RESUMO
The objective of the investigation was to improve phosphate solubilization in tomato plants by Bacillus licheniformis, a rhizobacterium that promotes plant growth. Ultraviolet (UV) radiation, Ethyl methanesulfonate (EMS) and Ethidium bromide (EtBr) mutagenesis produced twenty-one mutants. Phosphate solubilization was higher in the PM7 (physical mutant) (121.00 g mL-1) than in the wild type (82.00 g mL-1). PM7 showed high antifungal activity against Phytophthora capsici, Fusarium oxysporum and Dematophora necatrix besides increased siderophore production and HCN production. In a net-house experiment, PM7 improved root and shoot parameters, P assimilation and soil P availability in tomato plants. This study demonstrates the potential of PM7 as an effective rhizobacterium for enhancing nutrient availability and plant growth.
RESUMO
Expression of the cell cycle regulatory gene CDK6 is required for Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) cell growth, whereas expression of the closely related CDK4 protein is dispensable. Moreover, CDK6 silencing is more effective than treatment with the dual CDK4/6 inhibitor palbociclib in suppressing Ph+ ALL in mice, suggesting that the growth-promoting effects of CDK6 are, in part, kinase-independent in Ph+ ALL. Accordingly, we developed CDK4/6-targeted proteolysis-targeting chimeras (PROTACs) that inhibit CDK6 enzymatic activity in vitro, promote the rapid and preferential degradation of CDK6 over CDK4 in Ph+ ALL cells, and markedly suppress S-phase cells concomitant with inhibition of CDK6-regulated phospho-RB and FOXM1 expression. No such effects were observed in CD34+ normal hematopoietic progenitors, although CDK6 was efficiently degraded. Treatment with the CDK6-degrading PROTAC YX-2-107 markedly suppressed leukemia burden in mice injected with de novo or tyrosine kinase inhibitor-resistant primary Ph+ ALL cells, and this effect was comparable or superior to that of the CDK4/6 enzymatic inhibitor palbociclib. These studies provide "proof of principle" that targeting CDK6 with PROTACs that inhibit its enzymatic activity and promote its degradation represents an effective strategy to exploit the "CDK6 dependence" of Ph+ ALL and, perhaps, of other hematologic malignancies. Moreover, they suggest that treatment of Ph+ ALL with CDK6-selective PROTACs would spare a high proportion of normal hematopoietic progenitors, preventing the neutropenia induced by treatment with dual CDK4/6 inhibitors.
Assuntos
Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quinase 6 Dependente de Ciclina/metabolismo , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Perfilação da Expressão Gênica , Genes cdc , Humanos , Camundongos , Estrutura Molecular , Fosforilação , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/uso terapêutico , Resultado do Tratamento , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Objective: To prospectively assess safety outcome of TRUS guided prostate biopsy in patients taking low dose aspirin. Materials and methods: Consecutive patients, who were planned for 12 core TRUS guided prostate biopsy and satisfied eligibility criteria, were included in the study and divided into two Groups: Group A: patients on aspirin during biopsy, Group B: patients not on aspirin during biopsy, including patients in whom aspirin was stopped prior to the biopsy. Parameters included for statistical analysis were: age, serum prostate specific antigen (PSA), prostate volume, hemoglobin (Hb %), number of hematuria episodes, number of patient reporting hematuria, hematuria requiring intervention, number of patient reporting hematospermia and number of patient reporting rectal bleeding. Results: Of 681 eligible patients, Group A and B had 191 and 490 patients respectively. The mean age, prostate volume, serum PSA and pre-biopsy hemoglobin were similar in both Groups with no significant differences noted between them. None of the post-biopsy complications, including number of hematuria episodes (p=0.83), number of patients reporting hematuria (p=0.55), number of patients reporting hematospermia (p=0.36) and number of patients reporting rectal bleeding (p=0.65), were significantly different between Groups A and B respectively. None of the hemorrhagic complication in either group required intervention and were self limiting. Conclusion: Continuing low dose aspirin during TRUS guided prostate biopsy neither alters the minor bleeding episodes nor causes major bleeding complication. So, discontinuation of low dose aspirin prior to TRUS guided prostate biopsy is not required.
Assuntos
Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Aspirina/administração & dosagem , Biópsia com Agulha de Grande Calibre/métodos , Hemorragia/prevenção & controle , Inibidores da Agregação Plaquetária/administração & dosagem , Próstata/patologia , Ultrassonografia de Intervenção/métodos , Biópsia com Agulha de Grande Calibre/efeitos adversos , Hemorragia/etiologia , Contagem de Plaquetas , Estudos Prospectivos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Reprodutibilidade dos Testes , Fatores de Risco , Reto , Ultrassonografia de Intervenção/efeitos adversosRESUMO
OBJECTIVE: To prospectively assess safety outcome of TRUS guided prostate biopsy in patients taking low dose aspirin. MATERIALS AND METHODS: Consecutive patients, who were planned for 12 core TRUS guided prostate biopsy and satisfied eligibility criteria, were included in the study and divided into two Groups: Group A: patients on aspirin during biopsy, Group B: patients not on aspirin during biopsy, including patients in whom aspirin was stopped prior to the biopsy. Parameters included for statistical analysis were: age, serum prostate specific antigen (PSA), prostate volume, hemoglobin (Hb %), number of hematuria episodes, number of patient reporting hematuria, hematuria requiring intervention, number of patient reporting hematospermia and number of patient reporting rectal bleeding. RESULTS: Of 681 eligible patients, Group A and B had 191 and 490 patients respectively. The mean age, prostate volume, serum PSA and pre-biopsy hemoglobin were similar in both Groups with no significant differences noted between them. None of the post-biopsy complications, including number of hematuria episodes (p=0.83), number of patients reporting hematuria (p=0.55), number of patients reporting hematospermia (p=0.36) and number of patients reporting rectal bleeding (p=0.65), were significantly different between Groups A and B respectively. None of the hemorrhagic complication in either group required intervention and were self limiting. CONCLUSION: Continuing low dose aspirin during TRUS guided prostate biopsy neither alters the minor bleeding episodes nor causes major bleeding complication. So, discontinuation of low dose aspirin prior to TRUS guided prostate biopsy is not required.
Assuntos
Aspirina/administração & dosagem , Biópsia com Agulha de Grande Calibre/métodos , Hemorragia/prevenção & controle , Inibidores da Agregação Plaquetária/administração & dosagem , Próstata/patologia , Ultrassonografia de Intervenção/métodos , Idoso , Biópsia com Agulha de Grande Calibre/efeitos adversos , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Reto/diagnóstico por imagem , Reprodutibilidade dos Testes , Fatores de Risco , Ultrassonografia de Intervenção/efeitos adversosRESUMO
AIM: Present study was conducted to compare the effect of topical fluoride agents on color change of three aesthetic restorative materials. MATERIAL AND METHODS: Restorative material used were Ketac Fill type II (GIC), Filtek Z350(Composite) and Beuttifull II (Giomer). Topical Fluorides used were Pascal (1.23% APF gel) and Fluoride Varnish (Bifluoride). 24 samples of each restorative material were prepared, which were divided into 8 each, among three groups. Treatment of Group A with APF gel, Group B with Varnish was done and Group C with distilled water which was used as a control, followed by immersing of samples in artificial saliva for 48 hr. Samples were then subjected to colorimetric analysis. Data collected was statistically analysed using one way ANOVA and Tukys Post Hoc Test. RESULTS: GIC showed statistically significant change in color in both APF and Varnish group compared to composite and Giomer after 48 hr. CONCLUSION: Present study concludes that Topical fluoride agents have detrimental effect on color of aesthetic restorative materials. Giomer was least effected out of the three restorative materials and this can be used as alternative to other restorative material.