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1.
Heliyon ; 10(7): e27362, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560168

RESUMO

Background: Primary liver cancer (PLC) is a prevalent malignancy of the digestive system characterized by insidious symptom onset and a generally poor prognosis. Recent studies have highlighted a significant correlation between the initiation and prognosis of liver cancer and the immune function of PLC patients. Purpose: Revealing the expression of PLC-related immune genes and the characteristics of immune cell infiltration provides assistance for the analysis of clinical pathological parameters and prognosis of PLC patients. Methods: PLC-related differentially expressed genes (DEGs) with a median absolute deviation (MAD > 0.5) were identified from TCGA and GEO databases. These DEGs were intersected with immune-related genes (IRGs) from the ImmPort database to obtain PLC-related IRGs. The method of constructing a prognostic model through immune-related gene pairs (IRGPs) is used to obtain IRGPs and conduct the selection of central immune genes. The central immune genes obtained from the selection of IRGPs are validated in PLC. Subsequently, the relative proportions of 22 types of immune cells in different immune risk groups are evaluated, and the differential characteristics of PLC-related immune cells are verified through animal experiments. Results: Through database screening and the construction of an IRGP prognosis model, 84 pairs of IRGPs (P < 0.001) were ultimately obtained. Analysis of these 84 IRGPs revealed 11 central immune genes related to PLC, showing differential expression in liver cancer tissues compared to normal liver tissues. Results from the CiberSort platform indicate differential expression of immune cells such as naive B cells, macrophages, and neutrophils in different immune risk groups. Animal experiments demonstrated altered immune cell proportions in H22 tumor-bearing mice, validating findings from peripheral blood and spleen homogenate analyses. Conclusion: Our study successfully predicted and validated PLC-related IRGs and immune cells, suggesting their potential as prognostic indicators and therapeutic targets for PLC.

2.
Pharmacol Biochem Behav ; 92(4): 642-8, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19327378

RESUMO

Baicalein, a flavonoid obtained from the root of Chinese medicinal herb Scutellaria baicalensis, has been shown to exert a protective effect on neurons against several neuronal insults. The aim of this study was to explore the neuroprotective effect of baicalein in 6-hydroxydopamine (6-OHDA)-induced experimental parkinsonism in vitro and in vivo. In in vitro experiments, we found that baicalein (0.5, 5 microg/mL) could significantly ameliorate the 6-OHDA-induced SH-SY5Y cell apoptosis from 31.56% in the 6-OHDA group to 18.90%, 21.61% respectively, and also promote neurite outgrowth of PC12 cell. In in vivo experiments, baicalein had no effect on apomorphine (APO)-induced rotations, but it could significantly attenuate muscle tremor of 6-OHDA-lesioned rats. The burst frequency and amplitude are 13.43%, 35.18% compared to 6-OHDA group. Moreover, baicalein treatment could also increase tyrosine hydroxylase (TH)-positive neurons to 265.52% of the 6-OHDA group. The neuroprotective action of baicalein was coincident with an attenuated astroglial response within the substantia nigra. Neuroprotective effect of baicalein as demonstrated by the increasing the number of dopaminergic neurons may have been, in part, caused by anti-apoptotic, pro-differentiation and anti-inflammatory mechanisms of baicalein. Therefore, baicalein can be a promising candidate for prevention or treatment of Parkinson's disease, owing to its anti-apoptotic, pro-differentiation and anti-inflammatory action.


Assuntos
Flavanonas/farmacologia , Fármacos Neuroprotetores/farmacologia , Transtornos Parkinsonianos/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/fisiopatologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Masculino , Degeneração Neural/tratamento farmacológico , Degeneração Neural/patologia , Degeneração Neural/fisiopatologia , Degeneração Neural/prevenção & controle , Oxidopamina/toxicidade , Células PC12 , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/fisiopatologia , Fitoterapia , Plantas Medicinais , Ratos , Ratos Sprague-Dawley , Scutellaria baicalensis , Substância Negra/efeitos dos fármacos , Substância Negra/patologia , Substância Negra/fisiopatologia , Tirosina 3-Mono-Oxigenase/metabolismo
3.
Neurosci Lett ; 441(1): 16-20, 2008 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-18586394

RESUMO

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes the damage of dopaminergic neurons as seen in Parkinson's disease (PD). Oxidative stress has been implicated in the pathogenesis of PD. Baicalein, isolated from the traditional Chinese herbal medicine Huangqin (Scutellaria baicalensis Georgi), has been shown to have antioxidant effects. Here we investigated the effect of baicalein on MPTP-induced neurotoxicity in mice. Pretreatment with baicalein for a week was followed by challenge with MPTP for 4 consecutive days; the subsequent behavioral, biochemical and immunohistochemical manifestations in mice were determined and compared to those in untreated mice and mice challenged only with MPTP. The present study showed that baicalein could improve the abnormal behavior in MPTP-treated mice. The protective effect may be caused by increasing the levels of DA and 5-HT in the striatum, increasing the counts of dopaminergic neurons, inhibiting oxidative stress and the astroglia response. These results suggest that baicalein possesses potent neuroprotective activity and may be a potential anti-Parkinson's disease drug that is worthy of further study.


Assuntos
Comportamento Animal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Flavanonas/uso terapêutico , Intoxicação por MPTP/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Animais , Monoaminas Biogênicas/metabolismo , Contagem de Células/métodos , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Interações Medicamentosas , Flavanonas/química , Proteína Glial Fibrilar Ácida/metabolismo , Intoxicação por MPTP/metabolismo , Intoxicação por MPTP/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/química , Desempenho Psicomotor/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/metabolismo
4.
Leuk Res ; 30(8): 935-42, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16445979

RESUMO

We investigated the efficacy and safety of a combination regimen in 63 patients with primary refractory anemia (RA). The daily treatment protocol comprised all-trans retinoic acid (ATRA) (30 mg/m(2)), calcitriol (0.1 microg/m(2)), and androgen (stanozolol 3mg/m(2), or danazol 300 mg/m(2)) in three separate doses for eight consecutive weeks. Hematologic improvement was observed in 43 (68.3%) patients. The treatment administered was generally well tolerated, with no severe regimen-related toxicity. The overall survival rates at 3 and 5 years were 68.72% and 53.18%, respectively. These results indicate that this combination regimen is an effective and well-tolerated treatment for patients with RA.


Assuntos
Androgênios/administração & dosagem , Anemia Refratária/tratamento farmacológico , Calcitriol/administração & dosagem , Tretinoína/administração & dosagem , Adolescente , Adulto , Idoso , Androgênios/efeitos adversos , Anemia Refratária/diagnóstico , Calcitriol/efeitos adversos , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Tretinoína/efeitos adversos
5.
Leuk Res ; 29(1): 3-9, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15541469

RESUMO

UNLABELLED: We evaluated the efficacy and toxicity of vaccination in 29 patients with relapsed or refractory acute leukemia using inactivated autologous leukemia cells combined with interleukin-2 (IL-2), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-6. MHC-I, MHC-II, and B7-1 expression status on the surface of leukemia cells and the cytokine profile of IFN-gamma and IL-10 in serum before and after vaccination was detected. RESULTS: Five achieved a complete remission (CR) and six a partial remission (PR) in this vaccination procedure. Adverse effects were erythema, swelling erosion, and even ulcers at vaccination sites and low grade fever during the first three days of vaccination. No other significant side effects were observed. The expression of MHC-I and MHC-II on leukemia cells was 100% and 90% positive, respectively. B7-1 was exclusively expressed on some cases of M4 and M5. The efficacy of the vaccine was statistically associated with the expression status of B7-1 on leukemia cells (P < 0.01). The serum level of IL-10 reduced significantly in the five patients who achieved complete remission (CR) after vaccination as compared with when they were originally diagnosed (P < 0.01). CONCLUSION: We presented here a promising immunotherapy in the treatment of acute leukemia, especially for F.A.B. M5.


Assuntos
Vacinas Anticâncer/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Interleucina-2/administração & dosagem , Interleucina-6/administração & dosagem , Leucemia/terapia , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Feminino , Febre/etiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Humanos , Interleucina-2/efeitos adversos , Interleucina-6/efeitos adversos , Leucemia/imunologia , Masculino , Pessoa de Meia-Idade , Pele/efeitos dos fármacos
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