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1.
Pharmacol Res ; 204: 107200, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38710241

RESUMO

Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6 (LRP6), a vital component of the Wnt signaling pathway, has emerged as an intriguing candidate. As a cell-surface receptor and vital co-receptor, LRP6 is frequently overexpressed in various cancer types, implicating its pivotal role in driving tumor progression. The pursuit of LRP6 as a target for cancer treatment has gained substantial traction, offering a promising avenue for therapeutic intervention. Here, this comprehensive review explores recent breakthroughs in our understanding of LRP6's functions and underlying molecular mechanisms, providing a profound discussion of its involvement in cancer pathogenesis and drug resistance. Importantly, we go beyond discussing LRP6's role in cancer by discussing diverse potential therapeutic approaches targeting this enigmatic protein. These approaches encompass a wide spectrum, including pharmacological agents, natural compounds, non-coding RNAs, epigenetic factors, proteins, and peptides that modulate LRP6 expression or disrupt its interactions. In addition, also discussed the challenges associated with developing LRP6 inhibitors and their advantages over Wnt inhibitors, as well as the drugs that have entered phase II clinical trials. By shedding light on these innovative strategies, we aim to underscore LRP6's significance as a valuable and multifaceted target for cancer treatment, igniting enthusiasm for further research and facilitating translation into clinical applications.


Assuntos
Antineoplásicos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Terapia de Alvo Molecular , Neoplasias , Animais , Humanos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos
2.
BMC Cancer ; 20(1): 132, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070301

RESUMO

BACKGROUND: Microvascular invasion (MVI) is an independent risk factor for poor prognosis in hepatocellular carcinoma (HCC). However, there is still a lack of preoperative markers to predict MVI in HCC. This study intends to explore the potential application value of the gamma-glutamyl transpeptidase (GGT) to lymphocyte count ratio (GLR) in predicting MVI in HCC and provide guidance for clinical diagnosis and treatment. METHODS: From March 2010 to December 2015, 230 HCC patients who underwent surgical treatment in the Affiliated Hospital of Guilin Medical University were selected. Clinicopathological parameters between the MVI group (n = 115) and the non-MVI group (n = 115) were comparatively analyzed. The GLR was used as the potential risk factor for HCC with MVI, and its optimal cut-off value was estimated by using the receiver operating characteristic (ROC) curve. The Kaplan-Meier method was used to analyze the survival of HCC patients, and univariate and multivariate Cox regression analyses were used to establish independent predictors affecting postoperative HCC patients. RESULTS: The GLR levels in the MVI group and non-MVI group were 84.83 ± 61.84 and 38.42 ± 33.52 (p <  0.001), respectively. According to ROC curve analysis, the optimal cut-off value of GLR was 56.0, and the area under the ROC curve (AUC) was 0.781 (95% CI, 0.719-0.833) for the risk prediction of MVI in HCC patients. Multivariate analysis showed that tumor size > 5 cm, HCC combined with MVI and GLR >  56.0 were independent risk factors for poor prognosis in HCC patients. In addition, compared with the non-MVI group, patients in the MVI group had shorter progression-free survival (PFS) and overall survival (OS). CONCLUSION: GLR could be a predictive biomarker of HCC after operation and a potential predictor of HCC combined with MVI.


Assuntos
Biomarcadores/sangue , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Linfócitos/patologia , Microvasos/patologia , gama-Glutamiltransferase/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/enzimologia , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/enzimologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
3.
Med Sci Monit ; 25: 5589-5593, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31352466

RESUMO

BACKGROUND The aim of our study was to elucidate the biological targets and pharmacological mechanisms for calycosin (CC) against colorectal cancer (CRC) through an approach of system pharmacology. MATERIAL AND METHODS Using a web-based platform, all CRC-causing genes were identified using a database of gene-disease associations (DisGeNET), and all well-known genes of CC identified using the databases of prediction of protein targets of small molecules (Swiss Target Prediction), drug classification, and target prediction (SuperPred). The carefully selected genes of CRC and CC were concurrently constructed by using a database of functional protein association networks (STRING), and use of software for visualizing complex networks (Cytoscape), characterized with production of protein-protein interaction (PPI) network of CC against CRC. The important biological targets of CC against CRC were identified through topological analysis, then the biological processes and molecular pathways of CC against CRC were further revealed for testing these important biotargets by enrichment assays. RESULTS We found that the key predictive targets of CC against CRC were estrogen receptor 2 (ESR2), ATP-binding cassette sub-family G member 2 (ABCG2), breast cancer type 1 susceptibility protein (BRCA1), estrogen receptor 1 (ESR1), cytochrome p450 19A1 (CYP19A1), and epidermal growth factor receptor (EGFR). Visual analysis revealed that the biological processes of CC against CRC were positively linked to hormonal metabolism, regulation of genes, transport, cell communication, and signal transduction. Further, the interrelated molecular pathways were chiefly related to endogenous nuclear estrogen receptor alpha network, forkhead box protein A1 (FOXA1) transcription factor network, activating transcription factor 2 (ATF2) transcription factor network, regulation of telomerase, plasma membrane estrogen receptor signaling, estrogen biosynthesis, androgen receptor, FOXA transcription factor networks, estrogen biosynthesis, and phosphorylation of repair proteins. CONCLUSIONS Use of system pharmacology revealed the biotargets, biological processes, and pharmacological pathways of CC against CRC. Intriguingly, the identifiable predictive biomolecules are likely potential targets for effectively treating CRC.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Isoflavonas/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Aromatase/genética , Proteína BRCA1/genética , Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Neoplasias Colorretais/fisiopatologia , Biologia Computacional/métodos , Bases de Dados Genéticas , Receptores ErbB/genética , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Isoflavonas/farmacologia , Proteínas de Neoplasias , Fenômenos Farmacológicos e Toxicológicos , Mapas de Interação de Proteínas/genética , Transdução de Sinais , Análise de Sistemas
4.
Lipids Health Dis ; 18(1): 71, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30909920

RESUMO

BACKGROUND: Obesity increases the risk of developing diabetes mellitus. Clinical studies suggest that risk factors like palmitic acid (PA) and lipopolysaccharide (LPS) exist simultaneously in diabetes with obesity. Combination of PA and LPS even at low concentration can induce strong inflammatory reaction. Monocyte chemoattractant protein-1 (MCP-1) is an important inflammatory chemokine related to insulin resistance and type II diabetes. Our previous study using PCR array revealed that LPS and PA synergistically induce MCP-1 mRNA expression in macrophage cells RAW264.7, while the protein expression of MCP-1 in this case was not investigated. Moreover, the underling mechanism in the synergistic effect of MCP-1 expression or production induced by treatment of LPS and PA combination remains unclear. METHODS: Protein secretion of MCP-1 was measured by the enzyme-linked immunosorbent assay (ELISA) and mRNA levels of MCP-1 and Toll-like receptor 4 (TLR4) were measured by real-time PCR. Statistical analysis was conducted using SPSS software. RESULTS: LPS could increase MCP-1 transcription as well as secretion in RAW264.7, and PA amplified this effect obviously. Meanwhile, combination of LPS with PA increased TLR4 mRNA expression while LPS alone or PA alone could not, TLR4 knockdown inhibited MCP-1 transcription/secretion induced by LPS plus PA. Moreover, not NF-κB inhibitor but inhibitors of mitogen-activated protein kinase (MAPK) signaling pathways, including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 MAPK were found to block MCP-1 generation stimulated by LPS plus PA. CONCLUSION: LPS and PA synergistically induced MCP-1 secretion in RAW264.7 macrophage cells, in which MCP-1 transcription mediated by MAPK/TLR4 signaling pathways was involved. Combined treatment of PA and LPS in RAW264.7 cells mimics the situation of diabetes with obesity that has higher level of PA and LPS, MAPK/TLR4/ MCP-1 might be potential therapeutic targets for diabetes with obesity.


Assuntos
Quimiocina CCL2/genética , Lipopolissacarídeos/farmacologia , MAP Quinase Quinase 1/genética , Ácido Palmítico/farmacologia , Receptor 4 Toll-Like/genética , Animais , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/genética , Diabetes Mellitus/patologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Regulação da Expressão Gênica/genética , Humanos , Camundongos , Obesidade/tratamento farmacológico , Obesidade/genética , Obesidade/patologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo
5.
Mol Carcinog ; 57(7): 817-830, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29722068

RESUMO

For postmenopausal cardiovascular disease, long-term estrogen therapy may increase the risk of breast cancer. To reduce this risk, estrogen may be replaced with the phytoestrogen formononetin, but how formononetin acts on vascular endothelial cells (ECs) and breast cancer cells is unclear. Here, we show that low concentrations of formononetin induced proliferation and inhibited apoptosis more strongly in cultured human umbilical vein endothelial cells (HUVECs) than in breast cancer cells expressing estrogen receptor α (ERα) (MCF-7, BT474) or not (MDA-MB-231), and that this differential stimulation was associated with miR-375 up-regulation in HUVECs. For the first time, we demonstrate the presence of a feedback loop involving miR-375, ras dexamethasone-induced 1 (RASD1), and ERα in normal HUVECs, and we show that formononetin stimulated this feedback loop in HUVECs but not in MCF-7 or BT474 cells. In all three cell lines, formononetin increased Akt phosphorylation and Bcl-2 expression. Inhibiting miR-375 blocked these changes and increased proliferation in HUVECs, but not in MCF-7 or BT474 cells. In ovariectomized rats, formononetin increased uterine weight and caused similar changes in levels of miR-375, RASD1, ERα, and Bcl-2 in aortic ECs as in cultured HUVECs. In mice bearing MCF-7 xenografts, tumor growth was stimulated by 17ß-estradiol but not by formononetin. These results suggest selective action of formononetin in ECs (proliferation stimulation and apoptosis inhibition) relative to breast cancer cells, possibly via a feedback loop involving miR-375, RASD1, and ERα. This differential effect may explain why formononetin may not increase the risk of postmenopausal breast cancer.


Assuntos
Neoplasias da Mama/prevenção & controle , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Receptor alfa de Estrogênio/genética , Isoflavonas/farmacologia , MicroRNAs/genética , Proteínas ras/genética , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética , Linhagem Celular Tumoral , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Células MCF-7 , Camundongos , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ratos , Ratos Wistar , Regulação para Cima/efeitos dos fármacos
6.
Biometals ; 30(6): 903-915, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28993927

RESUMO

Rhodium (II) complex with 2-benzoylpyridine (Rh(L)2Cl2) is a new, synthetic, active metal-complex, which is produced by the reaction of 2-benzoylpyridine (L) with rhodium chloride hydrate (RhCl3·nH2O). The crystal structure was determined by X-ray diffraction which is mono-nuclear. In order to explore the biological properties of the novel complex, a series of studies were performed. The results showed that Rh(L)2Cl2 had the anti-tumor activity in HepG2 and other cell lines and has been shown to induce G1 cell cycle arrest and apoptosis in HepG2 cells. The anti-cancer effect of Rh(L)2Cl2 is regulated by increased expression of caspase-3 and PARP via the mitochondrial and the death receptor pathways. Bcl-2 family proteins might play an important role in the Rh(L)2Cl2-induced changes in these two pathways. Further studies indicated that Rh(L)2Cl2 increased the level of reactive oxygen species (ROS), but that Rh(L)2Cl2-induced apoptosis was ROS-independent. In conclusion, Rh(L)2Cl2 is a potential new anti-tumor drug, which induces HepG2 cell death via the mitochondrial and death receptor pathways and has no obvious toxicity to normal liver cell.


Assuntos
Antineoplásicos/farmacologia , Compostos Organometálicos/farmacologia , Ródio/química , Ródio/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células , Cristalografia por Raios X , Células Hep G2 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Compostos Organometálicos/química , Proteínas Proto-Oncogênicas c-bcl-2 , Piridinas/química , Espécies Reativas de Oxigênio/metabolismo
7.
Mol Carcinog ; 55(3): 312-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25663261

RESUMO

Formononetin is an O-methylated isoflavone that is isolated from the root of Astragalus membranaceus, and it has antitumorigenic effects. Our previous studies found that formononetin triggered growth-inhibitory and apoptotic activities in MCF-7 breast cancer cells. To further investigate the potential effect of formononetin in promoting cell proliferation in estrogen receptor (ER)-positive cells, we used in vivo and in vitro studies to elucidate the possible mechanism. ERα-positive cells (HUVEC, MCF-7) were treated with formononetin. The CCK8 assay, Hoechst 33258, and flow cytometry were used to assess cell proliferation and apoptosis. mRNA levels of ERα, Bcl-2, and miR-375 were quantified using real-time polymerase chain reaction. ERα, p-Akt, and Bcl-2 expression was determined using Western blot. Compared with the control, low formononetin concentrations (2-6 µM) stimulated ERα-positive cell proliferation (HUVEC, MCF-7). The more sensitive HUVEC cells were used to study the relevant signaling pathway. After treatment with formononetin, ERα, miR-375, p-Akt, and Bcl-2 expression was significantly upregulated. The proliferative effect of formononetin was also blocked by a miR-375 inhibitor or raloxifene pretreatment. Additionally, in the in vivo studies, uterine weight in ovariectomized mice treated with formononetin increased significantly, but the weight dramatically decreased with raloxifene or miR-375 inhibitor pretreatment before formononetin. This study demonstrated that formononetin promoted ERα-positive cell proliferation through miR-375 activation and this mechanism is possibly involving in a miR-375 and ERα feedback loop.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Receptor alfa de Estrogênio/metabolismo , Isoflavonas/farmacologia , MicroRNAs/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos/química , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Astragalus propinquus/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/prevenção & controle , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Isoflavonas/química , Células MCF-7 , Camundongos , Fitoestrógenos/química , Fitoestrógenos/farmacologia
8.
Tumour Biol ; 37(5): 5911-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26592251

RESUMO

Betaine homocysteine methyltransferase (BHMT) catalyzes the synthesis of methionine using betaine and homocysteine (Hcy), which is restricted to the liver and kidney. Impaired BHMT pathway has been associated with hepatocellular carcinogenesis in Bhmt-/- mice model, and decreased BHMT was observed in a small sample of human hepatocellular carcinoma (HCC) patients. However, the prognostic significance of BHMT in HCC has not been elucidated. This study aimed to examine the expression of BHMT in HCC and investigate the relationship between its expression and prognosis of HCC patients. BHMT expression was analyzed in 68 paired HCC samples (HCC tissues vs matched adjacent non-cancerous liver tissues), 115 paraffin-embedded HCC sections (primary cohort), and 65 paraffin-embedded HCC sections (validation cohort) using immunohistochemistry (IHC). The results of IHC analysis showed that BHMT was decreased in tumorous tissues in 85.2 % (58/68) of cases compared to the corresponding adjacent non-tumorous liver tissues. Further correlation analyses indicated that the decreased BHMT expression was closely correlated with serum α-fetoprotein (AFP) (p = 0.011), tumor size (p = 0.039), and vascular invasion (p = 0.017). Moreover, HCC patients with low BHMT expression had shorter overall survival (OS) and time to recurrence (TTR) than those with high BHMT expression in both primary cohort (p < 0.0001) and validation cohort (p < 0.05) assessed by the Kaplan-Meier method. In addition, multivariate analysis showed that BHMT was an independent prognostic factor for OS and TTR in the two cohorts (all p < 0.005). Collectively, our study demonstrated that BHMT could be served as a potential prognostic marker for HCC patients.


Assuntos
Betaína-Homocisteína S-Metiltransferase/genética , Betaína-Homocisteína S-Metiltransferase/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Adulto , Idoso , Biomarcadores Tumorais , Carcinoma Hepatocelular/patologia , Regulação para Baixo , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Carga Tumoral
9.
Health Qual Life Outcomes ; 14: 98, 2016 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-27356505

RESUMO

BACKGROUND: This study aimed to assess ethnic differences in health-related quality of life (HRQoL) among the rural elderly, and to examine the influence of ethnic culture, residential segregation and socioeconomic development on HRQoL. METHODS: A total of 6,511 rural elderly aged 60 years and older from 5,541 households in 116 villages across eight ethnic groups in Guangxi Zhuang Autonomous region were selected and assessed for HRQoL. The EQ-5D index values were calculated based on the Chinese Time Trade-Off values set. The EQ-5D descriptive system scores, visual analogue scale scores, and index values were described by ethnic group. The EQ-5D index was modeled against ethnic culture, residential segregation and socioeconomic development using villages as random effects. RESULTS: The median (IQR) of HRQoL among all the ethnic groups was 0.88 (0.80, 0.96). Pain/discomfort was the most prevalent problem, followed by anxiety/depression. After controlling for sociodemographic characteristics, a significant difference in HRQoL among ethnic groups persisted, but this was not true for residential segregation. CONCLUSION: Social welfare and health policies designed to improve the health of the rural elderly should focus more on older, female, less-educated, Yao minority individuals as well as lower-income households.


Assuntos
Cultura , Nível de Saúde , Qualidade de Vida , População Rural/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , China , Estudos Transversais , Feminino , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Características de Residência , Fatores Socioeconômicos , Inquéritos e Questionários
10.
Cell Physiol Biochem ; 35(2): 722-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25613518

RESUMO

BACKGROUND: Calycosin and genistein are the two main components of isoflavones. Previously, we reported that these compounds display antitumor activities in the breast cancer cell lines MCF-7 and T47D. In the present study, we investigated the mechanism of action of calycosin and genistein, and their respective efficacies as potential therapies for the treatment of breast carcinoma in the clinic. METHODS: MCF-7 cells were treated with calycosin or genistein. Cell proliferation and apoptosis were measured using CCK8 assay and Hoechst 33258. The expression level of phosphorylated Akt protein was determined by western blotting. Expression level of HOTAIR was quantified by real-time PCR. RESULTS: Both calycosin and genistein inhibited proliferation and induced apoptosis in MCF-7 breast cancer cells, especially after treatment with calycosin. Treatment of MCF-7 cells with calycosin or genistein resulted in decreased phosphorylation of Akt, and decreased expression of its downstream target, HOTAIR. CONCLUSION: Calycosin is more effective in inhibiting breast cancer growth in comparison with genistein, through its regulation of Akt signaling pathways and HOTAIR expression.


Assuntos
Neoplasias da Mama/metabolismo , Genisteína/farmacologia , Isoflavonas/farmacologia , Fitoestrógenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Apoptose , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Feminino , Humanos , Células MCF-7 , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
11.
Cell Physiol Biochem ; 35(2): 639-46, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25613180

RESUMO

BACKGROUND: Biochanin A and formononetin are O-methylated isoflavones that are isolated from the root of Astragalus membranaceus, and have antitumorigenic effects. Our previous studies found that formononetin triggered growth-inhibitory and apoptotic activities in MCF-7 breast cancer cells. We performed in vivo and in vitro studies to further investigate the potential effect of biochanin A in promoting cell proliferation in estrogen receptor (ER)-positive cells, and to elucidate underlying mechanisms. METHODS: ERα-positive breast cancer cells (T47D, MCF-7) were treated with biochanin A. The MTT assay and flow cytometry were used to assess cell proliferation and apoptosis. mRNA levels of ERα, Bcl-2, and miR-375 were quantified using real-time polymerase chain reaction. Compared with the control, low biochanin A concentrations (2-6 µM) stimulated ERα-positive cell proliferation (T47D, MCF-7). The more sensitive T47D cells were used to study the relevant signaling pathway. RESULTS: After treatment with biochanin A, ERα, miR-375, and Bcl-2 expression was significantly upregulated. Additionally, in the in vivo studies, uterine weight in ovariectomized mice treated with biochanin A increased significantly. CONCLUSION: This study demonstrated that biochanin A promoted ERα-positive cell proliferation through miR-375 activation and this mechanism is possibly involving in a miR-375 and ERα feedback loop.


Assuntos
Anticarcinógenos/administração & dosagem , Receptor alfa de Estrogênio/genética , Genisteína/administração & dosagem , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Animais , Anticarcinógenos/farmacologia , Neoplasias da Mama , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Retroalimentação Fisiológica/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genisteína/farmacologia , Humanos , Células MCF-7 , Camundongos
12.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(4): 396-401, 2014 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-24812891

RESUMO

OBJECTIVE: To evaluate the anginal attack-relieving efficacy and safety of Kuanxiong Aerosol (KA) in patients with coronary heart disease (CHD). METHODS: A total of 780 patients confirmatively diagnosed as CHD angina from November 2011 to December 2012 in 13 medical centers in the mainland area were assigned to 2 groups by blocked randomization, the treatment group (376 cases) and the control group (374 cases). When the angina attacked, patients in the treatment group received sublingual spray three times, 0.6 mL each time, while those in the control group sublingually dissolved Nitroglycerin Tablet (NT), 0.5 mg each tablet. The effective rate of angina relief, efficacy of electrocardiogram (ECG), and the incidence of adverse reactions were observed. RESULTS: The 3 min and 5 min remission rates of angina attack were 53.72% (202/376) and 94.41% (355/376) in the treatment group, and 47.86% (179/374) and 90.64% (339/374) in the control group. The 95% confidence interval (CI) of the difference between the 2 groups of 3 min and 5 min remission rates of angina attacks were [(-1.84%, 12.32%) and (-1.33%, 6.85%) respectively, P > 0.05]. The total improvement rates of ST-T changes in the treatment group and the control group after treatment were 74.07% and 73.13% respectively (P > 0.05). The adverse reaction rate was 9.31 (35/376 cases) in the treatment group and 22.46% (84/374 cases) in the control group (P < 0.01). CONCLUSION: KA was not inferior to NT in relieving anginal attacks and improving ischemic ECG changes, and had obviously less adverse reaction.


Assuntos
Angina Pectoris/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Óleos Voláteis/uso terapêutico , Fitoterapia , Idoso , Doença das Coronárias/tratamento farmacológico , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Aging (Albany NY) ; 16(12): 10380-10401, 2024 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-38874510

RESUMO

Prostate cancer is one of the serious health problems of older male, about 13% of male was affected by prostate cancer. Prostate cancer is highly heterogeneity disease with complex molecular and genetic alterations. So, targeting the gene candidates in prostate cancer in single-cell level can be a promising approach for treating prostate cancer. In the present study, we analyzed the single cell sequencing data obtained from 2 previous reports to determine the differential gene expression of prostate cancer in single-cell level. By using the network pharmacology analysis, we identified the therapeutic targets of formononetin in immune cells and tissue cells of prostate cancer. We then applied molecular docking to determine the possible direct binding of formononetin to its target proteins. Our result identified a cluster of differential gene expression in prostate cancer which can serve as novel biomarkers such as immunoglobulin kappa C for prostate cancer prognosis. The result of network pharmacology delineated the roles of formononetin's targets such CD74 and THBS1 in immune cells' function of prostate cancer. Also, formononetin targeted insulin receptor and zinc-alpha-2-glycoprotein which play important roles in metabolisms of tissue cells of prostate cancer. The result of molecular docking suggested the direct binding of formononetin to its target proteins including INSR, TNF, and CXCR4. Finally, we validated our findings by using formononetin-treated human prostate cancer cell DU145. For the first time, our result suggested the use of formononetin for treating prostate cancer through targeting different cell types in a single-cell level.


Assuntos
Isoflavonas , Simulação de Acoplamento Molecular , Neoplasias da Próstata , Análise de Célula Única , Masculino , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Humanos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
14.
J Gastrointestin Liver Dis ; 33(1): 44-56, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554427

RESUMO

BACKGROUND AND AIMS: The incidence and mortality of hepatocellular carcinoma (HCC) are increasing. It is urgent to develop more effective HCC biomarkers for diagnosis and treatment. This project intends to verify the expression of enhancer of zeste 1 polycomb repressive complex 2 subunit (EZH1) and its mechanism in HCC. METHODS: This study integrates global microarray and high-throughput sequencing datasets, combined with internal immunohistochemistry, to analyze the expression and prognostic value of EZH1 in HCC. Functional enrichment analysis was conducted to investigate transcriptional targets, which were achieved by intersecting HCC over-expressed genes, EZH1 co-expressed genes and putative transcriptional targets. The relationship between EZH1 and anticancer drugs was detected by drug sensitivity analysis. RESULTS: In this study, 84 datasets from 40 platforms (3,926 HCC samples and 3,428 non-cancerous liver tissues) were included to show the high expression of EZH1 in HCC. Immunohistochemistry with 159 HCC samples and 62 non-HCC samples confirmed the high expression level. HCC patients with high EZH1 expression had worse survival prognoses. Gene ontology and Reactome analysis revealed that metabolism-related pathways, including autophagy, are critical for HCC. Interestingly, as one of the EZH1 potential transcriptional targets, autophagy-related 7 (ATG7) appeared in the above pathways. ATG7 was positively correlated with EZH1, upregulated in HCC, and mediated poor prognosis. Upregulation of EZH1 was found to be in contact with HCC anti-tumor drug resistance. CONCLUSIONS: The upregulation of EZH1 expression can promote the occurrence of HCC and lead to poor clinical progression and drug resistance; these effects may be mediated by regulating ATG7.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Complexo Repressor Polycomb 2/genética , Complexo Repressor Polycomb 2/metabolismo , Regulação para Cima , Relevância Clínica , Prognóstico , Regulação Neoplásica da Expressão Gênica
15.
Hematology ; 28(1): 2288480, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38063157

RESUMO

OBJECTIVES: This study aimed to evaluate the characteristics of patients with hematological malignancies (HM) and SARS-CoV-2 infection and analyze the risk factors of their severity and mortality. METHODS: A retrospective study including inpatients diagnosed HM and SARS-CoV-2 infection between December 2022 and February 2023 were conducted. Demographic information, medical history, comorbidities, diagnosis, treatment related information and outcomes were extracted from electronic medical database. The primary outcome of this study were the severity of SARS-CoV-2 infection and case-fatality rate. The clinical characteristic and outcomes of the patients were summarized and analyzed. RESULTS: A total of 74 patients with HM and SARS-CoV-2 infection were included. Out of the total cases, 85.1% (63) had a mild /moderate SARS-CoV-2 infection, and 14.9% (11) were severe/ critical infection cases. A total of 8 deaths occurred in all cases for a case-fatality rate of 10.8%. Multivariate analysis identified patients with acute myeloid leukemia (AML) (P = 0.043, OR:5.274, 95%CI:1.053-26.407), primary hematological disease in active state (P = 0.005, OR:13.905, 95%CI:2.180-88.704) were independent risk factors for the severity of SARS-CoV-2 infection and patients with AML had 11.145-fold higher risk of non-survival (P = 0.020, OR:11.145, 95%CI:1.460-85.103) in comparison to the patients with other types of HM. There were no significant differences in the severity and case-fatality rate (P > 0.05) between the patients receiving chemotherapy drugs administration waiting <14 days and ≥14 days after negative SARS-CoV-2 testing. CONCLUSION: The primary hematological disease in active state may be the main risk factor for negative outcome of the patents. Waiting 14 days for chemotherapy initiation after negative SARS-CoV-2 testing is unnecessary.


Assuntos
COVID-19 , Neoplasias Hematológicas , Leucemia Mieloide Aguda , Humanos , COVID-19/complicações , SARS-CoV-2 , Estudos Retrospectivos , Teste para COVID-19 , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/tratamento farmacológico
16.
Digit Health ; 9: 20552076231184993, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37426579

RESUMO

Objective: To reveal the characteristics, development trend and potential opportunities of China-ASEAN collaboration in the medical and health field based on bibliometrics. Methods: Scopus and International Center for the Study of Research Lab (ICSR Lab) was used to analyze the scale, collaboration network and distribution, impact of cooperative papers, collaboration dominance and evolution of the literature on China-ASEAN medical and health collaboration in the Scopus database from 1992 to 2022. Results: From 1992 to 2022, 19,764 articles on medical and health collaboration between China and ASEAN were filtered for analysis. The number of China-ASEAN collaborations has shown a clear upward trend over the years, indicating a gradually closer and improved collaboration relationship overall. The institutional collaboration network between China and ASEAN countries was obviously clustered, and the network connectivity was limited. The substantial differences between the median and mean values of citation impact of China-ASEAN medical and health research collaboration reflected that the collaboration was 'less' but 'better'. The dominance share of collaboration between China and the main ASEAN countries was fluctuating upward and has become more and more stable after 2004. Most of the China-ASEAN collaboration focused on their own characteristic research topics. In recent years, collaboration in infectious diseases and public health had expanded significantly, while other research topics had maintained in a complementary development trend. Conclusion: Collaboration between China and ASEAN in the medical and health field has exhibited a progressively closer relationship, and the trend of complementary research has remained stable. However, there are still areas of concern, including the limited scale of collaboration, narrow scope of participation and weak dominance.

17.
Front Pharmacol ; 14: 1290175, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37908979

RESUMO

Owing to their unique physical and chemical properties and remarkable biological activities, marine biological resources are emerging as important sources of raw materials for producing health products, food, and cosmetics. Collagen accounts for approximately 70% of the sea cucumber body wall, and its hydrolysis produces small-molecule collagen polypeptides with diverse biological functions, such as anticancer, antihypertensive, immune-enhancing, memory-enhancing, and cartilage tissue repairing effects. Notably, the potential of sea cucumber polypeptides in combination with anticancer therapy has garnered considerable attention. Determining the composition and structure of sea cucumber polypeptides and exploring their structure-activity relationships will aid in obtaining an in-depth understanding of their diverse biological activities and provide scientific insights for the development and utilization of these polypeptides. Therefore, this review focuses on the amino acid structures and activities of sea cucumber polypeptides of varying molecular weights. This study also provides an overview of the biological activities of various sea cucumber polypeptides and aims to establish a scientific basis for their development.

18.
Front Plant Sci ; 13: 912627, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795347

RESUMO

This study investigates the reliability of phytolith assemblage analysis for characterizing subtropical vegetation and explores the potential for using these modern phytolith-vegetation relationships for paleoenvironmental interpretation in southeastern China. The samples were collected from five common subtropical vegetation communities in the Daiyun Mountains, southeastern China, with the above-ground vegetation recorded at each plot. Constrained ordination analysis was used to determine the most important factor governing the variations in phytolith assemblages that could be quantitatively reconstructed with weighted averaging partial least squares regression (WAPLS). The relationship between modern phytolith assemblages and the parent vegetation, as well as production, dispersal, and taphonomic processes, was discussed. Results demonstrated that the main subtropical biomes in southeastern China could be well distinguished by soil phytolith assemblages. In particular, the overall amount of tree coverage was well represented by topsoil phytolith assemblages. Grass silica short cell phytoliths (GSSCP) tended to occur in higher proportions in open habitats (shrub-meadow) at higher elevations, whereas non-grass phytolith morphotypes attained higher frequencies under mixed and broadleaf forests at lower elevations. Human-induced deforestation might increase the frequency of GSSCP within the bulk phytolith assemblage. Our results constitute the primary phytolith reference data for the subtropical zone in southeastern Asia where vegetation change during the Holocene period, particularly forest shifts, anthropogenic deforestation, and early agriculture are poorly documented.

19.
Cell Death Dis ; 13(9): 768, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068200

RESUMO

Angiogenesis is a fundamental process underlying the occurrence, growth and metastasis of hepatocellular carcinoma (HCC), a prevalent tumour type with an extremely poor prognosis due to abundant vasculature. However, the underlying mechanism of angiogenesis in HCC remains largely unknown. Herein, we found that sphingosine-1-phosphate receptor 1 (S1PR1) plays an important role in HCC angiogenesis. S1PR1 was found to be selectively and highly expressed in the blood vessels of HCC tissues compared with those of paratumour tissues. Functionally, high expression of S1PR1 in endothelial cells (ECs) promoted angiogenesis and progression of HCC in vitro and in vivo. Mechanistically, proangiogenic factors (S1P, IL-6, VEGFA) in conditioned medium from HCC cells induced the upregulation of S1PR1 in ECs via the phosphorylation of STAT3 at Y705. Further study also revealed that S1PR1 promotes angiogenesis by decreasing ceramide levels via CerS3 downregulation. Interestingly, we demonstrated that S1PR1 downregulates CerS3 by inducing CerS6 translocation into the nucleus to inhibit CerS3 at the transcriptional level in ECs. In addition, we found that a high concentration of Lenvatinib significantly downregulated the expression of S1PR1 and obviously enhanced S1PR1 knockdown-mediated angiogenesis inhibition, indicating that S1PR1 may be a target by which Lenvatinib combats angiogenesis in HCC. Thus, S1PR1 may be an important target for suppressing angiogenesis in HCC, and inhibiting S1PR1 is a promising approach to antitumor therapy in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Ceramidas/metabolismo , Células Endoteliais/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Neovascularização Patológica/metabolismo , Transdução de Sinais , Receptores de Esfingosina-1-Fosfato
20.
J Hepatocell Carcinoma ; 8: 23-33, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33604313

RESUMO

BACKGROUND: Currently, there is still a lack of effective biomarkers for the recurrence monitoring and survival prognosis assessment of hepatocellular carcinoma (HCC) patients with alpha-fetoprotein (AFP)-negative (≤20 ng/mL) after radical resection. METHODS: The clinicopathological data of 606 patients (303 in the AFP-negative group and 303 in the AFP-positive group) who underwent radical resection of HCC were analyzed retrospectively. RESULTS: The gamma-glutamyl transpeptidase to lymphocyte count ratio (GLR) of patients in the AFP-negative group was lower than that in the AFP-positive group (p <0.001). The GLR level of the early-recurrence group was higher than that of the non-early-recurrence group (p =0.003). GLR had fair accuracy in predicting the early-recurrence of HCC patients [c-index=0.654 (95% CI=0.606-0.702); AUC=0.681 (95% CI=0.625-0.733)]. Univariate analysis showed that patients with tumor size <5 cm, no microvascular invasion, single tumor, no metastasis, BCLC stage 0-A, no recurrence, and GLR ≤45.0 had longer disease-free survival (DFS) and overall survival (OS) among AFP-negative HCC patients. In addition, multivariate Cox proportional hazards regression analysis showed that tumor size <5 cm (p =0.003), no recurrence (p <0.001), and GLR <45.0 (p <0.001) were independent predictors of longer OS. CONCLUSION: GLR may be a potential indicator for early recurrence monitoring and prognosis evaluation in HCC patients with AFP-negative after radical resection.

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