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1.
BMC Emerg Med ; 24(1): 82, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745146

RESUMO

PURPOSE: The classification of trauma patients in emergency settings is a constant challenge for physicians. However, the Injury Severity Score (ISS) is widely used in developed countries, it may be difficult to perform it in low- and middle-income countries (LMIC). As a result, the ISS was calculated using an estimated methodology that has been described and validated in a high-income country previously. In addition, a simple scoring tool called the Kampala Trauma Score (KTS) was developed recently. The aim of this study was to compare the diagnostic accuracy of KTS and estimated ISS (eISS) in order to achieve a valid and efficient scoring system in our resource-limited setting. METHODS: We conducted a cross-sectional study between December 2020 and March 2021 among the multi-trauma patients who presented at the emergency department of Imam Reza hospital, Tabriz, Iran. After obtaining informed consent, all data including age, sex, mechanism of injury, GCS, KTS, eISS, final outcome (including death, morbidity, or discharge), and length of hospital stay were collected and entered into SPSS version 27.0 and analyzed. RESULTS: 381 multi-trauma patients participated in the study. The area under the curve for prediction of mortality (AUC) for KTS was 0.923 (95%CI: 0.888-0.958) and for eISS was 0.910 (95% CI: 0.877-0.944). For the mortality, comparing the AUCs by the Delong test, the difference between areas was not statistically significant (p value = 0.356). The diagnostic odds ratio (DOR) for the prediction of mortality KTS and eISS were 28.27 and 32.00, respectively. CONCLUSION: In our study population, the KTS has similar accuracy in predicting the mortality of multi-trauma patients compared to the eISS.


Assuntos
Traumatismo Múltiplo , Humanos , Masculino , Feminino , Estudos Transversais , Adulto , Pessoa de Meia-Idade , Irã (Geográfico) , Traumatismo Múltiplo/mortalidade , Traumatismo Múltiplo/diagnóstico , Escala de Gravidade do Ferimento , Valor Preditivo dos Testes , Serviço Hospitalar de Emergência , Idoso , Índices de Gravidade do Trauma
2.
BMC Health Serv Res ; 23(1): 70, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690961

RESUMO

BACKGROUND: Basic emergency management in urban and rural areas is a critical challenge, which can affect the pre-hospital mortality rate. Therefore, Non-hospital Healthcare Center (NHHC) must be prepared to manage such emergency cases that may occur in the geographic area where these centers act. The main aim of the study was to develop and validate an toolbar for NHHCs' preparedness to provide initial emergency care. METHODS: This study was designed based on a sequential exploratory mixed- method in two phases, in each of which there are three steps. In the phase I, the literature systematic review and qualitative methods (Focus Group Discussions (FGDs) and Semi-Structured Interviews (SSIs)) were applied to identify the domains and items. In the phase II, content validity, feasibility, and reliability of the toolbar were performed. Content validity was assessed using a modified Kappa coefficient based on clarity and relevance criteria. Feasibility of the toolbar was randomly assessed through its implementation in 10 centers in Tabriz. Reliability was randomly assessed in a pilot on 30 centers. Reliability was assessed by measuring internal consistency, test-retest reliability, and inter-rater agreement. The main statistical methods for assessing reliability include Cronbach's alpha, Intra-class Correlation Coefficient, and Kendal's Tau-b. All the statistical analyses were performed using Stata 14. RESULTS: In the phase I, primary version of the toolbar containing 134 items related to assessing the preparedness of NHHCs was generated. In the phase II, item reduction was applied and the final version of the toolbar was developed containing 126 items, respectively. These items were classified in 9 domains which include: "Environmental Infrastructures of Centers", "Protocols, Guidelines and Policies", "Medical Supplies and Equipment", "Emergency Medicines", "Human Resources", "Clinical Interventions", "Maintenance of equipment", "Medicine Storage Capability", and "Management Process". The toolbar had acceptable validity and reliability. CONCLUSIONS: This study provided a standard and valid toolbar that can be used to assess the preparedness of NHHCs to deliver initial emergency care.


Assuntos
Serviços Médicos de Emergência , Administração de Serviços de Saúde , Humanos , Reprodutibilidade dos Testes , Tratamento de Emergência , Inquéritos e Questionários , Atenção à Saúde , Psicometria
3.
Altern Lab Anim ; 51(4): 249-257, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37345436

RESUMO

The significance of angiogenesis in tumour progression has been widely documented. Hence, the identification of anti-angiogenic agents with fewer common side effects would be valuable in cancer therapy. In this study, we evaluated the anti-angiogenic and anti-proliferative effects of a hydro-alcoholic extract of fenugreek seed (HAEF) on human umbilical vein endothelial cells (HUVECs). Human umbilical vein endothelial cells were treated with various concentrations of HAEF and the half-maximal inhibitory concentration (IC50) value was estimated by using the MTT assay. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase enzyme (MMP-2 and MMP-9) gene expression profiles were evaluated by using quantitative RT-PCR (qRT-PCR). Moreover, MMP activities and PI3K, Akt and cyclin D1 protein expression levels were evaluated by gel zymography and Western blotting, respectively. HAEF reduced HUVEC viability, with an IC50 value of 200 µg/ml. The qRT-PCR results demonstrated that treatment with HAEF markedly reduced MMP-2/MMP-9, VEGF and bFGF gene expression, as compared to the control group. We also found that MMP-2/MMP-9 enzyme activity and PI3K/Akt/cyclin D1 protein expression were notably decreased in cells treated with HAEF. Our results suggest that HAEF can potentially inhibit angiogenesis, and also affect cellular proliferation by targeting the PI3K/Akt/cyclin D1 pathway. Thus, fenugreek seed extract merits further investigation as a source of compounds with anti-cancer properties.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Fator A de Crescimento do Endotélio Vascular , Humanos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/farmacologia , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/farmacologia , Ciclina D1/metabolismo , Ciclina D1/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo , Fatores de Crescimento do Endotélio Vascular/metabolismo , Fatores de Crescimento do Endotélio Vascular/farmacologia , Proliferação de Células , Movimento Celular
4.
BMC Health Serv Res ; 22(1): 273, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35232439

RESUMO

BACKGROUND: Trauma is a major cause of death worldwide, especially in Low and Middle-Income Countries (LMIC). The increase in health care costs and the differences in the quality of provided services indicates the need for trauma care evaluation. This study was done to develop and use a performance assessment model for in-hospital trauma care focusing on traffic injures. METHODS: This multi-method study was conducted in three main phases of determining indicators, model development, and model application. Trauma care performance indicators were extracted through literature review and confirmed using a two-round Delphi survey and experts' perspectives. Two focus group discussions and 16 semi-structured interviews were conducted to design the prototype. In the next step, components and the final form of the model were confirmed following pre-determined factors, including importance and necessity, simplicity, clarity, and relevance. Finally, the model was tested by applying it in a trauma center. RESULTS: A total of 50 trauma care indicators were approved after reviewing the literature and obtaining the experts' views. The final model consisted of six components of assessment level, teams, methods, scheduling, frequency, and data source. The model application revealed problems of a selected trauma center in terms of information recording, patient deposition, some clinical services, waiting time for deposit, recording medical errors and complications, patient follow-up, and patient satisfaction. CONCLUSION: Performance assessment with an appropriate model can identify deficiencies and failures of services provided in trauma centers. Understanding the current situation is one of the main requirements for designing any quality improvement programs.


Assuntos
Melhoria de Qualidade , Centros de Traumatologia , Atenção à Saúde , Grupos Focais , Hospitais , Humanos
5.
Mol Biol Rep ; 48(2): 1433-1437, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33555528

RESUMO

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine involved in the regulation of the immune system and potentially the progression of cervical neoplastic lesions. In this study, we aimed to explore the possible relationship between polymorphisms of the TNF-α gene and susceptibility to cervical cancer. The relationship between a single nucleotide polymorphism (SNP) in the TNF-α gene (rs1800629) and the risk of cervical cancer was evaluated in a total of 445 subjects with (n = 153), or without (n = 292) cancer. Genotyping was performed using a Taq-Man based real time PCR method. Logistic regression analysis showed that individuals with AG/AA genotypes had an increased risk of cervical cancer compared to those with a GG genotype (OR 3.79, 95% CI 2.4-5.7, < 0.001). Our findings demonstrated that a genetic variant in the TNF-α gene (rs1800629) was associated with increased level and risk of developing cervical cancer, suggesting its potential use as a genetic risk factor for cervical neoplasia.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Fator de Necrose Tumoral alfa/genética , Neoplasias do Colo do Útero/genética , Adulto , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia
6.
Int Q Community Health Educ ; 41(2): 159-161, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32220221

RESUMO

We presented a commentary on published studies on the "preparedness of non-hospital centers in dealing with life-threatening emergencies" to emphasize the importance of developing, validating, and piloting an instrument to assess the preparedness of these centers when life-threatening emergencies occur in their geographic area.


Assuntos
Emergências , Humanos
7.
J Cell Physiol ; 235(5): 4146-4152, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31663122

RESUMO

Hepatocellular carcinoma (HCC) is one of the common malignant human tumors with high morbidity worldwide. Aberrant activation of the oncogenic phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling is related to clinicopathological features of HCC. Emerging data revealed that microRNAs (miRNAs) have prominent implications for regulating cellular proliferation, differentiation, apoptosis, and metabolism through targeting the PI3K/AKT/mTOR signaling axis. The recognition of the crucial role of miRNAs in hepatocarcinogenesis represents a promising area to identify novel anticancer therapeutics for HCC. The present study summarizes the major findings about the regulatory role of miRNAs in the PI3K/AKT/mTOR pathway in the pathogenesis of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/genética , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Serina-Treonina Quinases TOR/genética
8.
J Cell Physiol ; 235(2): 1349-1357, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31313829

RESUMO

Here, we have investigated the therapeutic potency of EW-7197, a transforming growth factor-ß type I receptor kinase inhibitor, against postsurgical adhesion band formation. Our results showed that this pharmacological inhibitor prevented the frequency and the stability of adhesion bands in mice model. We have also shown that downregulation of proinflammatory cytokines, reduce submucosal edema, attenuation of proinflammatory cell infiltration, inhibition of oxidative stress, decrease in excessive collagen deposition, and suppression of profibrotic genes at the site of surgery are some of the mechanisms by which EW-7197 elicits its protective responses against adhesion band formation. These results clearly suggest that EW-7197 has novel therapeutic properties against postsurgical adhesion band formation with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in postsurgery patients.


Assuntos
Compostos de Anilina/farmacologia , Aderências Teciduais/prevenção & controle , Fator de Crescimento Transformador beta/antagonistas & inibidores , Triazóis/farmacologia , Células 3T3 , Animais , Apoptose/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/prevenção & controle , Camundongos , Estresse Oxidativo , Distribuição Aleatória
9.
J Cell Physiol ; 235(6): 5141-5145, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31721206

RESUMO

There is a growing body of data reporting the association of genetic alterations in chromosome 9P21 with the risk of developing cancer. In the current study, we studied the association of a genetic variant in CDKN2A/B, rs1333049, with the risk of developing breast cancer. A total of 339 participants with and without breast cancer entered to the study. Genotyping was done by the TaqMan real-time polymerase chain reaction (RT-PCR) method and gene expression analysis was ran by RT-PCR. Our data showed that the minor allele homozygote in the total population was 10%, whereas for heterozygote was 38%. The dominant genetic model demonstrated that individuals with breast cancer had advanced TNM classification. Moreover, the logistic regression revealed that individuals who had CC/CG genotypes might have an enhanced risk of developing breast cancer when compared to the holders of GG genotype (e.g., OR = 2.8; 95% CI,1.4-5.4; p = .001), after regulated for confounders; age and body mass index. Furthermore, our analysis showed that the CDKN2A/B gene was downregulated in patients (p < .001). We showed a meaningful relationship of CDKN2A/B with the risk of breast cancer, cancer, showing the importance of studies in great sample size and several centers for studying the value of the marker as a risk classification in the management of patients with breast cancer.


Assuntos
Neoplasias da Mama/genética , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Predisposição Genética para Doença , Adulto , Idoso , Alelos , Neoplasias da Mama/epidemiologia , Ciclina B/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
10.
BMC Health Serv Res ; 20(1): 1129, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287801

RESUMO

BACKGROUND: Management of Life-threatening Emergency (LTE) patients in urban and rural areas is an important challenge, which can affect pre-hospital mortality rate. Therefore, Non-hospital Health Center (NHHC) must be prepared to manage such emergency cases that may occur in the geographic area where these centers act. The aim of this study was to explore domains related to the preparedness of NHHCs to manage LTE patients through resorting to healthcare providers' and experts' perspectives. METHODS: A qualitative exploratory study was applied using Semi-Structured Interviews (SSIs) and Focus Group Discussions (FGDs). Prior to beginning data collection, the study and its objectives were explained to the participants and their informed consents were obtained. Then, SSIs and FGDs were conducted by two trained researchers using an interview guide, which was developed through literature review and consulting experts. In total, 12 SSIs were done with the providers at different NHHCs in Tabriz. In addition, 2 FGDs were conducted with the specialists in Emergency Medicine (EM) and Primary Health Care (PHC), and the executives of health centers, with over 5 years of work experience, and Emergency Medical Services (EMS) experts. Purposive sampling method was used in this study. All SSIs and FGDs were audio recorded and subsequently transcribed. Framework Analysis was employed to manually analyze the interview transcripts from all the SSIs and FGDs. RESULTS: The interview transcripts analysis resulted in the emergence of 3 themes and 11 sub-themes, categorized according to Donabedian's triple model. 5 sub-themes were related to input, including medical equipment and supplies, environmental infrastructures of the centers, emergency medicines, human resource, and protocols, guidelines and policies. 4 sub-themes were related to process, including providing clinical services, medicine storage capacity, maintenance of equipment, and management process. Finally, 2 sub-themes were related to outcome, which were patients' satisfaction with the quality of care and improved survival of LTE patients. CONCLUSIONS: The results of this study can provide a new perspective for health managers and policy makers on how to evaluate the preparedness of NHHCs in managing LTE patients. In addition, it will be used to develop instruments to measure the preparedness of these centers.


Assuntos
Serviços Médicos de Emergência , Serviço Hospitalar de Emergência , Emergências , Grupos Focais , Humanos , Pesquisa Qualitativa
11.
Drug Chem Toxicol ; 43(5): 514-521, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30714419

RESUMO

Ulcerative colitis is a chronic inflammatory bowel disease with high incidence and prevalence worldwide. To investigate the therapeutic potency of crocin, as a pharmacologically active component of saffron, in dextran sodium sulfate (DSS)-induced colitis mice model. Experimental colitis was induced by 7-day administration of DSS dissolved in water at a concentration of 1.5% (w/v). The animals were randomly divided into four groups (n»6 for each group). (1) Control group received regular drinking water for four weeks, (2) the second group of mice received regular drinking water for three weeks and then received DSS for one week, (3) and (4) the other two groups received 50-ppm or 200-ppm crocin for three weeks, respectively, and then treated with DSS for one week. Our results showed that Crocin attenuates colitis disease activity index including body weight loss, diarrhea, rectal bleeding, and colon shortening in crocin pre-tread mice. Comparison of histology of colon tissues between groups showed that crocin significantly decreases colon histopathological score, at least partially, by eliciting anti-inflammatory responses in DSS-induced colitis mice. These results clearly showed that crocin is a novel therapeutic agent with low toxicity as well as great clinical significance in treatment of colitis.


Assuntos
Carotenoides/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Animais , Carotenoides/efeitos adversos , Carotenoides/farmacologia , Colite Ulcerativa/induzido quimicamente , Colo/efeitos dos fármacos , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL
12.
Chin J Traumatol ; 23(5): 265-270, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32680704

RESUMO

PURPOSE: Various organizations and institutions are involved in road traffic injury (RTI) and crash registration such as police, forensic medicine organization, hospitals and emergency medical services. But there is a substantial uncertainty in interpreting the data, duplicated data collection and missing data in relation to RTI in most systems. This study aims to identify data sources for RTI surveillance in Iran and to explore traffic safety data source domains, data elements and detailed information by each data source. METHODS: This is a qualitative study which was conducted in 2017 in Iran. Data were collected employing semi-structured interviews with informants in road safety organizations in relation to traffic safety including Police, Ministry of Health and Medical Education as well as Forensic Medicine Organization and other authorities-in-charge. For completing the preliminary extraction information, the minimum data set was used and compared in each system. RESULTS: Eight different organizations relevant to road traffic safety were identified. The main domain of data provided by each one consists of Emergency Medical System form, Police KAM114 form, Ministry of Transport and Road Administration, Red Crescent Organization/Disaster Management Information System, Ministry of Health and Medical Education, Forensic Medicine Organization, Insurance Company and Ministry of Justice. Each system has its own database, based upon its scope and mainly at crash and post-crash status and little on pre-crash circumstance. CONCLUSION: All current registry systems are not surveillance systems for RTI prevention. Huge data have been collected in various registry systems in Iran, but most of the collected variables are duplicated in each system. On the other hand, some variables like alcohol and substance abuse, child seat belt, helmet use in relation to RTI prevention are missed in all systems. Accordingly, it is a critical need to integrate and establish a comprehensive surveillance system, with focus on the goal of each system and collection of minimum data in each organization, which currently is underway.


Assuntos
Acidentes de Trânsito/prevenção & controle , Acidentes de Trânsito/estatística & dados numéricos , Coleta de Dados/métodos , Gestão da Segurança/organização & administração , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/prevenção & controle , Humanos , Irã (Geográfico)/epidemiologia , Sistema de Registros , Segurança
13.
J Cell Physiol ; 234(8): 14123-14132, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30633353

RESUMO

The Wnt/ß-catenin pathway is one of the most common pathways dysregulated in breast cancer, and may, therefore, be a potential-therapeutic target. We have investigated the effects of PNU-74654 in breast cancer, as a Wnt/ß-catenin inhibitor, either alone or in combination with fluorouracil (5-FU). PNU-74654 suppressed cell growth at an IC 50 of 122 ± 0.4 µmol/L and synergistically enhanced the antiproliferative activity of gemcitabine by modulating the Wnt pathway. Using a 3D cell culture model, we found that the PNU-74654 caused tumor shrinkage. It reduced the migration of MCF-7 cells (by an 18% reduction in invasive behavior) after the treatment with PNU-74654 through perturbation of E-cadherin and MMP3/9. PNU-74654/5-FU combination enhanced the percentages of cells in S-phase and significantly increased apoptosis. Moreover, our data showed that this agent was able to inhibit the growth of tumor in a xenograft model, although this effect was more pronounced in the animals treated with PNU-74654 plus 5-FU. These data show the ability of PNU-74654 to specifically target Wnt pathway, interfere with cell proliferation, induce-apoptosis, reduce-migration, and synergistically interact with 5-FU, supporting further studies on this novel therapeutic-approach for breast cancer.


Assuntos
Apoptose/efeitos dos fármacos , Benzamidas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Trombina/genética , Animais , Benzamidas/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Feminino , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Xenoenxertos , Humanos , Células MCF-7 , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Camundongos , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/genética
14.
J Cell Physiol ; 234(7): 11654-11661, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30478959

RESUMO

EW-7197 is a transforming growth factor-ß type I receptor kinase inhibitor with potential anti-inflammatory and antifibrotic properties. Here, we investigate the potential therapeutic effects of EW-7197 in a murine model of ulcerative colitis. EW-7197 attenuated the colitis disease activity index by improving rectal bleeding, body weight, and degree of stool consistency. EW-7197 also reduced colorectal tissue damage and the colon histopathological score by reducing crypt loss, mucosal damage, and tissue inflammation. Moreover, EW-7197 appeared to ameliorate the inflammatory and fibrotic responses by reducing oxidative stress, reducing submucosal edema and inflammatory cell infiltration, downregulating proinflammatory and pro-fibrotic genes, and inhibiting excessive collagen deposition in inflamed and fibrotic ulcerative colitis tissues. These results suggest that EW-7197 has potentially useful therapeutic properties against colitis, with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in patients with colitis.


Assuntos
Compostos de Anilina/uso terapêutico , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colo/patologia , Inflamação/complicações , Inflamação/tratamento farmacológico , Triazóis/uso terapêutico , Compostos de Anilina/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Colo/efeitos dos fármacos , Fibrose , Inflamação/patologia , Masculino , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Triazóis/farmacologia
15.
J Cell Biochem ; 120(12): 19245-19253, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31512778

RESUMO

Colorectal cancer (CRC) is the leading cause of cancer death worldwide. Dysregulation of RAS/MAPK signaling axis is frequently found in CRC patients. The RAS/MAPK axis regulates cancer cell proliferation, apoptosis, inflammation, migration, and metastasis. Oncogenic or tumor-suppressor microRNAs (miRNAs) for RAS/MAPK signaling play a key role in the pathogenesis of CRC and are considered as novel potential biomarkers for diagnosis and prognosis of human malignancies. This review summarizes the current knowledge of mechanisms of action of RAS/MAPK miRNAs in the development and progression of CRC for a better understanding and hence a better management of this disease.


Assuntos
Neoplasias Colorretais/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , MicroRNAs/metabolismo , Proteínas ras/metabolismo , Animais , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Sistema de Sinalização das MAP Quinases/genética , MicroRNAs/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Proteínas ras/genética
16.
Biochem Cell Biol ; 97(2): 85-90, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30273495

RESUMO

Heat-shock protein-70 (HSP70) is critical to the folding, stability, and activity of several client proteins including many responsible for cancer cell proliferation, apoptosis, drug toxicity, and metastasis. Up-regulation of HSP70 is positively associated with increased tumorigenicity as well as poor survival in colon cancer patients, supporting the diagnostic, prognostic, and therapeutic potencies of HSP70 in colorectal cancer. The administration of specific pharmacological inhibitors or gene knock-down for HSP70 suppresses tumor progression and enhances tumor cell chemosensitivity. This review summarizes the different tumorigenic properties of HSP70 and the potential therapeutic potency of HSP70 inhibitors in terms of a novel strategy for colorectal cancer therapy, for a better understanding, and hence better management of this disease.


Assuntos
Apoptose , Proliferação de Células , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico HSP70/biossíntese , Proteínas de Neoplasias/biossíntese , Regulação para Cima , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Metástase Neoplásica
17.
IUBMB Life ; 71(12): 1929-1936, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31359579

RESUMO

Colorectal cancer (CRC) is among the leading causes of cancer-related mortality, despite extensive efforts in the identification of new treatment options. Hence, there is a need for the development of novel agents with therapeutic potential in treatment of CRC. Dorsomorphin has demonstrated antiproliferative activity against different malignancies. Here we have investigated the pharmaceutical potential of dorsomorphin in two-dimensional and three-dimensional cell-culture models of CRC. The antiproliferative, antimigratory, apoptotic activity and effect of this agent on cell cycle was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, wound healing assay, and flow cytometry, respectively, while the expression of genes involved in Wnt/Pi3K pathways was assessed at mRNA and/or proteins by reverse transcription polymerase chain reaction (RT-PCR) or western blot. Dorsomorphin inhibited CRC cell growth by modulating the cyclinD1, surviving and p-Akt. This agent was able to reduce the migratory behaviors of CRC cells, compared to control cells, through perturbation of E-cadherin. Also our data showed that dorsomorphin enhanced the percentage of the cells in sub-G1 and induced apoptosis in both late/early stages, as detected by annexin V. Also the regulatory effect of dorsomorphin on oxidant/antioxidant balance was assessed by cellular reactive oxygen species (ROS) generation. In particular, these data showed that dorsomorphin markedly increased the ROS production in CRC cells. Our finding demonstrated that dorsomorphin antagonizes cell growth and migration, through perturbation of Akt/mTOR/Wnt pathways in CRC, supporting further studies on the therapeutic potential of this novel anticancer agent in treatment of CRC.


Assuntos
Adenilato Quinase/antagonistas & inibidores , Neoplasias Colorretais/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Humanos , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos
18.
Andrologia ; 51(11): e13411, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31599008

RESUMO

The CatSper gene family is known to be solely expressed in sperm cells and is possibly associated with sperm motility and penetration through the zona pellucida. Despite its vital role in male fertility, factors regulating its expression are not widely known. The present study aimed at evaluating the effects of dioxin on CatSper2 gene and protein expression, testicular histopathology, sperm quality and biochemical parameters in a mice model. The experiments were performed on 32 Naval Medical Research Institute male mice (2-3 months). The animals were divided into four groups in a random manner: (a) control; (b) dioxin 1; (c) dioxin 2; and (d) dioxin 3. The treatment groups received 0.1, 0.5 and 1 µg/kg of dioxin intraperitoneally every day for 2 weeks. Administration of dioxin significantly downregulated the CatSper2 gene and protein expression. A greater reduction in gene and protein expression was found at higher doses of dioxin. At the same time, sperm parameters, especially sperm motility and count, decreased in mice exposed to dioxin. The results of testicular histopathology showed necrotic degeneration and epithelium thickness reduction in the dioxin groups in comparison with the controls. Besides, oxidative stress increased in seminiferous tubules.


Assuntos
Canais de Cálcio/metabolismo , Dioxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Canais de Cálcio/genética , Masculino , Camundongos , Distribuição Aleatória , Testículo/patologia
19.
Phytother Res ; 33(8): 2023-2033, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31215078

RESUMO

Unilateral ureteral obstruction (UUO) causes severe renal tubulointerstitial fibrosis. Because of many pharmacologic properties of thymoquinone (TQ), in this study, the effects of TQ against kidney fibrosis and dysfunction were investigated in rats with UUO. Forty male Wistar rats were divided into five groups: Sham operated, UUO, and the animals with UUO treated with losartan, captopril, or TQ. Collagen IV and transforming growth factor (TGF)-ß1 expressions, interstitial fibrosis, histological changes, and kidney function were assessed. UUO markedly increased renal expression of TGF-ß1 and collagen I and induced interstitial fibrosis (p < .001). Losartan, captopril, or TQ significantly downregulated the expression of these fibrotic markers and interstitial fibrosis (p < .01-p < .001). In UUO group, serum levels of urea and creatinine and protein excretion rate significantly increased, but glomerular filtration rate (GFR) and urine osmolarity showed a significant decrease (p < .001-p < .05). Administration of captopril and TQ caused no significant change in serum urea and protein excretion rate. Unlike losartan and captopril, TQ caused no significant alteration in GFR compared with Day 1. Losartan caused significant increases in serum urea and creatinine but significant decrease in urine osmolarity. TQ could be regarded as a potent therapeutic agent for treatment of UUO-induced kidney fibrosis and dysfunction.


Assuntos
Benzoquinonas , Fibrose , Nefropatias , Túbulos Renais , Rim , Obstrução Ureteral , Animais , Masculino , Ratos , Benzoquinonas/farmacologia , Benzoquinonas/uso terapêutico , Fibrose/tratamento farmacológico , Rim/efeitos dos fármacos , Rim/patologia , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Testes de Função Renal/métodos , Túbulos Renais/efeitos dos fármacos , Ratos Wistar , Obstrução Ureteral/tratamento farmacológico
20.
J Clin Nurs ; 28(17-18): 3252-3261, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31013377

RESUMO

AIMS AND OBJECTIVES: To investigate the impact of domestic violence-related factors on suicide attempt in married women. BACKGROUND: Suicide is a global public health concern that poses significant burden on individuals, families and communities. There is limited research on factors predicting suicide attempt in women. DESIGN: A retrospective case-control design was adopted. METHODS: Using a convenience sampling method, 610 participants, admitted to a teaching referral hospital in Northwest of Iran, were recruited to the study and assigned to case or control groups based on whether or not they had attempted suicide. The participants in two groups were matched in the terms of important demographic characteristics. Domestic violence-related factors were considered as independent variables and suicide attempt as dependent variable. Descriptive statistics, and simple and multivariate logistic regression analysis were used to analyse the data. Odds ratios (OR) of domestic violence-related factors were compared between the groups. We used STROBE checklist as an EQUATOR in this study. RESULTS: The mean age of participants in the case and control groups was 28.4 and 29.45 years, respectively. The infidelity was the strongest predictor of suicide attempt in women (OR 44.57, 95%CI 6.08-326. 63, p < 0.001), followed by being threatened to physical assault by husband (OR 37.01, 95%CI 11.54-118.67, p < 0.001), jealousy of husband (OR 23.46, 95%CI 11.63-47.30, p < 0.001), and previous attempts to divorce (OR 16.55, 95%CI 5.91-46.31, p < 0.001). Suicide attempt was significantly lower in women who reported a sense of peace in life or lived with their mother or father-in-law (p < 0.001). CONCLUSIONS: To reduce the risk of suicide in women, violence against women should be condemned and appropriate prevention measures be taken by health professionals. RELEVANCE TO CLINICAL PRACTICE: Recognising risk, assessment and referral of victims of domestic violence should be an integral part of healthcare systems.


Assuntos
Violência Doméstica/psicologia , Tentativa de Suicídio/estatística & dados numéricos , Adulto , Estudos de Casos e Controles , Violência Doméstica/estatística & dados numéricos , Feminino , Humanos , Irã (Geográfico) , Masculino , Casamento/psicologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Tentativa de Suicídio/psicologia
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