RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Tongguanteng injection (TGT), the water extract from the stem of the Traditional Chinese hebal medicine of Marsdenia tenacissima (Roxb.) Wight et Arn. has been used as anticancer remedy for decades. TGT was not only used in the treatment of many malignant cancers extensively, but also an adjuvant anticancer drug with chemotherapeutics clinically. AIM OF THE STUDY: To evaluate the effects of TGT on reversing paclitaxel (PTX) resistance and investigate the potential mechanism related to TAB1 in ovarian cancer (OC) in vitro and in vivo. MATERIALS AND METHODS: The synergistic effect and reversal ratio were determined by CCK8 assay and median-effect principle after the combination of TGT and PTX in OC A2780 and its PTX-resistant (A2780/T) cells. The biological functions in cell apoptosis, migration and invasion of A2780/T cells treated by PTX 4 µM with TGT 20, 40, 80 mgâ mL-1 for 24 h were evaluated by colony formation, flow cytometry, wound healing and transwell assays. Proteomics technique and bioinformatic analysis were used to indentify the change of TAB1 expression in A2780/T cells induced by TGT. The association between TAB1 expression and human OC was analyzed by gene expression databases. In A2780/T cells, western blotting and colony formation assays were used to investigate the relationship between TAB1 expression and PTX resistance after TAB1 overexpression by TAB1 plasmids. The mechanism of TGT and PTX regulating TAB1 and its related proteins were explored by western blotting and flow cytometry assays after TAB1 knock-down using siTAB1. Moreover, TUNEL staining, immunohistochemistry (IHC) and histopathology were used to observe the antitumor effects, TAB1 and p-p38 expression and the tissues impairments in nude mice xenograft model established by A2780/T cells after the co-treatment with TGT and PTX by in vivo. RESULTS: TGT combined with PTX showed the synergistic effect (CI<1), which could reverse the IC50 values of PTX in OC A2780 and A2780/T cells about 23.50 and 6.44 times, respectively. Besides, TGT combined with PTX could significantly inhibit the migration, invasion and promote apoptosis of A2780/T cells. We identified that TGT could induce TAB1 expression in A2780/T cells by proteomics analysis. TAB1 downregulation was significantly associated with tumorigenesis and poor prognosis in OC patients and PTX resistance in A2780/T cells. Furthermore, TGT could activate TAB1/TAK1/p38 MAPK signaling pathway targeting TAB1 and regulate the expression of Bax, Bcl-2 proteins to improve the sensitivity of A2780/T cells to PTX. TGT combined with PTX also showed a greater inhibition in tumor growth than PTX monotherapy in vivo. These promising results show the efficacy of TGT in reversing PTX resistance and provide a potential strategy that targeting TAB1/TAK1/p38 MAPK signaling pathway may improve the chemotherapy sensitivity in OC. CONCLUSIONS: Our results revealed that Tongguanteng injection could reverse paclitaxel resistance and the potential mechanism might be associated with the activation of TAB1/TAK1/p38 MAPK signaling pathway in OC in vitro and in vivo. TAB1 might be a pivotal target for reversing PTX resistance. This study will provide a theoretical basis for the combination of Tongguanteng injection and paclitaxel in clinic.
Assuntos
Antineoplásicos Fitogênicos , Antineoplásicos , Neoplasias Ovarianas , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Camundongos , Camundongos Nus , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Regulação para Cima , Proteína X Associada a bcl-2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
ABSTRACT: The physical and psychological condition of patients with gynaecological cancer has received much attention, but there is little research on spirituality in palliative care. This study aimed to investigate spiritual well-being and its association with quality of life, anxiety and depression in patients with gynaecological cancer. A cross-sectional study was conducted in China in 2019 with 705 patients diagnosed with primary gynaecological cancer. European Organisation for Research and Treatment of Cancer quality of life instruments (EORTC QLQ-SWB32 and EORTC QLQ-C30) and the Hospital Anxiety and Depression Scale were used to measure spiritual well-being, quality of life, anxiety and depression. Univariate and multiple linear regression analyses were performed to examine associations between spiritual well-being, quality of life, anxiety and depression. Functioning scales and global health status were positively correlated with spiritual well-being (Pâ<â.05). Anxiety and depression were negatively correlated with spiritual well-being (Pâ<â.05). Depression (-0.362, Pâ<â.001) was the strongest predictor of Existential score. Anxiety (-0.522, Pâ<â.001) was the only predictor of Relationship with self. Depression (-0.350, Pâ<â.001) and Global health (0.099, Pâ=â.011) were the strongest predictors of Relationship with others. Religion (-0.204, Pâ<â.001) and Depression (-0.196, Pâ<â.001) were the strongest predictors of Relationship with someone or something greater. Global health (0.337, Pâ<â.001) and Depression (-0.144, Pâ<â.001) were the strongest predictors of Global-SWB. Well spiritual well-being is associated with lower anxiety and depression, and better quality of life. Health providers should provide more spiritual care for non-religious patients and combine spiritual care with psychological counselling to help patients with gynaecological cancer, especially those who have low quality of life or severe symptoms, or experience anxiety or depression.
Assuntos
Adaptação Psicológica , Transtorno Depressivo/psicologia , Neoplasias dos Genitais Femininos/psicologia , Qualidade de Vida , Espiritualidade , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Psicometria , Inquéritos e QuestionáriosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoaiping injection, a traditional Chinese medical injection extracted from root of Marsdenia tenacissima (Roxb.) Moon, has been exclusively used on curing malignant tumor in China and as adjuvant therapeutic agent for chemotherapeutics, including paclitaxel. AIM OF THE STUDY: The goal of this study was to investigate the synergistic inhibitory efficacy of Xiaoaiping injection and paclitaxel on ovarian cancer. The mechanism may be associated with nuclear receptor pregnane X receptor (PXR) regulating its downstream molecules. MATERIALS AND METHODS: In vitro, MTT assay, flow cytometry and Hoechst dyeing were used to evaluate the SK-OV-3â¯cell proliferation, apoptosis and cell cycle respectively. The mRNA and protein expression of PXR and its downstream CYP450 enzymes, transporters and Bcl-2 families were measured by qRT-PCR and Western blot. Rhodamine 123 efflux experiment was conducted to detect the P-gp efflux ability. PXR plasmid and PXR siRNA were transiently transfected into SK-OV-3â¯cells respectively to establish PXR-overexpressed or PXR-interfered cells. In vivo, xenograft tumor mice model was established by SK-OV-3â¯cells to estimate the antitumor effect of Xiaoaiping injection combined with paclitaxel. The expressions of PXR and its downstream molecules in tumor tissues were determined to further clarify the potential mechanism. RESULTS: Xiaoaiping injection significantly enhanced the anti-proliferation, pro-apoptosis effect of paclitaxel on SK-OV-3â¯cells. The synergetic effect was displayed by Xiaoaiping injection inhibiting paclitaxel-induced PXR and CAR expression, which subsequently inhibited CYP450 enzymes CYP2C8 and CYP3A4, transporter P-gp and anti-apoptotic proteins Bcl-2 and Bcl-xl in SK-OV-3â¯cells. In PXR-overexpressed cells, Xiaoaiping injection down-regulated the expression of PXR and its downstream molecules. The result of xenograft tumor model showed that Xiaoaiping injection combined with paclitaxel enhanced anti-tumor effect on ovarian cancer in vivo. CONCLUSIONS: Xiaoaiping injection enhances anti-tumor effect of paclitaxel by inhibiting cell proliferation, inducing apoptosis process. The mechanism may be associated with Xiaoaiping injection inhibiting PXR and its downstream metabolic enzymes CYP2C8, CYP3A4, transporter P-gp and anti-apoptosis protein Bcl-2.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/farmacologia , Receptor de Pregnano X/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocromo P-450 CYP2C8/genética , Citocromo P-450 CYP2C8/metabolismo , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Sinergismo Farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Receptor de Pregnano X/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína bcl-X/genética , Proteína bcl-X/metabolismoRESUMO
The chemical composition of black tea during tea processing is in a state of flux. However, the dynamic changes of this sophisticated metabolic process are far from clear. GC-MS-based metabolomic analyses were performed to examine changes in volatile and non-volatile compounds throughout the five stages of tea processing. The results showed that the most striking differences were observed at the withering and rolling stages, during which 62 non-volatile and 47 volatile compounds were significantly changed. The levels of most monosaccharides decreased at the withering stage and increased in subsequent stages while di-saccharides decreased as the process progressed. Free amino acids increased sharply at the withering stage, and most kept increasing or remained stable afterwards. However, levels of catechin, epicatechin, epigallocatechin, and epigallocatechin gallate decreased after withering and remained at low levels afterwards. Among the 47 volatile compounds with altered levels, phenylpropanoids/benzenoids and carotenoid-derived volatiles, which contribute to the honey-like and rose-like fragrances and quality of Danxia2 tea, kept increasing during the processing, among them eight were newly produced. Furthermore, 19 volatiles with a grassy odor decreased during processing. This study provides a comprehensive profile of metabolic changes during black tea processing, which is potentially important for both quality control and improvement of the flavor of black teas.
Assuntos
Análise de Alimentos/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metabolômica/métodos , Chá/química , Aminoácidos , Camellia sinensis/química , Carotenoides/análise , Catequina/análogos & derivados , Aromatizantes/análise , Odorantes/análise , Folhas de Planta/química , Paladar , Compostos Orgânicos Voláteis/análiseRESUMO
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
To explore the clinical effect of Sanbitang recipe in treatment for the rheumatoid arthritis (RA) with kidney empty and cold-dampness symptom and its safety. A total 168 cases eligible patients were randomly divided into the traditional Chinese medicine (TCM) group, the chemical medicine group and the TCM combined with chemical medicine group, with 56 cases in each group. The TCM group was treated with Sanbitang recipe; The chemical medicine group was given methotrexate tablets; And Sanbitang recipe and methotrexate tablets was adopted in the TCM combined with chemical medicine group. A course of treatment was 16 weeks. Health assessment questionnaire (HAQ), disease activity scores 28-joint counts (DAS28), visual analogue scale (VAS), TCM symptom, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), cyclic citrullinated peptides (CCP) and rheumatoid factor (RF) were detected. The efficiencies and incidence of adverse reactions in the three groups were compared. The total effective rate of the TCM combined with chemical medicine group was 92.7%, which was higher than 79.2% of the TCM group and 82.4% of the chemical medicine group (P<0.05). There was no statistically significant difference between the TCM group and the chemical medicine group. This suggested that Sanbitang recipe was effective in treating rheumatoid arthritis (RA) with kidney empty and cold-dampness symptom. After treatment, the scores of HAQ, DAS28, VAS, ESR, CRP, CCP and RF of the TCM combined with chemical medicine group were significantly higher (P<0.05) among the three groups. There was no statistically significant difference between the TCM group and the chemical medicine group. This indicated that Sanbitang recipe could effectively alleviate the clinical symptoms of rheumatoid arthritis (RA) with kidney empty and cold-dampness symptom. In terms of efficiency and incidence of adverse reactions, the order from low to high was that the TCM group (3.8%, 2/53)Assuntos
Artrite Reumatoide/tratamento farmacológico
, Medicamentos de Ervas Chinesas/uso terapêutico
, Humanos
, Rim
, Medicina Tradicional Chinesa
, Metotrexato/uso terapêutico