Autophagic dysfunction of ß cell dysfunction in type 2 diabetes, a double-edged sword.

Diabetes is an age-related disease, most of which is type 2 diabetes, and islet ß cell dysfunction and insulin resistance are the main mechanisms of type 2 diabetes. Recent studies have revealed that autophagy plays an important role in maintaining the structure and function of islet beta cells and inhibiting insulin resistance and apoptosis induced by oxidative stress. In this review, we discussed the positive and negative effects of autophagy and its dysfunction on type 2 diabetes mellitus, which is the so-called double-edged sword, analysed its possible mechanism, and identified possible research hot spots.

Corrigendum to "TERT and Akt Are Involved in the Par-4-Dependent Apoptosis of Islet ß Cells in Type 2 Diabetes".

[This corrects the article DOI: 10.1155/2018/7653904.].

Study on Optimization of the Extraction Technology of Total Vitamin E in Euryale ferox by Box-Behnken Design-response Surface Methodology / 中国药房

OBJECTIVE： To optimize the extraction technology of total vitamin E in Euryale ferox. METHODS： With the extraction amount of total vitamin E as reference index， using extraction time， extraction times， ultrasound power and comminution degree as reference factors， single fator test and Box-Behnken design-response surface methodology was used to optimize the extraction technology of total vitamin E from E. ferox. The validation tests were conducted for 3 times （the amounts of E. ferox were 2.0， 20.0， 40.0 g）. RESULTS： The optimal extraction technology of vitamin E included that extraction time of 80 min， extraction times of 3 times， ultrasound power of 240 W， comminution degree of 80 mesh. In validation test， extraction rates of total vitamin E were 2.063， 2.103， 2.085 mg/g （RSD＝2.6％， 1.5％， 1.3％， n＝3）， the relative errors of which to predicted value （2.092 mg/g） were 0.14％， 0.53％ and 0.33％， respectively. CONCLUSIONS： The optimal extraction technology is reasonable， stable and feasible， and can be used for the extraction of total vitamin E in E. ferox.

TERT and Akt Are Involved in the Par-4-Dependent Apoptosis of Islet ß Cells in Type 2 Diabetes.

Islet ß cell apoptosis plays an important role in type 2 diabetes. We previously reported that Par-4-mediated islet ß cell apoptosis is induced by high-glucose/fatty acid levels. In the present study, we show that Par-4, which is induced by high-glucose/fatty acid levels, interacts with and inhibits TERT in the cytoplasm and then translocates to the nucleus. Par-4 also inhibited Akt phosphorylation, leading to islet ß cell apoptosis. We inhibited Par-4 in islet ß cells under high-glucose/fatty acid conditions and knocked out Par-4 in diabetic mice, which led to the up-regulation of TERT and an improvement in the apoptosis rate. We inhibited Akt phosphorylation in islet ß cells and diabetic mice, which led to aggressive apoptosis. In addition, the biological film interference technique revealed that Par-4 bound to TERT via its NLS and leucine zipper domains. Our research suggests that Par-4 activation and binding to TERT are key steps required for inducing the apoptosis of islet ß cells under high-glucose/fatty acid conditions. Inhibiting Akt phosphorylation aggravated apoptosis by activating Par-4 and inhibiting TERT, and Par-4 inhibition may be an attractive target for the treatment of islet ß cell apoptosis.

Simultaneous Determination of Six Effective Components in Dutong Pills by GC / 中国药师

Objective:To establish a GC method for the imultaneous determination of cinnamaldehyde, bornyl acetate, costunol-ide,dehydrocostus lactone,magnolol and honokiol in Dutong pills. Methods: The determination was performed on an HP-5 column (30 m ×0.32 mm,0.25 μm) with programmed temperature. The carrier gas was nitrogen with the flow rate of 2.0 ml·min-1. The injection volumn was 1 μl and the sample split ratio was 5:1. The inlet temperature was 280 ℃. The detector was a flame ionization detector with temperature at 300 ℃. Results:The linear ranges were 32.28-516.40 μg·ml-1for cinnamaldehyde(r=0.999 3), 27.06-433.00 μg·ml-1for bornyl acetate(r=0.999 2),25.65-410.40 μg·ml-1for costunolide(r=0.999 3),26.10-417.60 μg ·ml-1for dehydrocostus lactone(r=0.999 3),24.01-384.20 μg·ml-1for magnolol(r=0.999 0) and 18.32-293.10 μg·ml-1 for honokiol(r=0.999 4). The average recovery was 99.71%(RSD=0.67%),99.34%(RSD=1.18%),100.16%(RSD=0. 34%),100.40%(RSD=0.39%),99.32%(RSD=1.22%) and 99.58%(RSD=0.58%)(n=6),respectively. Conclusion:The method is simple,sensitive and accurate,can be used to supplement the insufficient quality control of Dutong pills.

Study on Remote Sensing Monitoring Method of Aquatic Medicine Materials Euryale ferox Salisb Based on Multi-source Satellite Remote Sensing Image / 世界科学技术-中医药现代化

Multi-source satellite remote sensing technology can be used to monitor the distribution and growth status of aquatic plant species on a large scale.In this paper,C,aoyou Lake was selected as the research area.Aquatic medicine material Euryaleferox Salisb was used as the research object.The spectral characteristics of plants in Euryaleferox Salisb growing area were analyzed by ASD portable spectrometer and the remote sensing image of Pléiades and GF-1.The spectral range of species was obtained.And the decision tree algorithm model was constructed,which were used to extract the information of Euryale ferox Salisb from remote sensing images.Through verification,the results showed that the accuracy of comprehensive classification was 83％.It was concluded that multi-source satellite remote sensing image and GIS spatial analysis technology can accurately reflect the area and distribution of aquatic medicine material Euryale ferox Salisb.

Gcm2 gene knock-out induces the hypoparathyroidism in adult mice / 中华内分泌代谢杂志

Objective To investigate the role of Glial cells missing 2 (Gcm2) in pathogenesis of hypoparathyroidism by knocking out Gcm2 gene in adult mice.Methods Tamoxifen was used to induce conditional knock-out of Gcm2 gene in Gcm2E2fl/flCre-ER mice.Genotypes of knock-out mice were identified by PCR.The protein expression level of Gcm2 was measured by Western blotting.The serum calcium and phosphorus were detected by the calcium and phosphorus assay kits, and the serum parathyroid hormone (PTH) level was detected by ELISA.Parathyroid cell proliferation was tested by Ki-67 immunohistochemical assay.The mRNA expression levels of PTH and calcium sensing receptor (CaSR) were detected by Real-time PCR.Bone mineral density was detected by micro CT.Results Gcm2 gene of parathyroid was confirmed to be knocked out by PCR.Compared with wild type and solvent control groups, Gcm2 knock-out group showed markedly lower protein expression of Gcm2, notably higher serum phosphorus and lower serum calcium and PTH concentrations (all P<0.01).The proliferation of parathyroid cells in Gcm2 knock-out mice were significantly higher(both P<0.01).The mRNA levels of PTH and CaSR in parathyroid gland of the knock-out group were significantly reduced (all P<0.01).Bone mineral density was significantly higher in Gcm2 knock-out group (all P<0.01).Conclusion Knockout of Gcm2 can lead to hypoparathyroidism in adult mice, indicating that Gcm2 is probably a therapeutic target for hypoparathyroidism.

Simultaneous Determination of 21 Inorganic Elements in Hypericum japonicum by ICP-MS / 中国药房

OBJECTIVE:To establish the method for simultaneous determination of 21 inorganic elements in Hypericum japoni-cum. METHODS:ICP-MS method was adopted. The power was 1300 W;flow rate of cooling gas was 1.5 L/min;flow rate of carrier gas was 0.8 L/min;flow rate of auxiliary gas was 0.2 L/min;integration time was 10 s;delay time of 1 s;repetition times was one time;measurement mode was standard curve method. SPSS 16.0 statistical software was used for relationship analysis and main component analysis. RESULTS:The linear range of iron,magnesium,calcium,aluminum,potassium,sodium,zinc,co-balt,nickel,barium,manganese,phosphorus,selenium,titanium,strontium,copper,arsenic,cadmium,chromium,lead,mer-cury were 50-250 μg/mL(r=0.9972),25-100 μg/mL(r=0.9989),25-100 μg/mL(r=0.9977),2.5-15 μg/mL(r=0.9996), 25-150 μg/mL(r=0.9991),2.5-15 μg/mL(r=0.9999),2.5-10 μg/mL(r=0.9999),2.5-10 μg/mL(r=0.9999),2.5-10 μg/mL(r=0.9999),2.5-10 μg/mL(r=0. 0.9999),2.5-10 μg/mL(r=0.9998),2.5-10 μg/mL(r=0.9996),0.5-2 μg/mL(r=0.9995),2.5-10μg/mL(r=0.9999),0.5-2 μg/mL(r=0.9983),2.5-10 μg/mL(r=0.9997),2.5-10 μg/mL(r=0.9999),2.5-10 μg/mL(r=0.9999), 2.5-10 μg/mL(r=0.9999),0.05-0.2 μg/mL(r=0.9992),0.05-0.2 μg/mL(r=0.9997),respectively. RSDs of precision,stability and reproducibility tests were all lower than 5.0%. The recoveries were 93.9%-106.9%(RSD were 0.22%-2.94%,n=6).CONCLU-SIONS:The method is simple,precise,stable and reproducible,and can be used for simultaneous determination of 21 inorganic el-ements in H. japonicum.

Nibble debridement combined with silver ions dressing in treatment of diabetic foot ulcer / 局解手术学杂志

Objective To explore the clinical efficacy of nibble debridement combined with silver ions dressing in treatment of diabetic foot ulcer.Methods The data of 238 patients with diabetic foot ulcer in people's hospital of Meishan from January 2012 to December 2016 were retrospectively analyzed.Of which 125 patients were treated by nibble debridement combined with silver ions dressing(nibble debridement group),113 patients were treated with surgical debridement combined with silver ions dressing(surgical debridement group).The clinical efficacy,wound healing time and complication between two groups were compared.Results The wound healing time of nibble debridement group was (37.5 ± 10.8) days,which was shorter than (45.3 ± 11.7) days of surgical debridement group,the difference was significant (P ＜0.05).The total effective rate of nibble debridement group was 92.80％,which was higher than 73.45％ of surgical debridement group,the difference was significant(P ＜ 0.05).No complication occurred in two groups.Conclusion The method of nibble debridement combined with silver ions dressing treatment has a better satisfactory clinical result,shorter wound healing time and lower medical costs for patients with diabetic foot ulcer.

Par-4/NF-κB Mediates the Apoptosis of Islet ß Cells Induced by Glucolipotoxicity.

Apoptosis of islet ß cells is a primary pathogenic feature of type 2 diabetes, and ER stress and mitochondrial dysfunction play important roles in this process. Previous research has shown that prostate apoptosis response-4 (Par-4)/NF-κB induces cancer cell apoptosis through endoplasmic reticulum (ER) stress and mitochondrial dysfunction. However, the mechanism by which Par-4/NF-κB induces islet ß cell apoptosis remains unknown. We used a high glucose/palmitate intervention to mimic type 2 diabetes in vitro. We demonstrated that the high glucose/palmitate intervention induced the expression and secretion of Par-4. It also causes increased expression and activation of NF-κB, which induced NIT-1 cell apoptosis and dysfunction. Overexpression of Par-4 potentiates these effects, whereas downregulation of Par-4 attenuates them. Inhibition of NF-κB inhibited the Par-4-induced apoptosis. Furthermore, these effects occurred through the ER stress cell membrane and mitochondrial pathway of apoptosis. Our findings reveal a novel role for Par-4/NF-κB in islet ß cell apoptosis and type 2 diabetes.

Exenatide Activates the APPL1-AMPK-PPARα Axis to Prevent Diabetic Cardiomyocyte Apoptosis.

OBJECTIVE: To investigate the effect and mechanism of the exenatide on diabetic cardiomyopathy. METHODS: Rats were divided into control group, diabetes group (D), diabetes treated with insulin (DI) group, and diabetes treat with exenatide (DE) group. We detected apoptosis rate by TUNEL, the adiponectin and high molecular weight adiponectin (HMW-adiponectin) by ELISA, and the expression of APPL1, p-AMPK/T-AMPK, PPARα, and NF-κB by immunohistochemistry and western blotting. RESULTS: Compared with the D group, the apoptosis in the Control and DE groups was decreased (P < 0.05); the adiponectin and HMW-adiponectin were increased (P < 0.05); the APPL1, p-AMPK/T-AMPK, PPARα, and LV -dP/dt were increased (P < 0.05); and the NF-κB, GRP78, and LVEDP were decreased (P < 0.05). Compared with DE group, the glucose levels in the DI group were similar (P < 0.05); the apoptosis and LVEDP were increased; the APPL1, p-AMPK/T-AMPK, PPARα, and LV -dP/dt were decreased (P < 0.05); the NF-κB and GRP78 were increased (P < 0.05); the adiponectin and HMW-adiponectin were significantly decreased (P < 0.05). CONCLUSION: Our model of diabetic cardiomyopathy was constructed successfully. After being treated with exenatide, the adiponectin and HMW-adiponectin and the APPL1-AMPK-PPARα axis were increased, the NF-κB and the apoptosis were decreased, the cardiac function of the diabetic rats was improved, and these effects were independent of glucose control.

Different methods of dressing change on wound after local debridement of diabetic foot / 局解手术学杂志

Objective To investigate the therapeutic effect of different methods of dressing on the wound after local debridement of dia-betic foot. Methods A total of 53 patients which underwent local debridement of diabetic foot were divided into control group and treatment group. Patients in control group were dressed on traditional measurement,while patients in the treatment group were dressed on the external medicinal wine for the diabetic foot basic on the traditional treatment. The local transcutaneous oxygen partial pressure,ulcer healing rate,av-erage healing time and the amputation rate were observed. Results The healing rate and percutaneous oxygen partial pressure of the treat-ment group were significantly increased than those in the control group (P<0. 05). The average healing time and amputation rate of the treat-ment group were significantly less than those in the control group (P<0. 05). Conclusion Dressing on external medicinal wine after local debridement of diabetic foot can improve the wound healing in the diabetic foot.

Effect of Bensulfuron Pollution on Levels of Bufadienolides from Venom Secreted by Toad / 分析化学

Ulta performance liqiuid chromatography-triple quadrupole tandem mass spectrometry ( UPLC-MS/MS) was used to monitor the relative levels of bufadienolides in toad venom in normal and bensulfuron-polluted groups. Methanol extract of toad venom was separated by UPLC ( ODS-C18 ) using a gradient elution of water contains 0. 1% formic acid and acetonitrile. Mass spectrometry was used in an ESI source operated in positive ion and MRM mode. The parameters in the source were set as follows: capillary voltage 3. 0 kV; sampling cone voltage 30 V; and desolvation temperature 500℃. In this method, external calibrations of 6 standards were typically constructed (R2=0. 9953-0. 9992). The LOD was 0. 42-4. 86 ng/mL. Intra- and inter-day precision was 3. 8%-6. 8% and 4. 0%-8. 8%, respectively. The recovery of standard was evaluated by spiking the standard compound into toad venom. Their average recoveries were 96. 9%-109. 6%, and RSDs were 2. 0%-8. 1%. This method was further employed into monitoring the levels of 36 bufadienolides. The levels of more than 20 bufadienolides were greatly different after bensulfuron pollution, suggesting that the bensulfuron pollution could change the chemical expression pattern of bufadienolides in toad venom.

Analysis of the Content of Water-soluble Proteins in Euryale ferox from Different Regions / 中国药房

OBJECTIVE:To analyze the content of water-soluble proteins in Euryale ferox from different regions. METHODS:The water-soluble proteins in E. ferox were extracted by cryogenic grinding. With the reference of bovine albumin,Coomassie bril-liant blue G-250 was used for coloration,visible spectrophotometry was conducted to determine the content of water-soluble pro-teins in E. ferox from different regions and clustering analysis was used to analyze the results. RESULTS:The linear range of bo-vine albumin was 0.005 01-0.150 3 mg/ml(r=0.999 2)with the average recovery of 98.95%(RSD=1.76%,n=6).RSDs of preci-sion,stability and reproducibility tests were no more than 2.04%. The average value of content of water-soluble proteins in samples was 0.457 7 mg/g. Cluster analysis showed that the content of water-soluble proteins in E. ferox from Yangtze River basin was high-er,followed by the southward and the northward was the least. CONCLUSIONS:The method is simple,reliable and reproducible, and suitable for the content determination of water-soluble proteins in E. ferox.

Evolution and Development of Animal Medicine Varieties in China / 中国中医药信息杂志

Animal medicine is an important part of traditional Chinese medicine with a long application history in China. Systematically understanding the history of the development of animal medicine is of great significance to scientific protection and rational use of animal medicine resources. It has certain guiding significance to protection of wild resources, exploitation of new substitutes, standardization and summary of artificial breeding, and artificial reproduction technology. Taking the development of bezoar as an example, this article expounded the following four aspects:the development history of animal medicine, national animal protection, technical development, and prospect forecast by summarizing the Chinese ancient medical books and consulting the relevant laws and regulations. The entire above are about to offer new ideas for the sustainable development, the development of new medicine resources, and the development of animal medicine related preparation product.

Clinical observation on treatment effect of negative pressure wound therapy followed by ultrasonic debridement surgical system in patients with diabetic foot / 局解手术学杂志

Objective To evaluate the treatment effect of negative pressure wound therapy ( NPWT) followed by ultrasonic debridement surgical system ( UDSS) in patients with diabetic foot. Methods Forty-seven diabetic foot ulcer patients( WagnerⅡ~Ⅲ) were divided into two groups,of which 26 patients treated with UDSS combined NPWT,and 21 patients treated with traditional surgical debridement combined NPWT were control group. Cure rate, markedly effective rate and adverse reaction and complication were compared between two groups. Results Compared with control group,the experiment group had higher markedly effective rate in the first week(P<0. 05),and healing rates were higher in the 2th,4th,6th,12th weeks (P<0. 05). There were no differences in the adverse reactions and complications between the two groups. Conclusion UDSS combined with NPWT can accelerate wound cure,may play an important role for the treatment of diabetic foot ulcer.

PAR-4: a possible new target for age-related disease.

INTRODUCTION: Apoptosis plays an important role in age-related disease, and prostate apoptosis response-4 (PAR-4) is a novel apoptosis-inducing factor that regulates apoptosis in most cells. Recent studies suggest that PAR-4 plays an important role in the progression of many age-related diseases. This review highlights the significance of PAR-4 and builds a strong case supporting its role as a possible therapeutic target in age-related disease. AREAS COVERED: This review covers the advancements over the last 15 years with respect to PAR-4 and its significance in age-related disease. Additionally, it provides knowledge regarding the significance of PAR-4 in age-related disease as well as its role in apoptotic signaling pathways, endoplasmic reticulum (ER) stress, and other mechanisms that may induce age-related disease. EXPERT OPINION: PAR-4 may be a potential therapeutic target that can trigger selective apoptosis in cancer cells. It is induced by ER stress and increased ER stress, and it is involved in the activity of the dopamine D2 receptor. Abnormal expression of PAR-4 may be associated with cardiovascular disease and diabetes. PAR-4 agonists and inhibitors must be identified before gene therapy can commence.

Rapid Analysis for Fingerprint of Euryales Semen by Near Infrared Spectroscopy / 医药导报

Objective To authenticate Euryales semen collected from seventeen regions by NIR fingerprint spectra and to establish a rapid analysis method. Methods Spectra were collected by VARIAN CARY5000 ultraviolet visible near infrared spectrophotometer,with correlation and origin clustering method for analysis by using Origin 7. 5 and SPSS 18. 0 software. Results The correlation of peaks for Euryales semen from 17 localities were significant, while the regions were distinguished clearly. Conclusion It is indicated that the method is rapid, lossless, and it can be applied to authenticate Euryales from different regions,which provides reference to rapid inspection of Chinese medicines.

Identification of Euryales Semen and Its Closely Related Species Using ITS2 Barcode / 世界科学技术-中医药现代化

Objective: To identify Euryales Semen and its closely related species using the ITS2 barcode. Method:The total genomic DNAs were extracted from twenty samples of Euryales Semen and its closely related species. The ITS2 regions of the samples were amplified and bidirectional sequenced. Obtained sequences were submitted to the GenBank with Sequin 12.3. ITS2 sequences of 102 samples belonging to thirty species were downloaded from GenBank. The 122 ITS2 sequences were aligned and the genetic distances were analyzed with MEGA 5.1. Identification analyses were performed using BLAST1 and nearest distance methods, and were presented intuitively by constructing neighbor-joining (NJ) tree. Result: The length of ITS2 region of Euryales Semen was 214 bp, which was only one haplotype. There was significant divergence of the ITS2 regions among the samples. The NJ tree showed that Euryales Semen could be obviously differed from its closely related species, which had good 408 monophyly. Conclusion: ITS2 regions as a DNA barcode can stably and accurately distinguish Euryales Semen from its closely related species and also provide a new technique to ensure clinical safety in utilization of tradi-tional Chinese medicines. The new exploration could broaden the application of DNA barcoding technology in identification of Traditional Chinese Medicine.

Molecular cloning of farnesyl pyrophosphate synthase from Alisma orientale (Sam.) Juzep. and its distribution pattern and bioinformatics analysis / 药学学报

Triterpenes, which have large application potential in the treatment of cancer, are the main active components of genuine medicinal material Alisma orientale (Sam.) Juzep. Farnesyl pyrophosphate synthase (FPPS) is one of the important rate-limiting enzymes in the synthetic pathway of triterpenes. In this study the FPPS full length cDNA of the A. orientale, was cloned via homology-based cloning approach and rapid amplification of cDNA ends (RACE). The full length of the FPPS cDNA was 1 531 bp (accession no. HQ724508), which contained a full 1 032 bp ORF that encoded 343 amino acids. The deduced protein sequence exhibited five conserved motifs, two of which is riched of Asp (DDXXD). The result of real-time quantitative PCR (QRT-PCR) showed that FPPS gene was expressed in different organs of A. orientale. The expression increased from October to the first ten-day period of December, and then decreased. The FPPS gene expression was higher in leaves but lower in leafstalk, tuber and root. HPLC analysis of active components 23-acetyl-alismol B of A. orientale. during different periods indicated that its change trend should be consistent with FPPS gene expression. It can be primarily deduced that FPPS gene should be an important control point in the synthetic pathway of Alisma terpenes. This study may facilitate the quality of medicinal plants through gene engineering in the future.