Antibacterial and anti-parasitic activities of Terfezia claveryi methanolic extract against some common pathogenic agents of infectious diarrhea

Objective: To assess the antidiarrheal effects of Terfezia claveryi methanolic extract against Escherichia coli, Salmonella typhimurium, Shigella flexneri, and Giardia lamblia. Methods: Antibacterial effects of the Terfezia claveryi methanolic extract were carried out by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration through micro broth dilution technique. Furthermore, reactive oxygen species production and protein leakage were evaluated. To evaluate the in vitro anti-giardial effects of Terfezia claveryi methanolic extract, Giardia lamblia WB (ATCC® 30957) trophozoites were treated with various concentrations of Terfezia claveryi methanolic extract for 10-360 min. In addition, the plasma membrane permeability of trophozoites treated with Terfezia claveryi methanolic extract was determined. The cytotoxicity effects of Terfezia claveryi methanolic extract against normal (HEK293T) and cancer (MCF-7) cells were also assessed using the MTT assay. Results: The MIC and minimum bactericidal concentration of Terfezia claveryi methanolic extract against bacterial strains were in the range of 0.52-1.04 and 1.04-2.08 mg/mL, respectively. The results revealed that reactive oxygen species production and protein leakage were significantly increased after the bacteria were treated with the Terfezia claveryi methanolic extract, especially at 1/3 and 1/2 MICs (P<0.001). Furthermore, Terfezia claveryi methanolic extract decreased the viability of Giardia lamblia trophozoites in a dose-dependent manner. Terfezia claveryi methanolic extract at 1, 2, and 4 mg/mL resulted in 100% mortality in Giardia lamblia trophozoites after 360, 240, and 120 min, respectively. Moreover, Terfezia claveryi methanolic extract altered the permeability of plasma membrane of Giardia lamblia trophozoites by increasing the concentration. MTT assay revealed that the 50% cytotoxic concentrations values for HEK293T and MCF-7 cells were 4.32 mg/mL and 6.40 mg/mL, respectively, indicating that Terfezia claveryi methanolic extract had greater cytotoxicity against cancer cells than normal cells. Conclusions: Terfezia claveryi methanolic extract had potent in vitro antibacterial and anti-parasitic effects on Escherichia coli, Salmonella typhimurium, Shigella flexneri, and Giardia lamblia by affecting cell membrane permeability and reactive oxygen species generation with no significant cytotoxicity on normal cells.

Therapeutic effects of benzoylaconitine and paeoniflorin in rats with collagen-induced arthritis

Abstract To explore the effects and mechanisms of benzoylaconitine and paeoniflorin on collagen-induced arthritis (CIA) rats. Weight, paw swelling, arthritis index and joint pathologic changes were examined in each group after CIA induction. PGE2, IL-1ß, IL-6, IL-10, TNF-α, VEGF, MMP-3, IgG and anti-CII Ab were assessed by ELISA; STAT1 and STAT3 expressions were analyzed immunohistochemically, and the ultrastructure of synovial cells was observed by transmission electron microscopy. Therapeutic effects were determined in CIA rats via injecting benzoylaconitine and paeoniflorin, which could alleviate the degree of swelling and arthritis index (AI) and pathological lesions of the sacroiliac gland; decrease the levels of PGE2, IL-1ß, TNF-α, VEGF and IgG in serum; reduce STAT1 and STAT3 expression in the membrane tissue; and inhibit the secretion and proliferation of synovial cells. These results showed that benzoylaconitine and paeoniflorin could significantly palliate the arthritic symptoms of CIA rats, and better therapeutic effects could be achieved if the two components were used in combination

Metformina: interacciones moleculares, celulares y su repercusión en la Obstetricia. Revisión bibliográfica / Metformin: Cellular and molecular interactions and its' impact in obstetrics. Literature review

Resumen OBJETIVO: Identificar los mecanismos celulares más reconocidos de la metformina y su relación con patologías en Obstetricia y determinar las moléculas y vías involucradas con potencial terapéutico. METODOLOGÍA: Estudio retrospectivo efectuado con base en la búsqueda de artículos registrados en Pubmed y Cochrane publicados en inglés entre los años 2000 a 2019 que contuvieran las palabras clave (MeSH): "Metformin"; "Celular mechanisms"; "AMPK"; "LKB1"; "Gestational diabetes", "Abortion" y "Preeclampsia". RESULTADOS: Se encontraron 1750 artículos que contenían las palabras clave de búsqueda; al final solo se analizaron 57. En estos se concluye que la intervención con este fármaco inhibe el complejo I de la cadena respiratoria mitocondrial, con repercusión en varios procesos celulares. La diabetes gestacional, el aborto y la preeclampsia se consideraron por su incidencia y relevancia obstétrica, y por la indicación de la metformina en su tratamiento. Se identificaron los mecanismos involucrados en el efecto colateral gastrointestinal y la asociación con los mecanismos celulares influidos por la metformina. En los padecimientos obstétricos se identificaron los procesos metabólicos para tratamiento común, la diabetes gestacional fue la más identificada por la experiencia en diabetes mellitus. CONCLUSIONES: Si bien la metformina tiene una indicación clara en pacientes con diabetes gestacional, los resultados son insuficientes para aborto; en preeclampsia los mecanismos intervenidos pueden tener mayor potencial terapéutico y preventivo.

Abstract OBJECTIVE: Identify the most recognized cellular mechanisms and their relations to obstetric pathology, determining molecular pathways for potential therapeutic use. METHODOLOGY: After a bibliographical search done in Pubmed and Cochrane database of MeSH terms: "metformin", "cellular mechanisms", "AMPK", "LKB1", "gestational diabetes", "abortion", "preeclampsia", in the periods comprehending 2000 through 2019, a total of 49 references were selected, on the basis of the criteria established by the objective of this review. RESULTS: With 49 selected references, we found that metformin regulates adenosine monophosphate protein kinase (AMPK) and LKB1, both who which participate in metabolic mechanisms, activating second messengers who stimulate or inhibit processes like gluconeogenesis, steroid and protein synthesis and cellular growth. This drug actually acts by inhibiting complex I of the mitochondrial respiration process, impacting various cell functions. Gestational diabetes, abortion and preeclampsia are three obstetric pathologies selected due to their incidence and relevance, as well as the fact that metformin is being used for their treatment. We also identified the mechanisms for gastrointestinal symptoms where OCT-1, PMAT and 5-HT are involved and may be therapeutic targets. The association of cell mechanisms influenced by metformin are part of various metabolic pathways, being the ones in gestational diabetes the most, well known due to experience with diabetes mellitus. CONCLUSIONS: Although metformin has a clear role in gestational diabetes, results are insufficient to identify its' role in abortion. As for preeclampsia, the mechanisms identified have a greater preventive and therapeutic potential.

Oncogenes, genes supressores de tumores, microRNAs e o desenvolvimento de tumores / Oncogenes, tumor supressor genes, microRNA and tumor development

O câncer é um processo invasivo decorrente da transformação celular que ocorre em resposta a distúrbios genéticos provocados por mutações ou amplificações de alguns genes que codificam para proteínas capazes de controlar a proliferação e divisão celular, tais genes mutados são chamados oncogenes. Os genes normais (não alterados) constituintes do genoma são denominados proto-oncogenes. Neste artigo serão discutidos os mecanismos moleculares que estão envolvidos com a transformação de proto-oncogenes em oncogenes. A ação de microRNA no controle da expressão gênica representa um mecanismo essencial no controle de várias proteínas envolvidas com a carcinogênese, como consequência este tema também será abordado. Finalmente, será descrito o papel essencial que os genes supressores de tumores ou genes supressores da proliferação celular (antioncogenes) desempenham no controle do desenvolvimento do câncer. O melhor entendimento dos mecanismos celulares envolvidos na carcinogênese são essenciais para descobertas de novas moléculas que poderão servir como biomarcadores de diagnóstico e/ou prognóstico do câncer, além de poderem auxiliar significativamente para a descoberta de futuras terapias antitumorais.

Molecular and cellular mechanisms of opiate addiction / 中国药理学通报

Addiction is gaining recognition as a leading cause of death, morbility and lost productivity. The urgent clinical and social need to do something about addiction promotes the development of addciton research. This paper reviews the main advances in this area in the latest thirty years, ranging from the initial targets of the major drugs of abuse, to the cAMP pathway in opiate tolerence and dependence and molecular and cellular mechanisms of addiction in VTA-NAc pathway.