The effect of celastrol in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cell lines

Background:Despite the availability of chemotherapy drugs such as 5-fluorouracil(5-FU),the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects.This study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines(AGS and EPG85-257).Materials and Methods:In this in vitro study,AGS and EPG85-257 cells were treated with different concentrations of celastrol,5-FU,and their combination.Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)assay.The synergistic effect of 5-FU and celastrol was studied using Compusyn software.The DNA content at different phases of the cell cycle and apoptosis rate was measured usingflow cytometry.Results:Co-treatment with low concentrations(10%inhibitory concentration(IC10))of celastrol and 5-FU significantly reduced IC50(p<0.05)so that 48 h after treatment,IC50 was calculated at 3.77 and 6.9μM for celastrol,20.7 and 11.6μM for 5-FU,and 5.03 and 4.57μM for their combination for AGS and EPG85-257 cells,respectively.The mean percentage of apoptosis for AGS cells treated with celastrol,5-FU,and their combination was obtained 23.9,41.2,and 61.9,and for EPG85-257 cells 5.65,46.9,and 55.7,respectively.In addition,the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis phase.Conclusions:Although celastrol could decrease the concentration of 5-fluorouracil that sufficed to suppress gastric cancer cells,additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol.

Hepatitis B virus infection, diabetes mellitus, and their synergism for cholangiocarcinoma development: A casecontrol study in Korea

AIM: To identify possible risk factors and their synergism for cholangiocarcinoma development.METHODS: A hospital-based, case-control study in which we included 276 cholangiocarcinoma patients [193 extrahepatic cholangiocarcinoma(ECC) and 83 intrahepatic cholangiocarcinoma(ICC)], diagnosed at a training hospital in Korea between 2007 and 2013, and 552 healthy controls matched 2:1 for age, sex, and date of diagnosis. Risk factors for cholangiocarcinoma and possible synergism between those factors were evaluated using conditional logistic regression and synergism index, respectively.RESULTS:There was an association between cholangiocarcinoma and hepatitis B virus(HBV) infection, diabetes mellitus(DM), cholecystolithiasis, choledocholithiasis, and hepatolithiasis, with the adjusted odds ratios(AORs) of 4.1, 2.6, 1.7, 12.4, and 39.9, respectively. Synergistic interaction on the additive model was investigated between HBV infection and DM(AOR = 12.2; 95%CI: 1.9-80.1). In the subgroup analyses, cholecystolithiasis, choledocholithiasis, hepatolithiasis, and DM were significant risk factors for ECC(AOR = 2.0, 18.1, 14.9, and 2.0, respectively), whereas choledocholithiasis, hepatolithiasis, HBV infection, and DM were risk factors for ICC(AOR = 8.6, 157.4, 5.3 and 4.9, respectively). Synergistic interaction was also observed between HBV infection and DM(OR = 22.7; 95%CI: 2.4-214.1). However, there was no synergistic interaction between other significant risk factors for cholangiocarcinoma.CONCLUSION: In this Korean study, HBV infection and DM were found to exert independent and synergistic effects on the risk for cholangiocarcinoma, including ICC. Exploring the underlying mechanismsfor such synergy may lead to the development of cholangiocarcinoma prevention strategies in high-risk individuals.

Cytotoxic synergism of Clostridioides difficile toxin B with proinflammatory cytokines in subjects with inflammatory bowel diseases

Clostridioides difficile(C.difficile)is progressively colonizing humans and animals living with humans.During this process,hypervirulent strains and mutated toxin A and B of C.difficile(TcdA and TcdB)are originating and developing.While in healthy subjects colonization by C.difficile becomes a risk after the use of antibiotics that alter the microbiome,other categories of people are more susceptible to infection and at risk of relapse,such as those with inflammatory bowel disease(IBD).Recent in vitro studies suggest that this increased susceptibility could be due to the strong cytotoxic synergism between TcdB and proinflammatory cytokines the tumor necrosis factor-alpha and interferon-gamma(CKs).Therefore,in subjects with IBD the presence of an inflammatory state in the colon could be the driver that increases the susceptibility to C.difficile infection and its progression and relapses.TcdB is internalized in the cell via three receptors:chondroitin sulphate proteoglycan 4;poliovirus receptor-like 3;and Wnt receptor frizzled family.Chondroitin sulphate proteoglycan 4 and Wnt receptor frizzled family are involved in cell death by apoptosis or necrosis depending on the concentration of TcdB and cell types,while poliovirus receptor-like 3 induces only necrosis.It is possible that cytokines could also induce a greater expression of receptors for TcdB that are more involved in necrosis than in apoptosis.Therefore,in subjects with IBD there are the conditions:(1)For greater susceptibility to C.difficile infection,such as the inflammatory state,and abnormalities of the microbiome and of the immune system;(2)for the enhancement of the cytotoxic activity of TcdB+Cks;and(3)for a greater expression of TcdB receptors stimulated by cytokines that induce cell death by necrosis rather than apoptosis.The only therapeutic approach currently possible in IBD patients is monitoring of C.difficile colonization for interventions aimed at reducing tumor necrosis factor-alpha and interferon-gamma levels when the infection begins.The future perspective is to generate bacteriophages against C.difficile for targeted therapy.

Risk Assessment of Synergism and Recombination on the Transgenic Plants Containing Viral Movement Protein and Replicase Genes

The transgenic tobacco plants transformed with movement protein gene of Tomato mosaic virus (ToMV) or Tobacco mosaic virus (TMV) and partial replicase gene of Cucumber mosaic virus (CMV) P1 isolate (CMV-P1), were inoculated with Potato virus X, Potato virus Y, TMV and CMV isolate RB (CMV-RB), respectively. Symptom observation showed there were no symptom differences in transgenic tobacco plants as compared with those in non-transgenie tobacco plants. ELISA also illustrated that the virus concentrations in the transgenic plants were similar to those in non-transgenic plants, indicating that no synergism is found in these plants. The transgenic tobacco plants expressing movement protein gene of ToMV or partial replicase gene of CMV-P1 were inoculated with TMV and CMV-RB, respectively. The local or systemic infected leaves were then used for elucidation of the possible virus recombination in transgenic plants with biological infectivity test, ELISA and immuno-capture RT-PCR. Within 16 months, no recombination was found between transformed genes and inoculated virus genomes. The research provides fundamental data for understanding of the possible risk of the transgenic plants expressing viral sequences.

Compatibility mechanism of Chinese medicine formula:state of the art and perspectives

Traditional Chinese medicine(TCM)has been practiced in China and surrounding countries for thousands of years and has gradually attracted the attention of Western countries.After reasonable compatibility,TCMs could play the key role of enhancing efficacy and reducing toxicity,which has significant therapeutic advantages in the treatment of complex diseases in clinical practice.While the TCM compatibility is not the simple addition of drugs.Under the appropriate dosage ratio,multiple TCMs can play a synergistic role to realize the overall regulation of TCM treatment.Therefore,it is of critical essential to study the compatibility of TCM formula to promote TCM modernization,new drug development and clinical application.Recently,under the guidance of TCM theory,many researches on the composition,pharmacodynamic activity and pharmacokinetic properties of TCM formula have emerged by integrating new technologies and new methods,revealing the scientific connotation of the compatibility of TCM formula from different perspectives and levels.This paper introduces the research progress of compatibility rules from different levels of compatibility,compatibility for synergistic enhancement and detoxification,and application of cutting-edge technology,with representative cases,in order to provide ideas and references for further study on TCM compatibility.

Synergism of Plasma and Catalyst on the Dehydrogenative Coupling of Methane

At atmospheric pressure and ambient temperature, pulse corona induced plasma was used as a new method for dehydrogenative coupling of methane. The synergism of plasma and catalyst on dehydrogenative coupling of methane was investigated. Experimental results have revealed that the synergism does exist, when positive corona within a suitable power range and an intermediate pulse repetition frequency (PRF) for a loaded 7-Mn2O3/7-A12O3 catalyst were chosen. In respect to the mechanism approach, a tentative model for general pathway was proposed to explain the role of plasma and catalyst partaking in the process of methane decomposition and C2 products formation.

A Rapid Parameter of Enzyme-Treated Cellulosic Material Revealed by Reducing Sugar Release

This study was conducted to evaluate the effectiveness of enzymes in purifying and reducing the degree of polymerization of cellulose for the production of dissolving pulp.Our goal was to determine the contributions of xylanase(X)and endoglucanase(EG)in the treatment of pulp,specifically by quantifying the formation of soluble and insoluble reducing sugars using the dinitrosalycilic acid(DNS)test.Predominantly,the release of soluble reducing sugars(RSSol)was enhanced after xylanase treatment,while endoglucanase(EG)treatment led to changes in insoluble reducing sugars(RSIns).The maximum synergism was observed for RSIns when a high ratio of endoglucanase to xylanase(320EG:5X/g pulp)was used.The relative contribution of endoglucanase to RSins was determined to be 15.6%of the total reducing sugar.The viscosity of pulps treated with xylanase decreased only by 7%,whereas endoglucanase treatment significantly reduced viscosity by 45%.Modifications in the particle size were observed after pulp treatment with the combination of endoglucanase and xylanase.In summary,the DNS test is a rapid and effective method for evaluating the efficiency of enzyme treatments on pulps.The measurement of RSIns correlates with changes in pulp viscosity to different extents,providing valuable insights into the effectiveness of enzyme treatments.

In vitro assessment of the synergism between extracts of Cocos nucifera husk and some standard antibiotics

Objective: To evaluate the interactions between the crude extracts of Cocos nucifera(C.nucifera) and six front line antibiotics(ampicillin sodium salt, penicillin G sodium,amoxicillin, chloramphenicol, ciprofloxacin and tetracycline hydrochloride), against some bacterial pathogens linked with human infection.Methods: The pulverized husk of C.nucifera was dissolved in 95% n-hexane and extracted using Soxhlet extraction method and sterile distilled water(aqueous).The antibacterial susceptibility of the crude extracts of C.nucifera was tested against environmental and clinical strains(6) obtained from the South African Bureau of Standards(SABS), Vibrio(6) and Listeria pathogens(6).The agar-well diffusion method was used for screening the extracts for their antibacterial activity.The minimum inhibitory concentration and minimum bactericidal concentration of the extracts were determined.Time-kill assay was used to evaluate bactericidal and/or bacteriostatic activity.The synergistic effect of the crude extracts and antibiotics was assessed and evaluated by adopting the checkerboard methods.Results: With the time-kill assay, the highest bactericidal activity was observed on Vibrio fluvialis EL041 with a-5.6 ± 0.2 log_(10)CFU/mL decrease in cell density as a result of the combination of the extracts and chloramphenicol at two-fold minimum inhibitory concentrations.Synergisms using the time-kill assay constituted about 72%, while indifference constituted about 28%.The checkerboard method revealed synergistic interaction in 67% of the combinations, and indifference in 33%.There was no specificity in the observed synergy to a particular class of antibiotics.Conclusions: This investigation suggests the crude extracts of C.nucifera to be a potential broad spectrum antimicrobial compound.Therefore, further study is needed to isolate the pure compounds from these crude extracts.

Effect of Mitigating Strength Retrogradation of Alkali Accelerator by the Synergism of Sodium Sulfate and Waste Glass Powder

This work aims to utilize waste glass powder(WGP)as a plementary material to mitigate the strength shrinkage caused by the alkaline accelerator.Waste glass power was used to replace cement by 0%,10%,and 20%to evaluate waste glass powder on the alkaline accelerator’s strength retrogradation.The results show that the strength improvement effect of unitary glass powder is inconspicuous.Innovative methods have been proposed to use sodium sulfate and waste glass powder synergism,using the activity of amorphous silica in glass powder.Compared with the reference group,the compressive strength of 28d mortar increases by 67%when the sodium sulfate content is 2.5%,and the replacement amount of waste glass powder is 10%.Besides,XRD and SEM analysis of hydration products also confirmed that the synergistic effect of sodium sulfate and waste glass powder could reduce strength inversion.The findings presented in this paper are pivotal for using waste glass to solve the problem of strength inversion caused by the alkaline accelerator.

Corrosion Inhibition Synergism between Lanthanum(Ⅲ) Ion and 8-Hydroxyquinoline for Zinc in Hydrochloric Acid

The effects of La 3+ ion and chelate reagent 8 hydroxyquinoline on the corrosion rate of zinc in hydrochloric acid were investigated by using weight loss method and electrochemical method. It is found that in a specific concentration range of La 3+ ion and 8 hydroxyquinoline, the obvious corrosion inhibition synergism is obtained. The mechanism of corrosion inhibition synergism was discussed on basis of adsorption theory.

Bioaccumulation and depuration of chromium in the selected organs and whole body tissues of freshwater fish Cirrhinus mrigala individually and in binary solutions with nickel

Contamination of aquatic ecosystems with heavy metals has been receiving increased worldwide attention due to their harmful effects on human health and other organisms in the environment. Most of the studies dealing with toxic effects of metals deal with single metal species, while the aquatic organisms are typically exposed to mixtures of metals. Hence, in order to provide data supporting the usefulness of freshwater fish as indicators of heavy metal pollution, it has been proposed in the present study to investigate the bioaccumulation and depuration of chromium in the selected organs of freshwater fingerlings Cirrhinus mrigala, individually and in binary solutions with nickel. The results show that the kidney is a target organ for chromium accumulation, which implies that it is also the ＂critical＂ organ for toxic symptoms. The results further show that accumulation of nickel in all the tissues of C. mrigala is higher than that of chromium. In addition, the metal accumulations of the binary mixtures of chromium and nickel are substantially higher than those of the individual metals, indicating synergistic interactions between the two metals. Theoretically the simplest explanation for an additive joint action of toxicants in a mixture is that they act in a qualitatively similar way. The observed data suggest that C. mrigala could be suitable monitoring organisms to study the bioavailability of water-bound metals in freshwater habitats.

Anti-listerial synergism of leaf essential oil of Metasequoia glyptostroboides with nisin in whole,low and skim milks

Objective:To examine the individual and synergistic anti-listcrial effect of nisin and leaf essential oil of Metasequoia glyptostroboides(M.glyptostroboides) against one of the leading foodhorne pathogens Listeria monocytogenes(L.monocytogenes) ATCC 19116 in milk samples.Methods:The whole(8%),low(1%) and skim(no fat content) milk samples were inoculated with L.monocytogenes ATCC 19116 along with leaf essential oil of M.glyptostroboides or nisin alone as well in eomhinations.Results:In this study,the leaf essential oil at the concentrations of 2% and 5% revealed strong anti-listerial effect against L.monocytogenes ATCC 19116 in all categories of milk samples.Nisin at the concentrations of 250 and 500 IU/mL displayed a strong inhibitory effect against ATCC 19116 as compared to the control group.Additionally,synergistic combinations of leaf essential oil(1%) and nisin(62.5,125.250 and 500 IU/mL) also had a remarkable anti-listerial synergism in all the tested milk samples including whole,low and skim milk after 14 days.Conclusions:As a major finding,the leaf essential oil of M.glyptostroboides might he a useful candidate for using in food industry to control the growth of foodhorne pathogenic bacteria as confirmed by its potent anti-listerial Synergistic effect with nisin against L.monocytogenes ATCC 19116 in different milk samples.

Synergistic Interaction and Gelation in Cationic Guar Gum-Sodium Alginate System

The synergistic interaction between the cationic guar gum (the ammonium hydroxy-propyl-trimethyl chloride of guar gum) and sodium alginate has been studied. The effects of the mass ratio of them, mixed temperature, balk salt ion concentration, incubation time and pH value on gelation were investigated. It has been observed that there was a gel strength maximum when the mass ratio was 0.6, the mixed temperature was 70°C, the balk salt ion concentration was 1.0 mol·L?1, the incubation time was 30 min and the pH value was 8. Interaction between molecules of these two polysaccharides was investigated by FT-IR spectrometry. Key words cationic guar gum - sodium alginate - gelation - synergism CLC number O 629.12 Foundation item: Supported by the National Natural Science Foundation of China(29574173)Biography: He Dong-bao (1945-), male, Associate professor, research direction: modifying and gelating of natural polysaccharides.

The role of the TrkB-T1 receptor in the neurotrophin-4/5 antagonism of brain-derived neurotrophic factor on corticostriatal synaptic transmission

This manuscript reviews the function and fundamental characteristics of the neurotrophins and their receptors to introduce the reader to the differential effects exhibited by the neurotrophins;brain-derived neurotrophic factor and neurotrophin 4/5 when acted together after sequential presentation.The neurotrophin 4/5 exhibits an inhibitory action on the modulatory effect of brain-derived neurotrophic factor in corticostriatal synapses when they are administered sequentially(brain-derived neurotrophic factor to neurotrophin 4/5).This inhibitory effect has not been previously documented and is relevant for these neurotrophins as both of them stimulate the TrkB receptor.The additive effect of these neurotrophins is also discussed and occurs when neurotrophin 4/5 exposure is followed by brain-derived neurotrophic factor in a mouse model of striatal degeneration.Occlusive and additive effects of both neurotrophins are accompanied by changes in the expression of the TrkB receptor isoforms,specifically TrkB-T1 and TrkB-FL,as well as differences in phosphorylation levels of the TrkB receptor.The results of the experiments described raise several questions to inquire about the role that TrkB-T1 receptor plays in striatal physiology,as well as the functional relevance of the interaction of brain-derived neurotrophic factor and neurotrophin 4/5 in the brain and more specifically at the striatal circuits in normal as well as pathological conditions.

Simultaneous Use of Entomopathogenic Fungus <i>Beauveria bassiana</i>and Diatomaceous Earth against the Larvae of Indian Meal Moth, <i>Plodia interpunctella</i>

The suppressive ability of entomopathogenic fungus Beauveria bassiana alone and in combination with diatomaceous earth (DE) was studied against the larvae of Indian meal moth, Plodia interpunctella (Hübner) (Lep., Pyralidae). This study clearly showed that simultaneous use of B. bassiana and DE against larvae of P. interpunctella, not only could reduce the required concentration of fungal conidia or DE, but also could shorten the time need for showing insecticidal effects. The LC50 value of fungus at 7 d after treatment was 9.8 × 105 conidia mg-1 diet. Larvae showed a dose response to B. bassiana, and the addition of diatomaceous earth at 500 and 2000 ppm resulted in a significant increase in mortality. Larval mortality reached to the maximum of 28.3% and 71.7% after 7 d exposure to 500 and 2000 ppm DE concentrations, respectively. The LC50 value for B. bassiana in the presence of DE 500 ppm was 4.6 × 104 con. mg-1 diet and of DE 2000 ppm was 1.65 × 103 con. mg-1 diet. According to our results, B. bassiana and DE can be considered as two suitable candidates for integration into IPM strategy.

Ceruloplasmin or Fibronectin Synergism with Quartz Dust on Stimulating Collagen Gene Transcription in Human 2BS Fibroblast

Human α1(Ⅰ), α2(Ⅰ) and α1(Ⅲ) cDNA probes and RNA dot hybridization were employed to quantitate collagen mRNA changes after adding silica dust into the media of human 2BS fibroblasts. At all dosages used (100, 200, 500 and 1000μg), the α1(Ⅰ), α2(Ⅰ)and α1(Ⅲ) mRNA levels increased one day after dusting. At the same dosage of silica (100μg), α1(Ⅲ) mRNA increased earlier than type Ⅰ collagen mRNA did. The type Ⅰ and type Ⅲ collagen mRNA contents in the experimental groups were higher than those in control on days 3, 5, 7 and 9. The effect of ceruloplasmin (Cp) and fibronectin (Fn) on collagen mRNA synthesis was also studied, after adding silica dust, Cp or Fn into the media of human 2BS fibroblast. The results showed that Cp and Fn have stimulating effect on collagen mRNA production. When both Cp and silica dust were added into cell culture media, the collagen mRNA level was increased more than those of adding either Cp or silica dust alone. Similar situations were found for Fn. Cp (or Fn) synergism with silica dust on stimulating transcription of human collagen gene was suggested

Effects of Synergism Between PVY and PVX on Virus Titer and Cell Ultrastructure in Tobacco Plants

The viruses titer and the ultrastructure of infected cells in tobacco host (Nicotiana tabacum cv. Samsun), which doubly infected with potato virus Y necrosis strain (PVYN) and potato virus X (PVX), were studied under greenhouse conditions. The results indicated that PVYN and PVX interacted synergistically. and tobacco plants which doubly infected with PVX and PVYN could greatly increase symptom severity as compared with that induced by the single virus. As determined by triple antibody sandwich enzyme-linked immunosor-bent assay (TAS-ELISA), the titer of PVX in the tobacco leaves infected with both PVYN and PVX was up to 9.10 times higher than the plants infected with PVX only. No significant differences in PVYN titer were detected between singly and doubly infected plants. The enhancement of PVX titer in doubly infected plants was evident in greenhouse and was independent of the virus strains, tested seasons, intervals between PVYN and PVX inoculation. When sections of doubly infected leaves were examined with an electron microscope, it could be frequently found that cells contained pinwheels and large masses of PVX-like particles, pinwheels and laminate inclusions, or all three structures, most of them were swollen, and their chloroplast and other organella were destructed heavily. This suggested that doubly infected cells were involved in the enhancement phenomenon, which seemed to be the result of an increase in the amount of PVX synthesized in them.

The Research on Synergic Development Mechanism of Oceanic Meteorology Modernization in the Huang-Bohai Region

To study the cooperative development mechanism of ocean meteorological modernization of Huang-Bohai,we analyze the situation of ocean meteorological modernization in Huang-Bohai with the method of an new five-force model and the analyses of strengths,weaknesses,opportunities and threats (SWOT analysis).As the research results shown,the advantages of ocean meteorological modernization of Huang-Bohai mainly include three aspects which are ocean meteorological observation system,ocean meteorological warning information release and the construction of ocean meteorological center;the disadvantages contain that stereo-observation ability of the ocean meteorology is insufficiency,and the precision forecast technology and the cooperative development are deficiency in ocean meteorology;opportunities also include three aspects which are "The Belt and Road",and development of new technology and new warning system on meteorology disasters;threats mainly contain the main influencing weather system,the potential social competition and hazard factors.The use of different functions and combination innovation of five forces,i.e.,attractiveness,cohesiveness,radiating power,repulsiveness and affinity,could promote the cooperative development of ocean meteorological modernization in the Huang-Bohai.

Mathematical Nanotechnology: Quantum Field Intentionality

Considering the finite actions of a field on the matter and the space which used to infiltrate their quantum reality at level particle, methods are developed to serve to base the concept of “intentional action” of a field and their ordered and supported effects (synergy) that must be realized for the “organized transformation” of the space and matter. Using path integrals, these transformations are decoded and their quantum principles are shown.

Synthesis, characterization and electrochemical evaluation of anticorrosion property of a tetrapolymer for carbon steel in strong acid media

A novel tetrapolymer(TP) consisting of carboxylate, sulphonate, phosphonate and sulfur dioxide based comonomers was synthesized using Butler cyclopoymerization technique. The synthesized tetrapolymer was characterized using FTIR,1H-NMR,13CNMR and elemental analysis. The performance of the tetrapolymer as a corrosion inhibitor for St37 carbon steel in 15% HCl and 15% H2SO4 acid media was assessed using electrochemical impedance spectroscopy(EIS), linear polarization resistance(LPR), potentiodynamic polarization(PDP) and electrochemical frequency modulation(EFM) techniques. The influence of addition of a small amount of KI on the corrosion inhibition efficiency of TP was also assessed. Results obtained showed that the tetrapolymer moderately inhibited the corrosion of St37 steel in the acid media with protection efficiency of 79.5% and 61.1% at the optimum concentration of 1000 mg·L^-1 studied in HCl and H2SO4 media respectively. On addition of 5 mmol·L^-1 KI to the optimum tetrapolymer concentration, the protection efficiency was upgraded to 90.6% and 93.5% in HCl and H2SO4 environment, respectively. The enhanced performance of the polymer in the presence of KI is due to synergistic action deduced from synergism parameter(S1) which was found to be greater than unity.The tetrapolymer afforded the corrosion inhibition of St37 steel in the acid media by virtue of adsorption of the polymer molecules on the steel surface which was confirmed by ATR-FTIR analysis of the adsorbed film extracted from the steel surface. TP + KI formed complex with St37 steel surface in H2SO4 solution but not in HCl solution.