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1.
J Med Food ; 27(10): 971-980, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39133117

RESUMO

Twelve polyphenol derivatives were obtained in a protective activity-guided isolation from the Portulaca oleracea L. extract on a cell model of human umbilical vein endothelial cells (HUVECs) under diethylhexyl phthalate (DEHP) exposure. Among them, methyl (3,4,5-trimethoxybenzoyl) valylprolinate (PP-10) performed the most protective activity and inhibited DEHP exposure-induced HUVECs' apoptosis. PP-10 also inhibited the DEHP-induced inflammatory cytokines (TNF-α, IL-6, IL-1ß, and IL-8) and adhesion molecule (ICAM-1 andVCAM-1) overexpression. Furthermore, DEHP-induced NLRP3 inflammasomes' and NF-κB signaling pathway activation was significantly inhibited after the PP-10 treatments. Of note, the current results suggest the potential application of Portulaca oleracea L. and PP-10 in the prevention of DEHP-induced inflammatory damages in HUVECs.


Assuntos
Dietilexilftalato , Células Endoteliais da Veia Umbilical Humana , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Extratos Vegetais , Portulaca , Transdução de Sinais , Humanos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Portulaca/química , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Dietilexilftalato/toxicidade , Dietilexilftalato/análogos & derivados , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/metabolismo , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/genética
2.
Clinics (Sao Paulo) ; 79: 100413, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39024795

RESUMO

OBJECTIVE: Atherosclerosis (AS) is a common pathogenesis of cardiovascular diseases. Puerarin (Pue) is a Chinese herbal remedy used to prevent and treat AS. Here, this research investigated the effect of Pue on AS progression. METHODS: ApoE-/- mice were induced with acrolein. Body weight, blood lipid index, inflammatory factors, mitochondrial oxidative stress, and lipid deposition were detected. IL-6 and TNF-α were detected by ELISA. Oil red staining and H&E staining were used to observe the aortic sinus plaque lesions. Serum expressions of inflammatory factors IL-6, TNF-a, SOD, GSH and MDA were detected by ELISA, the mRNA expression levels of HDAC1 in the aorta were detected by RT-qPCR, and IL-6 and TNF-α in the aorta were detected by immunohistochemistry. JNK, p-JNK, OPA-1, and HDAC1 were detected by Western blotting. RESULTS: Pue administration can effectively reduce lipid accumulation in AS mice induced by acrolein. Pue promoted the activity of SOD, GSH and MDA, and inhibited the formation of atherosclerotic plaques and the process of aortic histological changes. Pue reduced IL-6 and TNF-α. HDAC1 expression was down-regulated and p-JNK-1 and JNK protein expression was up-regulated. CONCLUSION: Pue reduces inflammation and alleviates AS induced by acrolein by mediating the JNK pathway to inhibit HDAC1-mediated oxidative stress disorder.


Assuntos
Acroleína , Aterosclerose , Histona Desacetilase 1 , Isoflavonas , Estresse Oxidativo , Animais , Aterosclerose/induzido quimicamente , Aterosclerose/metabolismo , Aterosclerose/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Histona Desacetilase 1/metabolismo , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Acroleína/farmacologia , Masculino , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Western Blotting , Aorta/efeitos dos fármacos , Aorta/patologia
3.
Naunyn Schmiedebergs Arch Pharmacol ; 397(2): 1037-1044, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37566305

RESUMO

The objective of this study is to examine the effect of empagliflozin on cardiac function in rats with chronic heart failure and the possible mechanism. Forty 6-week-old male SD rats were randomly divided into the control group, empagliflozin treatment group, and sham-operated group. SD rats in the control group and empagliflozin treatment group were subjected to ligation of the anterior descending coronary artery to induce an acute myocardial infarction model. SD rats in the sham-operated group were only subjected to threading of the anterior descending branch of the coronary artery without ligation. On the second day after surgery, the control group and sham operation group were given physiological saline by gavage, while the empagliflozin treatment group was given empagliflozin (30 mg/kg/day) by gavage. Sixteen weeks later, cardiac function, intracellular reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), serum brain natriuretic peptide, hypersensitive C-reactive protein (hs-CRP), iNOS expression levels, and myocardial morphological changes were observed. Compared with that in the control group, heart function in the empagliflozin-treated group was significantly improved, MMP was increased, intracellular ROS levels were decreased, and NT-proBNP and hs-CRP were significantly reduced, and HE staining showed that the cell oedema was less than that in the control group, tissue arrangement was more orderly, and iNOS expression was inhibited. Empagliflozin can improve cardiac function in rats with chronic heart failure, and the mechanism may involve inhibiting inflammation, reducing myocardial oxidative stress, and improving myocardial fibrosis.


Assuntos
Compostos Benzidrílicos , Proteína C-Reativa , Glucosídeos , Insuficiência Cardíaca , Ratos , Masculino , Animais , Espécies Reativas de Oxigênio , Ratos Sprague-Dawley
4.
J Transl Med ; 21(1): 21, 2023 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635690

RESUMO

BACKGROUND: Growth arrest-specific 6 (GAS6) is a vitamin K-dependent protein related to inflammation, fibrosis, as well as platelet function. Genetic ablation of GAS6 in mice protects against cardiac hypertrophy and dysfunction. Nonetheless, the association between plasma GAS6 levels and acute heart failure (AHF) patients is still unknown. METHODS: We measured plasma GAS6 concentrations in 1039 patients with AHF who were enrolled in the DRAGON-HF trial (NCT03727828). Mean follow-up of the study was 889 days. The primary endpoint is all-cause death. RESULTS: In total, there were 195 primary endpoints of all-cause death and 135 secondary endpoints of cardiovascular death during the mean follow-up duration of 889 days. The higher levels of GAS6 were associated with higher rates of all-cause and cardiovascular death (P < 0.05). Baseline plasma GAS6 levels were still strongly correlated with clinical outcomes in different models after adjustment for clinical factors and N-terminal pro-brain natriuretic peptide (NT-proBNP, P < 0.05). GAS6 could further distinguish the risks of clinical outcomes based on NT-proBNP measurement. CONCLUSION: Elevated plasma GAS6 levels were associated with an increased risk of all-cause and cardiovascular death in patients with AHF. Trial registration NCT03727828 (DRAGON-HF trial) clinicaltrials.gov.


Assuntos
Insuficiência Cardíaca , Peptídeos e Proteínas de Sinalização Intercelular , Biomarcadores , Insuficiência Cardíaca/diagnóstico , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Prognóstico , Volume Sistólico , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue
5.
J Am Heart Assoc ; 10(20): e022304, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34612058

RESUMO

Background Circulating microRNAs are emerging biomarkers for heart failure (HF). Our study aimed to assess the prognostic value of microRNA signature that is differentially expressed in patients with acute HF. Methods and Results Our study comprised a screening cohort of 15 patients with AHF and 5 controls, a PCR-discovery cohort of 50 patients with AHF and 26 controls and a validation cohort of 564 patients with AHF from registered study DRAGON-HF (Diagnostic, Risk Stratification and Prognostic Value of Novel Biomarkers in Patients With Heart Failure). Through screening by RNA-sequencing and verification by reverse-transcription quantitative polymerase chain reaction, 9 differentially expressed microRNAs were verified (miR-939-5p, miR-1908-5p, miR-7706, miR-101-3p, miR-144-3p, miR-4732-3p, miR-3615, miR-484 and miR-19b-3p). Among them, miR-19b-3p was identified as the microRNA signature with the highest fold-change of 8.4 and the strongest prognostic potential (area under curve with 95% CI, 0.791, 0.654-0.927). To further validate its prognostic value, in the validation cohort, the baseline level of miR-19b-3p was measured. During a follow-up period of 19.1 (17.7, 20.7) months, primary end point comprising of all-cause mortality or readmission due to HF occurred in 48.9% patients, while patients in the highest quartile of miR-19b-3p level presented the worst survival (Log-rank P<0.001). Multivariate Cox model showed that the level of miR-19b-3p could independently predict the occurrence of primary end point (adjusted hazard ratio,1.39; 95% CI, 1.18-1.64). In addition, miR-19b-3p positively correlated with soluble suppression of tumorigenicity 2 and echocardiographic indexes of left ventricular hypertrophy. Conclusions Circulating miR-19b-3p could be a valuable prognostic biomarker for AHF. In addition, a high level of circulating miR-19b-3p might indicate ventricular hypertrophy in AHF subjects. Registration URL: https://www.clinicaltrials.gov. Unique Identifier: NCT03727828.


Assuntos
MicroRNA Circulante , Insuficiência Cardíaca , Biomarcadores , MicroRNA Circulante/genética , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/genética , Humanos , Prognóstico
6.
Zhonghua Nan Ke Xue ; 26(8): 713-716, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-33377732

RESUMO

OBJECTIVE: To investigate the effects of bilateral microsurgical subinguinal varicocelectomy (BMSV) in patients with asthenozoospermia or oligozoospermia. METHODS: Totally 147 patients with male infertility received BMSV from January 2018 to May 2019, of whom 109 had complete data recorded. We retrospectively analyzed the clinical data, including the total sperm count per ejeculate, sperm concentration and sperm motility before and after surgery, and the rate of natural conception achieved during the follow-up. RESULTS: BMSV achieved a total effectiveness rate of 79.00% in improving the percentage of progressively motile sperm (a rise of ≥20%) and a marked effectiveness rate of 70.00% (a rise of ≥50%) in the 100 cases of asthenozoospermia as compared with the baseline, with a mean recovery time of (110.13 ± 37.43) days. Besides, a total effectiveness rate of 74.29% (an increase of ≥20%) and a marked effectiveness rate of 71.43% (an increase of ≥50%) were attained in the improvement of sperm concentration in the 35 cases of oligozoospermia, with a mean recovery time of (117.00 ± 48.79 ) days. A natural conception rate of 30.30% was observed during the follow-up. No severe adverse events occurred postoperatively. CONCLUSIONS: BMSV is significantly effective for the treatment of asthenozoospermia and oligozoospermia.


Assuntos
Astenozoospermia , Oligospermia , Varicocele , Astenozoospermia/cirurgia , Humanos , Masculino , Microcirurgia , Oligospermia/cirurgia , Estudos Retrospectivos , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Resultado do Tratamento , Varicocele/cirurgia
7.
Med Sci Monit ; 26: e921184, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32221273

RESUMO

BACKGROUND Retinal degeneration causes irreversible blindness. Human retinal progenitor cells (hRPCs) have the potential to treat retinal diseases. The vitreous cavity is a relatively immune-privileged site that is suitable for stem cell transplantation in the treatment of retinal diseases. This study aimed to evaluate the therapeutic efficacy and safety of intravitreal injection of hRPCs in retinal degeneration therapy. MATERIAL AND METHODS hRPCs were primary-cultured and injected into the vitreous cavity of RCS rats. To determine whether hRPCs formed teratomas in immune-deficient mice, hRPCs at different passages were transplanted into BALB/c-nu mice. The visual function was detected by electroretinography recording. Changes in the outer nuclear layer (ONL) were analyzed by histological testing and cell counting. The protective mechanism was further assessed by cytokine antibody array. RESULTS Intravitreal transplantation of hRPCs maintained retinal function and preserved retinal morphology. Importantly, grafted cells in the vitreous cavity were well tolerated, with no adverse effects. Teratoma was not formed in BALB/c-nu mice after hRPCs transplantation. The number of hRPCs-injected eyes and thickness of ONL in the hRPCs-treated group were higher than those in the untreated group and HBSS injection group. The cytokine antibody array revealed that hRPCs expressed GDF-15, PDGF-AA, EGF, and NT-4. CONCLUSIONS Our findings show that intravitreal injection of hRPCs is effective and safe in protecting photoreceptor cells in RCS rats, but were no longer effective at 12 weeks after transplantation. Moreover, hRPCs released multiple neurotrophic factors that may be involved in treating retinal disease.


Assuntos
Retina/citologia , Degeneração Retiniana/terapia , Transplante de Células-Tronco/métodos , Células-Tronco/fisiologia , Animais , Autorrenovação Celular , Células Cultivadas , Modelos Animais de Doenças , Feto/citologia , Humanos , Injeções Intravítreas , Camundongos , Cultura Primária de Células , Ratos , Retina/patologia , Degeneração Retiniana/patologia
8.
Coron Artery Dis ; 30(7): 542-546, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30998609

RESUMO

OBJECTIVE: To investigate the association of Wnt1-inducible signaling pathway protein 1 (WISP1) concentrations in circulation with the presence and severity of coronary artery disease (CAD). PARTICIPANTS AND METHODS: A total of 120 consecutive participants who underwent coronary angiography between May 2017 and July 2018 at our center were enrolled. Participants were divided into two groups based on the presence of CAD. Serum WISP1 levels were measured using enzyme-linked immunosorbent assay. Univariate and multivariate analyses were used to determine the association between variables and the presence of CAD. RESULTS: The average age of the study population was 59.8 years, 66.7% were male, and 58.3% were positive for CAD. Serum WISP1 levels were significantly higher in patients with CAD than non-CAD group (339.8 vs. 322.4 pg/ml, P = 0.012). Moreover, a stepwise increase in serum WISP1 levels was observed with the number of diseased vessels (zero-vessel, one-vessel, two-vessel, and three-vessel disease: 322.4, 324.7, 345.4, and 392.1 pg/ml, respectively, P < 0.001) or Gensini score (r = 0.376, P < 0.001). Importantly, serum WISP1 levels were positively associated with the presence of CAD ( ß = 1.011, 95% confidence interval: 1.001-1.021, P = 0.026). This association persisted after adjusting for age, sex, hypertension, type 2 diabetes mellitus, hypercholesterolemia, smoking, and high-sensitivity C-reactive protein ( ß = 1.011, 95% confidence interval: 1.000-1.021, P = 0.047). In addition, serum WISP1 concentrations were positively correlated with BMI (r = 0.212, P = 0.020), insulin (r = 0.237, P = 0.009), and homeostatic model assessment for insulin resistance (r = 0.223, P = 0.014). CONCLUSION: We demonstrated for the first time that serum WISP1 concentration is associated with the presence and severity of CAD.


Assuntos
Proteínas de Sinalização Intercelular CCN/sangue , Doença da Artéria Coronariana/sangue , Proteínas Proto-Oncogênicas/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença , Regulação para Cima
9.
RSC Adv ; 9(34): 19365-19374, 2019 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-35519370

RESUMO

Studies have reported that scorpion toxins have excellent anti-cancer effects; however, the anti-inflammatory activity of scorpion peptides has rarely been studied. Here, a series of Mesobuthus martensii Karsch peptides (MMKPs) were isolated and the amino acid sequence was identified. The MMKPs mitigated TNF-α-mediated inflammation in human umbilical vein endothelial cells (HUVECs). The results showed that MMKP-1 (His-Glu-Gly-His) treatment (43.0 µM) significantly attenuated the reactive oxygen species (ROS) generation and mitochondrial membrane potential collapse in HUVECs. Moreover, MMKP-1 down-regulated the intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions and blocked the NF-κB pathway to alleviate the damage caused by TNF-α. Of note, our study provides a good reference for the anti-inflammation research on scorpion oligopeptides.

10.
Zhonghua Nan Ke Xue ; 24(6): 516-519, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-30173456

RESUMO

OBJECTIVE: Human papilloma virus (HPV) is a necessary cause of cervical cancer and is also closely related to penile cancer, oropharyngeal cancer, and anal cancer in males. However, few studies are reported on male HPV. This study aimed to investigate HPV infection of the external genitalia in men whose female partners have cervical HPV infection. METHODS: We collected the relevant data on the male outpatients whose partners had cervical HPV infection in our Department of Urology and Andrology from August to December 2016. We obtained samples with nylon swabs from the glans penis, corona, inner layer of the prepuce and penile body and detected different types of HPV infection using the Hybribio HPV typing kit, PCR and membrane hybridization. RESULTS: Valid data were collected from 140 males, which showed 83.5% of HPV infection of the external genitalia, including 60 cases of HPV6 (43.2%), 27 cases of HPV16 (19.4%), 14 cases of HPV39 (10.1%), 13 cases of HPV18 (9.4%), 13 cases of HPV58 (9.4%), and 13 cases of HPV52 (9.4%). Redundant prepuce was found in 75.5% of the males, but there was no statistically significant difference in the incidence rate of HPV infection between the normal and redundant prepuce groups (P > 0.05). CONCLUSIONS: Men who have the female partners with positive cervical HPV are at high risk of HPV infection and therefore need to be screened and treated so as to reduce HPV infection in both sexes.


Assuntos
Doenças dos Genitais Femininos/virologia , Doenças dos Genitais Masculinos/virologia , Infecções por Papillomavirus/diagnóstico , Pênis/virologia , Feminino , Prepúcio do Pênis/virologia , Papillomavirus Humano 16/isolamento & purificação , Humanos , Masculino , Papillomaviridae/isolamento & purificação , Neoplasias Penianas/virologia , Pênis/anormalidades , Fimose/virologia , Reação em Cadeia da Polimerase , Parceiros Sexuais , Manejo de Espécimes , Neoplasias do Colo do Útero/virologia
11.
Neurosci Lett ; 657: 62-68, 2017 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-28774569

RESUMO

Retinal progenitor cell is a promising candidate in the treatment of retinal pigmentosa diseases. The limiting factors of stem cell transplantation are the proliferation and differentiation capacities of hRPCs, which may be governed by culture conditions. Previous studies have proved that the secretome of human Umbilical Cord Mesenchymal stem cells (hUCMSCs) and human Adipose derived stem cells (hADSCs), including more active cytokines and neurotrophic factors, have the paracrine potential of enhancing proliferation and differentiation in several cell types. The aim of this study was to investigate whether hRPCs could effectively proliferate, adhere and differentiate towards specific retinal cell types by treating with the condition medium (CM) of hUCMSCs (hUCMSCCM) or hADSCs (hADSCCM). Here, we show that hUCMSCCM or hADSCCM enhances the proliferation rate of the S and G2 phase cells, with an upregulation of Ki67 expression. Moreover, the upregulation expression of NF, Recoverin and Rhodopsin indicates that specialized retinal cells including ganglion cells and photoreceptors are favored over hRPCs differentiation due to hUCMSCCM or hADSCCM. Under FBS induced differentiation conditions, hRPCs treated with hUCMSCCM or hADSCCM increase the expression of retinal neuron and photoreceptor specific markers. These results suggest that hUCMSCCM and hADSCCM can stimulate the hRPC proliferation, promote its adherence and support hRPC neuronal and photoreceptor differentiation. These findings may provide a new strategy to improve the viability of hRPCs and photoreceptor differentiation capacities.


Assuntos
Adesão Celular/fisiologia , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Meios de Cultivo Condicionados , Células-Tronco Mesenquimais/fisiologia , Células-Tronco Neurais/fisiologia , Neurônios Retinianos/fisiologia , Bancos de Tecidos , Células Cultivadas , Humanos
12.
Free Radic Biol Med ; 104: 272-279, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28130183

RESUMO

The thiazolidine ring is a biologically active chemical structure and is associated with many pharmacological activities. However, the biological molecules that can interact with the thiazolidine ring are not known. We show that thiazolidine causes sustained activation of the TRPA1 channel and chemically reacts with glutathione, and the chemical reactivity of thiazolidine ring is required for TRPA1 activation. Reducing agents reverse thiazolidine-induced TRPA1 activation, and mutagenesis studies show that nucleophilic cysteine residues in TRPA1 are critical, suggesting an activation mechanism involving thioreactive chemical reactions. In vivo studies show that thiazolidine induces acute pain and inflammation in mouse and these responses are specifically dependent on TRPA1. These results indicate that thiazolidine compounds can chemically react with biological molecules containing nucleophilic cysteines, thereby exerting biological activities.


Assuntos
Dor Aguda/metabolismo , Inflamação/metabolismo , Canal de Cátion TRPA1/genética , Tiazolidinas/administração & dosagem , Dor Aguda/genética , Dor Aguda/patologia , Animais , Cisteína/metabolismo , Glutationa/metabolismo , Humanos , Inflamação/genética , Inflamação/patologia , Camundongos , Mutagênese , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/metabolismo , Canal de Cátion TRPA1/biossíntese
13.
Anticancer Drugs ; 28(1): 66-74, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27603596

RESUMO

Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively induces apoptosis in many tumor cells while leaving normal cells intact and is thus an attractive candidate for antitumor therapies. This paper reports that the combination of tunicamycin plus TRAIL produced a strong synergistic effect in TRAIL-sensitive human colon cancer HCT116 cells and TRAIL-resistant HT-29 cells. On a cellular mechanistic level, tunicamycin-enhanced TRAIL-induced apoptosis by death receptor (DR) 5 upregulation and DR4 deglycosylation. Knockdown of DR5 but not DR4 expression by specific shRNAs or siRNAs significantly increased tunicamycin-mediated and TRAIL-mediated cell viability. DR5 induction was regulated by C/EBP homologous protein (CHOP) and JNK as CHOP siRNA or JNK inhibitor SP600125 considerably abolished the DR5 induction. In addition, tunicamycin inhibited epidermal growth factor receptor glycosylation and the downstream signaling pathways, Akt and extracellular signal-regulated kinases activation, which might also be required for TRAIL sensitization by tunicamycin. In summary, tunicamycin effectively enhanced TRAIL-induced apoptosis might through JNK-CHOP-mediated DR5 upregulation and the inhibition of the epidermal growth factor receptor pathway.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias do Colo/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Tunicamicina/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Sinergismo Farmacológico , Receptores ErbB/metabolismo , Humanos , Ligante Indutor de Apoptose Relacionado a TNF/administração & dosagem , Fator de Transcrição CHOP/metabolismo , Tunicamicina/administração & dosagem , Regulação para Cima/efeitos dos fármacos
14.
Apoptosis ; 21(11): 1291-1301, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27629794

RESUMO

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potent cancer cell-specific apoptosis-inducing cytokine with little toxicity to most normal cells. Here, we report that gefitinib and TRAIL in combination produce a potent synergistic effect on TRAIL-sensitive human colon cancer HCT116 cells and an additive effect on TRAIL-resistant HT-29 cells. Interestingly, gefitinib increases the expression of cell surface receptors DR4 and DR5, possibly explaining the synergistic effect. Knockdown of DR4 and DR5 by siRNA significantly decreases gefitinib- and TRAIL-mediated cell apoptosis, supporting this idea. Because the inhibition of gefitinib-induced autophagy by 3-MA significantly decreases DR4 and DR5 upregulation, as well as reduces gefitinib- and TRAIL-induced apoptosis, we conclude that death receptor upregulation is autophagy mediated. Furthermore, our results indicate that death receptor expression may also be regulated by JNK activation, because pre-treatment of cells with JNK inhibitor SP600125 significantly decreases gefitinib-induced death receptor upregulation. Interestingly, SP600125 also inhibits the expression CHOP, yet CHOP has no impact on death receptor expressions. We also find here that phosphorylation of Akt and ERK might also be required for TRAIL sensitization. In summary, our results indicate that gefitinib effectively enhances TRAIL-induced apoptosis, likely via autophagy and JNK- mediated death receptor expression and phosphorylation of Akt and ERK.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Neoplasias do Colo/fisiopatologia , Quinazolinas/farmacologia , Receptores de Morte Celular/genética , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Gefitinibe , Células HT29 , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Receptores de Morte Celular/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Regulação para Cima/efeitos dos fármacos
15.
Clinics ; Clinics;70(1): 24-29, 1/2015. graf
Artigo em Inglês | LILACS | ID: lil-735868

RESUMO

OBJECTIVES: To investigate an unusual outbreak of tetrodotoxin poisoning in Leizhou, southeast China, a case series analysis was conducted to identify the source of illness. METHODS: A total of 22 individuals experienced symptoms of poisoning, including tongue numbness, dizziness, nausea and limb numbness and weakness. Two toxic species, Amoya caninus and Yongeichthys nebulosus, were morphologically identified from the batches of gobies consumed by the patients. Tetrodotoxin levels in the blood and Goby fish samples were detected using liquid chromatography-tandem mass spectrometry. RESULTS: The tetrodotoxin levels in the remaining cooked Goby fish were determined to be 2090.12 µg/kg. For Amoya caninus, the toxicity levels were 1858.29 µg/kg in the muscle and 1997.19 µg/kg in the viscera and for Yongeichthys nebulosus, they were 2783.00 µg/kg in the muscle and 2966.21 µg/kg in the viscera. CONCLUSION: This outbreak demonstrates an underestimation of the risk of Goby fish poisoning. Furthermore, the relationships among the toxic species, climates and marine algae present should be clarified in the future. .


Assuntos
Adulto , Idoso , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peixes Venenosos , Doenças Transmitidas por Alimentos/etiologia , Perciformes , Tetrodotoxina/intoxicação , Cromatografia Líquida , China/epidemiologia , Surtos de Doenças , Doenças Transmitidas por Alimentos/epidemiologia , Estudos Retrospectivos , Espectrometria de Massas em Tandem , Tetrodotoxina/sangue
16.
Int J Clin Exp Med ; 7(12): 5412-20, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25664050

RESUMO

AIMS: To investigate the relationships between carotid intima-media thickness (IMT) and conventional cardiovascular risk factors in Uygur population. METHODS: In totally 226 Uygur subjects, common carotid IMT values were detected, and the anthropometric and laboratory measurements were recorded. RESULTS: Correlation analysis showed that the factors of age, BMI, SBP, DBP, PP, hypertension, TC, LDL-C, TG, Apo B, diabetes mellitus, glucose, smoking status, creatinine, IHD, and stroke were significantly and positively associated with carotid IMT in Uygur males. In Uygur females, significant positive associations with carotid IMT were observed for age, BMI, SBP, DBP, PP, hypertension, TC, LDL-C, TG, diabetes mellitus, glucose, IHD, and stroke, and a significant inverse association was found for HDL-C. Multiple regression analyses suggested that LDL-C, age, TG, creatinine, BMI, smoking, hypertension, and diabetes were independently associated with carotid IMT in Uygur males. However, for carotid IMT in Uygur females, SBP, age, TG, HDL-C, BMI, and diabetes were independent determinants. CONCLUSION: Carotid artery IMT could be used as a predictive tool for atherosclerotic lesions and cardiovascular diseases in Uygur population, which might contribute to the prevention and management of the local disease.

17.
PLoS One ; 8(11): e81815, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24303074

RESUMO

Gliomas, the most malignant form of brain tumors, contain a small subpopulation of glioma stem cells (GSCs) that are implicated in therapeutic resistance and tumor recurrence. Topoisomerase I inhibitors, shikonin and topotecan, play a crucial role in anti-cancer therapies. After isolated and identified the GSCs from glioma cells successfully, U251, U87, GSCs-U251 and GSCs-U87 cells were administrated with various concentrations of shikonin or topotecan at different time points to seek for the optimal administration concentration and time point. The cell viability, cell cycle and apoptosis were detected using cell counting kit-8 and flow cytometer to observe the inhibitory effects on glioma cells and GSCs. We demonstrated that shikonin and topotecan obviously inhibited proliferation of not only human glioma cells but also GSCs in a dose- and time-dependent manner. According to the IC50 values at 24 h, 2 µmol/L of shikonin and 3 µmol/L of topotecan were selected as the optimal administration concentration. In addition, shikonin and topotecan induced cell cycle arrest in G0/G1 and S phases and promoted apoptosis. The down-regulation of Bcl-2 expression with the activation of caspase 9/3-dependent pathway was involved in the apoptosis process. Therefore, the above results showed that topoisomerase I inhibitors, shikonin and topotecan, inhibited growth and induced apoptosis of GSCs as well as glioma cells, which suggested that they might be the potential anticancer agents targeting gliomas to provide a novel therapeutic strategy.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Naftoquinonas/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Inibidores da Topoisomerase I/farmacologia , Topotecan/farmacologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
18.
Urol Int ; 90(4): 443-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23328488

RESUMO

OBJECTIVE: To compare the outcomes of two approaches (inguinal and subinguinal) of microsurgical varicocelectomy (MV) in Chinese infertile men. PATIENTS AND METHODS: 120 infertile men who met the inclusion criteria were randomly assigned to two groups and operated with MV using different approaches. The outcomes and complications were then compared. RESULTS: The two groups were similar in all aspects except the percentage of patients using analgesic at 27 h postoperatively (57.6% in the inguinal group, 37.5% in the subinguinal group; p < 0.05). Spontaneous pregnancy was achieved at a ratio of 33.9% in the inguinal group and 30.4% in subinguinal group. The median values of semen parameters were significantly improved postoperatively in both groups. CONCLUSIONS: Both approaches are effective methods in the repair of varicocele in infertile men, but more analgesic medication at the first day after operation may be required in inguinal group.


Assuntos
Fertilidade , Infertilidade Masculina/cirurgia , Microcirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Varicocele/cirurgia , Adulto , Analgésicos/uso terapêutico , Distribuição de Qui-Quadrado , China , Método Duplo-Cego , Feminino , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/etiologia , Infertilidade Masculina/fisiopatologia , Masculino , Microcirurgia/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Análise do Sêmen , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos , Varicocele/complicações , Varicocele/diagnóstico , Varicocele/fisiopatologia
19.
Int J Urol ; 20(2): 220-6, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22974480

RESUMO

OBJECTIVES: To compare the outcomes and complications of three methods of circumcision in a Chinese pediatric population. METHODS: A total of 120 children were randomly assigned to three groups. Group I was submitted to circumcision using the Shenghuan disposable device according to Yan's method; group II was submitted to circumcision using the same device, but according to Peng's methods; group III was operated on by using the conventional scalpel/suture technique. The three groups were compared mainly by the following outcomes: duration of surgery, intraoperative bleeding, postoperative pain, cosmetic effect, and the rates of edema, dehiscence, scarring, adhesion and infection. RESULTS: Groups I and II had less intraoperative bleeding. In terms of the duration of surgery, group I was the quickest. Pain scores in using the Shenghuan disposable device were higher at 6 h after surgery compared with the conventional scalpel/suture technique. The percentage of patients using paracetamol in group II was higher than that in group III at 12 h after surgery. Other complications were similar, and all three groups had successful outcomes. CONCLUSIONS: Circumcision using the Shenghuan disposable device represents a safer and time-saving option compared with the conventional scalpel/suture technique, with better cosmetic outcomes. Yan's method seems to be better than Peng's method when using the Shenghuan disposable device for circumcision in children.


Assuntos
Circuncisão Masculina/instrumentação , Equipamentos Descartáveis/estatística & dados numéricos , Instrumentos Cirúrgicos , Perda Sanguínea Cirúrgica/fisiopatologia , Criança , Pré-Escolar , China , Circuncisão Masculina/efeitos adversos , Circuncisão Masculina/métodos , Método Duplo-Cego , Desenho de Equipamento , Seguimentos , Humanos , Masculino , Bloqueio Nervoso/métodos , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Medição de Risco , Estatísticas não Paramétricas , Técnicas de Sutura , Resultado do Tratamento , Cicatrização/fisiologia
20.
Zhong Yao Cai ; 36(10): 1608-11, 2013 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-24761669

RESUMO

OBJECTIVE: To study the chemical constituents of Gastrodia elata. METHODS: The compounds were isolated by silica gel column chromatography and recrystallization and their structures were elucidated by spectral analysis. RESULTS: The structures of 14 compounds were identified as: p-hydroxybenzyl alcohol (1), p-hydroxybenzaldehyde (2), 3, 4-dihydroxybenzaldehyde (3), 4, 4'-dihydroxy, dibenzyl ether (4), 4-hydroxymethyl benzyl-4'-hydroxy-3'-(4"-hydroxy benzl) benzyl ether (5), 4-ethoxybenzyl alcohol (6), anisic alcohol (7), bis(3, 4-dihydroxyphenyl) methane (8), 4, 4'-dihydroxydiphenyl methane (9), 2, 4-bis(4'-hydroxy-benzyl)-phenol (10), 4-( methoxymenthyl) benzene-1, 2-diol (11), p-methylphenyl-1 -O-beta-D-glucopyranoside (12), N6-(4'-hydroxybenzl) -adenosine (13) and beta-sitosterol (14). CONCLUSION: Compounds 6 - 8 and 11 are isolated from this plant for the first time.


Assuntos
Gastrodia/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais/química , Benzaldeídos/química , Benzaldeídos/isolamento & purificação , Álcoois Benzílicos/química , Álcoois Benzílicos/isolamento & purificação , Etanol/química , Cromatografia Gasosa-Espectrometria de Massas , Estrutura Molecular , Extratos Vegetais/química , Raízes de Plantas/química
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