Synergistic effects of methotrexate and piperine on human osteosarcoma cell lines – An in-vitro study

Background: Osteosarcoma is a malignant cancer that effect bone and metastasizing to many vital organs such as lungs. There are many available drugs to treat the disease including tamoxifen, methotrexate (MTX), and cisplatin which have their own side effects and hurdles to become drugs of choice for the disease. On the other hand, introduction of herbal drugs as chemotherapeutic agents opened up new arena to potentiate the existing treatment by exhibiting synergy. Piperine (PPN) is widely used drug as anti-cancer agent as well as it has anti-inflammatory, analgesic properties, and also used in the treatment of abdominal pains, tuberculosis, arthritis, and respiratory illness. Aims and Objective: Thus, this study was designed to investigate the synergistic inhibitory potential of PPN and MTX on the MG63 osteosarcoma cell lines in vitro. Materials and Methods: The cell lines were cultured on DMEM medium and investigated for cytotoxicity of the drugs using MTT assay at 540 nm in UV. Three groups of cell lines administered with PPN, MTX, and PPN+MTX (1:1) in various concentrations and IC50 values were calculated based on the % cell viability graphs. Results: Results showed that the IC50 of PPN was 38.65, MTX was 123.98, and PPN+MTX was 15.13 proving the significant synergistic cytotoxic effect of PPN and MTX in inhibiting the proliferation of MG63 cell lines. Conclusion: Further research needs to be conducted in this field to elucidate the synergistic pathways in which PPN has shown a better anti-osteosarcoma effect when combined with MTX.

SMILESynergy: Anticancer drug synergy prediction based on Transformer pre-trained model / 生物医学工程学杂志

The synergistic effect of drug combinations can solve the problem of acquired resistance to single drug therapy and has great potential for the treatment of complex diseases such as cancer. In this study, to explore the impact of interactions between different drug molecules on the effect of anticancer drugs, we proposed a Transformer-based deep learning prediction model-SMILESynergy. First, the drug text data-simplified molecular input line entry system (SMILES) were used to represent the drug molecules, and drug molecule isomers were generated through SMILES Enumeration for data augmentation. Then, the attention mechanism in the Transformer was used to encode and decode the drug molecules after data augmentation, and finally, a multi-layer perceptron (MLP) was connected to obtain the synergy value of the drugs. Experimental results showed that our model had a mean squared error of 51.34 in regression analysis, an accuracy of 0.97 in classification analysis, and better predictive performance than the DeepSynergy and MulinputSynergy models. SMILESynergy offers improved predictive performance to assist researchers in rapidly screening optimal drug combinations to improve cancer treatment outcomes.

The synergism of hepatitis B and aflatoxicosis in hepatocellular carcinoma development: A mini-review

Hepatocellular carcinoma (HCC) is the twelfth most common cancer and the fifth leading cause of worldwide cancer related death. Chronic hepatitis B infection, caused by the hepatitis B virus (HBV) and exposure to aflatoxins is fundamental in the formation of HCC in developing countries. This review of scientific publications aims to establish the detrimental effects of aflatoxin-contaminated foods and highlights the correlation between aflatoxin and hepatitis B viral-associated hepatocellular carcinoma. Research has shown a significant increase in the occurrence of HCC in HBV-infected individuals exposed to fungal toxins. HBV demonstrates the ability to integrate and bind to p53 protein in the host DNA and propagate hepatocyte vulnerability through carcinogenic aflatoxin B1 (AFB1) damage. Although there has been clear evidence about the synergistic interaction of exposure to AFB1 and HBV infection in the induction of HCC, other literature has shown otherwise, mainly because incomplete and vague findings and hypotheses were made in regions where AFB1 and HBV pose a public health risk. Vaccination against hepatitis B and measures such as robust food safety systems to avoid hepatotoxicity and hepatocellular carcinogenesis induced by AFB1 is the most effective methods in the prevention of HCC induced by HBV and AFB1

Research on the Construction of the Community of Red Doctor’s Spirit Education from the Perspective of Synergy Theory / 中国医学伦理学

The red doctor’s spirit education community is a group of individuals or organizations that pay attention to and study the red doctor’s spirit education, and committed to red doctor’s spirit education. Based on shared values, theoretical basis, and practical goals, an organic unity consisting of educators, educational objects, educational mechanisms, educational platforms and other elements is formed through collaborative cooperation. In view of the theoretical and practical consistency between the idea of education community and the synergy theory, medical colleges and universities should find out the problems faced in the construction of the red doctor’s spirit education community from the perspective of synergy theory, and strive to optimize the main body of red doctor’s spirit education by strengthening the awareness of educational community; integrate the educational resources of the community and improve the content of red doctor’s spirit education; improve the education mechanism of the community and create a high-quality education community; build a community education platform, realize the co-construction and sharing of red doctor’s resources, constantly improve the effect of red doctor’s spirit education, and serve the growth and success of medical students.

Influence of the teaching model based on the synergy of medical education on the objective structured clinical examination scores and critical thinking ability of interns in emergency department / 中华医学教育探索杂志

Objective:To investigate the influence of the teaching model based on the synergy of medical education on the objective structured clinical examination (OSCE) scores and critical thinking ability of interns in emergency department.Methods:A total of 84 students who studied as interns in Emergency Department of our hospital from January 2020 to 2021 were selected as research subjects, and they were divided into observation group and control group using a random number table, with 42 students in each group. The students in the control group were taught using traditional methods, while those in the observation group were taught based on the synergy of medical education. Both groups received an OSCE examination, and the two groups were compared in terms of OSCE score, critical thinking ability, and evaluation of teaching. SPSS 22.0 was used to perform the t-test and the chi-square test. Results:Compared with the control group, the observation group had significantly higher scores of theoretical assessment, disease assessment, first aid measures, special skills, use of medical instruments, communication skills with SP, and medical record writing and a significantly higher total score of OSCE assessment ( P<0.05). After teaching, both groups had a significant increase in the score of critical thinking ability, and the observation group had a significantly higher score than the control group [(306.38±25.76) vs. (280.39±20.17)]. The observation group had a significantly higher degree of satisfaction with teaching than the control group ( P<0.05). Conclusion:The teaching model based on the synergy of medical education can improve the OSCE score of interns in emergency department and cultivate their critical thinking ability, and there is a relatively high degree of satisfaction with this teaching model.

A study of the practice of "three early education" combined with medical ethics literacy cultivation to improve medical students' post competence / 中华医学教育探索杂志

Clinical post competence and medical ethics literacy are the key qualities that applied medical talents should have. The synergy of medical education is an effective way to deepen the reform of competence-oriented medical education. Under the background of synergy of medical education and considering the orientation of training applied medical talents in our college, we explore a progressive path of "three early education", which means early exposure to specialties, early exposure to practice, and early exposure to clinical practice. Meanwhile, we strengthen the cultivation of medical students' medical ethics literacy throughout the whole process of "three early education", laying a solid foundation for medical students before they enter the stage of clinical practice training. Practice shows that the progressive "three early education" mode and the cultivation of medical ethics literacy throughout the whole process can effectively improve medical students' clinical post competence.

Influence of concurrent administration of the methanol leaf extract of Leptadenia hastata (Pers) decne (Apocynaceae) with metformin on blood glucose in diabetic rats

Objectives: Leptadenia hastata (Pers) Decne (Apocynaceae) is a common medicinal plant used in northern Nigeria either singly or together with conventional drugs to treat diabetes. This study investigated the influence of concurrent administration of the methanol leaf extract of L. hastata with metformin in streptozotocin/ nicotinamide-induced diabetic rats. Materials and Methods: Possible synergistic activity between the extract and metformin was assessed using 3 models of synergy analysis (Loewe additivity, Bliss independent and highest single agent [HSA] models). Eleven groups of Wistar rats (eight animals per group) consisting of ten groups of diabetic rats and one normal control group were used in this study. Six groups were administered with either the extract or metformin at three different doses each (50, 150 and 500 mg/kg for the extract and 30, 100 and 300 mg/kg for metformin), while another three groups were co-administered with the extract and metformin at three different ratios each (50 mg/kg: 30 mg/ kg, 150 mg/kg: 100 mg/kg and 500 mg/kg: 300 mg/kg). An oral glucose tolerance test (OGTT) was conducted at baseline and on day 14. Result: The results revealed that the extract-metformin combination brought about a synergistic reduction in the total area under the OGTT curve (based on Loewe and HSA models) as well as a synergistic reduction in blood glucose (based on Loewe, Bliss and HSA models). Conclusion: The methanol leaf extract of L. hastata produced a synergistic antidiabetic activity in streptozotocin/ nicotinamide-induced diabetic rats when combined with metformin.

Synergy in penicillin, cephalosporin, amphenicols, and aminoglycoside against MDR S. aureus isolated from Camel milk

Abstract This study investigated the synergy testing of penicillin, cephalosporin, amphenicols, and aminoglycoside in the camel milk (n=768 samples), subsequently used for isolation of MDR S. aureus targeting mecA gene. Antibiotic susceptibility of S. aureus showed >90% isolates were sensitive to ciprofloxacin and trimethoprim and resistant against oxacillin, ampicillin, and cefoxitin. Further, 50-85% of the S. aureus were sensitive to gentamicin, oxytetracycline, and chloramphenicol and resistant against cefotaxime, vancomycin, and cefixime. Minimum inhibitory concentration (MIC) of cefotaxime, (C) and ampicillin (A) in combination with gentamicin (G) was reduced by 99.34% and 70.46%, respectively, while with chloramphenicol (Ch), reduction was 57.49% and 60%, respectively. In addition, the Fractional Inhibitory Concentration Index (FICI) of G+A, Ch+C and Ch+G combinations showed synergy against 80%, 60%, and 30% of MDR S. aureus, respectively. Similarly, C+A and Ch+G displayed indifferent interaction against 70 % and 30% of isolates, respectively, while the later showed additive interaction against 10% of MDR S. aureus. Altogether, our results described effective combination of gentamicin and chloramphenicol with ampicillin and cefotaxime to combat MDR S. aureus

Óleo essencial de Pataqueira (Conobea scoparioides Cham. & Schltdl.) como conservante natural em Cosméticos / Pataqueira essential oil (Conobea scoparioides Cham. & Schltdl.) as a natural preservative in cosmetics

Um dos principais grupos de conservantes utilizados na maioria dos cosméticos são os parabenos que em muitos estudos demonstraram que podem provocar reações alérgicas como dermatite de contato, entre outras sensibilizações cutâneas. A fim de minimizar esses problemas, a indústria está produzindo cosméticos livres de conservantes ou de origem natural e em associações aos sintéticos. Dentre os conservantes naturais utilizados, podemos citar os óleos essenciais como uma alternativa viável. Diante deste contexto o presente trabalho visa avaliar experimentalmente o potencial antimicrobiano do óleo essencial de Conobea scoparioides Cham. & Schltdl., conhecida popularmente como pataqueira, o efeito de sua associação com parabenos e de sua eficácia como conservante em bases cosméticas. A composição do óleo essencial foi avaliada, indicando que este é composto em sua maior parte por terpenos, tendo éter metílico do timol (39,2%), timol (33,8 %) e α-felandreno (15,9%) como compostos majoritários. A atividade antimicrobiana do óleo essencial e do timol foi acessada através da concentração inibitória mínima (CIM), cujos resultados em µg/mL para o óleo essencial e o timol foram respectivamente: Staphylococcus aureus 650,70 e 284,90, Escherichia coli 721,53 e 271,20, Pseudomonas aeruginosa 1748,00 e > 2.000, Burkholderia cepacia 833,03 e 1.077,70, Candida albicans 521,43 e 172,61 e Aspergillus brasiliensis 300 e 400. O efeito sinérgico da associação do óleo essencial com os parabenos foi realizado através de um delineamento experimental centroide simplex para uma mistura de metilparabeno, propilparabeno e óleo essencial frente aos mesmos micro-organismos utilizados na determinação da atividade antimicrobiana. As concentrações ideais obtidas pela análise estatística para cada componente em µg/mL foram: 1120 para o metilparabeno, 350 para o propilparabeno e 675 para o óleo essencial. O teste de eficácia do sistema conservante em formulação cosmética foi efetuado empregando as concentrações ideais e mais duas concentrações superiores e uma abaixo do ideal. Para todas as cepas microbianas desafiadas o resultado do teste foi de redução total da carga microbiana inoculada nos sete dias de ensaio e nenhum aumento até o vigésimo oitavo dia o que demonstra a eficácia da associação do óleo essencial com os conservantes sintéticos. O óleo essencial de C. scoparioides apresentou um potencial antimicrobiano importante tanto sozinho como em associação com conservantes sintéticos. Estes resultados sugerem que esse óleo pode ser usado para compor um sistema conservante para formulações cosméticas contendo uma menor quantidade de sintéticos

One of the main groups of preservatives used in most cosmetics are parabens, that many studies have shown that they can cause allergic reactions such as contact dermatitis, among other skin sensitizations. To minimize these problems, the industry is producing cosmetics preservative free or using natural products instead and their combination with the synthetics. Among the natural preservatives used, we can mention essential oils as a viable alternative. In this context, the present work aims to experimentally evaluate the antimicrobial potential of the Conobea scoparioides Cham. & Schltdl. essential oil, popularly known as pataqueira, the effect of its association with parabens and its effectiveness as a preservative in cosmetic bases. The essential oil composition was analyzed, indicating that it is composed mostly of terpenes, with thymol methyl ether (39.2%), thymol (33.8%) and -phelandrene (15.9%) as major compounds. The antimicrobial activity of essential oil and thymol was accessed through the minimum inhibitory concentration (MIC), whose results in µg/mL for essential oil and thymol were respectively: Staphylococcus aureus 650.70 and 284.90, Escherichia coli 721, 53 and 271.20, Pseudomonas aeruginosa 1748.00 and > 2,000, Burkholderia cepacia 833.03 and 1,077.70, Candida albicans 521.43 and 172.61 and Aspergillus brasiliensis 300 and 400. The synergistic effect of the association of essential oil with parabens was performed through a centroid simplex experimental design for a mixture of methylparaben, propylparaben and essential oil against the same microorganisms used in the antimicrobial activity evaluation The ideal concentrations obtained by statistical analysis for each component in µg/mL were: 1120 for methylparaben, 350 for propylparaben and 675 for essential oil. The effectiveness test of the preservative system in cosmetic formulation was carried out using the ideal concentrations plus two higher concentrations and one below the ideal. For all challenged microbial strains, the test result was a total reduction of the inoculated microbial load in the seven days of testing and no increase until the twenty-eighth day, which demonstrates the effectiveness of the association of essential oil with synthetic preservatives. C. scoparioides essential oil showed an important antimicrobial potential both alone and in association with parabens. These results demonstrated that it can be used to compose a preservative system for cosmetic formulations containing lower amounts of synthetics

The effect and mechanism of epigallocatechol gallate combined with trastuzumab on the proliferation of HER2 overexpressing breast cancer cells / 药学实践杂志

Objective To study the effect and mechanism of epigallocatechol gallate (EGCG) combined with trastuzu-mab on the proliferation of human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cells. Methods Trastuzumab was expressed and purified. The cell proliferation of HER2 overexpressing breast cancer cells BT474 and SK-BR-3 treated with trastuzumab, EGCG, or trastuzumab plus EGCG was evaluated by CCK8 assay. The effects of EGCG and trastuzumab on the expression of HER2, epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK), protein kinase B (Akt), and their phosphorylated proteins in BT474 breast cancer cells were detected by Western blot. Results The results of cell proliferation assay indicated that EGCG and trastuzumab, alone or in combination, effectively inhibited the proliferation of BT-474 and SK-BR-3 cells. And within a certain concentration range, EGCG and trastuzumab showed a synergistic proliferation inhibitory effect on HER2 overexpressing breast cancer cells. Consistent with these results, Western blot results showed that trastuzumab and EGCG, alone or in combination significantly reduced the phosphorylation levels of Akt, MAPK, EGFR, and HER2 in BT474 cells. Moreover, the inhibition effect of EGCG plus trastuzumab was significantly more potent than either EGCG or trastuzumab. Conclusion EGCG and trastuzumab could synergistically inhibit the proliferation of HER2 overexpressing breast cancer cells, which may be related to the regulation of Akt and MAPK signaling pathways.

Research on the convergence mechanism of the medical-nursing combined care based on synergy theory / 中华医院管理杂志

Objective:To identify the key convergence points in the medical-nursing combined care among literature, and establish a mechanism for medical-nursing combined care integration from the perspective of the synergy theory, for the purpose of promoting the integrated development of such care in China.Methods:Relevant literature on the medical-nursing combined care were retrieved from the CNKI database from September 2013 to September 2021. The search formula used was TI= "the medical-nursing care integration" AND SU=(convergence+ transformation+ coordination+ mechanism), while supplementary searches were made using " pkulaw.com database" and Baidu Scholar database. The method of literature content analysis was used to screen key points of the medical-nursing combined care, and the convergence mechanism was built based on the perspective of the synergy theory.Results:A total of 42 literatures were included in this study, 8 key convergence points of medica-nursing combined care integration were identified. Namely the 4 key horizontal convergence points of medical care, aging care, rehabilitation and nursing, the 3 key vertical convergence points of home care, institution care and community care, and the one key convergence point of institutional medical care. Based on the synergy theory and the 8 key convergence points, the " 431" convergence mechanism of medical-nursing combined care was constructed. This mechanism refered to the horizontal linkage of healthcare, nursing, rehabilitation and aging care, the vertical redirection among home care, institution care and community care modes, and the development mode focusing on institutional aging care.Conclusions:At present, the poor convergence between aging care and nursing care in China is a key roadblock hindering the integrated development of aging and nursing care. Medical-nursing combined care should be conducive to the " 431" convergence development, achieving horizontal linkage, vertical redirection, and resource sharing, for the purpose of high-quality development of China′s aging care system.

Relationship Between the Fibrinogen-to-Albumin Ratio and SYNTAX Score in Patients with Non-St-Elevation Myocardial Infarction

ABSTRACT Background: Despite the association of fibrinogen-to-albumin ratio (FAR) with the extent, severity, and complexity of coronary artery disease (CAD) in patients with ST-elevation myocardial infarction (STEMI) and stable CAD, no studies to date have specifically addressed this issue in patients with non-STEMI (NSTEMI). Objectives: This study aimed to evaluate whether a relationship exists between FAR and the SYNergy between Percutaneous Coronary Intervention with TAXus (SYNTAX) score in patients with NSTEMI. Methods: In this prospective cross-sectional study, 330 patients with NSTEMI who had undergone coronary angiography in an academic medical center were divided into two groups: those with an intermediate/high (≥23) SYNTAX score (241 patients) and those with a low SYNTAX score <23 (89 patients). SYNTAX score was computed by two highly experienced cardiologists (who were blinded to the study data) using an online SYNTAX calculator. Fibrinogen and albumin levels were measured in all patients, and FAR was calculated. Results: Multivariate logistic regression analysis showed that FAR (odds ratio [OR]: 1.478, 95% confidence interval [CI]: 1.089-2.133, p = 0.002), low-density lipoprotein (OR: 1.058, 95% CI: 1.008-1.134, p = 0.026), and troponin I (OR: 1.219, 95% CI: 1.015-1.486, p = 0.031) were independent predictors of the SYNTAX score. In a receiver operating characteristics analysis, a cutoff FAR value of 95.3 had an 83% sensitivity and an 86% specificity (area under the curve [AUC]: 0.84, p < 0.001) for the prediction of SYNTAX scores ≥23 in NSTEMI patients. Conclusion: These results indicate that FAR is a useful tool to predict intermediate-high SYNTAX scores in NSTEMI patients.

Synergy of Centralized Drug Volume-based Purchasing and Medical Insurance Negotiation Policy / 中国药房

OBJECTIVE：To investigate the s ynergy between centralized drug volume-based purchasing （called“volume- based purchasing”for short ）and medical insurance negotiation policy. METHODS ：From the aspects of economic and social benefits ， the synergy of volume-based purchasing and medical insurance negotiation was analyzed by using the methods of literature analysis，policy interpretation and interview. The corresponding suggestions were put forward for the problems of the supply and use of drugs. RESULTS & CONCLUSIONS ：The synergy of volume-based purchasing and medical insurance negotiation in terms of economic benefits include medical insurance fund management optimization to improve fund utilization efficiency improvement ； medical insurance fund payment optimization to reduce transaction cost ；network promotion of medical security information platform to reduce the cost of information exchange. The synergy of volume-based purchasing and medical insurance negotiation in terms of social benefits includes relevant index assessment of drug quality evaluation to improve drug quality evaluation system ； medical service level improvement to form compound medical insurance payment mode under total budget management ；enterprise supervision driven by market to reduce the pressure of government supervision. The relevant departments should continue to strengthen the comprehensive management of medical institutions to reduce the phenomenon of irrational drug use ；strengthen policy convergence ，avoid the poor implementation of medical insurance drug adjustment policy ，so that the policy dividend of volume-based purchasing and medical insurance negotiation can benefit the people more through system reform ，optimal allocation of funds ，etc.

Modeling the neuro-protection of theaflavic acid from black tea and its synergy with nimodipine via mitochondria apoptotic pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Ischemic stroke presents a leading cause of mortality and morbidity worldwide. Theaflavic acid (TFA) is a theaflavin isolated from black tea that exerts a potentially neuro-protective effect. However, the dynamic properties of TFA-mediated protection remain largely unknown. In the current study, we evaluated the function of TFA in the mitochondria apoptotic pathway using mathematical modeling. We found that TFA-enhanced B-cell lymphoma 2 (Bcl-2) overexpression can theoretically give rise to bistability. The bistability is highly robust against parametric stochasticity while also conferring considerable variability in survival threshold. Stochastic simulations faithfully match the TFA dose response pattern seen in experimental studies. In addition, we identified a dose- and time-dependent synergy between TFA and nimodipine, a clinically used neuro-protective drug. This synergistic effect was enhanced by bistability independent of temporal factors. Precise application of pulsed doses of TFA can also promote survival compared with sustained TFA treatment. These data collectively demonstrate that TFA treatment can give rise to bistability and that synergy between TFA and nimodipine may offer a promising strategy for developing therapeutic neuro-protection against ischemic stroke.

Protective Effect of Glycyrrhizae Radix et Rhizoma-Granati Pericarpium Formula on Ultraviolet-induced Skin Damage / 中国实验方剂学杂志

Objective:To explore the potential synergistic protective mechanism of Glycyrrhizae Radix et Rhizoma-Granati Pericarpium formula compound by using the methods and tools of network pharmacology，and provide a basis for the modernization of traditional Chinese medicine（TCM） compounds and the discovery of new drugs. Method:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） was used to obtain the active components of Glycyrrhizae Radix et Rhizoma-Granati Pericarpium formula and their corresponding targets. The obtained targets were input to the UniProt database to inquire the gene names corresponding to the targets. By searching the CTD database，Genecards database and OMIM database of disease-related websites，the anti-sunburn targets were obtained. The interaction of the active targets was analyzed with online STRING database to screen the predicted core targets. The gene ontolog（GO） gene function enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis of the predictive targets were performed by using DAVID database. Cytoscape 3.6.1 software was used to make "drug-component-target" network diagram，"protein-protein interaction" network diagram and "component-target-pathway" network diagram. Online website Draw Venn Diagram was used to show the relationship between disease targets and drug predicted targets. R Studio software was used to draw the functional enrichment analysis diagram of GO gene and KEGG pathway. Molecular docking between the active ingredients and the core targets was performed using GOLD software. Result:The 16 active compounds were collected，such as liquiritin，glycyrrhizin，kaempferol and quercetin. The active components mainly acted on 5 core targets：protein kinase B1（AKT1），interleukin（IL）-6，vascular endothelial growth factor（VEGFA），tumor necrosis factor（TNF） and tumor suppressor gene （TP53） and played a role in anti-sunburn effect primarily through these pathways such as hepatitis B，pathways in cancer，toxoplasmosis，chagas disease（American trypanosomiasis），and TNF signaling pathway. Conclusion:Based on the method of network pharmacology，the present study has preliminarily explored the anti-sunburn targets and pathways of Glycyrrhizae Radix et Rhizoma-Granati Pericarpium formula，and further verified the characteristics of multi-component and multi-target treatment of diseases in TCM，so as to provide certain scientific ideas for the modernization research of Chinese herbal compound prescriptions.

Rapid determination of active components in Ginkgo biloba leaves by near infrared spectroscopy combined with genetic algorithm joint extreme learning machine / 中国中药杂志

Near-infrared spectroscopy(NIRS) combined with band screening method and modeling algorithm can be used to achieve the rapid and non-destructive detection of the traditional Chinese medicine(TCM) production process. This paper focused on the ginkgo leaf macroporous resin purification process, which is the key technology of Yinshen Tongluo Capsules, in order to achieve the rapid determination of quercetin, kaempferol and isorhamnetin in effluent. The abnormal spectrum was eliminated by Mahalanobis distance algorithm, and the data set was divided by the sample set partitioning method based on joint X-Y distances(SPXY). The key information bands were selected by synergy interval partial least squares(siPLS); based on that, competitive adaptive reweighted sampling(CARS), successive projections algorithm(SPA) and Monte Carlo uninformative variable(MC-UVE) were used to select wavelengths to obtain less but more critical variable data. With selected key variables as input, the quantitative analysis model was established by genetic algorithm joint extreme learning machine(GA-ELM) algorithm. The performance of the model was compared with that of partial least squares regression(PLSR). The results showed that the combination with siPLS-CARS-GA-ELM could achieve the optimal model performance with the minimum number of variables. The calibration set correlation coefficient R_c and the validation set correlation coefficient R_p of quercetin, kaempferol and isorhamnetin were all above 0.98. The root mean square error of calibration(RMSEC), the root mean square error of prediction(RMSEP) and the relative standard errors of prediction(RSEP) were 0.030 0, 0.029 2 and 8.88%, 0.041 4, 0.034 8 and 8.46%, 0.029 3, 0.027 1 and 10.10%, respectively. Compared with the PLSR me-thod, the performance of the GA-ELM model was greatly improved, which proved that NIRS combined with GA-ELM method has a great potential for rapid determination of effective components of TCM.

Señuelo dirigido a HIF-1 potencializa efectos citotóxicos de dos agentes quimioterapéuticos en MDA-MB-231 / HIF decoy improve cytotoxic effects of two chemotherapeutic agents on MDA-MB-231

RESUMEN Procesos oncogénicos como proliferación incontrolable, resistencia apoptótica, aumento de mecanismos angiogénicos y evasión inmune son regulados generalmente por factores de transcripción, como HIF-1. Por tanto, se ha señalado a esta molécula como un blanco terapéutico prometedor. Para explorar esta posibilidad, un oligonucleótido tipo "señuelo" dirigido a HIF-1 a (ODN) fue diseñado para evaluar su eficiencia en esquema tanto monoterapéutico, como en combinación con dos agentes quimioterapéuticos en un modelo in vitro de cáncer de mama. Después de comprobar, mediante citometría de flujo e inmunofluorescencia, la localización del blanco, el señuelo fue transfectado en la línea celular MDA-MB-231. Se estableció la IC-50 de HIF-1 a ODN, Cisplatino y Taxol con el método de Resazurina. Mecanismos de muerte celular fueron evaluados con el método de TUNEL. Por último, se estableció el índice de combinación (IC) de cada uno de los quimio-agentes en combinación con el ODN. Se evidencio que HIF-1 a ODN causa un efecto citotóxico en MDA-MB-231 de hasta un 90% hacia las 72h pos-tratamiento. Este efecto no se observa tanto en los controles del ensayo, como en el cultivo primario de células no tumorales (FIBRO), siendo este agente altamente selectivo hacia células tumorales, al activar mecanismos pro-apoptóticos. A su vez, HIF-1 a ODN potencializa la actividad tumorogénica de Cisplatino y Taxol en la línea celular tumoral. Por tanto, HIF-1 a ODN demostró tener actividad selectiva potencialmente antitumoral, al disminuir la proliferación celular e inducir apoptosis; optimizando de forma sinérgica, la eficacia de fármacos quimioterapéuticos de alto espectro, en tratamientos combinados.

ABSTRACT Oncogenic processes like uncontrollable proliferation, resistance to apoptosis, increases in angiogenic mechanisms and immune evasion are regulated by transcription factors such HIF-1. Therefore, this molecule is regarded as a potential therapeutic target. To explore this possibility, a HIF-1 α oligonucleotide decoy (ODN) was designed to evaluate its efficiency on both a mono-therapeutic scheme and a mixed treatment with two chemotherapeutic agents within an in vitro model of breast cancer. After confirming the target location with flow cytometry and immunofluorescence assays, that decoy was transfected over the MDA-MB-231 cell line. We established the HIF-1 α ODN, Cisplatin and Taxol IC-50 using Resazurin tests. Cell death mechanisms was evaluated with TUNEL. Finally, we obtained the combination index (IC) of each chemical agents with the ODN. This study showed that HIF-1 α ODN caused a cytotoxic effect (up to 90%) in MDA-MB-231 during 72 hours post treatment. That effect did not appear in either the assay controls nor in non-tumor cell cultures (FIBRO). This agent is highly selective towards tumor cells, activating pro-apoptotic mechanisms. Additionally, HIF-1 α ODN increases the tumorigenic action of Cisplatin and Taxol on the cell line, due to an additive effect. For these reasons, HIF-1 α ODN has potential antitumor selective activity, decreasing cell proliferation, inducing apoptosis, and optimizing, in a synergistic manner, the efficacy of wide spectrum chemotherapeutic compounds when it used in a combined treatment.

Cymbopogon giganteus Chiov. essential oil: Direct effects or activity in combination with antibiotics against multi-drug resistant bacteria

The discovery of new antimicrobial agents is necessary due to the emergence of multi-drug bacterialresistance. The aim of this work was to study the direct and indirect antimicrobial activity of a Beninesesample of Cymbopogon giganteus essential oil (EOCG) on multi-drug resistant clinical bacteria, its chemicalcomposition, and its cytotoxicity. Direct antimicrobial activity was tested by determination of minimalinhibitory concentration (MIC), and indirect activity, by determining Fractional Inhibitory ConcentrationIndex using checkerboard [fractional inhibitory concentration indices (FICI); synergy: FICI ≤ 0.5; additivity:0.5 < FICI ≤ 1]. EOCG composition was determined by GC-MS and GC-FID and cytotoxicity was determinedby 3-(4,5-dimethylthiazol-2-yl)-2,5-diphényltetrazolium bromide (MTT) assay. p-Menthane derivatives(54.87%) and limonene (12.07%) were detected as major compounds by GC analysis. Our results confirmedthe direct antimicrobial activity of EOCG, but here on clinical resistant strains (MIC from 0.125% v/v to 0.5%v/v). We also show synergistic effects between EOCG and amoxicillin with FICI ranges of 0.12–0.5 againsttwo Escherichia coli resistant clinical strains, synergistic to additive effects between EOCG and colistin oroxacillin/ampicillin, respectively, against Pseudomonas aeruginosa PA544 and Staphylococcus epidermidisSECN361 (two resistant clinical isolates). Our results also indicate that EOCG had low cytotoxicity(IC50: 67.06 ± 2.694 μg/ml).

Rapid Determination of Coating Film Thickness of Tianshu Tablets by Near Infrared Spectroscopy / 中国实验方剂学杂志

<b>Objective::To investigate the feasibility of near-infrared spectroscopy for detecting the coating film thickness of Tianshu tablets. <b>Method::Nine batches of Tianshu tablets were taken during the coating process. Then, their near-infrared diffuse reflection spectra were collected. The sample set was divided into calibration set and validation set by Kennard-Stone algorithm. The preprocessing method was selected. The synergy interval partial least squares (siPLS) and moving window partial least squares (mwPLS) were employed to screen the optimal spectral interval. And the corresponding quantitative calibration model of partial least squares (PLS) were established. Some evaluation parameters were adopted to assess the performance of the model. <b>Result::The method of first derivative and Norris Derivative smoothing combined with standard normal variate transformation was suitable for processing the spectra. The optimal PLS model was established in the preferred band interval of siPLS. The correlation coefficient between the predicted value and the measured value of calibration set was 0.966, and the correlation coefficient between the predicted value and the measured value of validation set was 0.991.Both root mean square error of calibration (RMSEC) and root mean square error of prediction (RMSEP) values were small, which showed the fitness and predictive performance of the model were favorable. <b>Conclusion::The near-infrared spectroscopy technique can be used to determine coating film thickness of Tianshu tablets with high accuracy, which provides technical supports for the in-line determination of coating thickness in the production process of traditional Chinese medicine tablets.

Study on synthesis and antifungal activities of galloyl piperazine derivatives / 药学实践杂志

Objective To design, synthesize and measure antifungal activities of galloyl piperazine derivatives. Methods Trimethoxyl gallic acid was used as starting material, reacted with piperazine in the presence of PyBOP/DIEA to afford the intermediates. The target compounds were obtained through the reaction with corresponding acids after deprotection gave. The antifungal activities of the target compounds were evaluated by FLC-resistant Candida albican isolated according to the CLSI recommended method. Results 11 target compounds were synthesized and six of them showed more potent antifungal activities than gallic acid. Conclusion Galloyl piperazine derivatives could enhance antifungal activities. Galloyl moiety was an important pharmacophore, which could improve antifungal activities with the introduction of cinnamic acid and 2,3-dichlorobenzoic acid.