Metabolomics in drug research and development: The recent advances in technologies and applications

Emerging evidence has demonstrated the vital role of metabolism in various diseases or disorders. Metabolomics provides a comprehensive understanding of metabolism in biological systems. With advanced analytical techniques, metabolomics exhibits unprecedented significant value in basic drug research, including understanding disease mechanisms, identifying drug targets, and elucidating the mode of action of drugs. More importantly, metabolomics greatly accelerates the drug development process by predicting pharmacokinetics, pharmacodynamics, and drug response. In addition, metabolomics facilitates the exploration of drug repurposing and drug-drug interactions, as well as the development of personalized treatment strategies. Here, we briefly review the recent advances in technologies in metabolomics and update our knowledge of the applications of metabolomics in drug research and development.

Evolution and development of potent monobactam sulfonate candidate IMBZ18g as a dual inhibitor against MDR Gram-negative bacteria producing ESBLs

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

A Review on the Probable Mode of Action of Agnikumara Rasa (B.R Jwaradhikara) - An Ayurvedic Herbal Formulation With Multifaceted Action

In Ayurveda, Agnimandya (reduced digestive power) is considered as a root cause for all diseases. Agnikumara rasa (B.R Jwaradhikara) is a well-known Ayurvedic formulation used by Ayurvedic practitioners that increases Agni (digestive fire) and is indicated in various diseases with specific Anupana (adjuvant). There are 6 constituents in this formulation and is indicated in the management of vitiation of Kapha and Vata humor. On analysing the properties of the ingredients, it was found that it is predominant of Katu rasa (pungent taste), Thikta rasa (bitter taste), Laghu (light), Ruksha (dry), Tikshna (sharp) properties, Ushna virya (hot potency), Katu vipaka (pungent taste after bio-transformation). These therapeutic properties are responsible for pharmacological actions of the formulation. This review paper is an attempt to analyse the mode of action of this formulation which gives a deep insight about the usage of the formulation with a better understanding, so that the physician can use the formulation according to his logic in conditions other than indicated.

Isolation, Identification and Mode of action of Partially Purified Bacteriocins from Lactic Acid Bacteria in Fermented Cassava Grits

The study on the isolation, identification and mode of action of partially purified bacteriocin from lactic acid bacteria found in fermented cassava grits was carried out. Fermented cassava grits were collected from different garri processing plants and transported with cold box to the laboratory for analysis. The viable microbial count after the partially purified bacteriocin from the various lactic acid bacteria isolates were grown against the food borne bacteria (Staphylococcus aureus and Bacillus subtilis) ranged from 0.98 x 103 CFU/ml for partially purified bacteriocin from isolate 6 at 8 hrs to 9.2 x103 CFU/ml for isolate 3 at 24 hrs. Similar results were obtained against Bacillus subtilis with microbial counts that ranged from 1.02 x102 CFU/ml for isolate 3 at 8 hrs to 9.2 x 102 CFU/ml at 24 hrs. Isolates 6, 7, 10 and 11 were bactericidal to both Staphylococcus aureus and Bacillus subtilis while isolate 3 was bacteriostatic. The viable microbial count after the partially purified bacteriocin was grown against the foodborne bacteria (Escherichia coli and Salmonella typhi) ranged from 1.0 x102 CFU/ml for partially purified bacteriocin from isolate 3 at 8 hrs to 7.1 x 102 CFU/ml for partially purified bacteriocin from isolate 6 at 24 hours. The microbial count against Salmonella typhi ranged from 6.50 x 102 CFU/ml for isolate 6 at 8 hrs to 8.5 x 102 CFU/ml for isolate 7 at 24 hrs. Partially purified bacteriocins from isolates 3 and 7 were bacteriostatic while isolates 6, 10 and 11 were bactericidal to Escherichia coli and Salmonella typhi. This result showed that the partially purified bacteriocins were very efficacious in killing or inhibiting the growth of some foodborne pathogens which can be applied in biopreservation.

Research progress on stimulator of interferon genes (STING) agonists / 中国药科大学学报

@#Stimulator of interferon genes (STING) is an important factor in the auto-immune response of our bodies.Considering the mechanism of activating CD8+ T cells after the activation of STING protein, the combination of STING agonists and immune checkpoint inhibitors for the treatment of tumor immunotherapy has good clinical application prospect.In this paper, the research progress of molecular types, mechanism of action and structural modifications of STING agonists were reviewed.The developing tendency were outlined to provide some references for further investigation.

Ultrastructural changes in methicillin-resistant Staphylococcus aureus (MRSA) induced by a novel cyclic peptide ASP-1 from Bacillus subtilis: A scanning electron microscopy (SEM) study / Cambios ultraestructurales en Staphylococcusaureus resistente a meticilina (SARM) inducidos por un nuevo péptido cíclico ASP-1 de Bacillussubtilis: un estudio con microscopio electrónico de barrido (MEB)

ABSTRACT Increasing antimicrobial resistance amongStaphylococcus aureusnecessitates a new antimicrobial with a different site of action. We have isolated a novel cyclic peptide-1 (ASP-1) fromBacillussubtiliswith potent activity against methicillin-resistantS. aureus(MRSA) at a minimum inhibitory concentration (MIC) of 8-64μg/ml. Scanning electron micrographs demonstrated drastic changes in the cellular architecture of ASP-1 treated cells ofS. aureusATCC 29213 and an MRSA clinical isolate at MICs, with damages to the cell wall, membrane lysis and probable leakage of cytoplasmic contents at minimum bactericidal concentrations. The ultrastructure alterations induced by ASP-1 have also been compared with those of oxacillin-treated MRSA cells at its MIC using scanning electron microscopy.

RESUMEN El incremento de la resistencia antimicrobiana entre los tipos deS. aureusexige un nuevo agente antimicrobiano con un sitio de acción diferente. Aislamos un nuevo péptido cíclico (ASP-1) deBacillussubtiliscon potente actividad frente aS. aureusresistente a meticilina (SARM) en una concentración inhibitoria mínima (CIM) de 8-64μg/ml. Las micrografías obtenidas con microscopio electrónico de barrido mostraron cambios drásticos en la arquitectura celular de las células deS. aureusATCC 29213 tratadas con ASP-1, y un aislamiento clínico de SARM a la CIM, con daños a la pared celular, lisis de la membrana y probable fuga de contenido citoplasmático a concentraciones bactericidas mínimas. Comparamos también, las alteraciones de la ultraestructura inducidas por ASP-1 con las de células de SARM tratadas con oxacilina a su CIM, utilizando microscopio electrónico de barrido.

Concepción teórico-metodológica para la formación del modo de actuación atención médica integral desde la Psicología / Theoretical-methodological conception in view of the formation of a model of action in comprehensive medical care from psychology

Introducción: El reciente perfeccionamiento curricular de la carrera de Medicina en la educación superior cubana suscita la búsqueda de alternativas científicas que contribuyan a la sistematización del proceso formativo de la atención médica integral en los servicios de la asistencia sanitaria esencial. Objetivo: Exponer una concepción teórico-metodológica para la formación del modo de actuación atención médica integral desde la disciplina Psicología. Métodos: El proceso investigativo asumió un enfoque metodológico mixto o multimodal, que siguió un diseño mixto explicativo secuencial, en el que se integraron métodos teóricos, empíricos, así como de análisis de la información y procesamiento de los datos. Este se desarrolló en la carrera de Medicina de la Universidad de Ciencias Médicas de Villa Clara entre septiembre de 2016 y enero de 2019, y abarcó los momentos de la exploración, el diseño y la evaluación del resultado científico propuesto. Resultados: Se pudo definir la connotación científica de la concepción teórico-metodológica propuesta, en respuesta a la estructura formal para la formación del modo de actuación atención médica integral y a la forma lógica de su vinculación con la disciplina Psicología. Conclusiones: Se estableció que una concepción teórico-metodológica para la formación del modo de actuación atención médica integral desde la disciplina Psicología debe integrar en su estructura los fundamentos generales que sustentan la lógica interna de esta, y los componentes teórico-conceptual y metodológico-instrumental que definen su organización e implementación práctica(AU)

Introduction: The recent curricular improvement of the medical major in Cuban higher education brings about the search for scientific alternatives that contribute to systematization of the training process for comprehensive medical care in essential healthcare services. Objective: To present a theoretical-methodological conception for the formation of a mode of action in comprehensive medical care from the psychology discipline. Methods: The research process followed a mixed or multimodal methodological approach, under a mixed sequential explanatory design, in which theoretical and empirical methods were integrated, as well as information analysis and data processing. This was developed, between September 2016 and January 2019, in the medical major of Villa Clara University of Medical Sciences, and covered the moments of exploration, design and assessment of the proposed scientific result. Results: It was possible to define the scientific connotation of the proposed theoretical-methodological conception, in response to the formal structure for the formation of a mode of action in comprehensive medical care and the logical way of its link with the psychology discipline. Conclusions: It was established that a theoretical-methodological conception for the formation of a mode of action in comprehensive medical care from the psychology discipline must integrate, into its structure, the general foundations that support its internal logic, as well as the theoretical-conceptual and methodological-instrumental components that define its organization and practical implementation(AU)

New Progress in Mechanism of Salviae Miltiorrhizae Radix et Rhizoma in Treatment of Diabetes and Its Complications / 中国实验方剂学杂志

Diabetes is a worldwide public health problem that seriously threats human health. Long-term metabolic disorders， as the main cause of multi-system complications and death in the later stage of diabetes， can cause multi-system damage， leading to chronic progressive lesions in the eyes， kidneys， nerves， heart， blood vessels and other tissues and organs， as well as functional decline and failure. The low risk of side effects and new treatment strategies remain an area to be explored in clinical treatment of diabetes. Salviae Miltiorrhizae Radix et Rhizoma （SM） is one of the commonly used herbs in traditional Chinese medicine （TCM）， with the main effect of activating blood circulation and removing blood stasis. In recent years， it has been found that SM shows good performance in lowering blood sugar and treating diabetes complications. Data mining information has also shown that the drugs of activating blood circulation and removing blood stasis are now common drugs in clinical treatment of diabetes， and SM has the highest use frequency， with significant curative effect. In addition， TCM is a kind of treatment with composite components and multiple targets， and so people are increasingly interested in its effective components and carry out extensive researches. This article summarized the experimental verification of SM extract and its components （tanshinone A， tanshinone B， tanshinone ⅡA， tanshinone I， protocatechuic aldehyde， polysaccharide， and total polyphenol acid） in various diabetes models in improving glucolipid metabolism， improving heart function in patients with diabetes， alleviating the motor and sensory deficits caused by diabetes， preventing the occurence of the diabetic retinopathy， recovery of liver and kidney structure and function damage in diabetic patients， and helping to resist high sugar-induced atrophic cavitation potential. It may inhibit hyperglycemia-induced vascular injury with polyol pathway activation， reduce the formation of advanced glycation end products， inhibit protein kinase C pathway activation and hexosamine pathway activation， and alleviate oxidative stress caused by excessive production of peroxides in mitochondrial electron transport chain during hyperglycemia to play a role of treatment， and provide reference for clinical application.

Research progress of KRAS inhibitors / 药学学报

The RAS (rat sarcoma) gene is one of the important oncogenes, and its mutation is present in about 30% human tumors. KRAS (kirsten rat sarcoma viral oncogene) is one of the three RAS subtypes, and KRAS mutations are more common than the mutations in other two RAS subtypes. In recent years, with the continuous research, new ideas have been provided for the treatment of cancers via targeting-KRAS. Efforts have been made to develop various KRAS inhibitors. Here, based on the mechanism of action, we classified KRAS inhibitors into two categories: inhibitors that directly target KRAS and inhibitors that indirectly act on KRAS. The representative KRAS inhibitors were summarized and introduced in this paper.

Bioinformatics analysis of key toxicity pathways in the mode of action of oral exposure to hexavalent chromium / 环境与职业医学

Background Oral exposure to hexavalent chromium [Cr(VI)] can lead to gastrointestinal tumorigenesis in mice, and the mechanism is not yet clear. To predict health risk due to chemical exposure, data mining and computational toxicology analysis has become an important tool in toxicology research, which can help to elucidate mode of action (MOA) and identify key toxicity pathways. Objective This study aims to identify and evaluate key events in the MOA of oral Cr(VI) exposure. Methods Gene sets established from Comparative Toxicogenomics Database (CTD) and Gene Expression Omnibus (GEO) respectively were imported into Ingenuity® Pathway Analysis (IPA) software for pathway enrichment analysis and biological function analysis to identify potential key toxicity pathways of target organs/tissues toxicity of oral exposure to Cr(Ⅵ). Next, the weight of evidence (WOE) of the identified key toxicity pathways in the MOA of oral exposure to Cr(VI) was evaluated based on the modified Bradford Hill principle. Results A total of 54 pieces of literature related to oral Cr(VI) exposure were screened in CTD, among which 18 and 9 were related to liver and intestine with 125 and 272 corresponding genes, respectively. The pathway enrichment and biological function analysis results showed that liver and intestinal perturbation pathways were mainly related to cell stress and injury, cell cycle regulation, and apoptosis, indicating that Nrf2 pathway and AHR pathway might be the key toxicity pathways involved in the cytotoxic-mediated MOA. Meanwhile, the dose (≥170 mg·L−1 sodium dichromate) and the time point (90 d) of the activation of Nrf2 pathway was similar to the emergence of crypt cell proliferation. It was proposed that Nrf2 pathway activation might be a key event for cytotoxic-mediated MOA of small intestinal tumors. The WOE results showed moderate validity of evidence in this hypothesis, with high validity of evidence for biological plausibility and dose-response manner. Conclusion Nrf2 pathway activation might be the key event in the cytotoxic-mediated MOA of small intestinal tumors induced by oral exposure to Cr(VI) via initiating or maintaining crypt cell proliferation.

La actuación profesional de los docentes universitarios y su preparación para la educación intercultural / Professional action of university teachers and preparation for intercultural education

RESUMEN Fundamento: La práctica de la educación intercultural en Cuba es un campo disciplinar que demanda mayor preparación en el modo de actuación profesional de los docentes universitarios. Objetivo: Construir un programa de preparación, centrado en la solución de conflictos, para perfeccionar el modo de actuación profesional de los docentes universitarios para la educación intercultural. Metodología: Se realizó una investigación en la Universidad de Sancti Spíritus José Martí Pérez, en la que se utilizó la metodología cualitativa basada en el estudio de caso del modo de actuación profesional de los docentes para la educación intercultural. Resultados: El diagnóstico pedagógico integral no se tuvo en cuenta para la identificación y solución de los conflictos interculturales, dependiendo del estatus de igualdad grupal alcanzado. La preparación en educación intercultural, centrada en la solución de conflictos, demostró la efectividad de trabajar en correspondencia al sistema de acciones propias de la dirección del proceso pedagógico. Conclusiones: El programa de preparación permitió reconocer la validez de la experiencia pedagógica practicada, así como la pertinencia de otras perspectivas foráneas compatibles y el manejo conceptual de los principios y competencias para la educación intercultural.

ABSTRACT Background: The practice of intercultural education in Cuba is a disciplinary field that requires greater preparation in the professional way of acting of university teachers. Objective: To build a preparation program, focused on conflicts resolution, to improve the professional performance of university teachers for intercultural education. Methodology: An investigation was carried out at the University of Sancti Spíritus José Martí Pérez, using the qualitative methodology based on the case study of the professional performance of teachers for intercultural education. Results: The comprehensive pedagogical diagnosis was not taken into account for the identification and solution of intercultural conflicts, depending on the group equality status achieved. The preparation in intercultural education, focused on conflict resolution, demonstrated the effectiveness of working in correspondence with the system of actions proper to the direction of the pedagogical process. Conclusions: The preparation program allowed to recognize the validity of the pedagogical experience practiced, as well as the relevance of other compatible foreign perspectives and the conceptual handling of the principles and competences for intercultural education.

Orthosiphon stamineus water extracts inhibit human herpes virus 1 KOS-1 and acyclovir-resistant strains by virucidal activity and suppressing virus early infection

Aim@#To determine the efficacy and mode of action of hot and cold water extracts of Orthosiphon stamineus leaves against two strains of human herpes virus 1 (HHV-1) i.e. KOS-1 and acyclovir (ACV)-resistant UKM-1 (UKM-1) strains. @*Methodology and results@#Hot and cold water extracts of O. stamineus were not cytotoxic to vero cells as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) (MTT) assay with 50% cytotoxicity concentration (CC50) values of 3.4 and 3.3 mg/mL respectively. Antiviral activity was determined by plaque reduction assay in post-treatment, pre-treatment and virucidal assays followed by time-addition and time removal assay to relate with the stages during the viral infection cycle. Both extracts displayed antiviral activity against HHV-1 KOS-1 and HHV-1 UKM-1 strains with 50% effective concentration (EC50) values between 0.12-0.15 mg/mL in reducing plaque formation. The calculated selectivity indices (SI) were 23 and 28 for hot and cold water extract respectively, indicating that they have good potential as antiviral agent. The extracts were virucidal towards both HHV-1 KOS-1 and HHV-1 UKM-1 strains which may directly affects the virus structure. This is supported with the fact that exposure of the extracts inhibit viral attachment and penetration to the vero cells. In time-of addition assay, both extracts were effective during the early stage of virus infection cycle for HHV-1 KOS-1 strain which is in parallel with the results from the attachment and penetration studies. For HHV-1 UKM-1 strain, contact to the extracts at any time during post-infection inhibits virus replication and also progeny release. @*Conclusion, significance and impact of study@#Cold and hot water extracts of O. stamineus have good potential as antiviral agent against HHV-1 strain KOS-1 and more importantly against UKM-1 strain which is ACV-resistant. The extracts displayed virucidal effect and inhibition of early virus replication cycle involving viral attachment and penetration to cells.

Recent updates on drug-resistance mechanisms in Mycobacterium tuberculosis and the role of PE/PPE proteins in drug resistance / 中国临床药理学与治疗学

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (M. tb) and mainly spread by airborne transmission, remains a global health problem. After the wide clinical utilization of antibiotics in treatment of TB, the drug resistance has become a major threat to global TB control and this threat has been heightened by the emergence and propagation of multi-drug resistant tuberculosis (MDR-TB), extensively drug-resistant tuberculosis (XDR-TB) and totally drug-resistant tuberculosis (TDR-TB). The research in the mode-of-action mechanisms of anti-TB drugs and the drug resistance mechanisms of M. tb will facilitate the novel anti-TB drugs development, the optimization of current anti-TB drugs and the development of new drug resistance diagnosis technologies. This review provides a comprehensive overview of mode-of-action mechanisms of new anti-TB drugs and mechanisms of resistance to these drugs in M. tb, with particular attention to the role of newly-identified mycobacterial outer-membrane channel proteins (PE/PPE proteins) in TB drug resistance.

Chemical control of leaf-cutting ants: how do workers disperse toxic bait fragments onto fungus garden?

ABSTRACT Leaf-cutting ants are controlled with toxic baits. For the method's greater efficiency, the baits must be distributed and processed by workers during fungus cultivation. To test hypotheses whether the mode of action of the active ingredients, which blocks the sodium channels and interrupts the production of ATP in the mitochondria, interferes with fragment distribution in nests; the dispersion of pellets fragments during fungus cultivation by workers was assessed, spatially referencing the fragment onto the fungus garden. Pellets fragments were randomly distributed, but the amount pellets fragments was influenced by the way that the active ingredient acts in the colony.

Cytotoxicity of naturally occurring phenolics and terpenoids from Kenyan flora towards human carcinoma cells

Background: Cancer constitutes a major hurdle worldwide and its treatment mainly relies onchemotherapy.Objectives: The present study was designed to evaluate the cytotoxicity of eleven naturally occurringcompounds including six phenolics amongst them were 4 chalcones and 2 flavanones as well as 5 terpenoids (3 clerodane and 2 trachylobane diterpenoids) against 6 human carcinoma cell lines and normalCRL2120 fibroblasts.Materials and methods: The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of thecompounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle and mitochondrialmembrane potential (MMP) were all analyzed via flow cytometry meanwhile levels of reactive oxygenspecies (ROS) was measured by spectrophotometry.Results: Chalcones: 20,40-dihydroxy-60-methoxychalcone (1); 40,60-dihydroxy-20,50-dimethoxychalcone(2); 20,40,60-trihydroxy-50-methoxychalcone (3); 20,60-diacetate-40-methoxychalcone (4), trachylobanediterpenoids: 2,6,19-trachylobanetriol; (ent-2a,6a)-form (10) and 2,18,19-trachylobanetriol; (ent-2a)-form (11) as well as doxorubicin displayed IC50 values below 110 mM in the six tested cancer cell lines. TheIC50 values of the most active compounds were between 6.30 mM and 46.23 mM for compound 1respectively towards breast adenocarcinoma MCF-7 cells and small lung cancer A549 cells and between0.07 mM and 1.01 mM for doxorubicin respectively against SPC212 cells and A549 cells. Compounds 1induced apoptosis in MCF-7 cells mediated by increasing ROS production and MMP loss.Conclusion: Chalcones 1e3 are potential cytotoxic phytochemicals that deserve more investigations todevelop novel anticancer drugs against human carcinoma.© 2018 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Publishing Services byElsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Probable Mode Of Action Of Kalyanaka Ghrita In Unmada (insanity) Based On Analysis Of Rasa Panchaka Of Ingredients- A Review

Aim: This review article is an attempt to analyse the probable mode of action of Kalyanaka ghrita in psychiatric conditions. Background: Unmada is a term that represents broad classes of mental ailments in Ayurvedic literature. Mental disorders impose an enormous burden on society, accounting for almost one in three years lived with disability globally. According to the WHO, every year, almost one million people die from suicide; a "global" mortality rate of 16 per 1,00,000 or one death every 40 seconds. Kalyanaka ghrita is a time tested and clinically proven polyherbal formulation which is widely and effectively used by Ayurvedic physicians in the management of psychiatric conditions. Results: While analysing the Rasapanchaka (Ayurvedic Principles of Drug-Action), it is found that of the 28 ingredients, 15 drugs are having Tikta rasa, 22 with Laghu guna, 19 with Ushna veerya and 18 with Katu vipaka. Considering Doshaharatwa, 12 drugs are Kaphapittahara. All these properties are against Kapha dosha. Conclusion: Kalyanaka ghrita may be more effective in the management of Kaphaja unmada, among all the 6 varieties of Unmada. Clinical Significance: Analysis of mode of action leads us to the inference that Kalyanaka ghrita may be more effective in the management of Kaphaja unmada, characterised by slow or weak voice and body movements, anorexia, desire for women (sex) and solitude, excessive sleep, vomiting, dribbling of saliva, symptoms pronounced just after intake of food, whitish discoloration of nails constitute Kaphaja unmada, a classical example being depression.

Application of Quercus infectoria extract as a natural antimicrobial agent for chicken egg decontamination / Aplicación de un extracto de Quercus infectoria como agente antimicrobiano natural para la desinfección de huevos de gallina

Egg contamination with microbial pathogens is an enduring worldwide concern. Natural products are frequently recommended as ideal alternatives to substitute synthetic and chemical antimicrobials. Oak galls (Quercus infectoria) are aberrant growths on oak trees that have many medicinal and pharmaceutical applications. Q. infectoria extract (QIE) antimicrobial action was assessed against many microbial species, and used for eggshell decontamination. QIE antimicrobial activity was evidenced against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella Typhimurium and Candida albicans, using different assay methods. Disinfection of eggshell microbial contamination, by immersion in 1% QIE solution, sharply reduced total colony count, yeasts and molds, Enterobacteriaceae. E. coli and S. aureus were completely inhibited after 60min of immersion in QIE. QIE biochemical analysis revealed elevated contents of phenolic and flavonoid compounds. The captured micrographs of S. aureus cells treated with QIE showed strong alterations in cell morphology; cells were entirely lysed and ruptured after 6h of treatment. QIE can be recommended as an effective and natural disinfectant for decontaminating eggshells from pathogenic microorganisms.

La contaminación de huevos con patógenos microbianos es un problema constante en todo el mundo. Con frecuencia se recomiendan diversos productos naturales como alternativas ideales para sustituir a los antimicrobianos sintéticos. Las agallas de roble (Quercus infectoria) son de crecimiento aberrante en los robles y tienen muchas aplicaciones medicinales y farmacéuticas. Se evaluó la acción antimicrobiana del extracto de Quercus infectoria (QIE) contra varias especies microbianas y también este se aplicó para la descontaminación de cáscaras de huevo. La actividad antimicrobiana del extracto de QIE se evidenció en relación con Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhimurium y Candida albicans, utilizando diferentes métodos de ensayo. La inmersión de las cáscaras de huevo en extracto de QIE al 1% logró una fuerte reducción del recuento total de colonias, de levaduras y de mohos, y de miembros de Enterobacteriaceae. La inmersión durante 60 min inhibió completamente el desarrollo de E. coli y S. aureus. El análisis bioquímico del extracto de QIE reveló que este tiene un contenido elevado de compuestos fenólicos y de flavonoides. Se documentó mediante micrografías la presencia de grandes alteraciones en la morfología celular de S. aureus tras la exposición al extracto de QIE: las células se lisaron completamente y se rompieron después de 6h de tratamiento. El extracto de QIE se puede recomendar como un desinfectante eficaz y natural para descontaminar cáscaras de huevos de microorganismos patógenos.

A new coumarin derivative, 4-acetatecoumarin, with antifungal activity and association study against Aspergillus spp

Abstract Fungal infections have become a concern for health professionals, and the emergence of resistant strains has been reported for all known classes of antifungal drugs. Among the fungi causing disease, we highlight those that belong to the genus Aspergillus. For these reasons, the search for new antifungals is important. This study examines the effects of a coumarin derivative, 4-acetatecoumarin (Cou-UMB16) both alone and together with antifungal drugs, and its mode of action against Aspergillus spp. Cou-UMB16 was tested to evaluate its effects on mycelia growth, and germination of Aspergillus spp. fungal conidia. We investigated its possible action on cell walls, on the cell membrane, and also the capacity of this coumarin derivative to enhance the activity of antifungal drugs. Our results suggest that Cou-UMB16 inhibits Aspergillus spp. virulence factors (mycelia growth and germination of conidia) and affects the structure of the fungal cell wall. When applying Cou-UMB16 in combination with azoles, both synergistic and additive effects were observed. This study concludes that Cou-UMB16 inhibits mycelial growth and spore germination, and that the activity is due to its action on the fungal cell wall, and that Cou-UMB16 could act as an antifungal modifier.

Metabolic disturbance and phytochemical changes in Andrographis paniculata and possible action mode of andrographolide

Objective:To explore the effect of gibberellic acid (GA3) and its inhibitor paclobutrazol (PBZ)on chemical composition and their pharmacological effects on Andrographis paniculata (Burm.f.) Wall.ex Nees,and to clarify action mode of andrographolide.Methods:The chemical composition was extracted by sequential extraction with hexane,dichloromethane,ethyl acetate and methanol,respectively.Andrographolide and its derivatives were evaluated by HPLC.Moreover,the metabolic profiling was analyzed by GC-MS.Inhibitory effect of crude extracts was tested against Staphylococcus aureus using agar well diffusion method.Mode of action was tested against mutant yeast by spotting assay.Andrographolide were tested for their mode of action against eukaryotes.Results:Among different solvents,dichloromethane gave the highest yield of crude (3.58％ DW),with the highest andrographolide content (8.3 mg/g DW).The effect of plant hormone (10 mg/L GA3 or PBZ) on phytochemical variations and bioactivity of Andrographis paniculata was demonstrated.It was found that PBZ promoted sesquiterpene compounds about 3.5 times over than GA3 treatment.But inhibitory effect of extracts against Staphylococcus aureus was highest in GA3 treated plants;andrographolide and 14-deoxy-11,12-didehydroandrographolide contents were significantly higher than those of water or PBZ.It was found that there were 11 strains involving in ergosterol biosynthesis,V-ATPase activity and homeostasis,and superoxide detoxification process.In this regard,andrographollde might cause the damage on the lipid bilayer of yeast cell and plasma membrane by interfering ergosterol biosynthesis.Conclusions:It is found that GA3 promotes andrographolide and 14-deoxy-11,12-didehydroandrographolide content while PBZ promotes sesquiterpene content.Andrographolide might cause the damage on the lipid bilayer of yeast cell and plasma membrane by interfering ergosterol biosynthesis.It might also affect mitochondria electron transport chain,leading to the occurrence of ROS,which can further harm cell organelles.However,the library screening is the first step to investigate mode of action of andrographolide.

Progress on Detection of Metals Ions by Functional Nucleic Acids Biosensor / 分析化学

Functional nucleic acids are natural or artificialnucleic acid sequences with specific functions and special structures. Special metal ions are essential trace elements for human health, but excessive metal ions will be harmful to human health. The functional nucleic acids are widely used in the detection of metal ions because of their advantages such as easy modification, low price, high stability and strong specificity. This review describes the function of functional nucleic acid and metal ions, mainly including cutting type, link type, metal ion-mediated base pairing, click chemical type, conformation change type, and other types. Then, biosensor of functional nucleic acid combined with different signal output is introduced. Finally, the research significance and problems of functional nucleic acid in metal ion detection are discussed, and the future development direction and application prospect of functional nucleic acid biosensor are prospected.