RESUMO
BACKGROUND: Radiation-induced brain injury is a neurological condition resulting from radiotherapy for malignant tumors, with its underlying pathogenesis still not fully understood. Current hypotheses suggest that immune cells, particularly the excessive activation of microglia in the central nervous system and the migration of peripheral immune cells into the brain, play a critical role in initiating and progressing the injury. This review aimed to summarize the latest advances in the cellular and molecular mechanisms and the therapeutic potential of microglia in radiation-induced brain injury. METHODS: This article critically examines recent developments in understanding the role of microglia activation in radiation-induced brain injury. It elucidates associated mechanisms and explores novel research pathways and therapeutic options for managing this condition. RESULTS: Post-irradiation, activated microglia release numerous inflammatory factors, exacerbating neuroinflammation and facilitating the onset and progression of radiation-induced damage. Therefore, controlling microglial activation and suppressing the secretion of related inflammatory factors is crucial for preventing radiation-induced brain injury. While microglial activation is a primary factor in neuroinflammation, the precise mechanisms by which radiation prompts this activation remain elusive. Multiple signaling pathways likely contribute to microglial activation and the progression of radiation-induced brain injury. CONCLUSIONS: The intricate microenvironment and molecular mechanisms associated with radiation-induced brain injury underscore the crucial roles of immune cells in its onset and progression. By investigating the interplay among microglia, neurons, astrocytes, and peripheral immune cells, potential strategies emerge to mitigate microglial activation, reduce the release of inflammatory agents, and impede the entry of peripheral immune cells into the brain.
Assuntos
Lesões Encefálicas , Microglia , Lesões por Radiação , Microglia/efeitos da radiação , Microglia/metabolismo , Animais , Humanos , Lesões por Radiação/metabolismo , Lesões por Radiação/terapia , Lesões Encefálicas/etiologia , Lesões Encefálicas/metabolismo , Doenças Neuroinflamatórias/etiologiaRESUMO
Sleep-dependent consolidation is important for novel word learning, but previous studies have neglected the potential modulating role of learning environments. The present study examines sleep-dependent consolidation effects by comparing learning in a virtual reality (VR) environment and in a traditional picture-word (PW) environment. Two groups of Chinese-English bilinguals were randomly assigned to a VR or PW environment. In both learning environments, they learned novel words in Korean, a language with which they had no prior experience. All participants learned one set of novel words on Day 1 and another set on Day 2. An explicit recognition task and an implicit primed lexical-decision task were employed to measure sleep-dependent consolidation effects from the two environments. Results revealed sleep-dependent consolidation effects in both explicit and implicit measures, but only the primed lexical-decision task showed an influence of learning environment, suggesting that novel words learned via VR had better consolidation. Taken together, our findings suggest that a VR environment that fosters a rich sensory experience facilitates sleep-dependent consolidation effects. We argue that these results provide new evidence and implications for the complementary learning system (CLS) model.
Assuntos
Aprendizagem , Semântica , Humanos , Sono , Aprendizagem Verbal , IdiomaRESUMO
OBJECTIVE: To detect the expression level of HK2 gene in the bone marrow of newly diagnosed patients with acute myeloid leukemia (AML) and investigate its influence on the clinical characteristics and prognosis. METHODS: The expression level of HK2 gene in the bone marrow of 90 newly diagnosed patients with AML that accompanying clinical characteristics and survival status were detected by RT-qPCR, and compared with 18 allogeneic hematopoietic stem cell transplantation (allo-HSCT) donors. The Chi-square test, Kaplan-Meier survival analysis, and Cox proportional hazards regression model were used to analyze the correlation of HK2 expression level with clinical characteristics and prognosis. RESULTS: Compared with allo-HSCT donors, the HK2 expression was significantly increased in newly diagnosed AML patients (P <0.01). Compared with patients with total response (OR, complete response + complete response with incomplete hematologic recovery) after 2 courses of induction chemotherapy, the expression of HK2 in patients without OR was significantly increased (P <0.05). There was a significant difference in the relative expression of HK2 between patients with and without OR after 2 courses of induction therapy (P <0.001). The median survival time of patients with high expression of HK2 was significantly shorter than that of patients with low expression of HK2 (P <0.05). The multivariate Cox proportional hazards regression analysis showed that prognostic stratification, the expression level of HK2, and whether two courses of induction therapy achieved OR were independent factors affecting the prognosis of AML patients (P <0.05). CONCLUSIONS: Compared with allo-HSCT donors, the expression level of HK2 gene is increased in the bone marrow of newly diagnosed AML patients. The prognosis of patients with high expression of HK2 is poor. The expression level of HK2 is an independent factor affecting the prognosis of AML patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Medula Óssea , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/terapia , Prognóstico , Estudos Retrospectivos , Transplante Homólogo/efeitos adversosRESUMO
Severe aplastic anemia (SAA) is a life-threatening hematological disorder. The major therapies include matched sibling donor (MSD)- hematopoietic stem cell transplantation (HSCT), matched unrelated donor (MUD)-HSCT and immunosuppressive therapy (IST). However, there are many problems that can occur after HSCT, and graft failure (GF) is one of the most serious complications. To find an effective treatment, we analyzed 10 cases of second HSCT to treat SAA pediatric patients who suffered from GF and concluded that second haploidentical family donors HSCT is an effective treatment. Moreover, adding a small dose of busulfan or 2 ~ 3 Gy total body irradiation (TBI) in nonmyeloablative regimens (NMAs) can promote the engraftment. Although the study also showed that PBSCs, as a source of stem cells, can promote the implantation of neutrophil cells, due to small sample size, more research is still needed.
Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/terapia , Criança , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Irmãos , Doadores de Tecidos , Condicionamento Pré-Transplante , Doadores não RelacionadosRESUMO
Cancer is one of the most difficult diseases and causes of death for many decades. Many pieces of research are continuously going on to get a solution for cancer. Quinoline and isoquinoline derivatives have shown their possibilities to work as an antitumor agent in anticancer treatment. The members of this privileged scaffold quinoline and isoquinoline have shown their controlling impacts on cancer treatment through various modes. In particular, this review suggests the current scenario of quinoline and isoquinoline derivatives as antitumor agents and refine the path of these derivatives to find and develop new drugs against an evil known as cancer.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Quinolinas/química , Quinolinas/farmacologia , Humanos , Estrutura Molecular , Neoplasias/tratamento farmacológicoAssuntos
Status Econômico , Hipertensão , Pressão Sanguínea , Humanos , Fatores Socioeconômicos , SístoleRESUMO
OBJECTIVE: To analyze and investigate the expression levels of HES1, C-MYC and NF-kB in peripheral blood of patients with T cell acute lymphoblastic leukemia (T-ALL) and their significance. METHODS: Sixty patients with T-ALL and 60 patients with acute myelogenous leukemia (AML) diagnosed in our hospital from June 2012 to March 2015 were enrolled in T-ALL group and AML group, respectively. Another 30 healthy people were enrolled in the control group. Peripheral blood was collected to detect the expression levels of HES1, C-MYC and NF-kB by RT-PCR. The general data and the expression of HES1, C-MYC and NF-kB in peripheral blood were compared among the patients with different type of leukemia, cytogenetical types and different prognosis. RESULTS: There was no significant difference in baseline data, such as age and sex among the 3 groups (Pï¼0.05). The Hb level, WBC and Plt count, BM blast cell ratio in T-ALL and AML groups all were significantly higher than those in control group (Pï¼0.01), but there were no statistical difference in above-mentioned indicators between T-ALL and AML groups (Pï¼0.05). The expression levels of HES1, C-MYC and NF-kB in peripheral blood among 3 groups were significantly differenct (Pï¼0.01), the expressions levels of HES1, C-MYC and NF-kB in T-ALL and AML groups were significantly higher than those in control were significantly group (Pï¼0.01), moreover, the expression levels of above-mentional indicators in T-ALL groups were significantly higher than than those in AML group (Pï¼0.01). The expression levels of HES1, C-MYC and NF-kB iin T-ALL patients with poor prognosis were significantly higher than those in T-ALL patients with favorable prognosis (Pï¼0.01); the expression levels of HES1, C-MYC and NF-kB in peripheral blood of patients with different theraptic efficacy were follow: complete remission groupï¼partial remission groupï¼no remission group (Pï¼0.01). CONCLUSION: The HES1, C-MYC and NF-kB are highly expressed in peripheral blood of the patients with T-ALL, moreover, the expression levels maybe different, because of the cytogenetic, and theraptic efficacy.
Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Leucemia Mieloide Aguda , NF-kappa B , Indução de Remissão , Linfócitos T , Fatores de Transcrição HES-1RESUMO
Microtubules are essential for the mitotic division of cells and have been an attractive target for antitumour drugs due to the increased incidence of cancer and significant mitosis rate of tumour cells. In the past few years, tubulin-colchicine binding site, as one of the three binding pockets including taxol-, vinblastine- and colchicine-binding sites, has been focused on to design tubulin-destabilizing agents including inhibitors, antibody-drug conjugates and degradation agents. The present review is the first to cover a systemic and recent synopsis of tubulin-colchicine binding site agents. We believe that it would provide an increase in our understanding of receptor-ligand interaction pattern and consciousness of a series of challenges about tubulin target druggability.
Assuntos
Antineoplásicos/farmacologia , Colchicina/farmacologia , Imunoconjugados/farmacologia , Neoplasias/tratamento farmacológico , Moduladores de Tubulina/farmacologia , Tubulina (Proteína)/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Sítios de Ligação/efeitos dos fármacos , Colchicina/química , Colchicina/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Imunoconjugados/química , Imunoconjugados/metabolismo , Mitose/efeitos dos fármacos , Neoplasias/metabolismo , Neoplasias/patologia , Tubulina (Proteína)/química , Moduladores de Tubulina/química , Moduladores de Tubulina/metabolismoRESUMO
OBJECTIVE: To identify and explore the prognostic risk factors of the hemophagocytic syndrome (HPS). METHODS: A retrospective study was conducted on 50 childhood patients with HPS who were admitted to our hospital between 2007 and 2011. All their medical records were reviewed and analyzed. For each patient, demographic, laboratory data and outcome information were collected. The patients were divided into deceased or survived groups based on the follow-up results. Comparative analysis of the data was done by using independent-samples test and logistic multiple and univariate regression. RESULTS: Among the 50 HPS patients, 30 were male and 20 female, age ranged from 3 months to 10 years. Reduction of serum albumin, cholinesterase and natural killer (NK) cells was found in the forty-six patients. The laboratory features showed an elevation of serum ferritin with hypofibrinogenemia and hypertriglyceridemia in most of the patients. Forty of patients had hemophagocyte in bone marrow at diagnosis of HPS. The positive serum EBV-IgM was found in thirty-five patients.During the observation period, 25 of 37 patients (67.6%) died, while 13 of whom died within a month after hospitalization. The deceased patients were more likely to have lower albumin, cholinesterase, NK cells level and more prolonged active partial thromboplastin time than the survived patients (P < 0.05). Multivariate logistic regression analysis revealed that duration of illness > 1 month, albumin level < 25 g/L, cholinesterase level < 2000 U/L, NK cell level 0-3% and positive EBV-IgM were related with the prognosis significantly (P < 0.05 for all comparisons). CONCLUSION: This study revealed that duration of illness > 1 month, decreases in albumin, NK cell and cholinesterase, and positive EBV-IgM were the risk factors related to mortality in children.