Enhancing the treatment of metabolic syndrome with integrative medicine

Metabolic syndrome, with the main clinical manifestations of obesity, dyslipidemia, elevated blood pressure, and elevated blood glucose levels, has become an increasingly prevalant global public health concern. Metabolic syndrome is a convergence of multiple risk factors related to cardiovascular disease. When the concept of metabolic syndrome was initially proposed, some researchers thought the concept was unnecessary, since there were already measures in place to describe the separate cardiovascular risk factors such as dyslipidemia, hypertension and diabetes. However, a large number of epidemiological investigations confirmed that even if blood glucose or blood pressure did not reach the cutoff point of the diseases,

Effects of Chinese herbal medicine Yiqi Huaju Formula on hypertensive patients with metabolic syndrome:a randomized,placebo-controlled trial

BACKGROUND： Patients with hypertension coupled with metabolic syndrome （MetS） are among the high risk population in cardiovascular and cerebrovascular diseases. To reduce the prevalence of cardiovascular and cerebrovascular diseases, it is essential to appropriately control b^ood pressure together with other cardiovascular risk factors. OBJECTIVE： The current study was designed to investigate the therapeutic effects on blood pressure, blood pressure variability and other cardiovascular risk factors by giving Yiqi Huaju Formula, a compound traditional Chinese herbal medicine, in addition to routine treatment to hypertensive patients coupled with MetS. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： A total of 43 patients with hypertension coupled with MetS were recruited into this study. The enrolled patients were randomly divided into the Chinese herbal formula group （anti-hypertensive drugs plus Yiqi Huaju Formula, CHF） and the control group （anti-hypertensive drugs plus placebo）. The CHF group enrolled 22 patients while the control group received 21 cases. Treatments were given for 12 weeks in both groups. MAIN OUTCOME MEASURES： Parameters examined include 24-hour ambulatory blood pressure monitoring, body mass index, waist circumference, waist-to-hip ratio, homeostatic model assessment for insulin resistance （HOMA-IR）, fasting glycosylated hemoglobin （HbAlc）, fasting plasma glucose, 2-hour postprandial plasma glucose （PPG）, fasting plasma insulin, serum lipid, etc. RESULTS： Compared with the control group, the CHF group had significant improvement （P〈0.01） in anthropometric parameters, FPG, HOMA-IR, blood pressure amplitude, blood pressure variability and blood pressure load. CONCLUSION： This study showed that integrated traditional Chinese and Western medicine treatment can achieve better results in controlling blood pressure as well as other cardiovascular risk factors. The mechanism of controlling of blood pressure may be associated with the improvement of insulin sensitivity due to the Yiqi Huaju intervention. TRIAL REGISTRATION IDENTIFIER： ChiCTR-TRC-11001633.

Effects of Chinese herbal medicine Yiqi Huaju Qingli Formula in metabolic syndrome patients with microalbuminuria:a randomized placebo-controlled trial

BACKGROUND： Microalbuminuria （MAU） is a key component of metabolic syndrome （MetS） and is an early sign of diabetic nephropathy as well. Although routine Western medicine treatments are given to MetS patients to control high blood pressure, hyperglycemia and dyslipidemia, some patients still experience progressive renal lesions and it is necessary to modify and improve the treatment strategy for MetS patients. OBJECTIVE： To investigate the efficacy of Yiqi Huaju Qingli Herb Formula, a compound traditional Chinese herbal medicine, in MetS patients with MAU when it is combined with routine Western medicine treatment. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： Sixty patients with MetS were randomized into the Chinese herbal formula group （CHF, Yiqi Huaju Qingli formula treatment in combination with Western medicine） and control group （placebo in combination with Western medicine）. All treatments were administered for 12 weeks. MAIN OUTCOME MEASURES： Urinary microalbumin （MA）, urinary albumin-to-creatinine ratio （UACR）, 24-hour total urine protein （24-hTP）, body mass index （BMI）, waist circumference （WC）, waist-to-hip ratio （WHR）, fasting plasma glucose （FPG）, 2-hour postprandial plasma glucose （2-hPPG）, glycosylated hemoglobin （HbAlc）, homeostasis model assessment for insulin resistance （HOMA-IR）, blood lipid profile and blood pressure were observed. RESULTS： Compared with the control group, CHF treatment significantly decreased BMI （P〈0.05）, WC （P〈0.01） and WHR （P〈0.01）. Both groups had significant decreases in FPG, 2-hPPG, HbAlc, HOMA-IR, MA, and UACR, with CHF treatment showing better effects on these parameters compared with the control treatment （P〈0.05）. Both treatments significantly reduced the levels of total cholesterol, low-density lipoprotein cholesterol and triacylglycerol （TAG）, and a greater reduction in TAG was observed with CHF treatment （P〈0.05）. The level of high-density lipoprotein cholesterol did not change in the control group after treatment （P〉0.05）, whereas it significantly increased with CHF treatment （P〈0.01）. Compared with before the treatment, significant decreases in systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were observed in both groups （P〈0.01）. However, there was no significant difference between the two groups （P〉0.05）. CONCLUSION： Combined treatment ofYiqi Huaju Qingli Formula and Western medicine significantly alleviated MAU, which may correlate with the improvement of insulin sensitivity and glucose and lipid metabolism. TRIAL REGISTRATION IDENTIFIER： This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-11001633.

Overview of Research Trends in Precious Chinese Medicines

Introduction Traditional Chinese medicine(TCM)has continued through centuries to this day since the ancient times and has contributed greatly to the well-being maintenance and disease treatment in China.[1-3]Before the ushering in of Western medicine into China in the 19th century,TCM had been the major healthcare and medical modality in Chinese communities.[4]This ancient art of healing has not diminished over time;conversely,it is now widely accepted by patients both in China and around the world owing to the shift of the disease spectrum and the rise of the“return to nature”paradigm.Moreover,TCM is attracting increasing attention from research circle worldwide.[5]At present,TCM is used in approximately 45%of the world’s countries,and a large amount of Chinese medicine raw materials is exported from China,and some of these Chinese medicines are collected directly from the wild.[6,7]Owing to the popularity of Chinese medicine around the world,the natural resources required for Chinese medicine production can hardly meet the rapidly increasing demand.Wild herbal resources are decreasing by approximately 30%every year.[5,8,9].

A Review on the Research of Precision Medicine for Cancer Based on the Integration of Traditional Chinese and Western Medicine

Objective:To summarize and expound the general situation of precision medicine for cancer according to the current international research hot spots and treatment frontiers of cancer.Methods:This article makes an inventory from five aspects of treatment methods,detection technology,new drug research and development,information data and traditional Chinese medicine,"from point to surface","from outside to inside"and"integration of Chinese and Western medicine",to explore the whole picture of tumor treatment and research.Results:With the rapid development of tumor precision medicine in recent years,the tumor treatment methods have been developed from single to multiple.The research technology has been changed from macro to micro.The therapeutic drugs have been changed from systemic chemotherapy to targeted therapy,immunotherapy and other technologies.The treatment concept has been changed from local to overall.And the integrated treatment methods of traditional Chinese and Western medicine have brought a new chapter to tumor treatment.Conclusion:Through a series of new technologies,new methods and new concepts,tumor precision medicine promotes the treatment of tumors with integrated Chinese and Western medicine into a new chapter.

Biomimetic Integrated Nanozyme for Flare and Recurrence of Gouty Arthritis

Flare and multiple recurrences pose significant challenges in gouty arthritis.Traditional treatments provide temporary relief from inflammation but fail to promptly alleviate patient pain or effectively prevent subsequent recurrences.It should also be noted that both anti-inflammation and metabolism of uric acid are necessary for gouty arthritis,calling for therapeutic systems to achieve these two goals simultaneously.In this study,we propose a biomimetic integrated nanozyme,HMPB-Pt@MM,comprising platinum nanozyme and hollow Prussian blue.It demonstrates anti-inflammatory properties by eliminating reactive oxygen species and reducing infiltration of inflammatory macrophages.Additionally,it rapidly targets inflamed ankles through the camouflage of macrophage membranes.Furthermore,HMPB-Pt@MM exhibits urate oxidase-like capabilities,continuously metabolizing locally elevated uric acid concentrations,ultimately inhibiting multiple recurrences of gouty arthritis.In summary,HMPB-Pt@MM integrates ROS clearance with uric acid metabolism,offering a promising platform for the treatment of gouty arthritis.

Role of deubiquitinase JOSD2 in the pathogenesis of esophageal squamous cell carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.

Huoxue Tongjiang decoction-resisted reflux esophagitis by activation stem cell factor/c-kit/interstitial cell of cajal pathway and regulating the T-helper 17/regulatory T-cells balance in rats

Background:Huoxue Tongjiang decoction(HXTJD)is an effective prescription for treating reflux esophagitis(RE).We investigated the effects of HXTJD on esophageal motility and mucosal inflammation in a rat RE model.Methods:Chemical composition of HXTJD was analyzed by ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry(MS).The change rates of mean contraction tension forces,mean amplitudes,and mean frequencies for the lower esophageal sphincter(LES)were recorded using the isolated tissue bath system,mechanical tension transducer,and PowerLab physiological recorder.After weighing the stomach,the phenol red labeling method was used to measure the gastric emptying rate.The LES ultrastructure was observed through transmission electron microscopy.Immunofluorescence and western blotting were used to detect the number of interstitial cells of Cajal(ICC)and the expression levels of c-kit protein,connexin43(Cx43),and stem cell factor(SCF).Flow cytometric analysis and enzyme-linked immunosorbent assay were conducted to detect the percentages of T helper 17(Th17)cells and regulatory T(Treg)cells and the serum concentrations of interleukin 6(IL-6),interleukin 17(IL-17),and interleukin 10(IL-10)in the rats.Results:We identified 28 chemical constituents in HXTJD.Regarding esophageal motility,we revealed that HXTJD increased the mean contraction tension forces,mean amplitudes,and mean frequency change rate of LES and the gastric emptying rate;decreased stomach weight;and improved the LES ultrastructure.Additionally,HXTJD increased the number of ICC-positive cells,and c-kit,Cx43,and SCF expression levels.Regarding esophageal inflammation,HXTJD significantly decreased the percentage of Th17 cells,and IL-6 and IL-17 concentrations,and increased the percentage of Treg cells and IL-10 concentration.Conclusion:HXTJD was found to be efficacious in the rat RE model.It may promote esophageal motility and alleviate the inflammatory response by activating the SCF/c-kit/ICC pathway and regulating the Th17/Treg cell balance.

Qingyi decoction attenuates intestinal epithelial cell injury via the calcineurin/nuclear factor of activated T-cells pathway

BACKGROUND Recent studies have demonstrated that dysfunction of the intestinal barrier is a significant contributing factor to the development of severe acute pancreatitis(SAP).A stable intestinal mucosa barrier functions as a major anatomic and functional barrier,owing to the balance between intestinal epithelial cell(IEC)proliferation and apoptosis.There is some evidence that calcium overload may trigger IEC apoptosis and that calcineurin(CaN)/nuclear factor of activated Tcells(NFAT)signaling might play an important role in calcium-mediated apoptosis.AIM To investigate the potential mechanisms underlying the therapeutic effect of Qingyi decoction(QYD)in SAP.METHODS A rat model of SAP was created via retrograde infusion of sodium deoxycholate.Serum levels of amylase,tumor necrosis factor(TNF-α),interleukin(IL)-6,D-lactic acid,and diamine oxidase(DAO);histological changes;and apoptosis of IECs were examined in rats with or without QYD treatment.The expression of the two subunits of CaN and NFAT in intestinal tissue was measured via quantitative realtime polymerase chain reaction and western blotting.For in vitro studies,Caco-2 cells were treated with lipopolysaccharide(LPS)and QYD serum,and then cell viability and intracellular calcium levels were detected.RESULTS Retrograde infusion of sodium deoxycholate increased the severity of pancreatic and intestinal pathology and the levels of serum amylase,TNF-α,and IL-6.Both the indicators of intestinal mucosa damage(D-lactic acid and DAO)and the levels of IEC apoptosis were elevated in the SAP group.QYD treatment reduced the serum levels of amylase,TNF-α,IL-6,D-lactic acid,and DAO and attenuated the histological findings.IEC apoptosis associated with SAP was ameliorated under QYD treatment.In addition,the protein expression levels of the two subunits of CaN were remarkably elevated in the SAP group,and the NFATc3 gene was significantly upregulated at both the transcript and protein levels in the SAP group compared with the control group.QYD significantly restrained CaN and NFATc3 gene expression in the intestine,which was upregulated in the SAP group.Furthermore,QYD serum significantly decreased the LPS-induced elevation in intracellular free Ca^(2+)levels and inhibited cell death.CONCLUSION QYD can exert protective effects against intestinal mucosa damage caused by SAP and the protective effects are mediated,at least partially,by restraining IEC apoptosis via the CaN/NFATc3 pathway.

Hypoxia inducible factor-1α mediates protective effects of ischemic preconditioning on ECV-304 endothelial cells

AIM: To investigate whether hypoxia inducible factor-1α (HIF-1α) is linked to the protective effects of ischemic preconditioning (IP) on sinusoidal endothelial cells against ischemia/reperfusion injury. METHODS: Sinusoidal endothelial cell lines ECV-304 were cultured and divided into four groups: control group, cells were cultured in complete DMEM medium; cold anoxia/warm reoxygenation (A/R) group, cells were preserved in a 4℃ UW solution in a mixture of 95% N2 and 5% CO2 for 24 h; anoxia-preconditioning (APC) group, cells were treated with 4 cycles of short anoxia and reoxygenation before prolonged anoxia- preconditioning treatment; and anoxia-preconditioning and hypoxia inducible factor-1α (HIF-1α) inhibitor (I-HIF-1) group, cells were pretreated with 5 μm of HIF-1α inhibitor NS398 in DMEM medium before subjected to the same treatment as group APC. After the anoxia treatment, each group was reoxygenated in a mixture of 95% air and 5% CO2 incubator for 6 h. Cytoprotections were evaluated by cell viabilities from Trypan blue, lactate dehydrogenase (LDH) release rates, and intracellular cell adhesion molecule-1 (ICAM-1) expressions. Expressions of HIF-1α mRNA and HIF-1α protein from each group were determined by the RT-PCR method and Western blotting, respectively. RESULTS: Ischemia preconditioning increased cell viability, and reduced LDH release and ICAM-1 expressions. Ischemia preconditioning also upregulated the HIF-1α mRNA level and HIF-1α protein expression. However, all of these changes were reversed by HIF-1α inhibitor NS398.CONCLUSION: Ischemia preconditioning effectively inhibited cold hypoxia/warm reoxygenation injury to endothelial cells, and the authors showed for the first time HIF-1α is causally linked to the protective effects of ischemic preconditioning on endothelial cells.

Role of miR-124 in the regulation of retinoic acid-induced Neuro-2A cell differentiation

Retinoic acid can cause many types of cells,including mouse neuroblastoma Neuro-2 A cells,to differentiate into neurons.However,it is still unknown whether microRNAs(miRNAs)play a role in this neuronal differentiation.To address this issue,real-time polymerase chain reaction assays were used to detect the expression of several differentiation-related miRNAs during the differentiation of retinoic acid-treated Neuro-2 A cells.The results revealed that miR-124 and miR-9 were upregulated,while miR-125 b was downregulated in retinoic acid-treated Neuro-2 A cells.To identify the miRNA that may play a key role,miR-124 expression was regulated by transfection of miRNA mimics or inhibitors.Morphological analysis results showed that inhibition of miR-124 expression reversed the effects of retinoic acid on neurite outgrowth.Moreover,miR-124 overexpression alone caused Neuro-2 A cells to differentiate into neurons,and its inhibitor could block this effect.These results suggest that miR-124 plays an important role in retinoic acid-induced differentiation of Neuro-2 A cells.

Prunus sunhangii: A new species of Prunus from central China

A new species of Rosaceae from Central China, Prunus sunhangii D. G. Zhang & T. Deng, sp. nov., is described and illustrated. The new species is placed in Prunus subgenus Cerasus by flower and fruit characteristics. It is most similar to Prunus cerasoides, but differs by having longitudinally 2-lobed apical petals, an acuminate leaf apex, 17—25 stamens, white petals, dark black drupes, brown hypanthium, and different phenology. The phylogenetic placement of this species was assessed based on morphological and molecular data. Molecular analysis(cp DNA + ITS) corroborated its placement in subgenus Cerasus,specifically Prunus section Serrula.

Clinical implication of FDG uptake of bone marrow on PET/CT in gastric cancer patients with surgical resection

AIM To determine the relationship between F-18 fluorodeoxyglucose(FDG) uptake of bone marrow(BM) on positron emission tomography/computed tomography(PET/CT) and clinical factors and to assess the prognostic value of FDG uptake of BM in gastric carcinoma.METHODS We retrospectively enrolled 309 gastric cancer patients who underwent staging FDG PET/CT and curative surgical resection. FDG uptake of primary tumor was visually classified as positive or negative FDG uptake. Mean FDG uptake of BM(BM SUV) and BM-to-liver uptake ratio(BLR) were measured. The relationships of BM SUV or BLR with clinical factors were evaluated. The prognostic values of BM SUV, BLR, and other clinical factors for predicting recurrence-free survival(RFS) and overall survival(OS) were assessed.RESULTS Of 309 patients, 38 patients(12.3%) experienced cancer recurrence and 18 patients(5.8%) died. Patients with advanced gastric cancer, positive FDG uptake, and recurrence had higher values of BM SUV and BLR than those with early gastric cancer, negative FDG uptake, and no recurrence(P < 0.05). BM SUV and BLR were significantly correlated with hemoglobin level, neutrophil-to-lymphocyte ratio, and platelet-tolymphocyte ratio(P < 0.05). On multivariate analysis, multiple tumors, T stage, lymph node metastasis, tumor involvement of resection margin, and BLR were significantly associated with RFS(P < 0.05). T stage, lymph node metastasis, hemoglobin level, and BLR were significantly associated with OS(P < 0.05). CONCLUSION BLR on PET/CT was an independent prognostic factor for RFS and OS in gastric cancer patients with curative surgical resection.

Negundoside,an irridiod glycoside from leaves of Vitex negundo,protects human liver cells against calcium-mediated toxicity induced by carbon tetrachloride

AIM： To evaluate the protective effect of 2′-p-hydroxy benzoylmussaenosidic acid [negundoside （NG）, against carbon tetrachloride （CCl4）-induced toxicity in HUH-7 cel Is.METHODS： CCI4 is a well characterized hepatotoxin, and inducer of cytochrome P450 2E1 （CYP2E1）-mediated oxidative stress. In addition, lipid peroxidation and accumulation of intracellular calcium are important steps in the pathway involved in CCl4 toxicity. Liver cells （HUH-7） were treated with CCI4, and the mechanism of the cytoprotective effect of NG was assessed. Silymarin, a known hepatoprotective drug, was used as control. RESULTS： NG protected HUH-7 cells against CCl4 toxicity and loss of viability without modulating CYP2E1 activity. Prevention of CCl4 toxicity was associated with a reduction in oxidative damage as reflected by decreased generation of reactive oxygen species （ROS）, a decrease in lipid peroxidation and accumulation of intracellular Ca^2＋ levels and maintenance of intracellular glutathione homeostasis. Decreased mitochondrial membrane potential （MMP）, induction of caspases mediated DNA fragmentation and cell cycle arrest, as a result of CCl4 treatment, were also blocked by NG. The protection afforded by NG seemed to be mediated by activation of cyclic adenosine monophosphate （cAMP） synthesis and inhibition of phospholipases （cPLA2）. CONCLUSION： NG exerts a protective effect on CYP2E1-dependent CCl4 toxicity via inhibition of lipid peroxidation, followed by an improved intracellular calcium homeostasis and inhibition of Ca^2＋-dependent proteases.

Isolation, purification and characterization of carboxymethyl cellulase (CMCase) from endophytic Fusarium oxysporum producing podophyllotoxin

Endophytic fungus Fusarium oxysporum is a rich source of cellulases. In the present study, the highest activity was reported at 28 ° C, pH 5.6 with 2% Carboxymethyl cellulose (CMC) as carbon source. CMC was purified using Sephadex G and DEAE cellulose chromatography to 15.9 folds and the molecular weight was determined to be 84 kDa by SDS-PAGE analysis and was subsequently characterized. The purified enzyme was stable over the pH range from 4.0 to 8.0 and at temperatures below 50 ° C. The enzyme was highly active on CMC and reduced or no activity on Avicel, cellobiose and it was suggested to be CMCase/endoglucanase. The activity of endoglucanase was enhanced in the presence of MgCl2, CoCl2, FeCl3, CaCl2, FeCl2 and intensive to HgCl2. The purified enzyme showed its optimum activity at pH 5.0 - 6.0 and was quite stable at 50 ° C for 30 min and retained 45% of original activity.

Selective ablation of type 3 adenylyl cyclase in somatostatin-positive interneurons produces anxiety-and depression-like behaviors in mice

BACKGROUND Major depressive disorder(MDD)is a highly disabling psychiatric syndrome associated with deficits of specific subpopulations of cortical GABAergic interneurons;however,the underlying molecular mechanism remains unknown.Type 3 adenylyl cyclase(ADCY3,AC3),which is important for neuronal excitability,has been implicated in MDD in a genome-wide association study in humans.Moreover,a study reported that ablation of AC3 in mice caused similar symptoms as MDD patients.AIM To determine if disruption of the AC3 gene in different subtypes of GABAergic interneurons of mice causes depression-like behaviors.METHODS Using immunohistochemistry,we investigated the expression of AC3 in two major subtypes GABAergic interneurons:Somatostatin-positive(SST+)and parvalbumin-positive(PV+)neurons.Genetic manipulations were used to selectively disrupt AC3 expression in SST+or PV+interneurons.A series of behavior tests including rotarod test,open field test(OFT),elevated plus maze test(EPM),forced swimming test(FST),and tail suspension test(TST)were used to evaluate the motor ability,anxiety-and depression-like behaviors,respectively.RESULTS Our results indicate that approximately 90.41%of SST+and 91.22%of PV+interneurons express AC3.After ablation of AC3 in SST+interneurons,the mice spent comparable time in the center area in OFT,but significantly less time in the open arms and low frequency of entries to the open arms in EPM.Furthermore,these mice showed prolonged immobility in FST and more freezing in TST.However,there were no significant changes in these behaviors after specific disruption of AC3 in PV+interneurons.CONCLUSION This study indicates that ablation of AC3 in SST+interneurons of mice increases anxiety-and depression-like behaviors in mice,supporting the general hypothesis that decreased AC3 activity may play a role in human depression.

Bioprospection of marine actinomycetes: recent advances,challenges and future perspectives

In exploring new sources for economically important products, marine environment draws particular attention because of its remarkable diversity and extreme conditions;it is known to produce metabolic products of great value. It represents untapped source for the discovery of novel secondary metabolites with varying potential such as antibiotic, anti-tumor, antifouling and cytotoxic properties. Marine actinomycetes distributed throughout the marine environment from shallow to deep sea sediments have proved to be a finest source for this discovery. Secondary metabolites derived from marine actinomycetes have proved their worth in industries based on the research on their properties and wide range applications. Spotlight of the review is range of marine based actinomycetes products and significant research in this field. This shows the capability of marine actinomycetes as bioactive metabolite producers. Additionally, the present review addresses some effective and novel approaches of procuring marine microbial compounds utilizing the latest screening strategies of drug discovery from which traditional resources such as marine actinobacteria has decreased due to declining yields. The aim is in the context of promoting fruitful and profitable results in the near future. The recent surfacing of new technologies for bioprospection of marine actinomycetes are very promising, resulting in high quality value added products, and will be de?ning a new era for bioactive compounds with medical and biotechnological applications.

Effect of Jianpi Jiedu Recipe on angiogenesis and the PTEN/PI3K/AKT signaling pathway in the course of Helicobacter pylori-induced gastric cancer in C57BL/6 mice

Objective： To reveal the effect of Jianpi Jiedu recipe （JPJDR） on angiogenesis and the PTEN （Phosphatase and tensinhomolog deleted on chromosome ten）/PI3K/AKT signaling pathway in the course of H. pylori infection-inducedcarcinogenesis of gastric mucosa in C57BL/6 mice. Methods： Two-hundred C57BL/6 mice were randomly divided intofive groups （control group, model group, JPJDR low-dose group, JPJDR medium-dose group, and JPJDR high-dosegroup）, 40 in each group. A mouse model of gastric cancer, induced by H. pylori standard strain infection, wasestablished. The mice of JPJDR low-dose, middle-dose, and high-dose groups were intragastrically administered 250,500, and 1000 mg/kg JPJDR per day, respectively. After 72 weeks, the H. pylori infection in gastric mucosa of the micewas analyzed by rapid urease test; the pathological changes in the gastric mucosa of mice were assessed byhistopathological examination, and micro-vessel density （MVD）, vascular endothelial growth factor （VEGF）, andPTEN/PI3K/AKT levels were determined. Results： The incidence of gastric cancer in each group （control group, modelgroup, JPJDR low-dose, medium-dose, high-dose group） was 0%, 26.3%, 13.2%, 10%, and 7.5% respectively. Theincidence of gastric cancer in the Chinese medicine group was significantly lower than that of the model group （P =0.020, P = 0.023, P = 0.007）. The expression of MVD and VEGF in the model group was significantly higher than thatin the control group （P = 0.002, P 〈 0.001）, while the expression of MVD and VEGF decreased in the Chinese medicinegroup. The expression of p-PTEN and p-AKT in the model group was significantly higher than that in the control group（All P 〈 0.001）, while Chinese medicine could reduce the expression of p-PTEN and p-AKT to varying extents.Conclusion： Long-term infection of C57BL/6 mice with H. pylori induces gastric carcinogenesis, by increasing gastricmucosal MVD, promoting the expression of VEGF, inhibiting the activity of PTEN, and activating the PI3K/AKTsignaling pathway. JPJDR can reduce the infection rate of H. pylori in mouse gastric mucosa, inhibit the expression ofMVD and VEGF, and reduce the inactivation of PTEN.

Adenylate cyclase activator forskolin alleviates intracerebroventricular propionic acid-induced mitochondrial dysfunction of autistic rats

Neuronal mitochondrial dysfunction increases inflammatory mediators and leads to free radical generation and anti-oxidant enzymatic alterations,which are major neuropathological hallmarks responsible for autism.Mitochondrial dysfunction in autism is associated with decreased ATP levels due to reduced levels of cyclic adenosine monophosphate.Rat models of autism were established by intracerebroventricular injection of propionic acid.These rat models had memory dysfunction,decreased muscle coordination and gait imbalance.Biochemical estimation of propionic acid-treated rats showed changes in enzyme activity in neuronal mitochondrial electron transport chain complexes and increases in pro-inflammatory cytokines,oxidative stress and lipid biomarkers.Oral administration of 10,20 and 30 mg/kg adenylate cyclase activator forskolin for 15 days reversed these changes in a dose-dependent manner.These findings suggest that forskolin can alleviate neuronal mitochondrial dysfunction and improve neurological symptoms of rats with autism.This study was approved by the RITS/IAEC,SIRSA,HARYANA on March 3,2014(approval No.RITS/IAEC/2014/03/03).

Comparative analysis of diverse toxins from a new pharmaceutical centipede,Scolopendra mojiangica

As the oldest venomous animals,centipedes use their venom as a weapon to attack prey and for protection.Centipede venom,which contains many bioactive and pharmacologically active compounds,has been used for centuries in Chinese medicine,as shown by ancient records.Based on comparative analysis,we revealed the diversity of and differences in centipede toxin-like molecules between Scolopendra mojiangica,a substitute pharmaceutical material used in China,and S.subspinipes mutilans.More than 6000 peptides isolated from the venom were identified by electrospray ionization-tandem mass spectrometry(ESI-MS/MS)and inferred from the transcriptome.As a result,in the proteome of S.mojiangica,246 unique proteins were identified:one in five were toxin-like proteins or putative toxins with unknown function,accounting for a lower percentage of total proteins than that in S.mutilans.Transcriptome mining identified approximately 10 times more toxin-like proteins,which can characterize the precursor structures of mature toxinlike peptides.However,the constitution and quantity of the toxin transcripts in these two centipedes were similar.In toxicity assays,the crude venom showed strong insecticidal and hemolytic activity.These findings highlight the extensive diversity of toxin-like proteins in S.mojiangica and provide a new foundation for the medical-pharmaceutical use of centipede toxin-like proteins.