Effects of oral Mirtogenol on retinal ganglion cell apoptosis index and intraocular pressure in the Wistar glaucoma model.

The purpose of this research is to determine how Mirtogenol affects intraocular pressure (IOP) and retinal ganglion cells (RGCs) of apoptosis index in Wistar glaucoma models, as well as the relationship between IOP and RGC apoptosis index. Twelve Wistar glaucoma models were divided into two groups for experimental research with a pretest-posttest and posttest-only. The treatment group got oral administration of Mirtogenol 12.3 mg twice a day for 2 weeks, whereas the control group received a placebo in the same way. Apoptotic index and IOP were evaluated both before and after the intervention. A parametric independent t-test was used to determine the difference between groups, and a parametric paired t-test was used to determine the difference within groups. The results showed that the RGC apoptosis index in treatment groups was considerably less when compared to control groups (P < 0.001). In the treatment group, the IOP is decreased compared to the control group (mean difference: -12.67 ± 3.79 vs. 0.69 ± 4.64, respectively, P = 0.002). A significant and solid correlation was found between IOP and RGC apoptosis index (R = 0.884, P < 0.001). Thus, Mirtogenol supplementation is expected to be used to prevent glaucoma progression.

Immunomodulatory, Apoptosis Induction and Antitumor Activities of Aqueous and Methanolic Extract of Calvatia Craniiformis in Mice Transfected with Murine Hepatocellular Carcinoma Cells.

OBJECTIVES: To evaluate the Immunomodulatory, apoptosis induction and antitumor effects of aqueous and methanolic extracts of Calvatia craniiformis regarding the size of tumour mass, caspase-8 expression and apoptotic index (AI%) in mice transfected with murine hepatocellular carcinoma cell line (H22) as an experimental therapeutic system for human hepatocellular carcinoma. MATERIAL AND METHODS: Forty-eight Balb/C albino mice were transfected in legs with H22 cells. Tumour size was measured twice a week. Caspase-8 protein expression and apoptotic index determination evaluated by Immunohistochemistry. RESULTS: Tumor size significantly differed between the two groups of mice transfected with H22 cells; the first was treated with C. craniiformis aqueous extract (0.3, 0.6, 1.2) mg/kg and the second group was treated with C. craniiformis methanolic extract (0.25, 0.5, 1.0) mg/kg compared with control group. The inhibitory activity of aqueous and methanolic extracts was dose and duration dependent. The size of the tumour mass was reduced up to 87.9% when treated with 1.2 mg/kg aqueous extract and 1 mg/kg for methanolic extract. Caspase-8 expression was increased in a dose-dependent manner among H22 bearing mice treated with C. craniiformis aqueous extract (0.3, 0.6, 1.2) mg/kg. At 0.3 mg/kg, the intensity of expression was strong in (33.33%) and very strong in (66.67%). While at 0.6 mg/kg and 1.2 mg/kg the intensity of expression was strong in (33.33%) and very strong in (100%) with a significant difference (P ≤ 0.001). H22 bearing mice treated with (0.25, 0.5, 1.0) mg/kg C. craniiformis methanolic extract shows increased caspase-8 expression in a dose-dependent manner. At 0.25 mg/kg, the intensity of expression was strong in (33.33%) and very strong in (66.67%). While at 0.5 mg/kg, the intensity of expression was strong in (33.33%) and very strong in (100%). At 1.0 mg/kg, the intensity of expression was strong in (16.67%) and very strong in (83.33%) with significant difference (P ≤ 0.001). AI% of H22 bearing mice treated with C. craniiformis aqueous and methanolic extracts were significantly increased (P ≤ 0.05) compared with the untreated control group. No significant difference was reported in AI% between aqueous and methanolic extracts treated groups. CONCLUSIONS: Extracts of C. craniiformis were highly efficient in tumour growth inhibition, causing a reduction in the tumour size clinically and increase the expression of caspase-8 gene product in tumour tissue, causing increase apoptotic index of H22 cells taken from the legs of inoculated mice leading to loss of legs due to bone necrosis. Antitumor activity of C. craniiformis aqueous, and the methanolic extract was dose and duration dependent.

Role of levothyroxine and vitamin E supplementation in the treatment of oxidative stress-induced injury and apoptosis of myocardial cells in hypothyroid rats.

OBJECTIVE: To explore the underlying mechanism and treatment of myocardial injury caused by hypothyroidism, we evaluated oxidative stress in serum and myocardial tissue of hypothyroid rats. The effect of levothyroxine (LT4) replacement therapy and vitamin E (VitE) supplementation on oxidative stress-induced injury and apoptosis of myocardial tissue is examined. METHODS: Male Sprague-Dawley rats were divided into five groups: normal control group, propylthiouracil group (PTU group), LT4 treatment group (PTU + LT4 group), vitamin E treatment group (PTU + VitE group), and combined treatment group (PTU + LT4 + VitE group). Superoxide dismutase (SOD) activity and malondialdehyde (MDA) expression in serum and myocardium were determined. Myocardial apoptosis index (AI) in each group was determined by TUNEL assay. RESULTS: SOD levels in serum were significantly increased in PTU + VitE and PTU + LT4 + Vit E groups, as compared to that in PTU and PTU + LT4 groups (P < 0.05). MDA levels in serum and myocardial tissue were significantly lower in PTU + LT4, PTU + VitE, and PTU + LT4 + VitE groups, as compared to that in the PTU group (P < 0.05). Myocardial apoptosis was significantly increased in PTU and PTU + VitE groups as compared to that in the normal control group (P < 0.05), while it was significantly lower in PTU + LT4 and PTU + LT4 + VitE groups, as compared to that in the PTU group (P < 0.05). CONCLUSION: In this study, levothyroxine replacement therapy and vitamin E supplementation appeared to ameliorate myocardial apoptosis in hypothyroid rats, the mechanism of which appears to be related to improved thyroid function and reduced oxidative stress.

[Age changes in connective tissue structures of the stomach.]

The study of paravasal connective tissue of the stomach was carried out on the preparations of 80 men corpses of three age groups: the first period of adulthood (n=20), the elderly (n=30) and senile (n=30) ages. With the help of standard histological and histochemical methods, the features of the age-related variability of the fiber composition were established; the level of apoptosis and proliferation in fibroblasts has been investigated with the help of immunohistochemical methods. The regularities of the structural organization of the paravasal connective tissue of the stomach during the period of biological stability (the first period of adulthood), as well as its age transformations at the stages of postnatal ontogeny (in the older age groups), were revealed.

Effect of trapidil in myocardial ischemia-reperfusion injury in rabbit.

OBJECTIVES: To evaluate the cardioprotective effects of trapidil on myocardial ischemia-reperfusion injury (MIRI) in rabbits. MATERIALS AND METHODS: Rabbits were subjected to 40 min of myocardial ischemia followed by 120 min of reperfusion. Blood for superoxide dismutase (SOD) and malondialdehyde (MDA) were estimated. At the end of reperfusion, the rabbits were sacrificed and the hearts were isolated for histological examination. An apoptotic index (AI) was determined using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL) method. The expression of apoptosis-related proteins Bax and Bcl-2 was analyzed using immunohistochemistry. Statistical analyses were performed by one-way analysis of variance (ANOVA), P < 0.05 considered statistically significant. RESULTS: Trapidil caused a significant (P < 0.05) increase in SOD activity, as decreased MDA levels and significantly (P < 0.05) reduced the expression of Bax as compared with the ischemia-reperfusion (IR) control group. CONCLUSION: Trapidil may attenuate the myocardial damage produced by IR injury and offer potential cardioprotective action.

Dl-3-n-butylphthalide inhibits myocardial infarction in acute myocardial ischemia / 安徽医科大学学报

Objective To observe the effects of Dl-3-n-butylphthalide ( NBP) on the mitochondria infarction, size of myocardial infarction and myocardial apoptosis after acute myocardial ischemia in rats. Methods 92 male SD rats were divided into sham operation group (8 rats) , model group (21 rats) , and low-dose NBP group (21 rats) , medium-dose NBP group (21 rats) , high-dose NBP group (21 rats) . The model and NBP groups were made into MI model by ligation of the left anterior descending ( LAD) coronary artery, but not in sham-operated group. Model group and NBP group were taken heart specimens after coronary artery ligation. Cardiomyocyte apoptosis was ana-lyzed by TUNEL in each group. Size of MI was analyzed by TTC staining in sham-operated group, model group and high-dose NBP group. Electron perspective microscopy was applicated in observing mitochondria infarction in model group and high-dose NBP group after myocardial infarction. The expressions of Bcl-2 protein and Bax protein were detected by Western blot. Results Compared with model group, butylphthalide significantly increased expression of Bcl-2 protein ( P <0.05 ) and the ratio of Bcl-2/Bax ( P <0.05 ) , inhibited mitochondria infarction ( P <0.05 ) , reduced myocardial infarct size ( P<0.01 ) and cardiomyocyte apoptosis ( P<0.05 ) . Conclusion Bu-tylphthalide significantly inhibits myocardial infarction by increasing expression of Bcl-2 protein and the ratio of Bcl-2/Bax and decreasing mitochondria infarction, reducing myocardial infarct size and cardiomyocyte apoptosis in rats during the acute myocardial ischemia process.

The HMGB1-TLR4 axis contributes to myocardial ischemia/reperfusion injury via regulation of cardiomyocyte apoptosis.

Toll-like receptor 4 (TLR4) and its ligand high mobility group box 1 (HMGB1), are known for playing central roles in ischemia-reperfusion injury in myocardium. However, the detailed mechanisms of TLR4 and HMGB1 are not fully understood. The aim of this study was to investigate the effects and possible mechanisms of the HMGB1-TLR4 axis and cardiomyocyte apoptosis on myocardial ischemic damage. Artificial oxygen ventilated anesthetized C3H/HeN mice and C3H/HeJ mice were subjected to 30 min of left anterior descending coronary artery occlusion followed by 6h of reperfusion. The myocardial infarct size, HMGB1 levels, apoptosis index, Bax, Bcl-2 and TNF-α mRNA levels were assessed. The results showed that a lowered amount of cardiomyocyte apoptosis and infarct size in the myocardium of TLR4-mutant mice after myocardial I/R and that TLR4 deficiency notably inhibited the expression of HMGB1 and TNF-a, both of which were up-regulated by ischemia/reperfusion. These findings suggest that the HMGB1-TLR4 axis plays a pathogenic role in triggering cardiomyocyte apoptosis during myocardial I/R injury and that the possible mechanism for this process is the result of released cytokines and inflammatory response involved in the HMGB1/TLR4-related pathway.

Expression of apoptosis signal-regulating kinase 1 in dibated cardiomyoprthy and its correlation with left ventricular ejection fraction / 中华实用儿科临床杂志

Objective To observe the changes of apoptosis signal-regulating kinase 1 (ASK1) expression in left ventricular myocardium of the dilated cardiomyopathy (DCM) rats induced by adriamycin and its correlation with left ventricular ejection fraction (LVEF).Methods One hundred and twenty SPF Wistar rats were divided into 2 groups as follows:control group (n =15),model group(n =105).Adriamycin was administered in the model group by intraperitoneal injection for 3 times in a week and repeated with a two-week interval for 6 times,while 9 g/L saline were administered in the control group in the same pattern,thus DCM rats model were constructed by the end of the 8th week.Both the model group and control group rats were drawn out and their LVEF were tested by the end of the 8th week and 12th week.Apoptosis index (AI) and the ASK1 in myocardium were tested respectively by apoptotic cells situ labeling,semi-quantitative analysis and Western blot.Results The AI of the control group,the 8th weekend model group and the 12th weekend model group were 0.53 ±0.27,16.13 ± 1.72,19.54 ±2.24.The AI of the 8th and the 12th weekend model groups were obviously higher than that in the control group.Comparing the differences among the 3 groups were statistically significant (F =18.98,P ＜ 0.05).The relative ASK1 expressions in ventricular myocardium of the control group,the 8th weekend model group and the 12th weekend model group were 0.169 ± 0.010,0.649 ± 0.071,0.781 ±0.077.Comparing the differences among the 3 groups were statistically significant (F =27.72,P ＜ 0.01).The LVEF (％) results of the control group,the 8th weekend model group and the 12th weekend model group were 75.41 ± 2.02,53.25 ±3.74,39.21 ±6.13.Comparing the differences among the 3 groups were statistically significant(F =154.87,P ＜0.01).There was a negative correlation between the ASK1 expression and LVFE in model group at the end of 12weeks(r =-0.86,P ＜ 0.01).Conclusions The ASK1 expression in myocardium of the DCM group increases obviously,thus apoptosis signal-regulating probably participates in the pathological process of DCM induced by ASK1.

Growth hormone receptor expression in human primary gastric adenocarcinoma.

The aim of this study was to determine the expression of growth hormone receptor (GHR) in patients with primary gastric adenocarcinoma. We investigated 48 specimens of primary gastric adenocarcinoma and their corresponding normal gastric mucosa. Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the expression of GHR. Immunohistochemical analyses revealed that GHR was expressed in human primary gastric adenocarcinoma (36/48, 75.0%) and appeared to be upregulated, compared to the normal mucosa (28/48, 58.3%, P < 0.001). A significant correlation was found between GHR expression and tumor stage (P < 0.001) and tumor differentiation (P < 0.001). The average positive rate of ki-67 in GHR-positive tumors was 16.06%, while the positive rate in GHR-negative tumors was 6.17% (P < 0.01). The average apoptosis index (AI) of GHR-positive tumors was 3.36%, which was significantly lower than that (7.33%) of GHR-negative tumors. In addition, 27 of 48 cases of tumors had GHR mRNA expression, while only 17 of all 48 cases of normal mucosa did so. Our results indicate that the frequency of GHR was significantly higher in primary gastric adenocarcinoma than that in normal gastric mucosa. GHR expression was significantly correlated with tumor differentiation and tumor grade. This finding supported a possible role of growth hormone in primary gastric adenocarcinoma pathophysiology.

Effect of levothyroxine and vitamin E treatment on oxidative stress and myocardial apoptosis in rats with hypothyroidism / 中华内分泌代谢杂志

Objective To investigate the oxidative stress status and cardiac myocyte apoptosis in rats with propylthiouracil-induced hypothyroidism and to examine the effect of levothyroxine ( LT4 ),vitamin E ( VitE ),and both supplementation on this experimental model.Methods Male Sprague Dawley rats were divided into normal control group( NC),propylthiouracil group( PTU ),LT4 treatment group( PTU + LT4 ),VitE treatment group ( PTU +VitE),LT4 and VitE combination therapy group (PTU + LT4 + VitE).Serum T3,T4,TSH levels,serum and myocardial superoxide dismutase ( SOD ) activity and malondialdehyde ( MDA ) content were determined.Cardiac myocyte apoptotic index was made with TUNEL.Results ( 1 ) Compared with NC group,T3 and T4 levels were significantly lower and TSH level was significantly higher in PTU group and PTU+VitE groups( P＜0.05 ).Compared with PTU group,T3 and T4 levels were significantly higher and TSH level was significantly lower in PTU + LT4 group and PTU + LT4 + VitE group( P＜0.05 ).There were no statistical differences in T3,T4,and TSH levels between PTU group and PTU + VitE group( P＞0.05 ).( 2 ) Compared to NC group,serum and myocardial MDA levels in PTU group increased significantly( P＜0.05 ),serum SOD activity decreased significantly ( P＜0.05 ),while myocardial SOD activity showed no significant difference( P＞0.05 ).( 3 ) Compared with NC group,myocardial apoptosis index was significantly higher in PTU and PTU + VitE groups( P＜0.05 ).Compared with PTU group,myocardial apoptosis index was significantly lower in PTU + LT4 group and PTU + LT4 + VitE group( P＜0.05 ).Conclusion LT4,VitE,and their combined treatment of hypothyroidism in rats reduce the myocardial cells apoptosis,which may be related to the improvement of thyroid function and amelioration of oxidative stress.

The Effect of Bone Marrow Mononuclear Cells Transplantation on Myocardial Apoptosis after Acute Myocardial Infarction in Rats / 医学研究杂志

Objective To observe the effect of allogenic bone marrow mononuclear cells(BM-MNCs) transplantation on myocardial apoptosis after acute myocardial infarction(AMI) in rats.Methods 40 Wistar rats were randomly divided into control group(n=20) and transplantation group(n=20).Myocardium around the infarcted left ventricular area of the rats in transplantation group were injected with BM-MNCs suspension beneath the epicardium.Myocardium the area of control group was injected with culture solution.Results After 4 weeks of the operation,the myocardial apoptosis index,the TNF-? content and the PDCD5 mRNA of transplantation group were all notably less than those of control group(P

Cell proliferation and apoptosis in squamous carcinoma of cervix after neoadjuvant chemotherapy / 第三军医大学学报

Objective To determine the effect of neoadjuvant chemotherapy (NAC) for cervix cancer on cell proliferation and apoptosis. Methods A total of 24 patients with squamous carcinoma of the cervix (SCC) were treated with one cycle of cisplatin combined with hydroxycamptothecine, bleomycin regimen. The expression of proliferating cell nuclear antigen (PCNA) and apoptosis index (AI) were detected before and after NAC with flow cytometry and TUNEL. Results Clinical response was 58.3% (14/24). Before and after NAC, the expression of PCNA were (0.386?0.078) and (0.125?0.040) respectively and AI were (0.052?0.027) and (0.248?0.078). Significant difference of PCNA and AI could be observed before and after NAC (t=22.859, t=16.06, P

Epithelial Cell Proliferation, Apoptosis, and Apoptosis Inhibition in Inverted Papillomas / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Inverted papillomas (IPs) are rare benign tumors of nasal epithelium with high recurrence rates and malignant transformation potential. Tumor development results from imbalance between cell proliferation and "programmed cell death", also named apoptosis. The purpose of this study was to compare cell proliferation, apoptosis, and apoptosis inhibition in hyperplastic epithelium from IPs and nasal polyps (NPs), and also to understand the mechanism of growth and malignant transformation of IPs. MATERIALS AND METHODS: IP samples were obtained after surgical removal of tumor in 15 patients, and NPs were sampled during endoscopic sinus surgery in 7 patients as a control. IP samples were classified in three groups: group I (n=9) -IP without dysplasia or carcinoma, group II (n=3) -IP with dysplasia, group III (n=3) -IP with carcinoma. Cell proliferation and apoptosis inhibition, respectively, were assessed by immunohistochemical identification of the Ki-67 and the oncoprotein Bcl-2. Apoptosis was evaluated by analyzing the DNA fragmentation using TUNEL method. RESULTS: Ki-67 index was increased in IPs compared to NPs (p=0.001). Of the IPs, Ki-67 index was increased progressively from IP without dysplasia or caccinoma, through IP with dysplasia, to reach the highest level in IP with carcinoma. Apoptotic index was also increased in IPs (p=0.002) with the highest level in IP without dysplasia or carcinoma. Of the IPs, apoptotic index was decreased as the tumor progress. Bcl-2 index was decreased in IPs (p=0.004), but, of the IPs, as the tumor progress, bcl-2 index was more decreased. CONCLUSION: Tumor development of IPs could result from the imbalance between hugely increasing epithelial cell proliferation and slightly increasing apoptosis, and the inhibition of apoptosis via bcl-2 oncoprotein seems to be involved in the growing process of IPs. Although we can not exactly mention due to limited number of cases, these imbalance may be involved in dysplastic or malignant transformation of IPs, but may be independent of the expression of bcl-2.

The correlation between expression of gastrin, somatostatin and cell apoptosis, p53 gene in colonic carcinoma / 中国普通外科杂志

Objective To explore the correlation between the expression of somatostatin (SS), gastrin (GAS), apoptosis index (AI),and p53 gene in colonic carcinoma. Methods The expression of GAS, SS, p53 and apoptosis cell were detected by immunohistochemistry (streptavidin-biotin-pero xidase complex, SABC) and in situ apoptosis detecting technic (TUNEL) . Results AI is higher in SS high and middle expression cases than in low expression cases(q=5.06,q=3.95,P