Objective: To establish the cardio-renal syndrome (CRS) model by coarctation of abdominal aorta (CAA) with renal ischemia reperfusion injury (RIRI), and to observe the mRNA expression of pro-renin receptor [(P)RR] in experimental rats. Methods: A total of 42 Wistar rats were randomly divided into 4 groups: Sham group, CAA group, RIRI group and CAA+RIRI group.n=10 in each group, 2 rats died during the modeling and all animals were treated for 16 weeks. Blood levels of BNP, creatinine (Cr), urea nitrogen (BUN), the activity of rennin, the contents of angiotensin-I (AT-I), AT-II and aldosterone were examined by laboratory test. The diastolic end inter-ventricular septum thickness (DEIVST), DELVPT, LVEF, ventricular weight index (VWI) and cardiac weight index were detected by small animal echocardiography. The histological changes of myocardium and kidney tissue were measured by HE staining, and the mRNA expressions of pro-renin receptor in myocardium and kidney tissues were measured by RT-PCR. Results: Compared with Sham group, blood levels of BNP were increased in the other 3 groups,P<0.05; compared with CAA group, CAA+RIRI group had increased levels of Cr and BUN,P<0.01; compared with Sham group and RIRI group, CAA+RIRI group showed increased blood level of aldosterone,P<0.05. Compared with CAA group, CAA+RIRI group presented increased rennin activity,P<0.05. Blood levels of AT-I and AT-II were not signiifcantly increased among 3 operation groups,P>0.05. Compared with CAA group, CAA+RIRI group had more obvious changes of DEIVST and LVEF,P<0.01. Compared with RIRI group, CAA+RIRI group had more obvious ventricular hypertrophy, higher VWI and cardiac weight index, allP<0.05. HE staining presented that CAA+RIRI group had broadening of myocardial cell bundle space, decreased left renal index, severe tubular atrophy and partial glomerular atrophy. RT-PCR demonstrated that compared with Sham group, the mRNA expressions of pro-renin receptor in myocardium and kidney tissues were decreased in the other 3 groups. Conclusion: Combined CAA+RIRI method may damage the cardial and renal tissues at the same time which was more severe than either CAA or RIRI. While CAA+RIRI model has better controllability and higher consistency that provides a methodological reference for pro-renin receptor in treating CRS in experimental rat’s model.

Objective To study the β3-adrenoceptor (β3-AR) in heart and lungs of elderly heart failure (HF) rats.Methods Forty-eight elderly HF Wistar rats were included in this study.A HF model of rats was established by ligating the aorta.The rats were divided into sham operation group (n=24) and HF group (n=24).The rats in each group were further divided into 4 subgroups at weeks 5,7,9 and 11 after operation (6 in each group).The hemodynamics,pathology and expression of β3-AR mRNA and protein in heart and lungs were detected at weeks 5,7,9 and 11 respectively after operation.Results The heart rate,LVESP,and dp/dtmax were significantly lower in HF group than in sham operation group at weeks 9 and 11 after operation while the LVEDP was significantly higher in HF group than in sham operation group at weeks 5,7,9 and 11 after operation (P＜0.01).Pulmonary edema occurred at week 7 after operation and myocardial necrosis was detected at week 9 after operation.The expression level of β3-AR mRNA in lungs was significantly lower in HF group at weeks 5,7,9 and 11 than at week 2 after operation (P＜0.05).The expression level of β3-AR mRNA in heart was significantly higher in HF group than in sham operation group at weeks 9 and 11 after operation (1.21±0.26 vs 0.98±0.22,1.26±0.23 vs 1.05±0.24,P＜0.01).Conclusion The β3-AR mRNA expression is downregulated in the lungs and upregulated in the heart.

Objective No consensus has yet been achieved on the relationship of serum albumin with the functional out-come of acute ischemic stroke.The aim of our study was to determine whether the serum albumin level was associated with the short-term functional outcome of acute ischemic stroke in well-nourished patients. Methods Totally, 113 patients with first-ever acute ischemic stroke were recruited from Nanjing Stroke Registration Program between January and June 2015.Baseline data including de-mographic and body parameters, vascular risk factors, and laboratory results were collected.The NIH Stroke Scale ( NIHSS) was used to evaluate the severity of neurological deficits and the modified Rankin Scale ( mRS ) employed to assess the short-term functional outcome.According to the mRS at discharge, the patients were divided into a good outcome group ( mRS<3 ) and a poor out-come group ( mRS≥3 ) .The independent predictors of the short-term functional outcome were evaluated by multivariate logistic regression analysis. Results Of the 113 acute ischemic stroke patients included, 52 (46.0%) were in the good outcome group, and 61 (54.0%) in the poor outcome group.Those in the former group had a significantly higher BMI, lower serum LDL-C, lower WBC count, and lower NIHSS at admission than those in the latter .Multivariate logistic regression analysis showed that low serum albumin, NIHSS at admission, and arteriole occlusion were independent predictors of the poor short-term functional outcome ( OR=0.684, 95% CI:0.490-0.956, P=0.026). Conclusion Low serum albumin is an independent predictor of poor short-term functional outcome in acute ischemic stroke patients in well-nourished status.

Humans ; Immunologic Factors ; Immunotherapy ; Mutation ; Neoplasms/therapy* ; Tumor Microenvironment

Cardiomyocyte apoptosis leads to the functional incapacitation of myocardial plasmodium and plays an important role in the pathogenesis of heart failure transformed from compensable cardiac hypertrophy. Mitochondria are the main source of apoptosis-inducing molecule of various cells, and the role of caspartate-specific cysteinyl proteinase (caspase)-dependent mechanism has generally been accepted in the cardiomyocyte apoptosis. However, the significance of caspase-independent apoptosis-inducing factor (AIF) mechanism is not yet understood. The purpose of this study was to evaluate hypoxia-reperfusion-induced alterations of AIF mRNA and protein expressions in hypertrophic cardiomyocytes. Cardiomyocyte hypertrophy was produced by angiotensin II (0.1 mumol/L). The cells were cultured under the condition of hypoxia (95% N2 and 5% CO2; the O2 partial pressure was lower than 5 mmHg) for 8 h or 12 h (named as H8h and H12h groups, respectively), and then exposed to normal culture environment (named as H8h/R and H12h/R groups, respectively). Apoptosis was detected with Hoechst 33258 staining. The AIF mRNA and protein expressions were detected by RT-PCR and Western blot and quantified by gel scanning. The results were as follows: (1) The level of AIF mRNA expression was 0.29+/-0.08 (optical density, relative value) in the control group (hypertrophic cardiomyocytes cultured in normal environment). Compared with that in the control group, the levels of AIF mRNA expression were significantly higher in the groups of H8h and H12h (0.52+/-0.04 and 0.85+/-0.10), indicating that this effect was time-dependent. A further increase of AIF mRNA expression was observed in the groups of H8h/R (1.09+/-0.12) and H12h/R (1.41+/-0.23). (2) The level of AIF protein expression was 0.29+/-0.04 in the control group. Compared with that in the control group, the levels of AIF protein expression were significantly higher in the groups of H8h and H12h (2.07+/-0.15 and 3.12+/-0.19). The AIF protein expression was increased further in the groups of H8h/R (4.57+/-0.25) and H12h/R (5.71+/-0.27). The nuclear translocation of AIF protein was obvious only in the groups of H8h/R and H12h/R. (3) The expressions of AIF mRNA and protein were almost completely inhibited by AIF siRNA transfection. The siRNA transfection also reduced the apoptosis of hypertrophic cardiomyocytes in the groups of H8h/R and H12h/R but not in the groups of H8h and H12h. The apoptosis rate was significantly reduced by both AIF siRNA transfection and Ac-DEVD-cmk, an inhibitor of caspase-3. This reduction induced by two factors was more evident than that by one factor. (4) AIF nuclear translocation induced by hypoxia-reperfusion was not affected by inhibition of the activity of caspase-3. These data suggest that AIF plays a pivotal role in the apoptosis of hypertrophic cardiomyocytes induced by hypoxia-reperfusion.
Apoptosis ; Apoptosis Inducing Factor ; metabolism ; Cardiomegaly ; Cell Hypoxia ; Myocytes, Cardiac ; cytology ; Reperfusion Injury

Animals ; Female ; Guinea Pigs ; Kidney ; microbiology ; pathology ; Leptospira interrogans ; isolation & purification ; pathogenicity ; Leptospirosis ; microbiology ; pathology ; Liver ; microbiology ; pathology ; Lung ; microbiology ; pathology ; Male ; Time Factors

The aim was to investigate the mechanism of arsenic trioxide (ATO) inducing apoptosis of K562 cells that express P210Bcr-Abl. Apoptosis was analyzed by cell proliferation assay, morphological changes, DNA-PI staining and cell cycle analysis. ELISA kits were also used to analyze the concentration of cytosolic cytochrome C and activation of caspase-3. Transcriptional levels of Bcl-XL and Bcr-Abl were assayed by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). The results showed that K562 cells were induced to apoptosis after exposure to 2.5 micromol/L ATO for at least 48 hours, and the cell cycle of K562 cells was arrested at the G2/M phase. Caspase-3 was activated and there was a cytosolic accumulation of cytochrome C. ATO could only reduce the transcriptional level of Bcl-XL, but could not down-regulate the Bcr-Abl transcriptional level. In conclusion, ATO can induce K562 cells to apoptosis. The signal pathway mediated by the cytosolic translocation of mitochondria cytochrome C is one of the mechanisms for ATO inducing apoptosis. And the decrease of Bcl-XL may induce more apoptosis.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Caspase 3 ; Caspases ; metabolism ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cytochromes c ; analysis ; Fusion Proteins, bcr-abl ; genetics ; Humans ; K562 Cells ; Oxides ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; bcl-X Protein

OBJECTIVETo investigate the effect of Compound Qingqin Liquid (CQL) on the expression level of angiotensin II (Ang II) and COX-2 mRNA transcription and protein expression in the renal tissue of rats with uric acid nephropathy.

METHODSSD rats were randomly divided into the blank control group, the model group, the positive drug group, the high, moderate, and low dose CQL group according to number randomization principle. The model was established by gastrogavage of adenine, accompanied with yeast feeding. Distilled water was given by gastrogavage to rats in the blank control group and the model group. Allopurinol at the daily dose of 9.33 mg/kg was given by gastrogavage to rats of the positive control group. CQL at the daily dose of 3.77 g/kg, 1.89 g/kg, and 0.09 g/kg was respectively given by gastrogavage to rats in the high, moderate, and low dose CQL groups. All treatment lasted for 6 weeks. Rats were randomly divided at week 4 (3 in the blank control group, and 6 in the rest groups), and the rest rats were killed at week 6. The renal tissue was extracted. The expression level of Ang II and COX-2 mRNA transcription were detected by RT-PCR. The expression level of Ang II was detected by ELISA. The expression level of COX-2 protein was detected by Western blot and immunohistochemical assay.

RESULTSCompared with the blank control group, except the mRNA expression of Ang II at week 4, the mRNA and protein expression of Ang II and COX-2 obviously increased at week 4 and 6 in the model group (P < 0.01, P < 0.05). The COX-2 protein expression at week 4 was obviously lower in the high and moderate dose CQL groups than in the model group and the low dose CQL group (P < 0.05); the average integral of optical density value was obviously lower in the positive control group than in the model group. Except the mRNA expression of Ang II in the high dose CQL group at week 6, the mRNA and protein expression of Ang II obviously decreased in the positive control group and each dose CQL group (P < 0.01, P < 0.05). Of them, the effects were better in the high and moderate dose CQL groups than in the positive control group and the low dose CQL group (P < 0.05, P < 0.01). Besides, the mRNA expression of COX-2, the average integral of optical density value were obviously lower in the positive control group and each dose CQL group than in the model group (P < 0.05). The protein expression of COX-2 was obviously lower in the high and moderate dose CQL groups than in the model group (P < 0.05). Of them, the mRNA expression of COX-2 was better in the moderate dose CQL group than in the positive control group (P < 0.05); the protein expression of COX-2 was better in the high dose CQL group than in the low dose CQL group (P < 0.05).

CONCLUSIONCQL was capable of lowering the expression level of Ang II, COX-2 mRNA transcription and protein expression, thus suppressing the inflammatory pathological injury of the renal tissue.

Angiotensin II ; metabolism ; Animals ; Cyclooxygenase 2 ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; metabolism ; Kidney Diseases ; drug therapy ; metabolism ; Male ; RNA, Messenger ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Uric Acid

Objective To analyze the risk of re-emergence of Oncomelania snail(O.snail) from 2015 to 2019, in order to improve the effectiveness of snail control. Methods Collection of report forms and schistosomiasis surveillance data was carried out from 2015 to 2019, and analyzed retrospectively. Results The area of snail-emergence was 6 241.98 hm² during 2015-2019, 44.29、4 610.18、813.92、446.09 and 327.50 hm² respectively, for each corresponding year.Among the re-emergence areas, flat-ground subtype was 1 185.49 hm²(18.99%), hilly subtype was 2 536.58 hm²(40.64%), and mountain subtype was 2 519.91 hm²(40.37%).The top 5 cities with O.snail re-emergence areas were Liangshanzhou(2016), Ya′an(2016), Deyang(2016), Meishan(2016), and Meishan(2017).The top 5 disticts with O.snail re-emergence areas were Renshou, Puge, Lushan, Tianquan and Dechang. Conclusion The re-emergence of O.snail attributes to several factors, such as low quality of annual snail survey, unitary method of elimination and complexity of snail habit environment.Surveillance and supervision on the sources of infection and snail spreading should continue with exploration of new method in eliminating snails especially in hilly regions.

Objective To observe effects of Heyutai Fuzhu Jiangtang Tablets combined with metformin in insulin resistance (IR); To discuss its mechanism of action. Methods 6–7 week old male ZDF (fa/fa) rats were randomly divided into model group,metformin group,Heyutai Fuzhu Jiangtang Tablets group(Jiangtang Tablets group),and metformin combined with Heyutai Fuzhu Jiangtang Tablets group.ZDF(fa/+)rats were chosen as normal group.Each medication group was given relevant medicine for gavage for 6 weeks. Body weight, FBG, TG, TC, FFA, FINS, HOMA-IR, OGTT and HE staining were tested. HE staining was used to observe the pathological changes of skeletal muscle. RT-PCR and Western blot were used to detect skeletal muscle corresponding gene and protein expression. Results Compared with Jiangtang Tablets group and metformin group, TC, FFA, FBG, and HOMA-IR in metformin combined with Heyutai Fuzhu Jiangtang Tablets group decreased significantly (P<0.05, P<0.01). Blood glucose level and AUC significantly decreased at each time point in OGTT. HE staining of skeletal muscle fibers arranged in order; nucleus increased and internal movement was not significant, without obvious infiltration of inflammatory cells. Expressions of skeletal muscle InsR, Akt, and Glut4 mRNA expression increased (P<0.05, P<0.01). Expressions of skeletal muscle p-InsR, p-Akt, and Glut4 protein expression increased (P<0.05, P<0.01). Conclusion Heyutai Fuzhu Jiangtang Tablets combined with metformin can improve IR in type 2 diabetic rats, and the effect is better than single-application.