RESUMO
Bacillus amyloliquefaciens JN68, which has been discussed with regards to its antimicrobial activities, was successfully isolated from healthy chicken intestines in the present study. Using the spot-on-the-lawn antagonism method, the preliminary study indicated that a suspension culture of the B. amyloliquefaciens JN68 strain can inhibit the growth of Aspergillus niger and Penicillium pinophilum. Furthermore, the cyclic lipopeptides (CLPs) produced by the B. amyloliquefaciens JN68 strain were further purified through acid precipitation and Bond Elut®C18 chromatography, and their structures were identified using the liquid chromatographyelectrospray ionizationmass spectrometry (MS)/MS method. Purified CLPs exerted broad spectrum antimicrobial activities on various pathogenic and foodborne bacteria and fungi, as determined using the agar well diffusion method. Listeria monocytogenes can induce listeriosis, which is associated with a high mortality rate. Methicillinresistant Staphylococcus aureus (MRSA) is a major pathogenic bacteria that causes nosocomial infections. Therefore, L. monocytogenes and MRSA are currently of great concern. The present study aimed to determine whether B. amyloliquefaciens JN68 extracts could inhibit L. monocytogenes and MRSA. The results indicated that extracts of B. amyloliquefaciens JN68 have CLP components, and can successfully inhibit the growth of L. monocytogenes and MRSA.
Assuntos
Anti-Infecciosos/farmacologia , Bacillus amyloliquefaciens/metabolismo , Lipopeptídeos/farmacologia , Listeria monocytogenes/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Anti-Infecciosos/isolamento & purificação , Antibiose , Bacillus amyloliquefaciens/isolamento & purificação , Galinhas , Intestinos/microbiologia , Lipopeptídeos/isolamento & purificação , Peptídeos Cíclicos/isolamento & purificaçãoRESUMO
Renal fibroblast proliferation is key in renal fibrosis and chronic kidney disease. Transforming growth factor-ß1 (TGF-ß1) has been demonstrated to be an important factor that induces cell proliferation in renal fibroblasts. Epidermal growth factor receptor (EGFR) is also recognized as a factor promoting renal fibroblast proliferation. In addition, mitogenactivated protein kinase signaling pathways are associated with TGFß1 and EGFRinduced cell proliferation. Gefitinib, an EGFR tyrosine kinase inhibitor, is predominantly used as an antitumor therapeutic agent in clinical therapeutic strategies. However, gefitinib has been suggested to exert antiproliferative effects on renal fibroblasts, however, highdose gefitinib may result in serious side effects. The present study aims to determine whether lowdose gefitinib reduces gefitinibinduced side effects and maintains the antiproliferative effects on renal fibroblasts. TGFß1 promotes cell proliferation in renal fibroblasts, and the current study demonstrates that lowdose gefitinib treatment exhibits antiproliferative effects similar to those of highdose gefitinib treatment. Thus, although highdose gefitinib is a conventional antitumor drug, lowdose gefitinib may be of use in renal fibrosis treatment. Furthermore, the present study demonstrates that a combined treatment with low-dose gefitinib and vitamin E has synergistic effects that reduce TGFß1induced fibroblast proliferation, cell-cycle arrest and the ERK phosphorylation pathway.
Assuntos
Proliferação de Células/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Rim/metabolismo , Quinazolinas/farmacologia , Fator de Crescimento Transformador beta1/biossíntese , Vitamina E/farmacologia , Animais , Linhagem Celular , Sinergismo Farmacológico , Fibroblastos/citologia , Gefitinibe , Rim/citologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Quinazolinas/agonistas , Ratos , Vitamina E/agonistasRESUMO
Retinoic acid (RA), vitamin D and 12-Otetradecanoyl phorbol-13-acetate (TPA) can induce HL-60 cells to differentiate into granulocytes, monocytes and macrophages, respectively. Similar to RA and vitamin D, ascorbic acid also belongs to the vitamin family. Highdose ascorbic acid (>100 µM) induces HL60 cell apoptosis and induces a small fraction of HL60 cells to express the granulocyte marker, CD66b. In addition, ascorbic acid exerts an antioxidative stress function. Oxidative stress is required for HL60 cell differentiation following treatment with TPA, however, the effect of ascorbic acid on HL60 cell differentiation in combination with TPA treatment remains to be fully elucidated. The aim of the present study was to investigate the cellular effects of ascorbic acid treatment on TPA-differentiated HL-60 cells. TPA-differentiated HL-60 cells were used for this investigation, this study and the levels of cellular hydrogen peroxide (H2O2), caspase activity and ERK phosphorylation were determined following combined treatment with TPA and ascorbic acid. The results demonstrated that lowdose ascorbic acid (5 µM) reduced the cellular levels of H2O2 and inhibited the differentiation of HL60 cells into macrophages following treatment with TPA. In addition, the results of the present study further demonstrated that lowdose ascorbic acid inactivates the ERK phosphorylation pathway, which inhibited HL60 cell differentiation following treatment with TPA.
Assuntos
Ácido Ascórbico/farmacologia , Diferenciação Celular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Peróxido de Hidrogênio/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Caspases/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células HL-60 , Humanos , Macrófagos , FosforilaçãoRESUMO
Human glioblastoma multiforme is one of the most aggressive malignant brain tumor types, and the mean survival time of patients with a brain tumor is <2 years when traditional therapies are administered. Thus, numerous studies have focused on the development of novel treatments for brain tumors. Frog ribonucleases, such as Onconase and Rana catesbeiana ribonuclease (RC-RNase), exert antitumor effects on various tumor cells, including cervical cancer, breast cancer, hepatoma, leukemia, pancreatic cancer and prostate cancer cells. In addition, frog Onconase has been applied as a treatment in clinical trials. However, the antitumor effects of frog ribonucleases on brain tumors are unclear. Previous studies have indicated that RC-RNase demonstrates a decreased cytotoxic effect in normal cells compared with Onconase. Therefore, the present study investigated the ability of RC-RNase to exert antitumor activities on human glioblastoma. It was found that RC-RNase inhibits the growth of the human glioblastoma DBTRG, GBM8901 and GBM8401 cells. In addition, the present study revealed that RC-RNase induces caspase-9/-3 activity and triggers the apoptotic cell death pathway in human glioblastoma cells. Notably, it was also demonstrated that RC-RNase effectively inhibits the growth of human glioblastoma tumors in a nude mouse model. Overall, the present study indicates that RC-RNase may be a potential agent for the treatment of human glioblastoma.
RESUMO
Acetaminophen (APAP) is a widely used analgesic and antipyretic drug. Generally, the therapeutic dose of APAP is clinically safe, however, high doses of APAP can cause acute liver and kidney injury. Therefore, the majority of previous studies have focussed on elucidating the mechanisms of APAP-induced hepatotoxicity and nephrotoxicity, in addition to examining ways to treat these conditions in clinical cases. However, few studies have reported APAP-induced intoxication in human stem cells. Stem cells are important in cell proliferation, differentiation and repair during human development, particularly during fetal and child development. At present, whether APAP causes cytotoxic effects in human stem cells remains to be elucidated, therefore, the present study aimed to investigate the cellular effects of APAP treatment in human stem cells. The results of the present study revealed that high-dose APAP induced more marked cytotoxic effects in human mesenchymal stem cells (hMSCs) than in renal tubular cells. In addition, increased levels of hydrogen peroxide (H2O2), phosphorylation of c-Jun N-terminal kinase and p38, and activation of caspase-9/-3 cascade were observed in the APAP-treated hMSCs. By contrast, antioxidants, including vitamin C reduced APAP-induced augmentations in H2O2 levels, but did not inhibit the APAP-induced cytotoxic effects in the hMSCs. These results suggested that high doses of APAP may cause serious damage towards hMSCs.
Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Narcóticos/efeitos adversos , Morte Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Animais , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Túbulos Renais/citologia , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Ratos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Methotrexate (MTX) has been widely used for rheumatoid arthritis therapy for a long time. MTX is also used as an anticancer drug for various tumors. However, many studies have shown that high-dose MTX treatment for cancer therapy may cause liver and renal damage. Alhough the mechanisms involved in MTX-induced liver and renal damage require further research, many studies have indicated that MTX-induced cytotoxicity is associated with increases in oxidative stress and caspase activation. In order to reduce MTX-induced side-effects and increase anticancer efficiency, currently, combination treatments of low-dose MTX and other anticancer drugs are considered and applied for various tumor treatments. The present study showed that MTX induces increases in H2O2 levels and caspase-9/-3 activation leading to cell death in hepatocellular carcinoma Hep3B cells. Importantly, this study is the first to demonstrate that vitamin C can efficiently aid low-dose MTX in inducing cell death in Hep3B cells. Therefore, the present study provides a possible powerful therapeutic method for tumors using a combined treatment of vitamin C and low-dose MTX.
Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Ácido Ascórbico/farmacologia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Metotrexato/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Oxigênio/metabolismoRESUMO
The complete nucleotide sequences of the S1 and N genes of three Japanese and one Taiwanese field strains of IBV are reported. These Japanese strains were found to have S1 sequences most similar to those of Australian strains and N sequences most similar to those of North American strains. This result suggested that these Japanese strains might all be recombinant viruses derived from recombination of Australia- and North America-related viruses. Moreover, the S1 proteins of all these Japanese and Taiwanese strains exhibit only a limited sequence homology to strains of Massachusetts and Connecticut serotypes that have been commonly used as vaccine strains. This result high lightens the importance of development of vaccines based on the local strains of IBV.