RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Fu Fang Gang Liu (FFGL) is an effective formula for treating wart proliferation caused by human papillomavirus (HPV) infection and has the potential to treat HPV-related cancers. However, scientific evidence of its anti-tumor activity against cervical cancer, the most common cancer caused by HPV, is lacking. AIM OF THE STUDY: To clarify the anti-tumor effect of an FFGL aqueous extract on human cervical cancer and its possible mechanism of cell cycle arrest in HeLa cells. MATERIALS AND METHODS: The anti-proliferative effect of FFGL on cervical cancer cells was assessed using the cell counting kit-8 assay. The proportion of apoptotic cells, cell cycle distribution, and cell division rate were determined using flow cytometry. Quantitative proteomics was used to identify differentially expressed proteins after FFGL treatment, and bioinformatics analysis was used to identify key nodal proteins affected by FFGL. Immunofluorescence and western blot analyses were used to explore changes in the expression of related proteins in the cell cycle and DNA damage pathways to elucidate the potential mechanism of action of FFGL against HeLa cell proliferation. RESULTS: FFGL inhibited cervical cancer cell proliferation and caused cell cycle arrest. According to quantitative proteomics, CyclinB1 may play an important role in the anti-proliferative effect of FFGL on HeLa cells. Additional experiments showed that FFGL aqueous extract caused ATM-mediated DNA damage, further phosphorylated CHK2, led to the inactivation of Cdc25C, inhibited the activity of the CDK1/CyclinB1 complex, and resulted in cell cycle arrest. CONCLUSIONS: FFGL can inhibit cervical cancer cell proliferation. Furthermore, it can increase CDK1 phosphorylation, block the cell cycle by causing DNA damage, and inhibit HeLa cell proliferation.
Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Células HeLa , Neoplasias do Colo do Útero/patologia , Proliferação de Células , DNA , ApoptoseRESUMO
OBJECTIVE: To elucidate the mechanisms of 4 effective components from a Chinese medicine formula, namely Qingre Huoxue Jiedu Formula (QHJ heat- and toxin-clearing and blood-activating formula), in the treatment of nerve growth factor (NGF)-induced psoriasis. METHODS: Keratinocyte proliferation and T cell proliferation models were developed using NGF. An NGF solution (NGF+DMEM, 100 ng/mL) was added to all induced groups and treated groups and were cultured for 24 h, while a solution with NTRK1 antagonist (K252a+DEME, 300 nmol/L) was added and cultured for 1 h. The models were used to evaluate the effects of the treatment with each of the 4 components of QHJ, namely shikonin, paeonol, astilbin and ursolic acid. Cell apoptosis and proliferation were measured by flow cytometry analysis and CCK8 assay, respectively. The mRNA expression levels of Bax, Bcl-xl, and NGF receptor (NGFR) were assessed by quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively. RESULTS: (1) All QHJ-treated groups showed significantly increased cell apoptosis and inhibition of cell proliferation compared with the NGF-induced groups (P<0.05). In addition, treatment with QHJ plus NTRK1 significantly enhanced cell apoptosis and inhibition of cell proliferation compared with cells treated with QHJ only (P<0.05), particularly in cells treated with ursolic acid. (2) QHJ-treated groups showed higher protein expression levels of Bax, Bcl-xl compared with other groups (P<0.05). Additionally, treatment with QHJ plus NTRK1 significantly increased the protein expression levels of Bax, Bcl-xl and NGFR compared with those treated with QHJ only (all P<0.05), especially in those treated with shikonin. CONCLUSION: The action mechanism of QHJ on psoriasis might be through enhancing cell apoptosis and inhibition of cell proliferation, and upregulating the expression level of Bax, Bcl-xl and NGFR.
Assuntos
Medicamentos de Ervas Chinesas , Psoríase , Apoptose , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Fator de Crescimento Neural/metabolismo , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológicoRESUMO
Chronic spontaneous urticaria (CSU) is a common itchy skin disease. Despite its prevalence, the neuropathology of CSU is uncertain. In this study, we explored resting state functional connectivity (rs-FC) changes in CSU, as well as how the symptom changes following intervention can modulate rs-FC. Forty patients and 40 healthy controls (HCs) were recruited. Following an intervention, 32 patients participated in a second scan approximately 6 weeks after the first scan. Compared with healthy controls, CSU subjects exhibited higher regional homogeneity (ReHo) values in the cerebellum, which were positively associated with urticaria activity scores over 7 days (UAS7) at baseline. After an intervention accompanied with clinical improvement, we found that ReHo values decreased at the cerebellum and increased at the bilateral primary somatosensory cortex (SI)/primary motor cortex (MI)/supplementary motor area (SMA). Using the cerebellum as a seed, CSU subjects exhibited increased rs-FC with reward regions when compared with HCs and exhibited decreased rs-FC at the right orbitofrontal cortex and right sensorimotor region following the intervention. The improvement rate values were positively associated with reduced rs-FC values in the two regions. Using the cluster of SI/MI/SMA as a seed, CSU patients exhibited decreased rs-FC with the left putamen, caudate, accumbens, and thalamus following the intervention. These results demonstrate the altered cerebellar activity and cerebellum-reward-sensorimotor loops in CSU.
Assuntos
Cerebelo/fisiopatologia , Córtex Motor/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Urticária/fisiopatologia , Urticária/terapia , Acupuntura , Adulto , Mapeamento Encefálico , Cerebelo/diagnóstico por imagem , Terapia Combinada , Feminino , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Imageamento por Ressonância Magnética , Masculino , Córtex Motor/diagnóstico por imagem , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Descanso , Recompensa , Índice de Gravidade de Doença , Córtex Somatossensorial/diagnóstico por imagem , Resultado do Tratamento , Urticária/diagnóstico por imagemRESUMO
OBJECTIVE: To observe the clinical efficacy of narrow band ultraviolet bin (NB-UVB) combined with Yuyin Recipe (YYR) in treating psoriasis vulgaris (PV). METHODS: One hundred and nineteen patients with PV were randomly assigned to 2 groups by envelop method, the 62 patients in the treated group were treated with NB-UVB and YYR bathing, and the 57 in the control group were treated with NB-UVB alone. The course of treatment for both groups was 8 weeks. PASI scoring was performed before treatment and at the 2nd, 4th, 6th and 8th week of treatment respectively, and the treatment effect was evaluated depending on the decreasing rate of PASI score. The accumulated dose and side-effect of NB-UVB applied was observed. RESULTS: The PASI scores in the treated group measured at various time points after treatment were significantly different to that of baseline (P < 0.05). The cure rate in the treated group and the control group was 69.35% and 24.56% while the total effective rate in them 96.77% and 71.93%, respectively, showing significant difference between the two groups (chi2 = 27.755, P <0.01). The difference of PASI decreasing rate between groups showed statistical significant from the 4th week (P <0.01). The total dose of NB-UVB applied in the treated group (9.95 +/- 4.76) was less than that in the control group (12.77 +/- 5.05) with the difference of statistical significance (t = 3.141, P <0.01). The adverse reaction occurrence in them was 4.84% (3/62) and 31.58% (18/57) respectively, also showing significant difference (chi2 = 119, P <0.01). CCONCLUSION: The combined use of TCM medicated bath with NB-UVB can enhance the curative effect, reduce the accumulated dosage and lessen the adverse reactions of ultraviolet radiation.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Psoríase/tratamento farmacológico , Adolescente , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/radioterapia , Raios Ultravioleta , Adulto JovemRESUMO
OBJECTIVE: To investigate the clinical efficacy of compound periploca liquid (CPL) in treating condyloma acuminatum (CA), and to explore its mechanisms at molecular level. METHODS: Eighty-one patients with CA were randomly divided into three groups, 30 patients in Group A were treated with CPL, 21 in Group B were treated with periploca syrup and 30 in Group C were treated with Youtuoxin (YXG). The clinical efficacy and adverse reaction occurred in the three groups was evaluated respectively. Besides, change of human papilloma virus (HPV) DNA in two patients with CA was determined by polymerase chain reaction (PCR) in vitro after being treated with CPL and periploca, the monarchic drug of CPL. RESULTS: The cure rate obtained in group A, B, and C was 56.67%, 42.86% and 63.33% respectively, the total effective rate in them was 83.33%, 71.43% and 86.67% respectively, the difference of therapeutic efficacy was insignificant among the three groups. But the adverse reaction occurrence in them (6.67%, 4.76% and 86.67%) was significantly different (P < 0.01). The recurrent rate in them was 14.29%, 12.5% and 47.1% respectively. PCR showed negative expression of HPV in the two samples of CA of same concentration after the verrucous homogenate suspension being treated with CPL or periploca syrup of different concentration, while it was positive after the suspension was treated with the group of normal saline without any drug. CONCLUSION: The therapeutic efficacies of CPL, periploca syrup and Youtuoxin are not significantly different, but the former two have advantages of less adverse effects and lower recurrent rate. And they are possibly having germicidal action on HPV-DNA in CA tissue in vitro.