Natto: A medicinal and edible food with health function / 中草药·英文版

Natto is a soybean product fermented by natto bacteria. It is rich in a variety of amino acids, vitamins, proteins and active enzymes. It has a number of biological activities, such as thrombolysis, prevention of osteoporosis, antibacterial, anticancer, antioxidant and so on. It is widely used in medicine, health-care food, biocatalysis and other fields. Natto is rich in many pharmacological active substances and has significant medicinal research value. This paper summarizes the pharmacological activities and applications of natto in and outside China, so as to provide references for further research and development of natto.

Mitochondrial oxidative stress in vascular endothelial cell and atherosclerosis / 药学实践杂志

The injury of vascular endothelial cell function is the beginning of the pathological process of atherosclerosis. Mitochondrial oxidative stress is closely related to vascular endothelial cell function, which causes the dysfunction of vascular endothelial cell by inducing mitophagy, reducing nitric oxide production, inflammation, cellular metabolic imbalance and apoptosis. Meanwhile, vascular endothelial cell could also maintain their homeostasis by regulating mitochondrial oxidative stress. The molecular signaling pathways of the vascular endothelial cell injury caused by mitochondrial oxidative stress in the pathological process of atherosclerosis were outlined in this review, which provided reference for further research on the molecular mechanism between mitochondrial oxidative stress and endothelial damage.

Quercetin Against Cerebral Ischemia-reperfusion Injury： A Review / 中国实验方剂学杂志

Cerebral ischemia-reperfusion injury （CIRI） is a further injury of brain tissue after the recovery of blood supply in ischemic stroke， which seriously affects the quality of life of patients. The pathological mechanism of CIRI is complex， mainly involving excitatory amino acid toxicity， apoptosis， inflammation， and oxidative stress. Studies have proved that Chinese herbal medicines and their active components have unique advantages and good application prospects in the prevention and treatment of CIRI. Quercetin is a flavonoid ubiquitous in a variety of Chinese medicinal herbs. It can alleviate CIRI and reduce brain injury through inhibiting inflammation， oxidation， and apoptosis， protecting blood-brain barrier， and activating mitophagy. However， little is known about the specific mechanism and molecular targets. In view of the low bioavailability and poor solubility of quercetin， researchers have developed a variety of delivery systems to facilitate the dispersion of quercetin， improve chemical stability， and increase clinical application. Furthermore， researchers have tested the long-term safety of quercetin and confirmed that low-dose quercetin has good safety. By reviewing the relevant studies in recent years， we summarized the targets， mechanism， delivery， and safety of quercetin in the treatment of CIRI， aiming to provide a theoretical basis for the further development and application of quercetin.

Advances in Basic Studies on Antitumor Effect and Underlying Molecular Mechanisms of Sinomenine / 中国实验方剂学杂志

Tumors are new organisms formed by uncontrollable cell proliferation of local tissues driven by various oncogenic factors. The cause of tumors is unknown with life-threating outcome. Tumors can be classified into benign tumors， borderline tumors， and malignant tumors according to their pathological properties. Among them， malignant tumor is commonly known as cancer， with no specific medicines or reliable cure means， so this is a hot spot and difficult point in current medical research. In ancient literatures， there are many records about the efficacy of Chinese herbal medicine in treating tumor， and modern pharmacological researches have shown that more and more active ingredients of traditional Chinese medicine（TCM） have gradually highlighted their inhibitory effect on various types of tumor. Caulis sinomenii has been used for treatment of rheumatic diseases in TCM for a long history. Sinomenine is a major bioactive alkaloid presented in C. sinomenii， which has demonstrated a wide range of pharmacological activities such as anti-inflammation， immunosuppression， analgesia and sedation， and due to its slightly soluble in water， it is commonly used in clinic in the form of hydrochloride， with its commercial name of Zhengqing Fengtongning. Recent studies show that sinomenine alone or combined with chemoradiotherapy can inhibit growth of several tumors significantly or in a synergistic way， so it is termed as an inhibitor of tumors. Anti-tumor effect of sinomenine involve inhibition of tumor cell proliferation， induction of tumor cell apoptosis， blockade of tumor cell cycle， suppression of tumor invasion and metastasis， induction of autophagy of tumor cells， and reversal of multidrug resistance of tumor cells. Upon combination with nanomaterials， it can enhance efficiency and reduce toxicity. Here we summarized and reviewed recent advances on basic anti-tumor research of sinomenine， and then made a classification and description according to its in vivo and in vitro pharmacological action and mechanism of action， so as to elucidate the great potential of sinomenine as a promising anti-tumor drug， and provide reference for further research on its anti-tumor mechanism.

Qual o papel do bloqueio sequencial do néfron na hipertensão resistente? / What is the role of sequential nephron blockade in resistant hypertension?

A hipertensão resistente (HAR) ocorre quando a pressão arterial (PA) permanece acima da meta recomendada após o uso de três fármacos anti-hipertensivos com ação sinérgica em suas doses máximas toleradas recomendadas, preferencialmente incluindo um diurético. A identificação da contribuição do volume intravascular e da renina sérica na manutenção dos níveis elevados da PA permite um tratamento mais eficaz da hipertensão, ao atuar sobre o controle do volume intravascular, equilíbrio de sódio e sobre os efeitos do sistema renina-angiotensina-aldosterona (SRAA) no rim. Bloqueio sequencial do néfron (BSN) consiste em um aumento progressivo na depleção de sódio usando um diurético tiazídico, um bloqueador do receptor mineralocorticoide (espironolactona), furosemida e, finalmente, amilorida. Os mecanismos de ação, as indicações e os efeitos adversos são discutidos na presente revisão.

Resistant hypertension (HAR) occurs when blood pressure (BP) remains above the recommended target after the use of three antihypertensive drugs with synergistic action at their maximum recommended tolerated doses, preferably including a diuretic. The identification of the contribution of intravascular volume and serum renin in maintaining high BP levels allows a more effective treatment of hypertension, by acting on the control of intravascular volume, sodium balance and on the effects of the renin-angiotensin-aldosterone system (RAS) in the kidney. Sequential nephron block (BSN) consists of a progressive increase in sodium depletion using a thiazide diuretic, a mineralocorticoid receptor blocker (spironolactone), furosemide and, finally, amiloride. Mechanisms of action, indications and adverse effects are discussed in the present review

Mechanism of Tripterygium wilfordii tablets for the treatment of rheumatoid arthritis based on integrated chemomics and network pharmacology / 国际药学研究杂志

Objective: To explore the mechanism of Leigongteng Pian(Tripterygium wilfordii tablets)for the treatment of rheumatoid arthritis(RA)based on chemomics and network pharmacology. Method: UPLC-Q-TOF/HRMS was used to analyze the chemical constituents of Tripterygium wilfordii tablets under the positive and negative ion modes. Thereafter,the ingredient targets of Tripterygium wilfordii tablets were predicted by Swiss Target Prediction and Pharm- Mapper databases,and the targets of RA diseases were obtained by Traditional Chinese Medicine Systems Pharmacology (TCMSP),Therapeutic Target Database(TTD)and Comparative Toxicogenomics Database(CTD). By taking the inter-section of ingredient targets and disease targets,the direct common targets of Tripterygium wilfordii tablets for the treat- ment of rheumatoid arthritis were obtained. Then the GeneMANIA database was used to obtain indirect targets,and the software of Cytoscape 3.7.1 was used to construct the protein-protein interaction(PPI)networks of potential targets,by which the key targets were screened. Enrichment of gene function and pathways of all potential targets were conducted by Gene Ontology(GO)database and Kyoto Encyclopedia of Genes and Genomes(KEGG)database to explore the mecha- nism of Tripterygium wilfordii tablets for the treatment of rheumatoid arthritis. Results: Thirtyone chemical constituents of Tripterygium wilfordii tablets were screened out and sixtysix potential targets were predicted. Twentyseven active com- ponents in the Tripterygium wilfordii tablets might be important components for the treatment of rheumatoid arthritis as in- dicated by the reverse screening. At the same time,five core targets were screened out,which might be involved in the key pathways that actively participate in the intervention and adjustion of rheumatoid arthritis. Conclusion: In this study,we found that the active components in Tripterygium wilfordii tablets could exert important biological effects via multiple targets and pathways,and these targets and pathways are all involved with the inflammation and immune regula- tion of RA.

Corticoterapia / Corticotherapy

Glicocorticosteroides são fármacos efetivos no tratamento de doenças inflamatórias e imunes. Agem em praticamente todas as células do corpo, antagonizando os efeitos patogênicos de inúmeras doenças. A maior parte de seus efeitos parece ser produto de sua ligação a receptores específicos armazenados no interior das células. Suas ações moduladoras da transcrição genética iniciam-se com a ligação ao seu receptor e posterior conexão aos genes alvo, num processo que conta com a participação de outros fatores e envolve múltiplos mecanismos (ação genômica). Os genes alvo incluem aqueles responsáveis por mediadores inflamatórios, como quimiocinas, citocinas, fatores de crescimento e seus receptores. Além de seus efeitos sobre o DNA, estimulando a produção de produtos anti-inflamatórios ou inibindo a transcrição de genes pró-inflamatórios, via acetilação ou deacetilação das histonas, respectivamente, os glicocorticosteroides possuem outros mecanismos de ação que não envolvem regulação genética (ação não genômica). Aparentemente, por mecanismos ainda não esclarecidos, os efeitos da corticoterapia são produto da associação das ações genômicas com as não genômicas. Os glicocorticosteroides representam o grande pilar terapêutico da asma, com efeitos sobre as células estruturais e funcionais do trato respiratório. Nessa situação particular, na qual costumam ser empregados continuadamente por períodos prolongados, com risco potencial de efeitos indesejáveis relevantes, é fundamental desvendar os processos envolvidos em seus mecanismos de ação para tentar desenvolver meios de reduzir os riscos associados e potencializar os efeitos desejados.

Glucocorticosteroids are effective drugs in the treatment of inflammatory and immune diseases. They act on virtually every cell in the body by antagonizing the pathogenic effects of numerous diseases. Most of its effects appear to be the product of its binding to specific receptors stored within cells. Its modulatory actions on genetic transcription begin with a linkage to its receptor and later connection to target genes, in a process that counts on the participation of other factors and involves multiple mechanisms (genomic action). Target genes include those responsible for inflammatory mediators, such as chemokines, cytokines, growth factors, and their receptors. In addition to its effects on DNA, stimulating the production of anti-inflammatory products or inhibiting the transcription of pro-inflammatory genes, via acetylation or deacetylation of histones, respectively, glucocorticosteroids have other mechanisms of action that do not involve genetic regulation (non-genomic effect). Apparently, by mechanisms not yet clarified, the effects of corticotherapy are the product of the association of genomic and non-genomic actions. Glucocorticosteroids represent the great therapeutic pillar of asthma, with effects on structural and functional cells of the respiratory tract. In this particular situation, where they are often used for prolonged periods, with a potential risk of relevant undesirable effects, it is essential to uncover the processes involved in their mechanisms of action in order to develop ways to reduce the associated risks and potentiate the desired effects.

Hidroarsenicismo: mecanismos de acción asociados a la toxicidad del arsénico / Hydroarsenicism: Mechanisms of action related to arsenic toxicity

La exposición crónica al arsénico (As) inorgánico a través del agua de bebida da lugar al desarrollo de la enfermedad conocida como hidroarsenicismo. Esta enfermedad presenta sintomatología característica, sin embargo, para la mayoría de los efectos tóxicos que produce del As aún no se conoce en detalle el mecanismo de acción tóxica. Los mecanismos moleculares de acción del arsenito (unión a grupos sulfhidrilos) y del arseniato (sustitución del fosfato) están bien identificados, sin embargo, las consecuencias a nivel subcelular, celular, tisular y orgánico de esos mecanismos todavía presentan muchos huecos por llenar. A nivel subcelular y celular, la generación de especies reactivas de oxígeno (ERO) y de nitrógeno (ERN) son los mecanismos de acción tóxica del As más estudiados últimamente. Se los ha vinculado con la diferenciación y proliferación de queratinocitos, con la disfunción endotelial, con la resistencia a la insulina, con la inducción de peroxidación lipídica en hígado, de necrosis tubular renal y con cambios en la expresión del receptor estrogénico. Por último, la respuesta celular a proteínas no plegadas (como consecuencia del estrés del retículo endoplásmico) podría ser un mecanismo para explicar la afectación de la inmunidad humoral y la celular.

Chronic exposure to inorganic arsenic (As) through drinking water leads to the development of the disease known as hydroarsenicism. This disease presents characteristic symptomatology but the mechanisms underlying most of the toxic effects produced by As are not fully understand. The molecular mechanisms of action of arsenite (binding to sulfhydryl groups) and arsenate (phosphate substitution) are well identified, however, the consequences at the subcellular, cellular, tissue and organic levels of these mechanisms still have many gaps to fill. At the subcellular and cellular level, the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the most studied mechanisms of toxic action. They have been linked to the differentiation and proliferation of keratinocytes, endothelial dysfunction, insulin resistance, induction of lipid peroxidation in the liver, renal tubular necrosis and changes in the expression of estrogen receptor. Finally, the cellular response to unfolded proteins (as a consequence of the stress of the endoplasmic reticulum) could be a mechanism to explain the affectation of humoral and cellular immunity.

Proteomics and its application to determine mechanism of action of traditional Chinese medicine / 中国中药杂志

There is no doubt that the traditional Chinese medicine(TCM) is effective, practical and scientific after it was used for thousands of years. However, the mechanisms of action of many TCM are still unclear because of their multi-component, multi-target and multi-level features, which hinder the modernization and internationalization of the TCM. Proteomics is to analyze the composition and activity of intracellular proteins which are changing dynamically from a holistic perspective. It is consistent with the holistic and dynamic views of the TCM and brings about the hope of clarifying the mechanism of action of the TCM. In recent years, great progress has been made in the application of proteomics to determine the mechanism of the TCM. This article introduced the core technologies of proteomics and systematically summarized the applications of proteomics in the study of the mechanism of the Chinese medicinal formulae, single Chinese medicine and monomeric compounds from the TCM to provide innovative ideas and methods for reference.

Study of synergistic mechanism in the combination ofberberine and evodiamine from the perspective of miRNA / 中国药理学通报

Aim To explore the mechanisms of action (MOA) of synergistic anticancer function in the combination of berberine and evodiamine.Methods We first analyzed the action of suppression in the drug combination from the cell level and validated the dose scope as well as ratio of concentration in synergistic effects of drug combination.Then, the miRNA chip of liver cancer cell BEL-7402 under different treatment was analyzed.By building the miRNA-mRNA network, the MOA of the synergistic drug combination was illustrated.Results Berberine and evodiamine used in combination could significantly synergistically suppress the proliferative ability of liver cancer cells.The special differentially expressed miRNAs (DEmiRNAs) mainly participated in some cancer proliferation-related pathways and biological processes, such as MAPK signaling pathway, endocytosis pathway and insulin signaling pathway.The special target genes influenced by the drug combination not only covered three kinds of membrane receptors, but also took part in the regulation of downstream pathways.Conclusions From the regulation of miRNAs, it is clear that berberine may play a primary role in the synergistical suppression activity of the drug combination in cancer cells.The discovery of synergistic MOA in the combination of berberine and evodiamine from the miRNA level will provide a new guidance to explore more synergistic drug combinations in the future.

Regulatory effect of decitabine on human acute myeloid leukemia cell line HL-60 and its mechanism / 白血病·淋巴瘤

Objective To investigate the effect of decitabine (DAC) on human acute myeloid leukemia (AML) cell line HL-60 and the regulating of natural killer (NK) cell activating receptor (NKG2D) ligands(NKG2DL), and to detect the molecular mechanism of JAK-STAT3-SOCS signaling pathway. Methods The effect of DAC on the proliferation of HL-60 was detected by using CCK-8 assay. The cell apoptosis was analyzed by using Annexin-V/PI double standard method. The expressions of receptor NKG2DL including MICA/B and ULBPs in HL-60 cells were detected by using flow cytometry (FCM). The killing activity of NK cells was analyzed by using carboxy fluorescein diacetate succinimidyl ester (CFSE). The expressions of JAK/STAT3 signaling pathway or molecules including STAT3, its upstream kinases JAK1, JAK2 and the negative regulator of STAT3,SOCS-1,SOCS-3 were examined by Western blot.Methylation level of the SOCS-1,SOCS-3 gene after the treatment of DAC was analyzed by using methylation-sensitive high resolution melting(MS-HRM). Results There was an obvious inhibitory effect of DAC on HL-60 cells. The cell viability of HL-60 treated with 0.2, 0.5, and 1.0 μmol/L DAC for 48 h was decreased by (25±11) %, (39±8) % and (50±7)%(P<0.01)respectively compared with those cells without DAC treatment.The incidence of apoptosis was (24.77±7.50) %, (27.10±4.48) % and (30.53±3.93) % after DAC treatment for 48h respectively, which were higher than that of untreated cells[(3.11±0.50)%](P<0.01).DAC induced a significant up-regulation of MICA/B, ULBP-1, ULBP-3 in HL-60 cells, and enhanced the sensitivity of HL-60 cells to NK cytotoxicity. Western blot results showed that a down-regulating expression of STAT3 and JAK1, JAK2 protein was detected, in addition to the phosphor-STAT3 and phosphor-JAKs in HL-60 cells after DAC treatment, but the expressions of SOCS-1 and SOCS-3 protein were increased. HRM results showed that DAC could inhibit the methylation of SOCS-3 gene. Conclusion DAC can inhibit the proliferation of HL-60 cells, upregulate the expression of NKG2DL and enhance the cytotoxicity of NK targeted to HL-60 cells, which might be related to the activity regulation of intracellular JAK-STAT3-SOCS signaling pathway.

Regulatory effect of decitabine on human acute myeloid leukemia cell line HL-60 and its mechanism / 白血病·淋巴瘤

Objective To investigate the effect of decitabine (DAC) on human acute myeloid leukemia (AML) cell line HL-60 and the regulating of natural killer (NK) cell activating receptor (NKG2D) ligands(NKG2DL), and to detect the molecular mechanism of JAK-STAT3-SOCS signaling pathway. Methods The effect of DAC on the proliferation of HL-60 was detected by using CCK-8 assay. The cell apoptosis was analyzed by using Annexin-V/PI double standard method. The expressions of receptor NKG2DL including MICA/B and ULBPs in HL-60 cells were detected by using flow cytometry (FCM). The killing activity of NK cells was analyzed by using carboxy fluorescein diacetate succinimidyl ester (CFSE). The expressions of JAK/STAT3 signaling pathway or molecules including STAT3, its upstream kinases JAK1, JAK2 and the negative regulator of STAT3,SOCS-1,SOCS-3 were examined by Western blot.Methylation level of the SOCS-1,SOCS-3 gene after the treatment of DAC was analyzed by using methylation-sensitive high resolution melting(MS-HRM). Results There was an obvious inhibitory effect of DAC on HL-60 cells. The cell viability of HL-60 treated with 0.2, 0.5, and 1.0 μmol/L DAC for 48 h was decreased by (25±11) %, (39±8) % and (50±7)%(P<0.01)respectively compared with those cells without DAC treatment.The incidence of apoptosis was (24.77±7.50) %, (27.10±4.48) % and (30.53±3.93) % after DAC treatment for 48h respectively, which were higher than that of untreated cells[(3.11±0.50)%](P<0.01).DAC induced a significant up-regulation of MICA/B, ULBP-1, ULBP-3 in HL-60 cells, and enhanced the sensitivity of HL-60 cells to NK cytotoxicity. Western blot results showed that a down-regulating expression of STAT3 and JAK1, JAK2 protein was detected, in addition to the phosphor-STAT3 and phosphor-JAKs in HL-60 cells after DAC treatment, but the expressions of SOCS-1 and SOCS-3 protein were increased. HRM results showed that DAC could inhibit the methylation of SOCS-3 gene. Conclusion DAC can inhibit the proliferation of HL-60 cells, upregulate the expression of NKG2DL and enhance the cytotoxicity of NK targeted to HL-60 cells, which might be related to the activity regulation of intracellular JAK-STAT3-SOCS signaling pathway.

Nuevas evidencias del uso de la metformina en el tratamiento del cáncer / New evidence of the use of metformin in the treatment of cancer

La metformina es una biguanida ampliamente usada en el tratamiento de la diabetes mellitus tipo 2. Evidencias recientes proponen nuevos usos para esta vieja droga. El cáncer, que constituye un problema de salud mundial, se desarrolla con más frecuencia y peor pronóstico en los pacientes con diabetes tipo 2. Sin embargo, se ha comprobado que cuando estos son tratados con metformina presentan menor incidencia, complicaciones y mortalidad por cáncer. Por tal motivo, durante casi una década, se llevaron a cabo numerosas investigaciones epidemiológicas, básicas, preclínicas y ensayos clínicos, para fundamentar las evidencias del efecto protector y antitumoral de este medicamento. En tal sentido, se encontró que posee efectos antineoplásicos, por mecanismos sensibilizadores de la insulina, y otros, como que son pro-apoptóticos, que alteran el desarrollo de la célula madre cancerosa e interfieren con la carcinogénesis. Esto ha abierto una amplia gama de aplicaciones de la metformina en la terapéutica del cáncer, que abarcan desde los efectos preventivos, hasta las coadyuvantes de los tratamientos estándares(AU)

Metformin is a widely used biguanide in the treatment of type 2 diabetes mellitus. Recent evidence indicates new uses for this old drug. Cancer is a worldwide health problem that develops more frequently in type 2 diabetic people with worse prognosis. However, it has been demonstrated that when they are treated with metformin, the incidence, complications and mortality rates are lower. For these reasons, a number of epidemiological, basic, preclinical research studies as well as clinical assays have been conducted for almost a decade in order to substantiate evidence from the protective and antitumor effect of this drug. It was found that it has some antineoplastic effects due to insulin sensitizing mechanisms and other pro-apoptotic ones that impair the cancer stem cell development and interfere in carcinogenesis. This has shown a wide range of applications of metformin in the treatment of cancer including the preventive and coadjuvant effects of the conventional treatments(AU)

Molecular mechanisms of dental fluorosis / 中华地方病学杂志

Endemic dental fluorosis has been reported in some regions of the world. China seemed to have high prevalence of endemic dental fluorosis, especially in southwest China. It is now most likely that excessive fluoride intake during enamel development play a key role in the pathogenesis of dental fluorosis. However, excessive intake of fluoride-induced cellular and molecular mechanisms of dental fluorosis are not entirely conclusive. Scholars at home and abroad have made a lot of research on pathogenesis of enamel fluorosis by using various experimental techniques. More recent studies mainly suggest that endoplasmic reticulum stress and calcium overload-associated apoptotic pathway may participate in fluoride excess-evoked pathogenesis of dental fluorosis. Furthermore, the functional changes of enamel matrix protein and protease activity may be involved in the pathological event. This paper summarized the recent research progress on this topic.

The main potentialities of resveratrol for drug delivery systems

Resveratrol (RSV), a natural polyphenol found in grapes, was found to be effective in the prevention and therapy of several diseases, however, it does have unfavourable physicochemical properties. In this context, an increasing number of studies have aimed at developing novel therapeutic systems for its delivery to overcome these disadvantages. This review focuses on the mechanisms of action and therapeutic applications. Finally, it also describes some tested formulations for RSV administration, controlled release and targeting, developed with the purpose of increasing RSV bioavailability.

O resveratrol (RSV) é um polifenol natural encontrado nas uvas, que se mostrou eficaz na prevenção e terapia de várias doenças. No entanto, apresenta propriedades físico-químicas desfavoráveis. Neste contexto, um número cada vez maior de estudos visando ao desenvolvimento de novos sistemas terapêuticos para a sua liberação vem sendo desenvolvido no sentido de ultrapassar estas desvantagens. Esta revisão discorre sobre os mecanismos de ação e aplicações terapêuticas do RSV. Finalmente, são abordadas algumas formulações de liberação controlada e vetorizada, testadas para administração do RSV, desenvolvidas com a finalidade de aumentar a biodisponibilidade do RSV.

Peroxisome proliferator-activated receptors α, γ agonists and tumors / 国际药学研究杂志

Peroxisome proliferator-activated receptors (PPAR) are members of the nuclear hormone receptor superfamily. So far, three PPAR isotypes (PPARα, PPARβ/δ and PPARγ) have been identified, PPARα and PPARγ agonists have been used in clinic for treatment of hyperlipidemia and diabetes mellitus, respectively. Meanwhile, candidates targeting PPARβ/δ have entered the clinical study. However, some pre-clinical and clinical studies have indicated that some agonists of PPARα/γ and PPARβ/δ can induce various tumors in mice, and PPARγ agonist pioglitazone may enhance the bladder cancer risk in humans. Therefore, the role of PPAR agonists in tumorigenesis has aroused much attention. This review mainly focuses on the progress in PPARα and PPARγ agonists in tumors, aiming to provide more information for the safe medication and further development of PPAR agonists.

Possible mechanism of enhanced external counterpulsation treating coronary heart disease / 心血管康复医学杂志

A lot of clinical trials proved that enhanced external counterpulsation (EECP) is a low-cost ,non-invasive , safe and effective method treating coronary heart disease .The present article made an overview on possible mecha-nism of EECP treating coronary heart disease .

Tratamiento farmacológico contra la obesidad / Drug treatment for obesity

La obesidad, una de las enfermedades más críticas del siglo XXI, se halla asociada con otros problemas de salud como la diabetes tipo 2, las enfermedades cardiovasculares y una expectativa de vida reducida, y ejerce un efecto importante sobre la economía. Pese a que se han desarrollado fármacos antiobesidad que actúan de diferentes maneras (disminuyendo el apetito, alterando el metabolismo o inhibiendo la absorción calórica), dichos fármacos han representado serias preocupaciones en cuanto a la seguridad en su uso, a tal punto que, debido a sus efectos secundarios, Se retiraron del mercado la sibutramina y el rimonabant; a consecuencia de estos reveses existen pocos medicamentos antiobesidad aceptados. Por otra parte, el conocimiento acerca del eje intestino-cerebro ayuda a entender cómo funciona el sistema gastroenteropancreático, con relación a una serie de péptidos y hormonas que participan en la regulación alimentaria y el cerebro, específicamente el hipotálamo como centro homeostático de los estados de hambre y anorexia, o del apetito, y por ende, del peso corporal. Esto nos lleva a estudiar aquellos fármacos que se encuentran en fase de investigación y desarrollo como las monoterapias y las combinaciones, para concluir que existen tres fármacos aprobados por la Agencia de Alimentos y Medicamentos (FDA, por sus siglas en inglés), dos de ellos recientemente (en el 2012), y otros que podrían llegar a ser aceptados para su uso terapéutico.

Obesity is one of the most critical diseases of the 21st century, which is associated with other health problems such as type 2 diabetes, cardiovascular disease and reduced life expectancy, and a strong effect on the economy. Over time, have developed anti-obesity drugs which work in different ways: by suppressing appetite, altering metabolism or inhibiting absorption heat. However, these drugs have had serious concerns about the safety of commonly prescribed use derivative side effects, leading the recent withdrawal of sibutramine and rimonabant. As a result of these setbacks, there are few anti-obesity drugs accepted. Knowledge about the gut-brain axis help you understand how the gastro-entero pancreatic, related to a series of peptides and hormones involved in food regulation and the brain, specifically the hypothalamus as a central regulator of the states of hunger and anorexia or appetite and body weight thereby. These lead us to study those drugs that are under research and development as monotherapies and combinations to conclude that there are three drugs already approved by the Food and Drug Administration or by its acronym U.S. FDA (two of them recently approved in 2012) and others which will become accepted for therapeutic use.

Research advances on related molecules and genes affecting the efficacy of gemcitabine for pancreatic cancer / 肿瘤研究与临床

Pancreatic cancer normally is lethal and difficult to treat.Recently,although chemotherapy drugs such as gemcitabine for the treatment achieved a certain effect, but the survival rate has not improved significantly. Over the past decade, a large number of studies that aimed to implicated in pancreatic tumor gemcitabine metabolism and resistance mechanisms. Recent data show that it is a great value for predicting efficacy in the treatment of pancreatic cancer with gemcitabine by detecting pancreatic cancer -related molecules and genes, especially in the field of individual therapy. This review describes advances in the studies of related molecules and genes affecting the efficacy of gemcitabine for pancreatic cancer.

2-ME-induced apoptosis of K562 cells and its mechanism / 中国基层医药

Objective To study the effect of 2-methoxyestradiol (2-ME) on proliferation,apoptosis and its mechanism.Methods K562 cells were treated with 2-ME of different concentrations and time in vitro.Cell apoptosis rate was measured by flow cytometry(FCM).Activity of NF-Kappa B in nucleus was detected by electrophoretic molility shift assay(EMSA).Results After treatment with 2-ME,K562 cells apoptotic rate increased significantly.After treatment with 4μmol/L 2-ME for 24h、36h、48h,the activity of Caspase-3 and Caspase-9 were significantly higher and activity of NF-Kappa B in nucleus was significantly lower.Conclusion The present study showed that 2-ME induced apoptosis of K562 cells via active Caspase-3 and Caspase-9 and inhibit the activity of NF-kappa B in nucleus.This study provided useful experimental data for clinical application of 2-ME.