Total Saponins of Dioscorea Mitigate Nonalcoholic Steatohepatitis in Mice by Regulating AMPK/SREBP-1c/ACC Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the role and mechanism of total saponins of Dioscorea （TSD） in mitigating nonalcoholic steatohepatitis （NASH） in mice. MethodForty-eight C57BL/6J mice were randomized into a normal group and a modeling group. The mice for modeling were fed with a high-fat and high-cholesterol diet + 20% fructose solution for 16 weeks and randomized into model， atorvastatin （4 mg·kg-1·d-1）， and high-， medium-， and low-dose （200， 60， and 20 mg·kg-1·d-1） TSD groups. The mice were administrated with corresponding doses of drugs by gavage for 8 weeks. The mouse activity， liver index， levels of total cholesterol （TC）， triglycerides （TG）， and free fatty acids （FFAs） in the liver， and levels of TC， TG， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， γ-glutamyl transferase （GGT）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the serum were measured. Hematoxylin-eosin staining， Masson staining， oil red O staining， and transmission electron microscopy were employed to observe the pathological changes， lipid accumulation， and morphological changes of liver ultrastructure. Western blot was employed to determine the protein levels of AMP-activated protein kinase （AMPK）， sterol regulatory element-binding protein-1c （SREBP-1c）， acetyl-CoA carboxylase （ACC）， and phosphorylated ACC （p-ACC） in the liver tissue. ResultCompared with the normal group, the activity of mice in the model group decreased(P<0.05， P<0.01), the levels of TC, TG, FFA and serum TC, TG, ALT, AST, GGT, IL-1β and TNF-α, liver coefficient and liver pathology scores were significantly increased, the expression of p-AMPK/AMPK and p-ACC proteins in liver tissues was significantly reduced, and the expressions of SREBP-1c and ACC proteins were significantly increased (P<0.01). Compared with the model group， atorvastatin increased the mouse activity （P<0.05）， while each dose of TSD caused no significant changed in the mouse activity. The levels of TC, TG, FFA in liver and serum TC, TG, ALT, AST, GGT, IL-1β, TNF-α, liver coefficient and liver pathological score in TSD and atorvastatin groups were significantly decreased, and the expressions of p-AMPK/AMPK and p-ACC in liver tissue were significantly increased. The expressions of SREBP-1c and ACC were significantly decreased (P<0.05,P<0.01). ConclusionTSD may alleviate NASH in mice by regulating the AMPK/SREBP-1c/ACC signaling pathway to reduce lipid synthesis.

Punicalagin inhibits hepatic lipid deposition in obese mice via AMPK/ACC pathway / 中国中药杂志

Hepatic lipid deposition is one of the basic manifestations of obesity, and nowadays pharmacological treatment is the most important tool. Punicalagin(PU), a polyphenol derived from pomegranate peel, is a potential anti-obesity substance. In this study, 60 C57BL/6J mice were randomly divided into a normal group and a model group. After establishing a model of simple obesity with a high-fat diet for 12 weeks, the successfully established rat models of obesity were then regrouped into a model group, an orlistat group, a PU low-dose group, a PU medium-dose group, and a PU high-dose group. The normal group was kept on routine diet and other groups continued to feed the high-fat diet. The body weight and food intake were measured and recorded weekly. After 8 weeks, the levels of the four lipids in the serum of each group of mice were determined by an automatic biochemical instrument. Oral glucose tole-rance and intraperitoneal insulin sensitivity were tested. Hemoxylin-eosin(HE) staining was applied to observe the hepatic and adipose tissues. The mRNA expression levels of peroxisome proliferators-activated receptor γ(PPARγ) and C/EBPα were determined by real-time quantitative polymerase chain reaction(Q-PCR), and the mRNA and protein expression levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), anterior cingulate cortex(ACC), and carnitine palmitoyltransferase 1A(CPT1A) were determined by Western blot. Finally, the body mass, Lee's index, serum total glyceride(TG), serum total cholesterol(TC), and low-density lipoprotein cholesterol(LDL-C) levels were significantly higher and high-density lipoprotein cholesterol(HDL-C) levels were significantly lower in the model group as compared with the normal group. The fat deposition in the liver was significantly increased. The mRNA expression levels of hepatic PPARγ and C/EBPα and the protein expression level of ACC were increased, while the mRNA and protein expression levels of CPT-1α(CPT1A) and AMPK were decreased. After PU treatment, the above indexes of obese mice were reversed. In conclusion, PU can decrease the body weight of obese mice and control their food intake. It also plays a role in the regulation of lipid metabolism and glycometabolism metabolism, which can significantly improve hepatic fat deposition. Mechanistically, PU may regulate liver lipid deposition in obese mice by down-regulating lipid synthesis and up-regulating lipolysis through activation of the AMPK/ACC pathway.

Knockdown of ACC1 promotes migration of esophageal cancer cell / 中华肿瘤杂志

Objective: To investigate the effect of acetyl-CoA carboxylase 1 (ACC1) knockdown on the migration of esophageal squamous cell carcinoma (ESCC) KYSE-450 cell and underlying mechanism. Methods: Lentiviral transfection was conducted to establish sh-NC control cell and ACC1 knocking down cell (sh-ACC1). Human siRNA HSP27 and control were transfected by Lipo2000 to get si-HSP27 and si-NC. The selective acetyltransferase P300/CBP inhibitor C646 was used to inhibit histone acetylation and DMSO was used as vehicle control. Transwell assay was performed to detect cell migration. The expression of HSP27 mRNA was examined by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and the expressions of ACC1, H3K9ac, HSP27 and epithelial-mesenchymal transition-related proteins E-cadherin and Vimentin were detected by western blot. Results: The expression level of ACC1 in sh-NC group was higher than that in sh-ACC1 group (P<0.01). The number of cell migration in sh-NC group was (159.00±24.38), lower than (361.80±26.81) in sh-ACC1 group (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-NC group were statistically significant compared with sh-AAC1 group (P<0.05). The migrated cell number in sh-NC+ si-NC group was (189.20±16.02), lower than (371.60±38.40) in sh-ACC1+ si-NC group (P<0.01). The migrated cell number in sh-NC+ si-NC group was higher than that in sh-NC+ si-HSP27 group (152.40±24.30, P<0.01), and the migrated cell number in sh-ACC1+ si-NC group was higher than that in sh-ACC1+ si-HSP27 group (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-NC+ si-NC group were significantly different from those in sh-ACC1+ si-NC and sh-NC+ si-HSP27 groups (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-ACC1+ si-NC group were significantly different from those in sh-ACC1+ si-HSP27 group (P<0.01). After 24 h treatment with C646 at 20 μmmo/L, the migrated cell number in sh-NC+ DMSO group was (190.80±11.95), lower than (395.80±17.10) in sh-ACC1+ DMSO group (P<0.01). The migrated cell number in sh-NC+ DMSO group was lower than that in sh-NC+ C646 group (256.20±23.32, P<0.01). The migrated cell number in sh-ACC1+ DMSO group was higher than that in sh-ACC1+ C646 group (87.80±11.23, P<0.01). The protein expressions of H3K9ac, HSP27, E-cadherin and Vimentin in sh-NC+ DMSO group were significantly different from those in sh-ACC1+ DMSO group and sh-NC+ C646 group (P<0.01). The protein expression levels of H3K9ac, HSP27, E-cadherin and Vimentin in sh-ACC1+ DMSO group were significantly different from those in sh-ACC1+ C646 group (P<0.01). Conclusion: Knockdown of ACC1 promotes the migration of KYSE-450 cell by up-regulating HSP27 and increasing histone acetylation.

Effect of ACC oxidase gene AhACOs on salt tolerance of peanut / 生物工程学报

ACC oxidase (ACO) is one of the key enzymes that catalyze the synthesis of ethylene. Ethylene is involved in salt stress response in plants, and salt stress seriously affects the yield of peanut. In this study, AhACO genes were cloned and their functions were investigated with the aim to explore the biological function of AhACOs in salt stress response, and to provide genetic resources for the breeding of salt-tolerant varieties of peanut. AhACO1 and AhACO2 were amplified from the cDNA of salt-tolerant peanut mutant M29, respectively, and cloned into the plant expression vector pCAMBIA super1300. The recombinant plasmid was transformed into Huayu22 by pollen tube injection mediated by Agrobacterium tumefaciens. After harvest, the small slice cotyledon was separated from the kernel, and the positive seeds were screened by PCR. The expression of AhACO genes was analyzed by qRT-PCR, and the ethylene release was detected by capillary column gas chromatography. Transgenic seeds were sowed and then irrigated with NaCl solution, and the phenotypic changes of 21-day-seedings were recorded. The results showed that the growth of transgenic plants were better than that of the control group Huayu 22 upon salt stress, and the relative content of chlorophyll SPAD value and net photosynthetic rate (Pn) of transgenic peanuts were higher than those of the control group. In addition, the ethylene production of AhACO1 and AhACO2 transgenic plants were 2.79 and 1.87 times higher than that of control peanut, respectively. These results showed that AhACO1 and AhACO2 could significantly improve the salt stress tolerance of transgenic peanut.

ROLE OF ACC DEAMINASE PRODUCING PLANT GROWTH PROMOTING RHIZOBACTERIA IN AMELIORATING THE SALINITY STRESS CONDITIONS: A REVIEW

Salinity in agricultural soil is a severe problem that affects the growth and production in numerous crops all over the world. The country's salt?affected land is estimated to be 6.74 million hectares. According to estimates, approximately 10% more land is becoming salinized each year, and by 2050, nearly half of all arable land will be contaminated by salt. Plants may have bacterial companions that shield them from the negative consequences of salt stress (SS). Plant growth?promoting bacteria (PGPR) can minimize the usage of agrochemicals while also improving plant production, nutrition, and biotic–abiotic stress tolerance. The enzyme 1? aminocyclopropane?1?carboxylic acid deaminase (ACCD) is found in certain bacteria and works by degrading ACC (ethylene precursor in higher plants) into ??ketobutyrate and ammonia (NH ), thereby reducing the ACC levels, thus, inhibits excessive biosynthesis of3 ethylene under numerous stress circumstances. This is one of the most effective methods for inducing plant tolerance to SS. The current review highlighted the recent works of ACCD under SS environment. Further, the relevance of reducing the negative effect of ROS and increasing plant development under SS were also discussed. We propose a path for the community to employ beneficial microorganisms to boost agricultural yield and achieve sustainable development by highlighting plant?microbe interactions in this review.

Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is an aggressive human cancer with increasing incidence worldwide. Multiple efforts have been made to explore pharmaceutical therapies to treat HCC, such as targeted tyrosine kinase inhibitors, immune based therapies and combination of chemotherapy. However, limitations exist in current strategies including chemoresistance for instance. Tumor initiation and progression is driven by reprogramming of metabolism, in particular during HCC development. Recently, metabolic associated fatty liver disease (MAFLD), a reappraisal of new nomenclature for non-alcoholic fatty liver disease (NAFLD), indicates growing appreciation of metabolism in the pathogenesis of liver disease, including HCC, thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment. In this review, we introduce directions by highlighting the metabolic targets in glucose, fatty acid, amino acid and glutamine metabolism, which are suitable for HCC pharmaceutical intervention. We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment. Furthermore, opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.

Acetyl-CoA Carboxylase 1 (ACC1) Affects the Proliferation of Clear Cell Renal Cell Carcinoma (ccRCC) by Regulating Cyclin D1/CDK4 / 中国生物化学与分子生物学报

Acetyl-CoA carboxylase (ACC) is the rate limiting enzyme of fatty acid synthesis pathway. Studies have shown that ACC1 is implicated in a variety of metabolic diseases and cancer. However, the role and mechanism of action of ACC1 in clear cell renal cell carcinoma (ccRCC) have not been reported. In this study, 786-O and Caki-1 clear cell renal carcinoma cells were used as research objects to investigate the effect of abnormal expression of ACC1 on their proliferation and unravel the underlying mechanism. Red oil-O-staining results showed that the lipid content of 786-O and Caki-1 cells was significantly higher than that of human kidney 2 (HK2) cells. By searching TCGA database, we found that the expression of ACC1 proteins in ccRCC was significantly higher than that in normal renal tissues (P < 0.001). Plus, ACC1 protein expression in all clinical TNM stages was significantly higher than that in normal tissues, and the higher the expression of ACC1, the higher the pathological grade. Furthermore, high expression of ACC1 mRNA is positively correlated with poor prognosis in ccRCC patients. Western blotting analysis showed that the expression of ACC1 in 786-O and Caki-1 cells was significantly higher than that in HK2 cells. The results of red oil-O-staining showed that knocking down ACC1 could significantly reduce the lipid content of 786-O and Caki-1 cells. The results of CCK-8 assays and clonogenicity analysis showed that knocking down ACC1 could significantly reduce the proliferation and colony forming ability of 786-O and Caki-1 cells. Flow cytometry analysis showed that after knocking down ACC1, the cell cycle was blocked at the G

The 70 thannual scientific sessions of the American College of Cardiology(ACC): Focus on chronic metabolic disease / 中华内分泌代谢杂志

The 70 thannual scientific sessions of the American College of Cardiology(ACC) were held online at Atlanta, USA from May 15 th to 17 th, 2021, covering clinical practice, guideline recommendations, and clinical academic research(especially the late-breaking clinical trial presentation) related to cardiovascular disease(CVD). Diabetes mellitus, as CVD risk equivalent, and obesity are important risk factors for CVD, and fatty liver as a chronic metabolic disease has also been proved to be associated with CVD. This report reviews the research advance and academic perspectives on diabetes and other chronic metabolic diseases.

Study of Serum Uric Acid Level in Patients with Systemic-Essential Hypertension in the Context of New 2017 ACC/AHA High Blood Pressure Clinical Practice Guideline.

Hypertension poses a challenge to public health as well as to the medical science. Final metabolite of purine in humans is uric acid, increased serum level of which is associated with cardio-renal risk, although serum uric acid (SUA) level appears to have different effects on blood pressure (BP), depending on level and how long subjects were exposed. We wanted to study the association between hyperuricemia and hypertension, in various aspects, in the context of new 2017 ACC/ AHA High Blood Pressure Clinical Practice Guidelines.METHODSThe study was conducted in a tertiary care hospital, Agartala, Tripura. It is a case control study. SUA estimation was in 160 hypertensive patients and 160 normotensive controls, by using uricase method. SPSS version 24 was used for data entry and analysis. Chi square test and unpaired t test were used, wherever applicable.RESULTSOut of 320 subjects, who were included in the study, 160 subjects were hypertensive and 160 subjects were normotensive. There was strong association between hypertension and hyperuricemia. Hyperuricemia is more common in males and in patients with stage II hypertension.CONCLUSIONSThe association between hyperuricemia and hypertension, has long been recognized. It remains unresolved whether the association of high uric acid level with high blood pressure is solely because of the underlying renal and metabolic abnormalities. Association of hyperuricemia and hypertension indicated that, hyperuricemia might be a target for the proposed therapeutic evaluation for the prevention of hypertension and provided impetus for the future design research work including interventional studies.

Conditional reprogramming: next generation cell culture

Long-term primary culture of mammalian cells has been always difficult due to unavoidable senescence. Conventional methods for generating immortalized cell lines usually require manipulation of genome which leads to change of important biological and genetic characteristics. Recently, conditional reprogramming (CR) emerges as a novel next generation tool for long-term culture of primary epithelium cells derived from almost all origins without alteration of genetic background of primary cells. CR co-cultures primary cells with inactivated mouse 3T3-J2 fibroblasts in the presence of RHO-related protein kinase (ROCK) inhibitor Y-27632, enabling primary cells to acquire stem-like characteristics while retain their ability to fully differentiate. With only a few years' development, CR shows broad prospects in applications in varied areas including disease modeling, regenerative medicine, drug evaluation, drug discovery as well as precision medicine. This review is thus to comprehensively summarize and assess current progress in understanding mechanism of CR and its wide applications, highlighting the value of CR in both basic and translational researches and discussing the challenges faced with CR.

Comparison of the effect between electroacupuncture and NSAIDs on pain memory based on cAMP/PKA/CREB pathway in anterior cingulate gyrus / 中国针灸

OBJECTIVE@#To observe the direct intervention effects of electroacupuncture (EA) and non-steroid anti-inflammatory drugs (NSAIDs) on pain memory, and to explore their effects on cAMP/PKA/cAMP pathway in anterior cingulate gyrus (ACC).@*METHODS@#Fifty clean healthy male SD rats were randomly divided into a control group, a model group, an indomethacin group, an EA group and a sham EA group, 10 rats in each group. Except the control group, the pain memory model was established in the remaining four groups by twice injection of carrageenan at foot; 0.1 mL of 2%λ-carrageenan was subcutaneously injected at the left foot of rats; 14 days later, when the pain threshold of rats of each group returned to the basic level, the second injection was performed with the same procedure. The rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36) for 30 min; the rats in the indomethacin group was treated with indomethacin intragastric administration with the dose of 3 mg/kg; the rats in the sham EA group was treated with EA without electricity at the point 0.3 mm forward "Zusanli" (ST 36) with the depth of 2 mm for 30 min; the rats in the control group was not given any invention. All the above interventions were performed 5 h, 1 d, 2 d and 3 d after the second injection of 2% λ-carrageenan. The left-side paw withdrawal thresholds (PWT) were observed before the first injection, 4 h, 3 d, 5 d after the first injection, before the second injection and 4 h, 1 d, 2 d, 3 d after the second injection. Three days after the second injection, the number of positive cells of cAMP, p-PKA, p-CREB and the number of positive cells of protein co-expression in the right ACC brain area were detected by immunofluorescence, and the relative protein expression of p-PKA and p-CREB were detected by Western blot.@*RESULTS@#Compared with the control group, the PWTs in the model group decreased significantly 4 h, 3 d and 5 d after the first injection and 1 d, 2 d and 3 d after the second injection (<0.05); compared with the control group, the positive expression of cAMP, p-PKA and p-CREB in the right ACC brain area in the model group increased significantly (<0.05), and the number of positive cells of the co-expression of cAMP/p-PKA and p-PKA/p-CREB also increased significantly (<0.05). Compared with the model group, indomethacin group and sham EA group, the PWTs in the EA group were increased significantly 1 d, 2 d and 3 d after the second injection (<0.05); compared with the model group, indomethacin group and sham EA group, the positive expression of p-PKA and p-CREB in the right ACC brain area in the EA group decreased significantly (<0.05), and the number of positive cells of co-expression of cAMP/p-PKA and p-PKA/p-CREB was decreased significantly (<0.05). Compared with the model group and sham EA group, the positive expression of cAMP in the right ACC brain area was decreased in the EA group (<0.05).@*CONCLUSION@#EA have a direct intervention effect on pain memory, which have significant advantage over NSAIDs in the treatment of chronic pain. The advantage effect of EA on pain memory may be related to the inhibition of cAMP/PKA/CREB pathway in ACC area.

Cytochrome P450 endoplasmic reticulum-associated degradation (ERAD): therapeutic and pathophysiological implications

The hepatic endoplasmic reticulum (ER)-anchored cytochromes P450 (P450s) are mixed-function oxidases engaged in the biotransformation of physiologically relevant endobiotics as well as of myriad xenobiotics of therapeutic and environmental relevance. P450 ER-content and hence function is regulated by their coordinated hemoprotein syntheses and proteolytic turnover. Such P450 proteolytic turnover occurs through a process known as ER-associated degradation (ERAD) that involves ubiquitin-dependent proteasomal degradation (UPD) and/or autophagic-lysosomal degradation (ALD). Herein, on the basis of available literature reports and our own recent findings of as well as experimental studies, we discuss the therapeutic and pathophysiological implications of altered P450 ERAD and its plausible clinical relevance. We specifically (i) describe the P450 ERAD-machinery and how it may be repurposed for the generation of antigenic P450 peptides involved in P450 autoantibody pathogenesis in drug-induced acute hypersensitivity reactions and liver injury, or viral hepatitis; (ii) discuss the relevance of accelerated or disrupted P450-ERAD to the pharmacological and/or toxicological effects of clinically relevant P450 drug substrates; and (iii) detail the pathophysiological consequences of disrupted P450 ERAD, contributing to non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) under certain synergistic cellular conditions.

Plant growth promoting rhizobacteria and their potential as bioinoculants on Pennisetum clandestinum (Poaceae)

Introduction: The sustainable production of pastures has become a fundamental challenge for the livestock sector where research with plant growth-promoting rhizobacteria as a viable solution, has nearly not been reported. Objective: In this study, we aimed to examine the potential to stimulate growth in Pennisetum clandestinum grass using four isolated bacterial strains from soils obtained from a Colombian tropical silvopastoral system. Methods: We previously identified genetically the strains and characterized two plant growth promoting activities. In addition, we evaluated the growth-promoting effect of the strains in Kikuyo grass under greenhouse conditions. Results: We found that the four bacterial strains were phylogenetically associated with Klebsiella sp. (strains 28P and 35P), Beijerinka sp. (37L) and Achromobacter xylosoxidans (E37), based on partial 16S rRNA gene sequencing. Moreover, the in vitro biochemical assays demonstrated that the strains exhibited some plant growth promoting mechanisms such as 1-aminocyclopropane-1-carboxylic acid deaminase activity and indole compound synthesis. Notably, bacterial inoculation under greenhouse conditions showed a positive influence on P. clandestinum growth. We found a significant (P < 0.05) effect on root and shoot length and shoot dry weight. Shoot length increased by 52 % and 30 % with 37L and 35P compared to those without inoculation treatment. Similarly, the use of 37L and 28P raised shoot dry weight values by 170 % and 131 %, respectively. In root development, inoculation with strains 37L and E37 increased root length by 134 % and 100 %, respectively. Conclusion: Beijerinckia sp. 37L was the most effective of the four strains at increasing P. clandestinum biomass and length.

Introducción: La producción sostenible de pastos se ha convertido en un desafío fundamental para el sector ganadero, donde investigaciones con bacterias promotoras de crecimiento vegetal, como una solución viable, han sido poco reportadas. Objetivo: El objetivo de este estudio fue examinar el potencial para estimular el crecimiento del pasto Pennisetum clandestinum utilizando cuatro cepas bacterianas aisladas de suelos obtenidos de un sistema silvopastoril tropical colombiano. Métodos: Anteriormente identificamos genéticamente las cepas y caracterizamos dos actividades que promueven el crecimiento de las plantas. Además, evaluamos el efecto promotor del crecimiento de las cepas en el pasto Kikuyo en condiciones de invernadero. Resultados: Encontramos que las cuatro cepas bacterianas se asociaron filogenéticamente con Klebsiella sp. (cepas 28P y 35P), Beijerinka sp. (37L) y Achromobacter xylosoxidans (E37), basados en la secuenciación parcial del gen 16S rRNA. Además, los ensayos bioquímicos in vitro demostraron que las cepas exhibían algunos mecanismos que promueven el crecimiento de las plantas tales como la actividad de la enzima desaminasa del ácido 1-aminociclopropano-1- carboxílico, y la síntesis del compuesto indol. En particular, la inoculación bacteriana bajo condiciones de invernadero mostró una influencia positiva en el crecimiento de P. clandestinum. Encontramos un efecto significativo (P < 0.05) en la longitud de la raíz y el tallo, y el peso seco del tallo. La longitud del tallo aumentó en un 52 % y 30 % con 37L y 35P, respectivamente, en comparación con aquellos sin tratamiento de inoculación. Igualmente, el uso de las cepas 37L y 28P aumentó los valores de peso seco del tallo en un 170 y un 131 %, respectivamente. En el desarrollo de la raíz, la inoculación con las cepas 37L y E37 aumentó la longitud de la raíz en 134 y 100 %, respectivamente. Conclusión: Beijerinckia sp. 37L fue la más efectiva de las cuatro cepas al aumentar la biomasa y la longitud de P. clandestinum.

Functional Attributes and Antagonism of Root-Associated Bacteria of Different Rice Cultivars from Acid Soil

Abstract: This study evaluated root endophyte bacteria and rhizobacteria in terms ofmultifaceted plant growth promotion (PGP) traits and antagonistic potential against majorfungal pathogens of rice (viz. Rhizoctonia solani, Bipolaris oryzae, Pyricularia oryzae,Ustilaginoidea virens and Sarocladium oryzae). Twenty bacterial isolates from each group(viz. endorhiza and rhizosphere) were isolated from different rice types of North EastIndia. Cultivated rice types were Upland rice (Mima, Kochi and Minil), Lowland HYV rice(Ranjit and Jaya) and Lowland scented rice (Keteki Joha and Kunkuni Joha). Thepopulation of rhizospheric bacteria was higher than the endophyte isolates. Thepopulation counts of endophyte bacteria were the highest in scented rice cultivar(Kunkuni Joha) and for rhizobacterial isolates; the population density was maximum inthe lowland HYV rice (Jaya). The endophytes were more efficient than the rhizobacteria interms of the activity of cellulase, pectinase, ACC-deaminase, production of IAA- likesubstances, solubilization of zinc and mineralization of organic phosphates. In contrast,the rhizobacterial isolates were more efficient in solubilization of inorganic phosphatesand antagonism against major rice fungal pathogens. Through 16S rDNA sequenceanalysis, the promising rhizobacterial isolates showing antagonism against all the fungalpathogens were identified as Brevibacillus reuszeri 12R, Lysinibacillus xylanticus 48R,Bacillus megaterium 58R and Serratia marcescens 79R. These results suggest that the rootbacterial endophytes and rhizobacteria characterized in this study could be successfullyused to promote plant growth and induce fungal resistance in rice plants and can be usedas bioinoculants for enhancing rice growth in the acid soil regions.

Matrine attenuates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity maintaining AMPK/UCP2 pathway

Oxidative stress and cardiomyocyte apoptosis are involved in the pathogenesis of doxorubicin (DOX)-induced cardiotoxicity. Matrine is well-known for its powerful anti-oxidant and anti-apoptotic capacities. Our present study aimed to investigate the effect of matrine on DOX-induced cardiotoxicity and try to unearth the underlying mechanisms. Mice were exposed with DOX to generate DOX-induced cardiotoxicity or normal saline as control. H9C2 cells were used to verify the effect of matrine . DOX injection triggered increased generation of reactive oxygen species (ROS) and excessive cardiomyocyte apoptosis, which were significantly mitigated by matrine. Mechanistically, we found that matrine ameliorated DOX-induced uncoupling protein 2 (UCP2) downregulation, and UCP2 inhibition by genipin could blunt the protective effect of matrine on DOX-induced oxidative stress and cardiomyocyte apoptosis. Besides, 5'-AMP-activated protein kinase 2 () deficiency inhibited matrine-mediated UCP2 preservation and abolished the beneficial effect of matrine in mice. Besides, we observed that matrine incubation alleviated DOX-induced H9C2 cells apoptosis and oxidative stress level activating AMPK/UCP2, which were blunted by either AMPK or UCP2 inhibition with genetic or pharmacological methods. Matrine attenuated oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity maintaining AMPK/UCP2 pathway, and it might be a promising therapeutic agent for the treatment of DOX-induced cardiotoxicity.

Mechanism of Prunellae Spica Extracts on Lipid Metabolism in ZDF Rats Based on AMPK/ACC Signalling Pathway / 中国实验方剂学杂志

Objective: To observe the effect of Prunellae Spica extracts (PS) on the lipid metabolism in Zuker Diabetes Fatty (ZDF) rats based on AMP-activated protein kinase/acetyl CoA carboxylase (AMPK/ACC) signaling pathway.Method: The 32 male ZDF (fa/fa) type 2 diabetic rats were randomly divided into model group,metformin group (180 mg·kg-1·d-1),and low and high-dose PS groups (12.25,24.5 mg·kg-1·d-1),with 8 in each group.8 male Zuker Lean (ZL) rats were selected as normal group.Body weight and fasting blood glucose were monitored at the 0th,4th and 8th weeks after administration.After 8 weeks,abdominal aorta blood was collected,serum was frozen at-20℃ by centrifugation,liver tissue was frozen at-80℃,fixed with 4% paraformaldehyde and embedded in paraffin.Serum triglyceride (TG),cholesterol (CHO),low density lipoprotein cholesterol (LDL-C) and free fatty acid (FFA) levels were measured by radioimmunoassay.Fat droplets in hepatocytes were measured by oil red O staining.Gene expressions of AMP-activated protein kinase-alpha 2(AMPKα2),Acetyl CoA carboxylase (ACC) in liver were detected by real-time polymerase chain reaction (Real-time PCR).Protein expressions of p-AMPKα were observed by immuno-histochemical (IHC) method.Result: Compared with the normal group,the T2DM model group showed significant increases in serum levels of TG,CHO,LDL-C,FFA and lipid droplets in hepatocytes.AMPKα2 mRNA expression was decreased,while ACC1 and ACC2 mRNA expressions were increased significantly.p-AMPKα protein expression in liver was decreased significantly (PPα2,down-regulation in mRNA expressions of ACC1 and ACC2,and up-regulation in protein expression of p-AMPKα(PPConclusion:PS can effectively improve liver lipid metabolism in ZDF rats.Its mechanism may be related to the regulation of AMPK/ACC signaling pathway in liver.

Antidiabetic activity of Callicarpa nudiflora extract in type 2 diabetic rats via activation of the AMPK-ACC pathway

Objective: To evaluate the antidiabetic effect of Callicarpa nudiflora extract in streptozotocin-induced diabetic rats. Methods: The chemical constituents in Callicarpa nudiflora extract were identified by UPLC-Q-TOF-MS. Callicarpa nudiflora extract (0.15 and 0.3 g/kg) was orally administered to streptozotocin-induced diabetic rats for 42 d. The effects of Callicarpa nudiflora extract on body weight, blood glucose, serum insulin, total cholesterol, triglyceride, LDL-C and HDL-C were investigated, and its effect on liver and pancreatic pathology was assessed by histopathological analysis. Moreover, the expression levels of adenosine 5'-monophosphate-activated protein kinase (AMPK), glucose transporter type 4 (GLUT4), phospho-AMPK/AMPK, and p-acetyl-coA carboxylase (P-ACC)/ACC in the skeletal muscles and liver were determined by reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. Results: A total of 34 compounds, including 8 iridoids, 14 phenylpropanoids, and 12 flavonoids, were identified from Callicarpa nudiflora extract. Callicarpa nudiflora extract significantly reduced blood glucose and significantly restored all other biochemical parameters to near normal levels, including serum insulin, total cholesterol, triglyceride, LDL-C, and HDL-C. Callicarpa nudiflora extract improved insulin resistance and reversed the damage in the liver and pancreas caused by diabetes. Furthermore, Callicarpa nudiflora extract increased the expression levels of phospho-AMPK, GLUT4, P-ACC, and insulin receptor substrate-1 and decreased the expression level of PPAR毭 in diabetic rats.Conclusions: Callicarpa nudiflora extract improved oral glucose tolerance, lipid metabolism, insulin resistance, and reversed the diabetes-related damage in the liver and pancreas by activating the AMPK-ACC pathway.

Imaging features of primary adenoid cystic carcinoma of the breast / 中国肿瘤临床

Objective: To investigate the imaging features of primary adenoid cystic carcinoma (ACC) of the breast. Methods: In total, 31 patients were confirmed to have primary ACC in the breast based on histopathological findings from January 2012 to September 2018 in Tianjin Medical University Cancer Institute and Hospital. Mammography and ultrasonography findings of these patients were retrospectively analyzed according to the breast imaging-reporting and data system (BI-RADS) recommended by the American College of Radiology (ACR) and compared with pathological findings. Results: Mammography findings in 31 cases of ACC of the breast were as follows: 25 cases with masses, including 16 high-density masses (14 were categorized as BI-RADS 4C or 5, one as 4A, and one as 4B); 7 equal-density masses (5 were categorized as BI-RADS 4B, one as 4A,and one as 3); and 2 mixed-density masses (one was categorized as BI-RADS 4A and one as 2). The other 6 patients presented with focal asymmetric density. No calcification was found in all cases. Ultrasonography findings included hypoechoic mass, mixed-echo mass, and non-mass-like hypoechoic or heterogeneous echoic areas. A total of 22 patients presented with hypoechoic masses; of these, 14 showed typical ultrasonographic findings of breast cancer and their tumors were categorized as BI-RADS 4C or 5. Three patients presented with mixed-echo masses, of which two showed a mixed-echo mass containing hyper-echoic areas and one showed a complex cystic and solid echo mass; all tumors were categorized as BI-RADS 4B. The remaining 6 patients presented with non-mass-like hypoechoic or heterogeneous echoic areas; all were without a tendency to distribute along the direction of the breast ducts. Conclusions: The mammographic and ultrasonographic appearances of primary ACC of the breast are similar to those of general carcinoma, with no specificity. Some specific findings, such as irregular high-density masses containing low-or fatty-density areas with indistinct margins on mammography and mixed-echo masses containing hyper-echo or non-mass-like heterogeneous echoic areas not distributed along the breast duct on ultrasonography, have certain significance. The final diagnosis depends on histopathology.

Use of New ACC/AHA 2017 guidelines for estimation of prevalence of hypertension among adult population visiting a Tertiary Care Hospital of Eastern India

Background: In November, 2017, the American College of Cardiology (ACC) and American Heart Association (AHA) released new guidelines for classification of hypertension among adults. JNC 7 guidelines are most used till now. The present study aimed to measure the burden of hypertension among adult population using new ACC/AHA guidelines and to compare it with JNC 7. Method: A descriptive cross sectional study was carried over a period of one month as a part of MBBS student project. Blood pressure of hospital visitors/attendants was measured using Omron HEM-8711 blood pressure monitor with standard technique. A total of 437 participants were got measured their blood pressure. Result: 31.6% of participants self-reported their hypertensive state. Out of 299 participants who were now aware about their blood pressure status, 55% labelled as hypertensive using new ACC/AHA guidelines as compared to only 22% with earlier JNC 7 guidelines.

Confronting system barriers for ST- elevation MI in low and middle income countries with a focus on India

Our previous research found seven specific factors that cause system delays in ST-elevation Myocardial infarction management in developing countries. These delays, in conjunction with a lack of organized STEMI systems of care, result in inefficient processes to treat AMI in developing countries. In our present opinion paper, we have specifically explored the three most pertinent causes that afflict the seven specific factors responsible for system delays. In doing so, we incorporated a unique strategy of global STEMI expertise. With this methodology, the recommendations were provided by expert Indian cardiologist and final guidelines were drafted after comprehensive discussions by the entire group of submitting authors. We expect these recommendations to be utilitarian in improving STEMI care in developing countries.