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Akkermansia muciniphila, a frequent colonizer in the gut mucous layer of individuals, has constantly been recognized as a promising candidate for the next generation of probiotics due to its biological advantages from in vitro and in vivo investigations. This manuscript comprehensively reviewed the features of A. muciniphila in terms of its function in host physiology and frequently utilized nutrition using the published peer-reviewed articles, which should present valuable and critical information to scientists, engineers, and even the general population. A. muciniphila is an important bacterium that shows host physiology. However, its physiological advantages in several clinical settings also have excellent potential to become a probiotic. Consequently, it can be stated that there is a coherent and direct relation between the biological activities of the gut microbiota, intestinal dysbiosis/eubiosis, and the population of A. muciniphila in the gut milieu, which is influenced by various genetical and nutritional factors. Current regulatory barriers, the need for large-scale clinical trials, and the feasibility of production must be removed before A muciniphila can be extensively used as a next-generation probiotic.
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Microbioma Gastrointestinal , Microbiota , Humanos , Verrucomicrobia , AkkermansiaRESUMO
BACKGROUND: Road traffic crashes and associated injuries and mortalities are one of the big public health challenges, especially in low/middle-income countries. Road safety lead agency (RSLA) is a vital factor in the sustainable prevention and promotes road safety. In the recent decades, various policy interventions have been conducted for road safety in Iran. This study aimed at exploring the challenges of RSLA from the perspectives of stakeholders at various levels. METHODS: A qualitative study was conducted. In-depth interviews and document reviews were used for data collection. To conduct interviews, different stakeholders at various levels such as policy-makers, senior national authorities, researchers and faculty members were selected. Data collection was conducted between November 2019 and June 2020. Thematic content analysis approach was used for data analysis. RESULTS: The experts' perspectives were analysed and then categorised under five main themes including the role and position of the lead agency, the role and duties of the actors and players, translating policy into practice, intrasectoral and intersectoral cooperation and coordination and evidence production and application and a total of 22 subthemes were identified. The current structure of the RSLA is one of the main challenges emphasised by the research participants. CONCLUSION: To achieve significant improvements in road safety at the national level, a strong management system and leadership body is a critical issue. Organisational reform to establish an effective unique lead agency is proposed to cope with RSLA challenges.
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Acidentes de Trânsito , Saúde Pública , Humanos , Acidentes de Trânsito/prevenção & controle , Irã (Geográfico)/epidemiologia , Pesquisa Qualitativa , Políticas , SegurançaRESUMO
INTRODUCTION: There are limited prospective studies assessing the post-diagnosis nutritional status of patients with gastric cancer (GC). This study aimed to assess the association between nutritional status and three-year survival of patients with GC. METHODS: In this prospective study, we included all histologically confirmed GC patients admitted to the Imam Reza Hospital in Tabriz, Iran from September 2016 to October 2019. The nutritional status of patients was assessed using the Patient-Generated Subjective Global Assessment (PG-SGA) form. All patients were followed up every six months for three years. The overall survival (OS) was calculated from the diagnosis date to the date of death or last visit. RESULTS: In this study, 302 patients (mean age: 67.39 ± 12.04 years) with GC were included. The median OS was 11.00 mo, (95% CI: 80.03, 13.96). Only 28.4% of patients were well-nourished, and survived significantly longer than malnourished patients (20.5 vs. 8 mo, P = 0.01). The mortality hazard rate in patients with moderate and severe malnutrition was 2.04 times higher than well-nourished patients. CONCLUSION: According to our results, the nutrition status of GC patients at the time of diagnosis was independently associated with their survival rate.
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Desnutrição , Neoplasias Gástricas , Idoso , Humanos , Desnutrição/diagnóstico , Pessoa de Meia-Idade , Avaliação Nutricional , Estado Nutricional , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/complicações , Redução de PesoRESUMO
Celiac disease (CD) as a chronic gluten-sensitive intestinal condition, mainly affects genetically susceptible hosts. The primary determinants of CD have been identified as environmental and genetic variables. The development of CD is significantly influenced by environmental factors, including the gut microbiome. Therefore, gut microbiome re-programming-based therapies using probiotics, prebiotics, postbiotics, gluten-free diet, and fecal microbiota transplantation have shown promising results in the modification of the gut microbiome. Due to the importance and paucity of information regarding the CD pathophysiology, in this review, we have covered the association between CD development and gut microbiota, the effects of infectious agents, particularly the recent Covid-19 infection in CD patients, and the efficacy of potential therapeutic approaches in the CD have been discussed. Hence, scientific literature indicates that the diverse biological functions of the gut microbiota against immunomodulatory responses have made microbiome-based therapy an alternative therapeutic paradigm to ameliorate the symptoms of CD and quality of life. However, the exact potential of microbiota-based techniques that aims to quantitatively and qualitatively alter the gut microbiota to be used in the treatment and ameliorate the symptoms of CD will be determined with further research in the future.
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The outbreak of coronavirus disease 2019 (COVID-19) has posed a serious threat to public health. There is an urgent need for discovery methods for the prevention and treatment of COVID-19 infection. Understanding immunogenicity together with immune responses are expected to provide further information about this virus. We hope that this narrative review article may create new insights for researchers to take great strides toward designing vaccines and novel therapies in the near future. The functional properties of the immune system in COVID-19 infection is not exactly clarified yet. This is compounded by the many gaps in our understanding of the SARS-CoV-2 immunogenicity properties. Possible immune responses according to current literature are discussed as the first line of defense and acquired immunity. Here, we focus on proposed modern preventive immunotherapy methods in COVID-19 infection.
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COVID-19 , Imunidade Adaptativa , Vacinas contra COVID-19 , Humanos , SARS-CoV-2RESUMO
INTRODUCTION: In the present study, we evaluated the association of nutritional status and quality of life (QoL) in patients with gastric cancer (GC). MATERIALS AND METHODS: In the present cross-sectional study, the study sample consisted of 299 patients with GC. The assessment of the nutritional status and QoL of patients was done after diagnosis and before initiation of any treatment. The nutritional status was assessed using Patient-Generated Subjective Global Assessment (PG-SGA). The 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTCQLQ-C30) was used for the assessment of QoL score. Statistical significance was reported at the p < 0.05 level. RESULTS: The mean age of participants was 67.39 ± 12.04 years and 65.5% of them were males. According to the PG-SGA, 28.5% of patients were in good nutritional condition. The patients with better nutrition status had significantly better global and functional categories scores (p < 0.001) except social functioning. Moreover, they had significantly lower scores in symptoms severity except for dyspnea, constipation, and diarrhea. The result of regression analysis indicated that after adjusting to confounders, nutrition status was significantly associated with global score and functional categories score except for social and emotional functioning scores. Moreover, in terms of symptom categories, there was a significant association between PG-SGA score and all symptoms except diarrhea and dyspnea. CONCLUSION: The results of the present study showed the significant association between nutrition status and functioning and symptom categories of QoL in patients with GC.
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Qualidade de Vida , Neoplasias Gástricas , Idoso , Estudos Transversais , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Estado Nutricional , Neoplasias Gástricas/complicaçõesRESUMO
BACKGROUND: Cohort studies play essential roles in assessing causality, appropriate interventions. The study, Post-crash Prospective Epidemiological Research Studies in IrAN Traffic Safety and Health Cohort, aims to investigate the common health consequences of road traffic injuries (RTIs) postcrash through multiple follow-ups. METHODS: This protocol study was designed to analyse human, vehicle and environmental factors as exposures relating to postcrash outcomes (injury, disability, death, property damage, quality of life, etc). Population sources include registered injured people and followed up healthy people in precrash cohort experienced RTIs. It includes four first-year follow-ups, 1 month (phone-based), 3 months (in-person, video/phone call), 6 and 12 months (phone-based) after crash. Then, 24-month and 36-month follow-ups will be conducted triennially. Various questionnaires such as Post-traumatic Stress Disorder Questionnaire, Patient Health Questionnaire, WHO Disability Assessment Schedules, Cost-related Information, etc are completed. Counselling with a psychiatrist and a medical visit by a practitioner are provided accompanied by extra tools (simulator-based driving assessment, and psychophysiological tests). Through preliminary recruitment plan, 5807, 2905, 2247 and 1051 subjects have been enrolled, respectively at the baseline, first, second and third follow-ups by now. At baseline, cars and motorcycles accounted for over 30% and 25% of RTIs. At first follow-up, 27% of participants were pedestrians engaged mostly in car crashes. Around a fourth of injuries were single injuries. Car occupants were injured in 40% of collisions. DISCUSSION: The study provides an opportunity to investigate physical-psychosocial outcomes of RTIs, predictors and patterns at follow-up phases postinjury through longitudinal assessments, to provide advocates for evidence-based safety national policy-making.
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Pedestres , Ferimentos e Lesões , Acidentes de Trânsito , Humanos , Motocicletas , Estudos Prospectivos , Qualidade de Vida , Ferimentos e Lesões/epidemiologiaRESUMO
BACKGROUND: The first large serosurvey in Iran found a SARS-CoV-2 antibody seroprevalence of 17.1% among the general population in the first wave of the epidemic by April, 2020. The purpose of the current study was to assess the seroprevalence of COVID-19 infection among Iranian general population after the third wave of the disease. METHODS: This population-based cross-sectional study was conducted on 7411 individuals aged ≥10 years old in 16 cities across 15 provinces in Iran between January and March, 2021. We randomly sampled individuals registered in the Iranian electronic health record system based on their national identification numbers and invited them by telephone to a healthcare center for data collection. Presence of SARS-CoV-2-specific IgG and IgM antibodies was assessed using the SARS-CoV-2 ELISA kits. The participants were also asked about their recent COVID-19-related symptoms, including cough, fever, chills, sore throat, headache, dyspnea, diarrhea, anosmia, conjunctivitis, weakness, myalgia, arthralgia, altered level of consciousness, and chest pain. The seroprevalence was estimated after adjustment for population weighting and test performance. RESULTS: The overall population-weighted seroprevalence adjusted for test performance was 34.2% (95% CI 31.0-37.3), with an estimated 7,667,874 (95% CI 6,950,412-8,362,915) infected individuals from the 16 cities. The seroprevalence varied between the cities, from the highest estimate in Tabriz (39.2% [95% CI 33.0-45.5]) to the lowest estimate in Kerman (16.0% [95% CI 10.7-21.4]). In the 16 cities studied, 50.9% of the seropositive individuals did not report a history of symptoms suggestive of COVID-19, implying an estimation of 3,902,948 (95% CI 3,537,760-4,256,724) asymptomatic infected individuals. CONCLUSIONS: Nearly one in three individuals were exposed to SARS-CoV-2 in the studied cities by March 2021. The seroprevalence increased about two-fold between April, 2020, and March, 2021.
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COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , COVID-19/epidemiologia , Criança , Estudos Transversais , Humanos , Imunoglobulina G , Irã (Geográfico)/epidemiologia , Estudos SoroepidemiológicosRESUMO
INTRODUCTION: Vitamin A is one of the vitamins that is suggested as adjuvant therapy in viral infections due to its immune enhancing role. In the present clinical trial, we intended to assess the effect of vitamin A supplementation on Coronavirus disease-2019 (COVID-19) in hospitalized patients. METHODS: The present pilot randomized controlled clinical trial was conducted on 30 hospitalized patients with COVID-19. Patients in the intervention group received 50000 IU/day intramuscular vitamin A for a maximum of two weeks. Patients in the control group continued their common treatment protocols. All participants were followed up until discharge from the hospital or death. The primary outcome of the study was time to achieve clinical response based on the six classes of an ordinal scale. Time to clinical response was calculated based on the days needed to improve two scores on the scale or patient's discharge. RESULTS: The time to clinical response was not significantly different between the two groups (7.23 ± 2.14 vs. 6.75 ± 1.85 days, respectively, p = 0.48). There was no significant difference between the groups regarding clinical response (hazard ratio: 1.76 [95% CI: 0.73, 4.26]). There were no significant differences between groups regarding the need for mechanical ventilation, duration of hospitalization, or death in the hospital. CONCLUSION: The results of this pilot clinical trial showed no benefit of vitamin A compared with the common treatment on outcome severity in hospitalized patients with COVID-19. Although the results are negative, there is still a great need for future clinical studies to provide a higher level of evidence.
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INTRODUCTION: This study aimed to collect and summarize test data and conduct a meta-analysis, with respect to the Multitarget Stool DNA test sensitivity and specificity, compared to colonoscopy. MATERIAL AND METHODS: All manuscripts were screened for eligibility according to inclusion criteria. Participants were a normal population at an average risk of developing CRC. Intervention was Stool based and DNA panel tests compared with colonoscopy, and outcome was detection of CRC and any pre-cancerous lesions. Inter-study and inconsistency (using the I-squared test) were assessed. RESULTS: Meta-analyses of the Mt-sDNA test showed a combined sensitivity of 89%, 51%, and 76% for the detection of CRC, advanced adenoma (AA), and combined CRC and AA, respectively. The overall specificity was 91%, 89%, and 90% for the detection of CRC, AA, and combined CRC and AA, respectively. CONCLUSION: Mt-sDNA had significantly acceptable diagnostic accuracy for CRC and AA diagnosis, but still has lower sensitivity and specificity than colonoscopy.
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Adenoma , Neoplasias Colorretais , Humanos , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Sangue Oculto , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Adenoma/diagnóstico , Adenoma/genética , DNA/análiseRESUMO
T regulatory cells (Tregs) and related-cytokines are effectively engaged in the process of tumor immune escape and functionally inhibit immune response against the tumor. This study aimed to investigate the association of Foxp3 gene single nucleotide polymorphism (SNP) (rs3761548) with serum IL-35, IL-10, and TGF-ß levels in gastric adenocarcinoma (GA) patients. The blood samples were obtained from 150 GA patients and 166 control subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was done to genotyping of Foxp3 gene polymorphism (rs3761548). The serum cytokines levels were measured using the ELISA method. According to genotyping, the AA, and AC genotypes and A allele demonstrated significantly greater risk of GA. Considering the Lauren classification, our results revealed a greater risk of GA progression in patients with AC + AA genotype compared to CC genotype. Moreover, significantly increased levels of IL-10, IL-35, and TGF-ß were observed in GA patients compared to controls and also in diffuse-type compared to the intestinal type of GA patients. The IL-35, IL-10 concentrations in GA patients displayed significant differences between the participants with CC, AC and AA genotypes. Further analysis indicated the prognostic role of serum IL-35, IL-10, and TGF-ß levels in GA patients. Our results confirmed that the Foxp3 polymorphism (rs3761548) could influence the predisposition to GA and the serum IL-10, IL-35, and TGF-ß levels. Thus, this polymorphism might be involved in the GA progression through influencing Tregs function and the secretion of immunomodulatory cytokines.
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Adenocarcinoma/sangue , Fatores de Transcrição Forkhead/genética , Interleucina-10/sangue , Interleucinas/sangue , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/sangue , Fator de Crescimento Transformador beta1/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Citocinas/metabolismo , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Risco , Linfócitos T Reguladores/metabolismoRESUMO
BACKGROUND: There are limited number of studies with controversial findings regarding the association between anemia at admission and coronavirus disease 2019 (COVID-19) outcomes. Therefore, in this research, we aimed to investigate the prospective association between anemia and COVID-19 outcomes in hospitalized patients in Iran. METHODS: In this prospective study, the data of 1274 consecutive patients hospitalized due to COVID-19 were statistically analyzed. All biomarkers, including hemoglobin and high-sensitivity C-reactive protein (hs-CRP) levels were measured using standard methods. Anemia was defined as a hemoglobin (Hb) concentration of less than 13 g/dL and 12 g/dL in males and females, respectively. Assessing the association between anemia and COVID-19 survival in hospitalized patients was our primary endpoint. RESULTS: The mean age of the participants was 64.43 ± 17.16 years, out of whom 615 (48.27%) were anemic subjects. Patients with anemia were significantly older (P = 0.02) and had a higher frequency of cardiovascular diseases, hypertension, kidney disease, diabetes, and cancer (P < 0.05). The frequency of death (anemic: 23.9% vs. nonanemic: 13.8%), ICU admission (anemic: 27.8% vs. nonanemic:14.71%), and ventilator requirement (anemic: 35.93% vs. nonanemic: 20.63%) were significantly higher in anemic patients than in nonanemic patients (P < 0.001). According to the results of regression analysis, after adjusting for significant covariate in the univariable model, anemia was independently associated with mortality (OR: 1.68, 95% CI: 1.10, 2.57, P = 0.01), ventilator requirement (OR: 1.74, 95% CI: 1.19, 2.54, P = 0.004), and the risk of ICU admission (OR: 2.06, 95% CI: 1.46, 2.90, P < 0.001). CONCLUSION: The prevalence of anemia in hospitalized patients with COVID-19 was high and was associated with poor outcomes of COVID-19.
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Anemia/complicações , COVID-19/complicações , COVID-19/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/epidemiologia , Feminino , Hemoglobinas/análise , Hospitalização , Humanos , Unidades de Terapia Intensiva , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Respiração Artificial , Índice de Gravidade de Doença , Taxa de SobrevidaRESUMO
Systemic administration of chemotherapeutics by nanocarriers (NCs) functionalized with targeting agents provides a localized accumulation of drugs in the target tissues and cells. Advanced nanoscaled medicaments can enter into the tumor microenvironment (TME) and overcome the uniquely dysregulated biological settings of TME, including highly pressurized tumor interstitial fluid in an acidic milieu. Such multimodal nanomedicines seem to be one of the most effective treatment modalities against solid tumors such as colorectal cancer (CRC). To progress and invade, cancer cells overexpress various oncogenes and molecular markers such as epidermal growth factor receptors (EGFRs), which can be exploited for targeted delivery of nanoscaled drug delivery systems (DDSs). In fact, to develop effective personalized multimodal nanomedicines, the type of solid tumor and status of the disease in each patient should be taken into consideration. While the development of such multimodal-targeted nanomedicines is largely dependent on the expression level of oncomarkers, the type of NCs and homing/imaging agents play key roles in terms of their efficient applications. In this review, we provide deep insights into the development of EGFR-targeting nanomedicines and discuss various types of nanoscale DDSs (e.g., organic and inorganic nanoparticles) for targeting of the EGFR-positive solid tumors such as CRC.
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Antineoplásicos Imunológicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Receptores ErbB/antagonistas & inibidores , Nanopartículas/química , Animais , Antineoplásicos Imunológicos/uso terapêutico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Nanomedicina/métodosRESUMO
BACKGROUND: The current recommendation for treating hepatitis C virus (HCV) in HIV patients includes the combination of sofosbuvir (SOF) and daclatasvir (DCV). DCV should be used at different doses to compensate for interactions with antiretroviral therapy (ART). Up to three pills a day might be required which will significantly add to the pill burden of these patients. In this study, we have used a single-tablet approach to treating HCV-HIV coinfection. METHODS: Patients coinfected with HIV and HCV were prospectively enrolled from 10 centers throughout the country. Patients received a single once-daily fixed dose combination (FDC) pill containing 400 mg SOF and 30, 60 or 90 mg DCV depending on the type of ART they were receiving for 12 or 24 weeks. (ClinicalTrials.gov ID: NCT03369327). RESULTS: Two hundred thirty-three patients were enrolled from 10 centers. Twenty-three patients were lost to follow-up and two patients died from causes unrelated to treatment. Two hundred eight patients completed the treatment course of which 201 achieved SVR (96.6%). CONCLUSION: Single-tablet combination of DCV and SOF is an effective and safe treatment for patients coinfected with HIV and HCV. The combination works well in patients on ART in which dose adjustment is required. Patients with cirrhosis, previous treatment failure and various genotypes respond identically. The expenses of genotyping can be saved.
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Coinfecção , Infecções por HIV , Hepatite C Crônica , Antivirais/uso terapêutico , Carbamatos , Coinfecção/tratamento farmacológico , Quimioterapia Combinada , Genótipo , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Imidazóis , Pirrolidinas , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resultado do Tratamento , Valina/análogos & derivadosRESUMO
Colorectal cancer (CRC) is still considered as the third most frequent cancer in the world. Microsatellite instability (MSI), inflammation, and microRNAs have been demonstrated as the main contributing factors in CRC. Subtype 1 CRC is defined by NK cells infiltration, induction of Th1 lymphocyte and cytotoxic T cell responses as well as upregulation of immune checkpoint proteins including programmed cell death-1 (PD-1). Based on the diverse features of CRC, such as the stage and localization of the tumor, several treatment approaches are available. However, the efficiency of these treatments may be decreased due to the development of diverse resistance mechanisms. It has been proven that monoclonal antibodies (mAbs) can increase the effectiveness of CRC treatments. Nowadays, several mAbs including nivolumab and pembrolizumab have been approved for the treatment of CRC. Immune checkpoint receptors including PD-1 can be inhibited by these antibodies. Combination therapy gives an opportunity for advanced treatment for CRC patients. In this review, an update has been provided on the molecular mechanisms involved in MSI colorectal cancer immune microenvironment by focusing on PD-ligand 1 (PD-L1) and treatment of patients with advanced immunotherapy, which were examined in the different clinical trial phases. Considering induced expression of PD-L1 by conventional chemotherapeutics, we have summarized the role of PD-L1 in CRC, the chemotherapy effects on the PD-1/PD-L1 axis and novel combined approaches to enhance immunotherapy of CRC by focusing on PD-L1.
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Antígeno B7-H1/genética , Neoplasias Colorretais/terapia , Instabilidade de Microssatélites/efeitos dos fármacos , Receptor de Morte Celular Programada 1/genética , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Microambiente Tumoral/efeitos dos fármacosRESUMO
BACKGROUND AND AIM: Many of the treatment regimens available for hepatitis C include sofosbuvir. Unfortunately, sofosbuvir has not been recommended for use in patients with severe renal impairment leaving these group of patients with very few options. Nevertheless, there are many reports in which these patients have been treated with sofosbuvir-containing regiments without important adverse events. This study aims at determining the safety and effectiveness of a sofosbuvir-based treatment in patients with severe renal impairment, including those on hemodialysis. METHOD: We enrolled subjects with hepatitis C and estimated glomerular filtration rate under ml/min/1.73m2 from 13 centers in Iran. Patients were treated for 12 weeks with a single daily pill containing 400-mg sofosbuvir and 60-mg daclatasvir. Patients with cirrhosis were treated for 24 weeks. Response to treatment was evaluated 12 weeks after end of treatment (sustained viral response [SVR]). ClinicalTrials.gov identifier: NCT03063879. RESULTS: A total of 103 patients were enrolled from 13 centers. Seventy-five patients were on hemodialysis. Thirty-nine had cirrhosis and eight were decompensated. Fifty-three were Genotype 1, and 27 Genotype 3. Twenty-seven patients had history of previous failed interferon-based treatment. Three patients died in which cause of death was not related to treatment. Six patients were lost to follow-up. The remaining 94 patients all achieved SVR. No adverse events leading to discontinuation of medicine was observed. CONCLUSIONS: The combination of sofosbuvir and daclatasvir is an effective and safe treatment for patients infected with all genotypes of hepatitis C who have severe renal impairment, including patients on hemodialysis.
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Antivirais/administração & dosagem , Hepatite C/tratamento farmacológico , Imidazóis/administração & dosagem , Insuficiência Renal/complicações , Sofosbuvir/administração & dosagem , Carbamatos , Quimioterapia Combinada , Feminino , Hepatite C/complicações , Hepatite C/virologia , Humanos , Cirrose Hepática/complicações , Masculino , Pirrolidinas , Diálise Renal , Segurança , Índice de Gravidade de Doença , Sofosbuvir/efeitos adversos , Resposta Viral Sustentada , Resultado do Tratamento , Valina/análogos & derivadosRESUMO
Hepatocellular carcinoma (HCC) is one of the lethal and difficult-to-cure cancers worldwide. Owing to the late diagnosis and drug resistance of malignant hepatocytes, treatment of this cancer by conventional chemotherapy agents is challenging, and researchers are seeking new alternative treatment options to overcome therapy resistance in this neoplasm. RNA interference (RNAi) is a potent and specific approach in targeting gene expression and has emerged as a novel therapeutic tool for many diseases, including cancers. Small interfering RNA (siRNA) is a type of RNAi that is produced intracellularly from exogenous synthetic oligonucleotides and can selectively knock down target gene expression in a sequence-specific manner. Various factors play roles in the initiation and progression of HCC and provide multiple candidate targets for siRNA intervention. In addition, due to the liver's unique architecture and availability of some hepatic siRNA delivery methods, this organ has received much more attention as a target tissue for such oligonucleotide action. Recent advances in designing nanoparticle systems for the in vivo delivery of siRNAs have markedly enhanced the potency of siRNA-mediated gene silencing under clinical development for HCC therapy. The utility of siRNAs as anti-HCC agents is the subject of the current review. siRNA-based gene therapies could be one of the main feasible approaches for HCC therapy in the future.
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Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , RNA Interferente Pequeno/genética , Terapêutica com RNAi , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Resultado do TratamentoRESUMO
BACKGROUND: The most recent results of Global Cancer Statistics indicated that gastrointestinal cancers, including gastric, colorectal, esophageal, and liver cancers, are among the most commonly diagnosed cancers worldwide. Previous reports from cancer registries in East Azerbaijan have shown that there is a high incidence of gastrointestinal cancer in this region, so we performed a trend analysis to determine the pattern of change over the last decade. METHODS: In total, 12 years of cancer registry data were collected from different sources in East Azerbaijan, and a data quality check was performed to ensure clean data. Using the 2000 World Health Organization standard population, we then generated age-standardized incidence rates (ASRs) for different cancers, and for each year from 1383 to 1394 of the Persian calendar (i.e., 19 March 2004 to 20 March 2015). Annual percent changes (APCs) and Average annual percent changes (AAPCs) in the ASRs for esophageal, gastric, small intestine, colorectal, anal, liver, gallbladder, and pancreatic cancers were calculated using Joinpoint Software (Version 4.5.0.1, June 2017). RESULTS: An increase in most types of cancer was observed during the study period. The ASR for colorectal cancer increased from 2.9 to 13.6 per 100,000 women (APC, 9.7%) and from 2.2 to 17.8 per 100,000 men (APC, 10.2%). The ASR for gastric cancer showed a slight increasing trend from 10.5 to 13.5 per 100,000 women (APC, 1.3%) and from 3.1 to 29.9 per 100,000 men (APC, 3.2%). However, trend analysis showed a decreasing pattern for the ASR of esophageal cancer in both genders (APC,- 3%), with APCs of - 1.1% in females and - 0.4% in males. CONCLUSIONS: The latest results of the East Azerbaijan Population-Based Cancer Registry indicate that gastrointestinal cancers remain common, with significant increasing trends in their ASRs. Improved screening and early detection are needed in this region.
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Neoplasias Gastrointestinais/epidemiologia , Azerbaijão/epidemiologia , Feminino , Neoplasias Gastrointestinais/diagnóstico , Saúde Global , Humanos , Incidência , Masculino , Vigilância da População , Sistema de RegistrosRESUMO
OBJECTIVE: Gastric cancer is the third-leading cause of cancer-related mortality and the fifth most common cancer globally. Polyunsaturated fatty acids (PUFAs) are considered as functional ingredients that improve the efficacy of chemotherapeutic drugs. The aim of this study is to investigate the effect of PUFAs administration on matrix metalloproteinases (MMPs). METHODS: This study was designed as a randomized, double-blind trial. Thirty-four newly diagnosed patients with gastric cancer were randomly divided into two groups: control group (n = 17) and case group (n =17). Both groups received the same dose (75 mg/m2) of cisplatin. Control group received cisplatin plus placebo and the case group received cisplatin plus PUFAs [3600 mg/day, for three courses (each course included 3 weeks)]. The mRNA and protein expression of MMPs determined by real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), respectively. RESULTS: The relative gene expression of MMP-1 and MMP-9 was significantly lower in case group than control. The protein expression of MMP-1 and MMP-9 was significantly lower in case group than control. CONCLUSION: According to the results of this study, PUFAs reduced the expression of MMPs in gastric cancer cells. It seems that PUFAs may have an inhibitory effect on invasion and metastasis of gastric cancer cells.
Assuntos
Adenocarcinoma/tratamento farmacológico , Cisplatino/uso terapêutico , Ácidos Graxos Insaturados/administração & dosagem , Expressão Gênica/efeitos dos fármacos , Metaloproteinases da Matriz/genética , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/enzimologia , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Metaloproteinase 1 da Matriz/análise , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/genética , Pessoa de Meia-Idade , Invasividade Neoplásica/prevenção & controle , Metástase Neoplásica/prevenção & controle , RNA Mensageiro/análise , Neoplasias Gástricas/enzimologiaRESUMO
A novel and sensitive chemiluminescence (CL) procedure based on the synergetic catalytic effects of gold nanoclusters (Au NCs) and graphene quantum dots (GQDs) was developed for the reliable measurement of cimetidine (CM). The initial experiments showed that the KMnO4 -based oxidation of alkaline rhodamine B (RhoB) generated a very weak CL emission, which was intensively enhanced in the simultaneous presence of Au NCs and GQDs. CL intermediates can be adsorbed and gathered on the surface of Au NCs, becoming more stable. GQDs participate in the energy transferring processes and facilitate them. These improving effects were simultaneously obtained by adding both Au NCs and GQDs into the RhoB-KMnO4 reaction. Consequently, the increasing effect of the Au NCs/GQDs mixture was more than that of pure Au NCs or GQDs, and a new nano-assisted powerful CL system was achieved. Furthermore, a marked quenching in the emission of the introduced CL system was observed in the presence of CM, so the system was examined to design a sensitive sensor for CM. After optimization of influencing parameters, the linear lessening in CL emission intensity of KMnO4 -RhoB-Au NCs/GQDs was verified for CM concentrations in the range 0.8-200 ng ml-1 . The limit of detection (3Sb /m) was 0.3 ng ml-1 . Despite being a simple CL method, good sensitivity was obtained for CM detection with reliable results for CM determination in human urine samples.