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Chronic heart failure (CHF) is a severe public health problem with increasing morbidity and mortality, any treatment targeting a single session is insufficient to tackle this. CHF is characterized by reduced cardiac output resulting from neurohumoral dysregulation and cardiac remodeling, which might be related to oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, autophagy, mitochondrial function, and angiogenesis. These molecular mechanisms interact with each other through crosstalk. Historically, Chinese medicinal herbs have been widely applied in the treatment of CHF, and therapeutic effects of Chinese medicinal herbs and their ingredients have been scientifically confirmed over the past decades. Traditional Chinese medicine (TCM) with multiple components can confront the different pathogenesis of CHF through multiple targets. This review analyzes commonly used TCM patent drugs and TCM decoctions that are applicable to different stages of CHF based on clinical trials. Diverse bioactive ingredients in Chinese medicinal herbs have been found to treat CHF via multiple molecular mechanisms. This review comprehensively covers the key works on the effects and underlying mechanisms of TCM, herbal ingredients and synergistic effects of constituent compatibility in treating CHF, providing additional ideas to address this threat.
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{L-End}Objective To analyze the effects of night shift work and overweight/obesity on blood pressure of workers in chemical fiber industry. {L-End}Methods A total of 1 004 workers of a chemical fiber factory were selected as the study subjects using convenient sampling method, and their blood pressure and body mass index were measured. Multiple linear regression model was used to analyze the relationship between night shift work and blood pressure, and multiple logistic regression was used to assess the independent impact and combined impact of night shifts and overweight/obesity on the risk of hypertension. {L-End}Results Compared with the non-night shift workers, the prevalence of hypertension in night shift workers was increased (5.3% vs 13.0%, P<0.05), with elevated systolic and diastolic blood pressure (both P<0.05). The results of multiple linear regression analysis showed that the systolic blood pressure and diastolic blood pressure of the night shift workers were higher than those of the non-night shift workers (both P<0.05), and the systolic blood pressure and diastolic blood pressure of overweight/obesity workers were higher than those of non-overweight/obesity workers (both P<0.01). The results of multiple logistic regression analysis showed that the risk of hypertension in night shift workers and overweight/obesity workers was higher than that in non-night shift workers and non-overweight/obesity workers [odds ratio (OR) and 95% confidence interval (CI) were 2.49 (1.04-5.99) and 2.65 (1.77-3.95), both P<0.05]. Night shift work and overweight/obesity showed a synergistic effect on blood pressure of workers. Compared to non-overweight/obesity non-night shift workers, overweight/obesity night shift workers had a higher risk of hypertension (OR=4.93, 95%CI: 1.70-14.29, P<0.01). {L-End}Conclusion Night shift work could lead to elevated blood pressure in workers in the chemical fiber industry, which is a potential risk factor for hypertension. The synergistic effect of night shift work and overweight/obesity may contribute to the increased risk of hypertension.
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Immune-checkpoint inhibitors have shown to prolong survival in patients with metastatic non-small cell lung cancer. Programmed death ligand 1 (PD-L1) expression is associated with a higher probability of response, although some patients with PD-L1 negative tumors may also respond or show durable stabilizations. However, the optimal strategy after progression to immunotherapy (IO) is not yet defined. Patients with oligometastatic disease may benefit from local treatments such as radiotherapy (RT), achieving significant local control rates. In addition, RT is claimed to have numerous immunogenic effects that could synergize with IO. We present the case of a complete responder to nivolumab that after a monotopic adrenal relapse received stereotactic body radiation therapy, followed by maintenance nivolumab achieving a partial response that is still ongoing. Aspects such as mechanisms of acquired resistance to PD-L1 inhibitors, the optimal management after progression, and the potential interplay between IO and RT are briefly reviewed and discussed
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Objective: To evaluate the synergistic anticancer effects of the combination of apigenin (Api) and tanshinone Ⅱ A (Tan IIA), and investigate the mechanisms of pharmacological effects and their potential applications as an anticancer therapy in clinics. Methods: MTT assay were used to determine anticancer effects of the combination of Api and Tan ⅡA on BGC823, MCF7, and SMMC7721 cells. AV-PI dual stain and PI staining method were used for detecting the effect of the two drugs combination on BGC823 cell apoptosis and cell cycle. Expression of p53, BAX/BCL-2, cyclin B1 and D1 proteins were determined by Western blotting. Circular dichroism method and DNA melting point method were explored to detect interaction among the two drugs and DNA. S180 tumor xenograft mice model was used to evaluate the antitumor effects of the two drugs combination. Results: Tan IIA combined with Api exerted synergistic inhibitory effects on the proliferation of BGC823 and other tumor cells with the CI of 0.28. After tumor cell treated by combination of Tan IIA and Api, the tumor cell apoptosis was significantly enhanced and the value of BAX/BCL-2 in cells was up-regulated (P < 0.01); The levels of cyclin B1, D1 protein were changed and cell cycle arrest was increased which mainly blocked in S phase. The interaction among the two drugs and DNA was in two different ways, leading to the curves of thermal denaturation of DNA changed significantly. Furthermore, the combination of Tan IIA and Api showed a stronger inhibitory effect on tumor volume and weight in S180 mice model than monotherapy, which was similar to cyclophosphamide therapy but less side effects. Conclusion Tan IIA combined with Api exerted synergistic antitumor effects. The two drugs interacted with DNA in different ways and aggravated the cell cycle arrest, which were the key mechanisms of their synergistic antitumor effects.
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Aims: This study aimed to find out any synergism of gentamicin with the solvent extracts of small tropical herb Phyllanthus niruri to combat methicillin resistant Staphylococcus aureus. Methodology: Bioactive constituents of Phyllanthus niruri were extracted by macerating ground dry powder of the leaves in water, n-hexane, chloroform, methanol and ethanol for 48-72 h followed by filtration and evaporation of solvents. Microdilution method was used to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of these extracts. The synergistic effects between gentamicin and the extracts were evaluated by the checkerboard assay to calculate the fractional inhibitory concentration index (FICI). In all cases, ten hospital associated MRSA strains were used. Results: The MIC of aqueous and methanolic extracts of P. niruri against different MRSA strains varies from 3.125 mg/ml to 12.5 mg/ml. For the MRSA strain the combination of methanolic extract with gentamicin decreased the MIC of extract from 6.25 mg/ml to 0.2 mg/ml and the MIC of gentamicin from 2048 µg/ml to 256 µg/ml showing a strong synergistic effect with a fractional inhibitory concentration index of 0.157. Steroids, flavonoids, phenolic compounds and quinones identified in the extracts may play role in synergistic relation. Conclusion: The present investigation shows that bioactive constituents from Phyllanthus niruri have an excellent synergy with gentamicin against MRSA and can be further explored as an alternative anti-staphylococcal agent.
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The poor survival of mesenchymal stem cells (MSCs) compromises the efficacy of stem cell therapy.Growth factor deprivation is one of the important factors that have challenged the survival of donor MSCs in cell therapy.In this study,the aim was to evaluate the effect of serum deprivation on the cell death of MSCs and to investigate the underlying mechanisms.Apoptosis of MSCs was evaluated with Hoechst 33342/PI staining.Signaling pathways involved in serum-deprivation induced apoptosis were analyzed using Western blotting.The results revealed that serum deprivation induced apoptosis in MSCs within 72 h of treatment.Serum deprivation was shown to lead to protein expression alterations in Bax,Bcl-2,casepase-3,casepase-8,GRP78,and CHOP during experiments.The data suggested that the mitochondria death pathway,the extrinsic apoptotic pathway and the endoplastic reticulum(ER) stress pathway were all involved in MSCs apoptosis.The increase in expression of CHOP and the simultaneous decrease in Bcl-2 expression suggest a synergistic effect in apoptosis induction in both the mitochondrion and the ER.
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The poor survival of mesenchymal stem cells (MSCs) compromises the efficacy of stem cell therapy.Growth factor deprivation is one of the important factors that have challenged the survival of donor MSCs in cell therapy.In this study,the aim was to evaluate the effect of serum deprivation on the cell death of MSCs and to investigate the underlying mechanisms.Apoptosis of MSCs was evaluated with Hoechst 33342/PI staining.Signaling pathways involved in serum-deprivation induced apoptosis were analyzed using Western blotting.The results revealed that serum deprivation induced apoptosis in MSCs within 72 h of treatment.Serum deprivation was shown to lead to protein expression alterations in Bax,Bcl-2,casepase-3,casepase-8,GRP78,and CHOP during experiments.The data suggested that the mitochondria death pathway,the extrinsic apoptotic pathway and the endoplastic reticulum(ER) stress pathway were all involved in MSCs apoptosis.The increase in expression of CHOP and the simultaneous decrease in Bcl-2 expression suggest a synergistic effect in apoptosis induction in both the mitochondrion and the ER.
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OBJECTIVE:To investigate the association of synergistic effects of Wuzhi capsules on tacrolimus with CYP3A5*3 (6986A>G,rs776746) gene polymorphisms. METHODS:One hundred and severty patients underwent renal transplantation receiving tacrolimus maintenance therapy after surgery were selected from our hospital during Jan. 1997-Dec. 2015,and then divided into Wuzhi capsules(+)group(74 cases)and Wuzhi capsules(-)group(96 cases)according to the use of Wuzhi capsules. Both groups received tacrolimus+mycophenolate mofetil+prednisone;Wuzhi capsules (+)group was additionally given Wuzhi capsules,one capsule each time,bid,for more than 12 months. Trough concentration of tacrolimus was detected by CMIA 0,1,3,6,12 months after medica-tion,and the blood concentrations(C0/D)were calculated at different time points after correcting daily dose. CYP3A5*3 gene polymor-phisms was detected by PCR-RFLP. The association of C0/D value with gene polymorphism was investigated by analysis of covariance. RESULTS:Among 170 patients,there were 65 cases of CYP3A5 GG genotype,83 cases of AG genotype and 22 cases of AA geno-type;genotype frequencies were 38.2%,48.8% and 12.9%,which was in line with Hardy-Weinberg balance (P>0.05). There was statistical significance in the distribution frequencies of GG,AG+AA genotype between Wuzhi capsules(+)group and Wuzhi capsules (-)group (P0.05). CON-CLUSIONS:Wuzhi capsules can increase C0/D of tacrolimus in CYP3A5*3 AG+AA genotype,but have no significant effect on C0/D of tacrolimus in GG genotype;CYP3A5*3 genotype should be considered when using Wuzhi capsules as synergist of tacrolimus.
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Aim To investigate the effects of com-bined treatment of SAHA and TRAIL on human breast cancer ER positive cell line MCF-7 . Methods MCF-7 cells were treated with SAHA and/or TRAIL. The inhibitory rates were detected by real-time cell prolifer-ation assays. Morphology changes of MCF-7 cells were observed through time-lapse live cell imaging acquisi-tion. Results Real-time cell proliferation assays showed that the anti-tumor efficacy of SAHA was sig-nificantly enhanced in combination with TRAIL. The results of time-lapse live cell imaging acquisition dem-onstrated that, with treatment of SAHA and TRAIL, the growth inhibition of MCF-7 cells was more obvious than that of in TRAIL or SAHA treatment alone. Con-clusion The combination treatment of SAHA and TRAIL has a synergistic effect of growth inhibition on breast cancer MCF-7 cells.
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Chemotherapy plays an important role in cancer treatment. However ,the low water-solubility and serious side effects are still the biggest obstacles in clinic. In addition,the wide use of chemotherapeutic drugs would result in the multidrug resis?tance(MDR)and the single chemotherapy could not meet the demand of clinic anymore. Combination therapy by two or more drugs used in the same time,has become the best choice for cancer patients. It not only enhances the cytotoxicity of the chemotherapeutic drugs due to the synergistic effect of the drugs,but also inhibits the MDR to improve uptake and cytotoxicity of the chemotherapeutic drugs when adding MDR inhibitors. The drug delivery system can improve the water-solubility due to the good biocompatibility of bio?degradable material which is the most property for drug delivery carriers. In addition,the targeting ability of the system and the con?trolled release of chemotherapeutic drugs can also reduce the side effects of drugs such as the cardiotoxicity of doxorubicin. The co-deliv?ery system loading two or more chemotherapeutic drugs in the same carrier can get better cytotoxicity than the combination therapy using free drugs due to the efficient delivery of chemotherapeutic drugs to cancer cells ,and are even better than the combination of single drug-loaded drug delivery systems because the chemotherapeutic drugs can get into the cancers cells in the same time. In addi?tion,with the rapid development of gene therapy,the co-delivery of drugs and genes has also been a hot topic these days. In this paper, we focus on the preparation,characteristics and application of drug+drug and drug+gene co-delivery system,which can produce the synergistic effects or inhibit the MDR of cancer cells.
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Chemotherapy plays an important role in cancer treatment. However, the low water-solubility and serious side effects are still the biggest obstacles in clinic. In addition, the wide use of chemotherapeutic drugs would result in the multidrug resistance (MDR)and the single chemotherapy could not meet the demand of clinic anymore. Combination therapy by two or more drugs used in the same time, has become the best choice for cancer patients. It not only enhances the cytotoxicity of the chemotherapeutic drugs due to the synergistic effect of the drugs, but also inhibits the MDR to improve uptake and cytotoxicity of the chemotherapeutic drugs when adding MDR inhibitors. The drug delivery system can improve the water-solubility due to the good biocompatibility of biodegradable material which is the most property for drug delivery carriers. In addition, the targeting ability of the system and the controlled release of chemotherapeutic drugs can also reduce the side effects of drugs such as the cardiotoxicity of doxorubicin. The co-delivery system loading two or more chemotherapeutic drugs in the same carrier can get better cytotoxicity than the combination therapy using free drugs due to the efficient delivery of chemotherapeutic drugs to cancer cells, and are even better than the combination of single drug-loaded drug delivery systems because the chemotherapeutic drugs can get into the cancers cells in the same time. In addition, with the rapid development of gene therapy, the co-delivery of drugs and genes has also been a hot topic these days. In this paper, we focus on the preparation, characteristics and application of drug+drug and drug+gene co-delivery system, which can produce the synergistic effects or inhibit the MDR of cancer cells.
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Aims: To evaluate the possible in vitro interaction between methanolic extract of root of Adiantumcapillus-veneris and certain known antimicrobial drugs i.e. Oxacillin, Ceftazimide, Cefriaxone, Ofloxacin, Meropenem, Erythromycin, Cefuroxime, Cefoxitin, Cefotaxime and Ampicillin. Methodology and results: The study was carried out against ten bacterial strains (Staphylococcus aureus, S. epidermidis, Salmonella typhi, Klebsiella pneumoniea, Shigella dysentriea, Proteus vulgaris, Pseudomonas aeruginosa, Providencia species, Citrobacter freundii and Escherichia coli isolated from urine, pus and blood samples. Both disc diffusion and well diffusion methods were used to determine antimicrobial activity of plant extract in combination with antibiotics. Antimicrobial sensitivity showed that Meropenem was the most effective antibiotic with zone of inhibition (ZI) of 25-33 mm among all tested antibiotics followed by Ofloxacin (10-26.5 mm), Ceftriaxone (8-20 mm), while Oxacillin showed no activity against almost all bacterial strains. The study showed that most bacterial strains were resistant to most of the antibiotics used, ranging from 20-60%. The methanolic extract (mEXT) of A. capillus-veneris used alone was active against most of the bacterial isolates with maximum activity against E. coli with 16 mm ZI. The study also indicated that there was an increased activity in case of combination of mEXT with antibiotics. The combined effects of plant extract with antibiotics were synergistic against most of the bacterial strains. The mEXT showed maximum synergistic effect with Ceftazimide with ZI of 42 mm followed by Meropenem (40 mm) and Ceftriaxone (28 mm) against multidrug-resistant (MDR) bacterial strains. Conclusion, significance and impact of study: The data suggests that plant extract could be used as alternative to antibiotics. These results give scientific backing that combination between plant extract and antibiotics would be useful in fighting the emerging drug-resistant bacterial pathogens.
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Anti-Infective Agents , Plants, MedicinalABSTRACT
Objective: To evaluate the in vitro interaction between methanolic extracts of Terminalia catappa (Combretaceae) (T. catappa) and Carica papaya (caricaceae) (C. papaya) leaves and certain known antimicrobial drugs like penicillin G (P), ampicillin (AMP), amoxyclav (AMC), cephalothin (CEP), polymyxin B (PB), rifampicin (RIF), amikacin (AK), nilidixic acid (NA), gentamicin (GEN), chloramphenicol (C), ofloxacin (OF) against five Gram positive and five Gram negative bacteria.Methods:Evaluation of synergy interaction between plant extracts and antimicrobial agents was carried out using disc diffusion method. Results: The results of this study showed that there is an increased activity in case of combination of methanolic plant extracts and test antimicrobial agents. The more potent result was that the synergism between methanolic extract of C. papaya and antibiotics showed highest and strong synergistic effect against tested bacterial strains;though methanolic extract of C. papaya alone was not showing any antibacterial activity.Conclusions:These results indicate that combination between plant extract and the antibiotics could be useful in fighting emerging drug-resistance microorganisms.
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Objective: To evaluate the in vitro interaction between methanolic extracts of Terminalia catappa (T. catappa) (Combretaceae) and Carica papaya (C. papaya) (caricaceae) leaves and certain known antimicrobial drugs like penicillin G (P), ampicillin (AMP), amoxyclav (AMC), cephalothin (CEP), polymyxin B (PB), rifampicin (RIF), amikacin (AK), nilidixic acid (NA), gentamicin (GEN), chloramphenicol (C), ofloxacin (OF) against five Gram positive and five Gram negative bacteria. Methods: Evaluation of synergy interaction between plant extracts and antimicrobial agents was carried out using disc diffusion method. Results: The results of this study showed that there is an increased activity in case of combination of methanolic plant extracts and test antimicrobial agents. The more potent result was that the synergism between methanolic extract of C. papaya and antibiotics showed highest and strong synergistic effect against tested bacterial strains;though methanolic extract of C. papaya alone was not showing any antibacterial activity. Conclusions: These results indicate that combination between plant extract and the antibiotics could be useful in fighting emerging drug-resistance microorganisms.
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Objective To explore the synergistic effects of substrate stiffness and cytokine TGF-β1 on phenotypic transformation of hepatocytes by establishing an in vitro culture model with the substrate stiffness that is relevant to hepatic cells physiologically and pathologically. Methods Immunofluorescence and Western blotting were adopted to observe the morphological adjustment, motion characteristics, cytoskeleton arrangement of hepatocytes on polyacrylamide substrates with different stiffness, as well as the changes in expression of integrin and phenotypic markers E-cadherin, albumin and alpha-smooth muscle actin (α-SMA). Image analysis software was also used for quantitative study on the obtained data. Results On the 3.6 kPa substrates, the scattered single cells were actively deformed and relocated, but the bulk cell population had little change in polarization and microfilament organization. Muscle actin was assembled as cortical ring in cell periphery. There was more abundant expression of E-cadherin and albumin, but less expression of integrin and α-SMA in TGF-β1 treated group as compared to the control group. On the 30 kPa substrates, the motion and deformation of cells were not so active, and expression of both E-cadherin and albumin in TGF-β1 treated group was decreased, while that of α-SMA was increased as compared to the control group. For 30 kPa and 3.6 kPa control groups and 30 kPa and 3.6 kPa TGF-β1 treated groups, expression of both E-cadherin and albumin was reduced (P<0.05), but that of alpha-SMA was increased (P<0.05), while no significant differences were found in both 10 kPa control group and TGF-β1 treated group, as well as in 30 kPa and 3.6 kPa control groups and TGF-β1 treated groups. Conclusions The increase of substrate stiffness can induce transformation of hepatocyte phenotype and promote the influence of TGF-beta 1 on behavior of hepatocyte metabolism.
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An improved and practical synthesis of racemic 11-demethylcalanolide A [(±)-1] was developed. This improved process involved Pechmann reaction on phloroglucinol with ethyl butyrylacetate to give 5, 7,-dihydroxy-4-n-propylcoumarin(3). Poly phosphoric acid (PPA) catalyzed acylation of compound(3) with crotonic acid, then intramolecular cyclization was achieved simultaneously in one step to afford the key intermediate chromanone(4). A microwave assisted synthetic method preparing chromene(6) using chromenynation of chromanone(4) with 1, 1-diethoxy-methyl-2-butene was conducted. Luche reduction of chromene(6) using NaBH<,4> with CeCl3·7H2O preferably gave (±)-1. The overall yield of this four step synthesis of (±)-1 was around 32% increasing one fold more than that of the previous method. An in vitro investigation showed that (±)-1 exhibited inhibitory activities against both wild-type and drug-resistant HIV-1 in HIV-1 RT and cell culture assay, and significant synergistic effects in combination with AZT, T-20, and indinavir. Its LD50 of acute toxicity in mice by intragastric administration and by intraperitoneal injection were 735.65mg·kg-1 and 525.10mg·kg-1, respectively. The C<,max> and AUC<,0-∞> were 0.54μg·mL-1 and 1.08(μg·mL-1)·h, respectively. The dynamics study of the inhibition of mice sera on HIV-1 RT showed that mice treated with 100mg·kg-1 (±)-1 once intraperitoneally were similar to that of 5mg·kg-1 of known clinical effective anti-HIV-1 drug neverapine. The results suggested that further investigation of the anti-HIV candidate (±)-1 was warranted.
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Objective To observe the antimutagenic action of sodium selenite and vitamin E on condensates of cooking oil fumes(COF) Methods SCE (sister chromatid exchanges) were observed and contrasted before and after addition of sodium selenite or vitamin E at a certain dose to the culture of human peripheral blood lymphocytes treated by COF Results Sodium selenite added to lymphocytic culture treated by COF at 37 ℃ for 4 hour incubation significantly lowered the frequencies SCEs of lymphocytes and very significant synergistic effects on lowering frequencies of SCEs were observed during adding both sodium selenite(terminal concentration 0 9?10 -7 mol/L) and vitamin E(torminal concentration 0 1% (v/v) to lymphocytic culture treated ty COF for 4 hour incubation Conclusion Combined sodium selenite and vitamin E at certain concentrations in cultured lymphocytes for 4 hour incubation showed very significant synergistic effects on lowering the mutagenicity of lymphocytes induced ty COF.Sodium selenite alone was also shown to be effective in lowering the frequencies of SCEs of human peripheral blood lymphocytes
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A total of 104 marine bacterial strains were isolated from Stelletta tennui around Sanya area of South China Sea by dilution-plate method and were screened for anti-microbial activity on Escherichia coli, Staphylococcus aureu, Pseudomonas fluorescens, Bacillus subtilis, Aspergillus niger, Candida albicans and Pacecilomyces variotii by agar diffusion, paper disc diffusion assay and cell concentration counts methods. It was found that 23 strains, which are 22.2% of the total isolated strains, have anti-microbial activities. Among the 23 strains, A05, A08, A72 and A75 were morphologically, physiologically and biochemically characterized and identified to be the genus Bacillus. At the same time, it was proved that there are positive and negative synergistic effects between or among active strains, e.g., as for A72-75 combination, an obvious enhanced anti-microbial activities on inhibiting Candida albicans and Pseudomomas fluorescens growth was observed than A72 or A75.