RESUMO
In recent years, there has been significant progress in the research of oncolytic viruses for the therapy of gliomas. The latest clinical trial results related to the modification, effectiveness, and safety of oncolytic viruses have brought hope for the development of glioblastoma treatments. Modified oncolytic viruses, particularly those based on the herpes simplex virus, have gained approval in Japan. Clinical trials involving recombinant poliovirus have shown better-than-expected survival outcomes with a strong safety profile. Notably, the first-time report of adenovirus in combination with immune checkpoint inhibitors for glioblastoma has demonstrated promising survival benefits and safety. However, challenges remain, including the selection of administration routes and the sustainability of treatment effects during oncolytic virus therapy. Therefore, further preclinical and clinical studies are required to improve the effectiveness and optimize treatment strategy for glioblastoma using oncolytic viruses.
RESUMO
OBJECTIVE: It is still unknown whether early tirofiban treatment improves prognosis in patients with cancer-related ischemic stroke without intravenous thrombolytic therapy. The purpose of this study was to assess the safety and efficacy of tirofiban in patients with cancer-associated ischemic stroke. PATIENTS AND METHODS: A retrospective analysis was performed on 75 patients with cancer and mild to moderate ischemic stroke, 34 of whom received tirofiban treatment and 41 aspirin treatment. The aspirin group received aspirin 100 mg QD, while the tirofiban group received continuous intravenous administration of tirofiban at a dosage of 0.1 µg/kg/min for 48 hours before switching to oral aspirin. RESULTS: The 24-hour and 7-day National Institute of Health Stroke Scale (NIHSS) scores for the tirofiban group were lower than those for the aspirin group (p=0.017 and p=0.035, respectively). The proportion of intracerebral hemorrhage occurring within 7 days did not differ significantly between the two groups (p>0.05), and neither did the 90-day Modified Rankin Scale (mRS) scores nor the incidence of ischemic stroke. CONCLUSIONS: Early administration of tirofiban in the treatment of mild to moderate ischemic stroke is safe, which can reduce 24-hour and 7-day NIHSS scores and has potential value.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Neoplasias , Acidente Vascular Cerebral , Humanos , Tirofibana/uso terapêutico , Acidente Vascular Cerebral/complicações , AVC Isquêmico/tratamento farmacológico , Estudos Retrospectivos , Isquemia Encefálica/complicações , Resultado do Tratamento , Aspirina , Neoplasias/complicaçõesRESUMO
Abstract Plants adjust their shoot growth to acclimate to changing environmental factors, such as to enhanced Ultraviolet-B (UV-B) radiation. However, people have ignored that plant roots can also respond to UV-B light. Here, we find the morphology curled wheat roots under UV-B radiation, that we call, "bending roots." The curly region is the transition zone of the root after observed at the cellular level. After exposed to enhanced UV-B radiation for 2 d (10.08 KJ/m2/d), cell size decreased and actin filaments gathered in wheat roots. We also find that H2O2 production increased and that content of the indole-3-acetic acid (IAA) increased remarkably. The pharmacological experiment revealed that actin filaments gathered and polymerized into bundles in the wheat root cells after irrigated H2O2 and IAA. These results indicated that actin filaments changed their distribution and formed the "bending root," which was related to H2O2 production and increase in IAA. Overall, actin filaments in wheat root cells could be a subcellular target of UV-B radiation, and its disruption determines root morphology.
Resumo As plantas ajustam o crescimento da parte aérea para se adaptarem a fatores ambientais variáveis, como o aumento da radiação ultravioleta B (UVB). No entanto, as pessoas ignoram que as raízes das plantas também podem responder à luz UVB. Neste estudo, verificamos a morfologia das raízes enroladas de trigo sob radiação UVB, o que chamamos de "raízes dobradas". A região encaracolada é a zona de transição da raiz no nível celular. Depois de exposição à radiação UVB aprimorada por 2 dias (10,08 KJ/m2/d), o tamanho das células diminuiu, e os filamentos de actina se reuniram. Também constatamos que a produção de H2O2 aumentou e que o conteúdo do ácido indol-3-acético (IAA) aumentou notavelmente. O experimento farmacológico revelou que os filamentos de actina se reuniram e polimerizaram em feixes nas células da raiz de trigo após irrigação com H2O2 e IAA. Esses resultados indicam que os filamentos de actina alteraram sua distribuição e formaram a "raiz dobrada", relacionada à produção de H2O2 e ao aumento do IAA. No geral, os filamentos de actina nas células da raiz de trigo podem ser um alvo subcelular da radiação UVB, e sua interrupção determina a morfologia da raiz.
Assuntos
Triticum , Peróxido de Hidrogênio , Raios Ultravioleta , Citoesqueleto de Actina , Raízes de PlantasRESUMO
Plants adjust their shoot growth to acclimate to changing environmental factors, such as to enhanced Ultraviolet-B (UV-B) radiation. However, people have ignored that plant roots can also respond to UV-B light. Here, we find the morphology curled wheat roots under UV-B radiation, that we call, "bending roots." The curly region is the transition zone of the root after observed at the cellular level. After exposed to enhanced UV-B radiation for 2 d (10.08 KJ/m2/d), cell size decreased and actin filaments gathered in wheat roots. We also find that H2O2 production increased and that content of the indole-3-acetic acid (IAA) increased remarkably. The pharmacological experiment revealed that actin filaments gathered and polymerized into bundles in the wheat root cells after irrigated H2O2 and IAA. These results indicated that actin filaments changed their distribution and formed the "bending root," which was related to H2O2 production and increase in IAA. Overall, actin filaments in wheat root cells could be a subcellular target of UV-B radiation, and its disruption determines root morphology.
Assuntos
Peróxido de Hidrogênio , Triticum , Citoesqueleto de Actina , Raízes de Plantas , Raios UltravioletaRESUMO
Objective: To investigate the role of neutrophil elastase inhibitor, sivelestat, in preventing and treating nonalcoholic steatohepatitis (NASH) and its underling mechanisms. Methods: A total of forty 4-week-old male C57BL/6J ApoE-/-mice were equally divided into the following four groups: standard chow (SC)+isotonic saline; SC+sivelestat; high-fat, high-cholesterol (HFHC) diet+isotonic saline; and HFHC+sivelestat. These mice were treated with above methods for 12 weeks. Blood and liver tissue samples were collected to measure biochemical parameters, hepatic steatosis and non-alcoholic fatty liver disease (NAFLD) activity score (inflammation) were evaluated by oil red O staining and HE staining, respectively. The mRNA and protein expression levels of hepatic inflammatory cytokines, CD68, and F4/80 were determined by quantitative RT-PCR and immunohistochemistry, respectively. Comparison of means between the four groups was made by one-way analysis of variance, and comparison between any two groups was made by the LSD or SNK method (for data with homogeneity of variance) or the Tamhane or Dunnett method (for data with heterogeneity of variance). Results: Mice fed with an HFHC diet for 12 weeks developed typical pathological features of NASH compared with those fed with SC. Compared with mice fed with HFHC diet without sivelestat, those treated with HFHC and sivelestat exhibited the following features: (1) significantly reduced fast blood glucose, blood cholesterol, and hepatic biochemical parameters, as well as increased insulin sensitivity; (2) significantly reduced NAFLD activity score (5.71±1.11 vs 3.16±1.16, P < 0.05); (3) reduced monocyte chemoattractant protein-1 and tumor necrosis factor -α; (4) significantly reduced mRNA levels of CD68 and F4/80; and (5) reduced expression of CD68 in the liver. Conclusion: Sivelestat alleviates the hepatic steatosis and inflammation of NASH in mice by inhibiting the activation of Kupffer cells.
Assuntos
Glicina/análogos & derivados , Células de Kupffer/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Inibidores de Serina Proteinase/farmacologia , Sulfonamidas/farmacologia , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Glicina/farmacologia , Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Abstract Plants adjust their shoot growth to acclimate to changing environmental factors, such as to enhanced Ultraviolet-B (UV-B) radiation. However, people have ignored that plant roots can also respond to UV-B light. Here, we find the morphology curled wheat roots under UV-B radiation, that we call, bending roots. The curly region is the transition zone of the root after observed at the cellular level. After exposed to enhanced UV-B radiation for 2 d (10.08 KJ/m2/d), cell size decreased and actin filaments gathered in wheat roots. We also find that H2O2 production increased and that content of the indole-3-acetic acid (IAA) increased remarkably. The pharmacological experiment revealed that actin filaments gathered and polymerized into bundles in the wheat root cells after irrigated H2O2 and IAA. These results indicated that actin filaments changed their distribution and formed the bending root, which was related to H2O2 production and increase in IAA. Overall, actin filaments in wheat root cells could be a subcellular target of UV-B radiation, and its disruption determines root morphology.
Resumo As plantas ajustam o crescimento da parte aérea para se adaptarem a fatores ambientais variáveis, como o aumento da radiação ultravioleta B (UVB). No entanto, as pessoas ignoram que as raízes das plantas também podem responder à luz UVB. Neste estudo, verificamos a morfologia das raízes enroladas de trigo sob radiação UVB, o que chamamos de raízes dobradas. A região encaracolada é a zona de transição da raiz no nível celular. Depois de exposição à radiação UVB aprimorada por 2 dias (10,08 KJ/m2/d), o tamanho das células diminuiu, e os filamentos de actina se reuniram. Também constatamos que a produção de H2O2 aumentou e que o conteúdo do ácido indol-3-acético (IAA) aumentou notavelmente. O experimento farmacológico revelou que os filamentos de actina se reuniram e polimerizaram em feixes nas células da raiz de trigo após irrigação com H2O2 e IAA. Esses resultados indicam que os filamentos de actina alteraram sua distribuição e formaram a raiz dobrada, relacionada à produção de H2O2 e ao aumento do IAA. No geral, os filamentos de actina nas células da raiz de trigo podem ser um alvo subcelular da radiação UVB, e sua interrupção determina a morfologia da raiz.
RESUMO
UNLABELLED: Chemical composition and antioxidant, antimicrobial activities of the essential oils from Thymus marschallianus Will. and Thymus proximus Serg. growing in the wild in Xinjiang were studied. Samples were collected from the aerial parts of the plants with simultaneous distillation-extraction apparatus. The yields ranged between 1.22%+/- 0.01 and 0.16%+/- 0.01 (weight/dry weight), respectively, 53 and 60 kinds of volatiles, representing 99.6% and 99.7% of the essential oils, respectively, were identified in extracts from T. marschallianus and T. proximus by GC/MS analysis. The main components were Thymol (28.0% to 32.9%), p-Cymene (7.7% to 25.4%), and gamma-Terpinene (18.0% to 22.4%). Antioxidant activities of the oils were evaluated using metal chelating, reductive potential, 2,2-diphenyl-1-picrylhydrazyl, hydroxyl radical, and modified thiobarbituric acid reactive substances assay. Antimicrobial activities of the oils were investigated on Escherichia coli, Staphylococcus aureus, Bacillus subtilis, yeast, Rhizopus, and Penicillium. The inhibition zones (IZ) and minimum inhibitory concentration (MIC) values were 5.0 to 35.7 mm in diameter and 1.81 to 4.52 microL/mL, respectively. PRACTICAL APPLICATION: Due to the economical impacts of spoiled foods and the consumer's concerns over the safety of foods, a lot of attention has been paid to naturally derived compounds. Fresh and dried Thymus species as well as their processed products have been widely used as flavorings since ancient times; however, during the last few decades, they also have become a subject for a search of natural antioxidants and antimicrobial agents. Biological activities of Thymus essential oils depend on their chemical composition, which is determined by the genotype and influenced by environmental conditions. Recent studies have showed that Thymus species have strong antimicrobial and antioxidant activities. To the best of our knowledge, the properties of Thymus species growing wild in the Xinjiang have not been reported before.
Assuntos
Antioxidantes/análise , Óleos Voláteis/química , Óleos de Plantas/química , Thymus (Planta)/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Compostos de Bifenilo/análise , Quelantes/isolamento & purificação , China , Escherichia coli/efeitos dos fármacos , Sequestradores de Radicais Livres/isolamento & purificação , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Penicillium/efeitos dos fármacos , Picratos/análise , Óleos de Plantas/isolamento & purificação , Óleos de Plantas/farmacologia , Rhizopus/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Terpenos/análise , Terpenos/farmacologia , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Timol/isolamento & purificação , Timol/farmacologia , Leveduras/efeitos dos fármacosRESUMO
BACKGROUND: Previous studies indicate that N-ratio has significant superiority in minimizing 'stage migration' for patients with >15 lymph nodes retrieved. Whether the result is applicable to patients with < or =15 lymph nodes retrieved is still in question. PATIENTS AND METHODS: Overall survival rates of 2159 gastric cancer patients who underwent radical resection were compared between patients with different number and level of lymph nodes retrieved according to pN [International Union Against Cancer (Union Internationale Contre le Cancer)/AJCC N stage], n (JGCA N stage) and rN (N-ratio) staging system. RESULTS: Patient number was significantly different between insufficient and sufficient number or level retrieved group in pN and n system, respectively, but not in rN system, while overall survival rates were not significantly different between those groups. The 5-year survival rates of patients with insufficient nodes retrieved were significantly lower than those with sufficient nodes retrieved in pN and n system, but not in rN system. The hazard risk for patients with insufficient nodes retrieved was significantly higher than that for patients with sufficient nodes retrieved in pN and n system, but not in rN system. CONCLUSION: The rN stage has more potential advantages in minimizing stage migration phenomenon for patients with insufficient number or level of lymph nodes retrieved.
Assuntos
Gastrectomia , Excisão de Linfonodo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , China , Humanos , Estimativa de Kaplan-Meier , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Neoplasias Gástricas/mortalidade , Fatores de Tempo , Resultado do TratamentoRESUMO
The features and composition of Rotational Gamma Knife are mainly introduced in this paper. The open architecture double PLCs and motion controller are used to fit special requirements of the Rotational Gamma Knife and thus to ensure its high reliability. In the end, safety measures which should be taken for patients, doctors and equipments are discussed.