( HE )staining. The optimal dose group( DOX 2 group )was selected comprehensively. Experiment 2: SD rats( n=36 )were randomly divided into control group( normal saline ), DOX 2 group(15 mg·kg-1)and DOX 2+Mdivi-1 group( 15 mg·kg-1+daily abdominal injection of Mdivi-1(1 mg ·kg-1 ;)). Western blot was used to detect the protein expression of myocardial mitochondrial dynamics. Results Compared with the control group, hearts in DOX groups were enlarged and the heart function was reduced. Under the microscope, hypertrophy of cardiac cells and loose arrangement of cardiac fibers were observed in DOX group, and the higher the cumulative dose of DOX in rats, the more severe the degree of heart failure and the higher the mortality rate of rats. Compared with control group, the expression of mitochondrial dynamin-related protein 1( DRP1 )and related signaling pathway protein FUN14 domain containing 1( FUNDC1 )in DOX 2 group increased. The expression of optic atrophy 1( OPA1 )decreased, the expression of FUNDC1 and DRP1 protein decreased, and the expression of OPA1 protein was enhanced after the use of mitochondrial dynamics inhibitor(Mdivi-1). Conclusions DOX can cause chronic heart failure, and the mechanism may be related to DRP1/FUNDC1 mediated mitochondrial fission and fusion.

[Ex vivo assessment of the potency of optical coherence tomography for the detection of early occlusal caries].

OBJECTIVE: This study aimed to evaluate the potency of optical coherence tomography (OCT) to detect early occlusal caries compared with clinical visual examination. METHODS: Approximately 97 sites of occlusal fissures on 77 extracted accessional human teeth were scored by three examiners using conventional visual examination and OCT. Results of histological examination on these sites obtained by polarimicroscope served as a gold standard to analyze the sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV). Results of the area under receiver operating characteristic (ROC) curve (AUC) by visual examination and OCT were also analyzed. The Spearman's rank correlation coefficient with histology and the inter-examiner reliability were compared. RESULTS: For sites of enamel demineralization limited to the outer 1/2 of the enamel layer, the detection rate of OCT (14/25) was obviously higher than that of the clinical and visual examination (3/25). SE, SP, PPV and NPV of OCT during diagnosis of the early occlusal caries (0.83, 0.64, 0.87 and 0.57) were higher than that of the visual examination (0.79, 0.60, 0.85 and 0.50). AUC (95%CI) of OCT and the visual examination were 0.737 (0.569-0.822) and 0.696 (0.614-0.859), respectively. No statistically significant difference was observed between the results. Results of OCT correlated well with histology (r=0.559, P<0.05). The inter-examiner reliability of OCT was medium. CONCLUSIONS: OCT can accurately detect early occlusal lesions atraumatically with high sensitivity and effectiveness. OCT exhibits the potential of auxiliary clinical diagnosis enhancing detection rate and finally implementing early diagnosis and early intervention of early occlusal lesions in clinical practice.

Experimental Research Progress of Replenishing Qi and Activating Blood Circulation Traditional Chinese Medicine on Mitochondrial Quality Control in Treatment of Chronic Heart Failure / 中国实验方剂学杂志

Heart failure is a complex clinical syndrome，which is the final result of compensatory failure of heart injury caused by various reasons. Long-term persistent cardiac stress leads to mitochondrial dysfunction，which in turn further damages cardiomyocytes and leads to disease progression. Timely removal of damaged mitochondria in cardiomyocytes and maintaining a good living environment of viable mitochondria is not only an effective means to protect cardiomyocytes，but also a new way to prevent and treat heart failure and ventricular remodeling. Mitochondrial quality control is a series of cellular activities for mitochondria to maintain their structural and functional stability，including oxidative stress response，regulation of mitochondrial dynamics，mitochondrial autophagy，intracellular calcium regulation and so on. Traditional Chinese medicine（TCM） mostly uses drugs of replenishing Qi and activating blood circulation in the treatment of chronic heart failure，and Qi and mitochondria are similar in function. According to TCM，the performance of the body as "static，descending and inhibitory" in the case of Qi deficiency can also be compared with the energy defect of mitochondria. The classical method of tonifying qi and activating blood circulation in TCM can be applied here. In recent years，TCM takes mitochondria as the target and carries out many related experimental studies from the point of view of myocardial energy supply. It is found that Chinese herbs for replenishing Qi and activating blood circulation can participate in regulating the quality control mechanism of intracellular mitochondria with multiple targets and links. It is proved by experiments that Chinese herbs for replenishing Qi and activating blood circulation can exert myocardial protective effect through this mechanism.

Effect of acidic culture conditions on the proliferation, apoptosis, and migration ability of human tongue squamous cell carcinoma cells and its related mechanism / 华西口腔医学杂志

OBJECTIVES@#This study aims to explore the effect of acidic culture conditions on the proliferation, apoptosis, and migration ability of human tongue squamous cell carcinoma SCC15 and CAL27 cells and its potential molecular mechanism.@*METHODS@#After acidic culture for different periods, methyl thiazolyl tetrazolium (MTT) method was adop-ted to detect the cell proliferation of SCC15 and CAL27. Flow cytometry was employed to detect the apoptosis level of SCC15 and CAL27 cells. The migration ability of SCC15 and CAL27 after acidic culture was detected by scratch hea-ling test. Real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) was used to detect the mRNA expression of cyclooxygenase 2 (COX-2) and survivin in SCC15 and CAL27 cells after acidic culture.@*RESULTS@#After culture for 24 h under acidic microenvironment, SCC15 and CAL27 cells grew rapidly and reached the stationary phase after adjustment for 3 days. The apoptosis levels of SCC15 and CAL27 cells decreased after acidic culture, but the most significant reduction occurred after 6 h of acidic culture. The scratch healing rates of SCC15 and CAL27 cells increased after acidic culture. The results of FQ-PCR showed that the mRNA expression levels of COX-2 and survivin in SCC15 and CAL27 cells increased after acidic culture.@*CONCLUSIONS@#Extracellular acidic microenvironment can inhibit the apoptosis of tongue squamous carcinoma cells, promote their migration, and induce more adaptable and malignant tongue squamous carcinoma cells. The mechanism may be related to COX-2 and survivin and their signal pathways.

Ex vivo assessment of the potency of optical coherence tomography for the detection of early occlusal caries / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study aimed to evaluate the potency of optical coherence tomography (OCT) to detect early occlusal caries compared with clinical visual examination.</p><p><b>METHODS</b>Approximately 97 sites of occlusal fissures on 77 extracted accessional human teeth were scored by three examiners using conventional visual examination and OCT. Results of histological examination on these sites obtained by polarimicroscope served as a gold standard to analyze the sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV). Results of the area under receiver operating characteristic (ROC) curve (AUC) by visual examination and OCT were also analyzed. The Spearman's rank correlation coefficient with histology and the inter-examiner reliability were compared.</p><p><b>RESULTS</b>For sites of enamel demineralization limited to the outer 1/2 of the enamel layer, the detection rate of OCT (14/25) was obviously higher than that of the clinical and visual examination (3/25). SE, SP, PPV and NPV of OCT during diagnosis of the early occlusal caries (0.83, 0.64, 0.87 and 0.57) were higher than that of the visual examination (0.79, 0.60, 0.85 and 0.50). AUC (95%CI) of OCT and the visual examination were 0.737 (0.569-0.822) and 0.696 (0.614-0.859), respectively. No statistically significant difference was observed between the results. Results of OCT correlated well with histology (r=0.559, P<0.05). The inter-examiner reliability of OCT was medium.</p><p><b>CONCLUSIONS</b>OCT can accurately detect early occlusal lesions atraumatically with high sensitivity and effectiveness. OCT exhibits the potential of auxiliary clinical diagnosis enhancing detection rate and finally implementing early diagnosis and early intervention of early occlusal lesions in clinical practice.</p>

Effect of yanggan yishui granule on collagen I, III, and IV, and FN in spontaneously hypertensive rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Yanggan Yishui Granule (YGYSG) on collagen protein I, III, and IV, as well as fibronection (EN) in spontaneously hypertensive rats (SHR), and to explore its possible renal protective mechanisms.</p><p><b>METHODS</b>Fourty SHR were randomly divided into four groups, i.e., the model group, the Benazepril group, the low dose YGYSG group, and the high dose YGYSG group, 10 in each group. A normal control group was set up with recruited Wistar-Kyoto (WKY) rats. After 6 weeks of treatment, the expression of collagen protein I, III, and IV, as well as FN in the 5.1 image analysis system.</p><p><b>RESULTS</b>In the WKY-control group, there was only a small amount of brown particles in the mesenchymal region, the glomerular basement membrane, or the mesangial region. The expression of collagen I, Ill, and IV, as well as EN significantly increased more in the model group than in the normal control group (P < 0.01). After treatment, the expression of collagen I, III, and IV, as well as FN significantly decreased in each treated group, showing statistical difference when compared with the model group (P < 0.01). Besides, decresed expression of collagen I, III, and IV was shown in the low dose YGYSG group and the Benazepril group (P > 0.05). The expression of collagen I, III, and IV could be further reduced in the high dose YGYSG group, showing statistical difference when compared with the Benazepril group and the low dose YGYSG group (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>YGYSG might play an important role in the renal protective effect through reducing the synthesis of renal collagen I, III, and IV, as well as FN, increasing the degradation of renal collagen I, III, and IV, as well as FN, thereby reducing excessive deposition of renal extracellular matrix (ECM).</p>

Effect of yanggan yishui granule on plasma Ang II, TGF-beta1, CTGF content, and renal cortical Ang II , TGF-beta1, and CTGF mRNA expressions in spontaneously hypertensive rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Yanggan Yishui Granule (YGYSG) on 12-week-old spontaneously hypertensive rats (SHR) on plasma angiotensin II (Ang II), transforming growth factor beta1 (TGF-beta1), connective tissue growth factor (CTGF) content and renal cortical Ang II, TGF-beta1, CTGF mRNA expressions, and to further explore the mechanism of YGYSG in the kidney protection.</p><p><b>METHODS</b>Forty 12-week-old male SHR were randomized into the model group, the Bella Plymouth group (at the daily dose of 1.8 mg/kg), the YGYSG low dose group (at the daily dose of 5.4 g/kg), and the YGYSG high dose group (at the daily dose of 27 g/kg), 10 in each group. Another ten Wistar-Kyoto (WKY) rats were included as the control group. Equal volume of normal saline was given to SHR by gastrogavage in the model group and the normal control group, once a day for six weeks. The plasma Ang II, TGF-beta1 and CTGF concentrations, and the renal cortical Ang II, TGF-beta1, CTGF mRNA expressions were measured in each group.</p><p><b>RESULTS</b>Bella Plymouth was superior to YGYSG in reducing plasma Ang II, TGF-beta1 and CTGF, while the high and low dose YGYSG showed no significant difference (P>0.05). In reducing plasma Ang II, TGF-beta1 and CTGF mRNA expressions, low doses YGYSG was similar to the role of Bella Plymouth, and the role of high dose YGYSG was superior to low dose YGYSG and Bella Plymouth.</p><p><b>CONCLUSION</b>YGYSG played a role in kidney protection mainly through reducing the Ang II , TGF-beta1 and CTGF expressions of kidney.</p>

Effect of calmodulin antagonist O-4-ethoxyl- butyl-berbamine on the proliferation of human breast cancer cell line MCF-7 and its relevant mechanism / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the effect of calmodulin antagonist O-(4-ethoxyl-butyl)-berbamine (EBB) on proliferation of human breast cancer cell MCF-7 and its possible mechanism.</p><p><b>METHODS</b>MTT assay was used to analyze the effect of EBB on tumor cells growth. Flow cytometry was used to detect its impact on the cell cycle of MCF-7 cells. Immunofluoresce labeling technique and laser scanning confocal microscope were used to reveal the changes of the microtubule, microfilament, mitochondrion, and endoplasmic reticulum in the cells.</p><p><b>RESULTS</b>The IC50 value of EBB in MCF-7 cells was (13.0 +/- 3.7) micromol/L. MCF-7 cells were arrested at S phase after EBB treatment. Meanwhile, depolymerization of the microtubule and microfilament, impairment of the mitochondrion and swelling of endoplasmic reticulum were observed.</p><p><b>CONCLUSION</b>EBB arrests MCF-7 cells at S phase by inhibiting the growth of MCF-7 cells, which may be related to the changes of structures and functions of the microtubule, microfilament, mitochondrion, and endoplasmic reticulum.</p>

The safety and outcome of patients with acute myocardial infarction transferred for primary angioplasty / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the safety and outcome of patients with acute myocardial infarction (AMI) transferred for primary percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>Data from patients with ST elevation AMI urgently transferred from first admitted hospitals to our cath-lab to receive primary PCI were analyzed. According to time intervals from symptom onset to transfer, the patients were divided into early transfer (< 6 h, n = 26), delayed transfer (6 - 24 h, n = 39) and late transfer (24 h to 1 week, n = 18) group. The major cardiac events during transfer periods and one month after PCI were obtained and echocardiogram and left ventricular systolic functions were compared among groups.</p><p><b>RESULTS</b>There was no serious cardiac event during transfer period and all 83 patients received primary PCI with a mean transfer-to-balloon time about 180 minutes. Success rate of PCI was 92.3% in early transfer group, 89.7% in delayed transfer group, and 94.4% in late transfer group (P > 0.05). At one month follow-up after PCI, 0, 10.3% and 16.7% of patients developed heart failure in early, delayed transfer and late transfer group respectively (P > 0.05 vs. early), the LVEF of early transfer group (53.2% +/- 9.7%) was also significantly higher than delayed transfer group (48.6% +/- 8.2%, P < 0.05) and late transfer group (43.1% +/- 10.3%, P < 0.01).</p><p><b>CONCLUSIONS</b>Transfer patients with AMI for primary PCI is safe in the observed time intervals during acute phase. Early transferred patients are associated with better outcome at 1 month post PCI compared to delayed and late transferred AMI patients.</p>