Qi-Tai-Suan, an oleanolic acid derivative, ameliorates ischemic heart failure via suppression of cardiac apoptosis, inflammation and fibrosis / 中国天然药物

Although anti-thrombotic therapy has been successful for prevention of deaths from acute myocardial infarction (MI), by far, there are few preventive and therapeutic options for ischemic heart failure (IHF) after MI. Qi-Tai-Suan (QTS) is an oleanolic acid (OA) derivative which once underwent a clinical trial for treating hepatitis. In this study, we investigated the potential cardioprotective effect of QTS on IHF. IHF mouse model was constructed by coronary artery ligation in male C57BL/6J mice, and the protective effects of QTS on IHF were examined by echocardiography measurement, histological and TUNEL analysis, etc. We found that QTS exhibited promising cardioprotective effect on IHF. QTS treatment significantly improved cardiac function of IHF mice and the symptoms of heart failure. Notably, QTS had much better oral bioavailability (F = 41.91%) in mice than its parent drug OA, and took effects mainly as its original form. Mechanistically, QTS ameliorated ischemic heart failure likely through suppression of cardiac apoptosis, inflammation and fibrosis. Taken together, QTS holds great promise as a preventive and therapeutic agent for ischemic heart failure and related diseases.

Lipid-lowering effects of oleanolic acid in hyperlipidemic patients / 中国天然药物

Oleanolic acid (OA) is a pentacyclic triterpenoid compound extracted from olea europaeal, a traditional Chinese medicine herb. OA has been used in the clinic as a hepatoprotective medicine in China since 1970s. In our previous study, we observed that OA could ameliorate hyperlipidemia in animal models. In the present study, we conducted a small-scale clinical trial to evaluate the hypolipidemia effect of OA in hyperlipidemic patients. Hyperlipidemic patients were administrated with OA for four weeks (4 tablets once, three times a day). The blood samples of the patients were collected before and after OA treatment. The biological parameters were measured. Furthermore, three patients' blood samples were studied with DNA microarray. After OA administration, the TC, TG, and HDLC levels in serum decreased significantly. DNA microarray analysis results showed that the expressions of 21 mRNAs were significantly changed after OA treatment. Bioinformatics analysis showed 17 mRNAs were up-regulated and 4 mRNAs were down-regulated significantly after OA treatment. Five mRNAs (CACNA1B, FCN, STEAP3, AMPH, and NR6A1) were selected to validate the expression levels by qRT-PCR. Therefore, OA administration differentially regulated the expression of genes involved in lipid metabolism. The data showed a clinical evidence that OA could improve hyperlipidemia and also unveiled a new insight into the molecular mechanisms underlying the pharmacological effect of OA on hyperlipidemia.

Lipid-lowering effects of oleanolic acid in hyperlipidemic patients / 中国天然药物

Oleanolic acid (OA) is a pentacyclic triterpenoid compound extracted from olea europaeal, a traditional Chinese medicine herb. OA has been used in the clinic as a hepatoprotective medicine in China since 1970s. In our previous study, we observed that OA could ameliorate hyperlipidemia in animal models. In the present study, we conducted a small-scale clinical trial to evaluate the hypolipidemia effect of OA in hyperlipidemic patients. Hyperlipidemic patients were administrated with OA for four weeks (4 tablets once, three times a day). The blood samples of the patients were collected before and after OA treatment. The biological parameters were measured. Furthermore, three patients' blood samples were studied with DNA microarray. After OA administration, the TC, TG, and HDLC levels in serum decreased significantly. DNA microarray analysis results showed that the expressions of 21 mRNAs were significantly changed after OA treatment. Bioinformatics analysis showed 17 mRNAs were up-regulated and 4 mRNAs were down-regulated significantly after OA treatment. Five mRNAs (CACNA1B, FCN, STEAP3, AMPH, and NR6A1) were selected to validate the expression levels by qRT-PCR. Therefore, OA administration differentially regulated the expression of genes involved in lipid metabolism. The data showed a clinical evidence that OA could improve hyperlipidemia and also unveiled a new insight into the molecular mechanisms underlying the pharmacological effect of OA on hyperlipidemia.

The expression of C1q/TNF-related protein-1 in patients with acute ischemic stroke and its predictive value for the severity of neurological deficits / 实用医学杂志

Objective To investigate the expression of C1q/TNF-related protein-1(CTRP1)in patients with acute ischemic stroke and its predictive value for the severity of neurological deficits. Methods A total of 452 patients with newly diagnosed ischemic stroke(IS)from February 2014 to February 2017 in our hospital were selected as the study subjects,and 403 healthy subjects were selected as control group in the physical examination center. The National Institutes of Health Stroke Scale(NIHSS)was used to evaluate the neurological status of pa-tients at admission and at 6 months after discharge. The expression of CTRP1 in plasma was detected by enzyme-linked immunosorbent assay(ELISA). Multiple linear regression was used to analyze the relationship between neu-rological deficit and CTRP1. Results The expression level the CTRP1in the healthy control group[(119.53 ± 17.62)ng/mL],unexplained causes IS[(145.81 ± 18.96)ng/mL],large atherosclerotic IS[(153.17 ± 19.21) ng/mL],cardiac IS[(156.56 ± 20.96)ng/mL]and small artery occlusion IS[(169.23 ± 22.34)ng/mL]in-creased gradually with statistically significant difference(P < 0.05). The level of CTRP1in the healthy control group[(119.53 ± 17.62)ng/mL],mild neurologic impairment group[(156.29 ± 19.86)ng/mL],moderate neuro-logic impairment group[(168.74 ± 18.53)ng/mL]and severe neurologic impairment group[(175.96 ± 19.15)ng/mL]increased gradually with statistically significant difference (P < 0.05). Multiple linear regression analysis showed that CTRP1,age,diabetes,Hs-CRP and LDL-C were independent factors of neurological deficits at 6 months after discharge in IS patients. Conclusion CTRP1 can effectively predict the severity of neurological defi-cits in patients with acute IS.

Asiatic acid mitigates hyperglycemia and reduces islet fibrosis in Goto-Kakizaki rat, a spontaneous type 2 diabetic animal model / 中国天然药物

The Goto-Kakizaki (GK) rat is a spontaneous type 2 diabetic animal model, which is characterized by a progressive loss of beta islet cells with fibrosis. In the present study, the hypoglycemic effect of asiatic acid (AA) in GK rats was examined. GK rats receiving AA at a daily dose of 25 mg·kg(-1) for four weeks showed a significant reduction in blood glucose levels. Age-matched normal Wistar rats were given 0.5% sodium carboxymethyl cellulose (CMC-Na) solution for the same periods and used as control. Compared to the normal Wistar rats, GK rats treated with AA showed improvement in insulin resistance partially through decreasing glucose level (P < 0.01) and insulin level (P < 0.05). Furthermore, the results of immunohistochemistry indicate that AA treatment reduced islet fibrosis in GK rats. Fibronectin, a key protein related to islet fibrosis, was over-expressed in GK rats, which was reversed significantly by AA treatment (P < 0.05). These findings suggest that AA has a beneficial effect on lowering blood glucose levels in GK rats and improves fibrosis of islets in diabetes, which may play a role in the prevention of islets dysfunction.

Efficacy of and Patient Compliance with a Ketogenic Diet in Adults with Intractable Epilepsy: A Meta-Analysis

BACKGROUND AND PURPOSE: Despite the successful use of a ketogenic diet in pediatric epilepsy, its application in adults has been limited. The aim of this meta-analysis was to summarize the findings of relevant published studies in order to identify the efficacy of and compliance with a ketogenic diet and its main subtypes (i.e., classic ketogenic diet and modified Atkins diet) in adults with intractable epilepsy, and to provide useful information for clinical practice. METHODS: Electronic searches of PubMed, EMBASE, Google Scholar, and the ISI Web of Science were conducted to identify studies of the efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy; the included studies were reviewed. Meta-analyses were performed using STATA to determine combined efficacy rates and combined rates of compliance with the ketogenic diet and its main subtypes. RESULTS: In total, 12 studies qualified for inclusion, and data from 270 patients were evaluated.The results of the meta-analysis revealed combined efficacy rates of all types of ketogenic diet, a classical ketogenic diet, and a modified Atkins diet were 42%, 52%, and 34%, respectively; the corresponding combined compliance rates were 45%, 38%, and 56%. CONCLUSIONS: The results indicate that a ketogenic diet is a promising complementary therapy in adult intractable epilepsy, and that while a classical ketogenic diet may be more effective, adult patients are likely to be less compliant with it than with a modified Atkins diet.

Maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase / 中国天然药物

AIM@#To investigate the molecular signaling mechanism by which the plant-derived, pentacyclic triterpene maslinic acid (MA) exerts anti-diabetic effects.@*METHOD@#HepG2 cells were stimulated with various concentrations of MA. The effects of MA on glycogen phosphorylase a (GPa) activity and the cellular glycogen content were measured. Western blot analyses were performed with anti-insulin receptor β (IRβ), protein kinase B (also known as Akt), and glycogen synthase kinase-3β (GSK3β) antibodies. Activation status of the insulin pathway was investigated using phospho-IRβ, as well as phospho-Akt, and phospho-GSK3β antibodies. The specific PI3-kinase inhibitor wortmannin was added to the cells to analyze the Akt expression. Enzyme-linked immunosorbent assay (ELISA) was used to measure the effect of MA on IRβ auto-phosphorylation. Furthermore, the effect of MA on glycogen metabolism was investigated in C57BL/6J mice fed with a high-fat diet (HFD).@*RESULTS@#The results showed that MA exerts anti-diabetic effects by increasing glycogen content and inhibiting glycogen phosphorylase activity in HepG2 cells. Furthermore, MA was shown to induce the phosphorylation level of IRβ-subunit, Akt, and GSK3β. The MA-induced activation of Akt appeared to be specific, since it could be blocked by wortmannin. Finally, MA treatment of mice fed with a high-fat diet reduced the model-associated adiposity and insulin resistance, and increased the accumulated hepatic glycogen content.@*CONCLUSION@#The results suggested that maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase.

Touch DNA of shed skin cells from the deployed airbag to address drunken driving crimes / 法医学杂志

In the criminal cases of driving under the influence (DUI), DNA evidence can be collected from the deployed airbag of the motor vehicle and submitted to the crime lab for touch DNA analysis. The evidence can be acquired when the skin cells are observed on the surface of the airbag in a traffic accident. However, the low quantity or quality of the evidence collected from a crime scene prevents further identification analysis in many cases. In the current study, we reported a case of identifying touch DNA extraction from the shed skin cells from the deployed airbag of a motor vehicle. We managed to collect DNA evidence from the shed skin cells in an airbag using a proper approach of collection and extraction. The 5.87 ng of extracted DNA was sufficient for genotyping and forensic identification, which helped to identify the driver of the car in collision with a pier in the street. In DUI cases and other traffic accidents, therefore, the amount of touch DNA extracted from the deployed airbag can be sufficient for DNA marker genotyping and further analysis.

Synthesis of A B C-ring subunit of C-nor-D-homo-steroidal alkaloids: towards the total synthesis of cyclopamine / 中国天然药物

A practical approach to the synthesis of the A, B and C-ring subunit of cyclopamine has been developed. This synthetic tactic highlights the utility of mandelate acetal-mediated resolution of the fused ring ketone (±)-4 and IBX-mediated oxidation cascades from 12 to 9. The availability of advanced intermediates from enantiomerically pure (+)-4 and 2 could provide efficient access to biologically active and structurally diverse C-nor-D-homo-steroidal alkaloids such as cyclopamine.

Cell apoptosis and proliferation in the transition and peripheral zones in human prostate / 中华男科学杂志

<p><b>OBJECTIVE</b>To determine and compare the difference of cell apoptosis and proliferation in the transition and peripheral zones in the human prostate.</p><p><b>METHODS</b>Seventeen normal prostate glands from organ donors were sampled from normal men according to McNeal/s zonal anatomy, and 20 hyperplastic transition zones obtained from prostatectomy specimens of BPH patients. Cell proliferation and Bcl-2 expression were assessed by immunostaining using PCNA and anti-Bcl-2 antibodies, while apoptotic bodies were specifically stained using TUNEL. Bcl-2 mRNA expression was detected by RT-PCR.</p><p><b>RESULTS</b>In the normal epithelium, the rates of cell proliferation and apoptosis were markedly decreased in the transition zone as compared with the peripheral zone. The proliferation index was significantly increased in the hyperplastic transition zone in BPH, while the apoptosis index significantly decreased in comparison with the normal prostate. Bcl-2 was significantly greater in the normal transition epithelium than in the peripheral zone, and over-expressed in the hyperplastic transition zone. There was a significant negative correlation between the Bcl-2 expression and the apoptosis of the epithelial cells in the hyperplastic transition zone (r(s) = -0.867, P < 0.01).</p><p><b>CONCLUSION</b>The hyperplastic transition zone may result from both an increase of cell proliferation and a failure of cell apoptosis. Increased expression of Bcl-2 may participate in the BPH process by blocking cell apoptosis.</p>

Effects of BMP-2 gene therapy on vascularization in repairing bone defects / 中华整形外科杂志

<p><b>OBJECTIVE</b>To study the effects of BMP-2 gene therapy on vascularization in repairing bone defects.</p><p><b>METHODS</b>The isolated rabbit mesenchymal stem cells (rBMSC), after being transfected by adenovirus carrying BMP-2 gene (Ad-BMP-2) and seeded on xenogeneic bone scaffolds, were used to repair 1.5 cm-long radius bone defects. Five methods were in use in the experiments: Ad-BMP-2 infected rBMSC plus antigen-free bovine cancellous bone (BCB, Group A), rBMSC-BCB plus reconstructed hBMP-2 (Group B1), Ad-LacZ infected rBMSC-BCB (Group C), rBMSC-BCB (Group D) and only BCB scaffolds (Group E). After 4, 8, and 12 weeks of the operations, capillary vessel ink infusion, vascular endothelial growth factor ( VEGF) immunohistochemical staining and histological examination were conducted.</p><p><b>RESULTS</b>After 4 weeks of the operations, usually in Group A one newly formed artery was found in every pore between the trabeculae of the BCB. The density of these intraosseous vessels was high in the periphery and decreasing towards the center of the grafts; by transmission electron microscopy, osteoblasts were always next to vascular endothelial cells and gradually developed into osteocytes with the increase of capillary vessel; VEGF expression were apparently enhanced in mesenchymocytes.</p><p><b>CONCLUSIONS</b>BMP-2 gene therapy, by up-regulating VEGF expression, indirectly induces vascularization of grafts and is of great value to the treatment of bone in union and bone defects.</p>

Repair of segmental bone defect by using gene modified tissue engineering bone combined with vascular bundle implantation / 中华创伤杂志

Objective To evaluate the effects of bone morphogenetic protein 2(BMP-2)gene modified tissue engineering bone combined with vascular bundle implantation in repairing segmental bone defect.Methods The isolated rabbit hone marrow stromal cells(MSCs),after being transfected by adenovirus carrying BMP-2 gene(Ad-BMP-2),were seeded on bovine cancellous bone scaffolds(BCB) to construct gone modified tissue engineering hone.The rabbit models with radial defects(2.0 cm long) were made and repaired with four methods including gene modified tissue engineering bone with vascular bundle implantation(Group A),gene modified tissue engineering bone(Group B),nongene modified tissue engineering bone with vascular bundle implantation(Group C),and only BCB scaffolds(Group D).After 4,8,and 12 weeks of operation,X-ray,histological examination,biomechanics analysis and capillary vessel ink infusion were conducted to observe angiopoiesis and osteogenesis.Results Group A gained better effect in the volume and activity of new bones than other groups,with vascular bundle sending out new branches into the transplanted bones and productive regeneration of capillary vessel.The defect in Group A was repaired satisfactorily.Group B showed better effect in speed and quality of bone formation than Group C under induction of BMP-2 gent.Mainly fibrous tissues but not new bones were observed in Group D.Conclusion BMP-2 gene therapy with vascular bundle implantation has very strong osteoinduction ability and quite good vascularization effect and is of great value to the treatment of bone nonunion and bone defects.

Diagnosis and treatment of enterovesical fistula(report of 12 cases) / 中华泌尿外科杂志

Objective To assess the diagnosis and treatment of enterovesical fistula.Methods The clinical data of 12 cases (10 men and 2 women;mean age,57 years) of enterovesical fistula were retro- spectively analyzed.Of the 12 cases,7 (58%) had colovesical fistula,3 (25%) had ileovesical fistula,and 2 (17%) had rectovesical fistula.The etiology of fistula was intestinal malignancy in 7 cases,Crohn disease in 3 ,and bladder cancer in 1,and intestinal diverticulitis in 1.The clinical features included fecaluria in 10 cases,recurrent urinary tract infection (UTI) in 6,abdominal pain in 4,and pneumaturia in 3.Five patients (5/9) had a definite diagnosis by CT;3 (3/6),by cystoseopy;2 (2/5),by cystography;and 1 (1/5),by barium enema.Among the 10 patients undergoing surgical intervention,resection of the involved bowl with one-stage anastomosis and partial cystectomy was performed in 4;resection of the bowl with one-stage anasto- mosis and repair of the fistula or single bladder drainage in each of 2;one-stage transverse colostomy and two- stage radical colectomy with partial cystectomy in 1;palliative proximal colostomy in 3;and conservative ther- apy in 2.Results One patient died of septic shock 10 d after admission.Nine patients were followed for 3 months to 16 years (mean,6.5 years).One patient had intestinal fistula recurrence and was cured with re- operation;1 patient with conservative therapy and 1 with palliative surgery died of tumor metastasis;and 1 died of cerebrovascular accident 2 years later without fistula recurrence previously.Five patients undergoing surgery had a better survival with no complication.Conclusions The major cause of enterovesical fistula is intestinal malignancy.Fecaluria and recurrent UTI are the most common symptoms.CT and cystoscopy are the preferred adjunctive examinations.Surgical intervention is the major therapeutic choice.