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The pathogenesis of SARS-CoV-2 infection, causative pathogen of the known COVID-19 pandemic is not well clarified. In this regard oxidative stress is one of the topics that need to be investigated. Therefore, the present research was performed to explore the relationship between the oxidant/antioxidant system and COVID-19 exacerbation. Sera were collected from 120 patients with COVID-19 infection and 60 healthy volunteers as the control group. The patient group consisted of 60 cases with mild disease and 60 severely ill patients. Serum levels of total antioxidant capacity (TAC) and nitric oxide (NO) as well as serum activities of the two main antioxidant defense enzymes, superoxide dismutase (SOD) and catalase (CAT), were measured. TAC levels were considerably lower in patients compared with healthy individuals (p < 0.05) and also between patients with mild and severe diseases (p < 0.05). A rather decreasing trend was also found in NO concentration as well as SOD and CAT activity, though, the observed differences were not statistically significant (p > 0.05). These findings suggest that COVID-19 patients may be susceptible to depleted total antioxidant capacity. Moreover, showing such variations in blood samples of infected individuals could be considered as a predictive marker of COVID-19 severity.
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Antioxidantes/metabolismo , Biomarcadores/sangue , COVID-19/sangue , Adulto , COVID-19/fisiopatologia , Estudos de Casos e Controles , Catalase/sangue , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Estresse Oxidativo/fisiologia , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Superóxido Dismutase/sangueRESUMO
BACKGROUND: The JC polyomavirus has been blamed to contribute in colorectal cancer (CRC), however, the topic is still controversial. Varying detection rate of JCPyV genome has been reported mainly due to technical reasons. Here, we provide summative data on the topic, with emphasize on technical issues. METHODS: Formalin-fixed paraffin-embedded tissue samples from 50 patients with CRC, consisting of tumoral and non-cancerous marginal tissue (totally 100 samples) were included in the study. After DNA extraction, specific JCPyV T-Ag sequences were targeted using Real-time PCR. To unwind the supercoiled JCPyV genome, pretreatment with topoisomerase I, was applied. Immunohistochemical (IHC) staining was performed using an anti-T-Ag monoclonal antibody. RESULTS: In the first attempts, no samples were found to be positive in Real-time PCR assays. However, JCPyV sequences were found in 60% of CRC tissues and 38% of non-cancerous colorectal mucosa after application of pre-treatment step with topoisomerase I enzyme (P = 0.028). T-Ag protein was found in the nuclear compartment of the stained cells in IHC assays. CONCLUSIONS: The presence of JCPyV in CRC tissues, as well as T-Ag localization in the nucleolus, where its oncogenic effect takes place, may provide supporting evidence for JCPyV involvement in CRC development. The study highlights the importance of using topoisomerase I to enhance JCPyV genome detection. Also, colorectal tissue is one of the permissive human tissue for JC resistance after preliminary infection.
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Neoplasias Colorretais/virologia , DNA Topoisomerases Tipo I/farmacologia , Genoma Viral/genética , Vírus JC/isolamento & purificação , Nucléolo Celular/genética , Nucléolo Celular/virologia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , DNA Topoisomerases Tipo I/química , Feminino , Humanos , Vírus JC/genética , Vírus JC/patogenicidade , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/genética , Infecções por Polyomavirus/patologia , Infecções por Polyomavirus/virologia , Replicação Viral/genéticaRESUMO
BACKGROUND: Angiotensin II receptor blockers (ARBs) have a potential role in reducing inflammation and fibrosis. We have integrated systems and molecular biology approaches to investigate the therapeutic potential of ARBs in preventing postsurgical adhesion band formation. MATERIAL AND METHODS: we have followed the ARRIVE guidelines point by point during experimental studies. Telmisartan (1 and 9 mg/kg), valsartan (1 and 9 mg/kg), and losartan (1 and 10 mg/kg) were administered intraperitoneally in different groups of male albino Wistar rat. After 7 d of treatment, macroscopic evidence and score of fibrotic bands based on scaling methods was performed. Moreover, the anti-inflammatory and antifibrosis effects of telmisartan on reduction of fibrotic bands were investigated by using histopathology, ELISA, and real-time polymerase chain reaction methods. RESULTS: Telmisartan, but not losartan or valsartan, prevented the frequency as well as the stability of adhesion bands. Telmisartan appears to elicit anti-inflammatory responses by attenuating submucosal edema, suppressing proinflammatory cytokines, decreasing proinflammatory cell infiltration, and inhibiting oxidative stress at the site of peritoneal surgery. We also showed that telmisartan prevents fibrotic adhesion band formation by reducing excessive collagen deposition and suppression of profibrotic genes expression at the peritoneum adhesion tissues. CONCLUSIONS: These results support the potential application of telmisartan in preventing postsurgical adhesion band formation by inhibiting key pathologic responses of inflammation and fibrosis in postsurgery patients.
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Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Telmisartan/administração & dosagem , Aderências Teciduais/prevenção & controle , Animais , Avaliação Pré-Clínica de Medicamentos , Injeções Intraperitoneais , Masculino , Distribuição Aleatória , Ratos WistarRESUMO
One of the most prevalent malignancies is esophageal squamous cell carcinoma (ESCC), which is associated with high morbidity and mortality. Substance P (SP), as one of the peptides released from sensory nerves, causes the enhancement of cellular excitability through the activation of the neurokinin-1 (NK1) receptor in several human tumor cells. Aprepitant, a specific, potent, and long-acting NK1 receptor antagonist, is considered as a novel agent to inhibit proliferation and induce apoptosis in malignant cells. Since the antitumor mechanism of aprepitant in ESCC is not completely understood, we conducted this study and found that aprepitant induced growth inhibition of KYSE-30 cells and arrested cells in the G2/M phase of the cell cycle. Aprepitant also caused apoptotic cell death and inhibited activation of the PI3K/Akt axis and its downstream effectors, including NF-κB in KYSE-30 cells. Besides, quantitative real-time (qRT)-PCR analysis showed a significant down-regulation of NF-κB target genes in KYSE-30 cells, indicating a probable NF-κB-dependent mechanism involved in aprepitant cytotoxicity. Thus, the present study recommends that SP/NK1R system might, therefore, be considered as an emerging and promising therapeutic strategy against ESCC.
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Carcinoma de Células Escamosas do Esôfago/etiologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores da Neurocinina-1/metabolismo , Transdução de Sinais , Apoptose/efeitos dos fármacos , Compostos Azo , Caspases/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Suscetibilidade a Doenças , Carcinoma de Células Escamosas do Esôfago/patologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Ésteres do Ácido SulfúricoRESUMO
BACKGROUND: The thioredoxin (Trx) system is a reducing complex, consisting of Trx, Trx reductase (TrxR), and NADPH, that scavenges reactive oxygen species. The system is a natural protective mechanism to prevent apoptosis and progression of oxidative stress-related diseases. The present study was conducted to explore possible changes in TrxR activity and gene expression as a response to the oxidative stress during HTLV-1 infection. MATERIALS AND METHODS: Blood samples were collected from 40 HTLV-1-infected patients and 40 age- and sex-matched healthy controls. The patient group consisted of chronic asymptomatic carriers and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM-TSP) patients. A commercial kit was used to measure the TrxR enzyme activity, and real-time polymerase chain reaction was performed to evaluate TrxR gene expression in extracted peripheral blood mononuclear cells (PBMCs). RESULTS: A decreasing pattern of TrxR enzyme activity was observed among control, carrier, and HAM-TSP groups (mean ± SD; controls, 0.1734 ± 0.056; carriers, 0.134 ± 0.065; and HAM-TSP, 0.0928 ± 0.047 µmol/min/mL). Cellular TrxR gene expression showed the same decreasing trend. The fold differences of gene expression in carriers and HAM-TSP groups compared with healthy controls were 0.8 and 0.7 vs 1, respectively. CONCLUSION: We found a reduction in TrxR expression as well as serum enzyme activity in HTLV-1-infected individuals, particularly in HAM-TSP patients. The reduced TrxR activity during HTLV-1 infection may hamper the natural protective mechanisms, thereby contributes to virus-induced complications.
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Expressão Gênica , Infecções por HTLV-I/patologia , Tiorredoxina Dissulfeto Redutase/sangue , Adulto , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Background: Infections with herpes simplex virus type 2 (HSV-2) and varicella-zoster virus (VZV) are associated with serious maternal and neonatal health consequences. The literature review reveals a research gap regarding the seroprevalence of HSV-2 and VZV among women of reproductive age in Mashhad, Northeast of Iran. The present study aims to evaluate the seroprevalence of these viruses among a group of women in Mashhad, Iran. Methods: Sera were collected by health center personnel using a cluster sampling method from healthy women with specific age characteristics residing in three distinct socioeconomic regions of the city. The participants, aged 20-35, were divided into three groups (20-25, 26-30, and 31-35 years). The levels of VZV and HSV-2 IgG antibodies were evaluated using commercial ELISA kits. Subsequently, the results were analyzed using SPSS software. Results: A total of 93 women were included in the study. Anti-HSV-2 IgG antibody was detected in 3 out of 93 participants (7.5%), while anti-VZV IgG antibody was found positive in 80 out of 93 individuals (83.3%). The HSV-2 positive cases were concurrently positive for the VZV antibody. There was no significant difference in the positivity of anti-HSV-2 and anti-VZV antibody positivity within age groups or socioeconomic status (P > 0.05). Conclusions: The high seroprevalence of VZV among nonvaccinated participants indicates a widespread presence of the virus and underscores its potentially serious impact on community health. Therefore, it is recommended that a VZV vaccination program be considered by the health system. Furthermore, the reactivation of latent HSV-2, whether symptomatic or asymptomatic, during pregnancy should not be disregarded as a life-threatening threat.
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Introduction. Human T-cell lymphotropic virus type 1 (HTLV-1), a well-known member of the retroviridae family, potentially causes serious outcomes including adult T-cell leukaemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM-TSP). Oxidative stress plays a key role in progression and clinical exacerbation of several chronic infections. We have previously shown a reduction in serum total antioxidant capacity (TAC) during HTLV-1 infection and this study was set out to investigate the reasons for TAC reduction.Hypothesis/Gap Statement. Oxidant/antioxidant imbalance during HTLV-1 infection may result from disruptions in oxidant levels or antioxidant defence system.Aim. This study aimed to analyse the key enzymes and oxidant molecules playing important roles in virus-induced oxidative stress.Methodology. We measured serum activities of the major antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) as well as serum concentrations of the main oxidant markers: nitric oxide (NO) and malondialdehyde (MDA). Totally 40 HTLV-1 infected patients and 40 healthy controls were enrolled in this study. The patient group consisted of chronic carriers and patients with HAM-TSP (N=20).Results. The current study found that serum levels of MDA and NO were significantly higher in patient groups particularly in HAM-TSP patients (P<0.05). In addition, a reductive trend was observed in the serum activities of CAT, SOD, and GPX in HTLV-1 infected patients compared with healthy controls (P<0.05).Conclusion. Reduced activities of CAT, SOD, and GPX antioxidant enzymes along with the observed elevated concentrations of oxidant molecules may contribute to oxidative stress and worse outcomes during HTLV-1 infection.
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Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Antioxidantes , Biomarcadores , Infecções por HTLV-I/complicações , Humanos , Oxidantes , Estresse Oxidativo , Paraparesia Espástica Tropical/complicações , Paraparesia Espástica Tropical/patologia , Superóxido DismutaseRESUMO
During chronic HTLV-1 infections oxidative stress occurs and contributes in viral pathogenesis. Glutaredoxin (Grx) system is one of the most effective antioxidant components. The system maintains the cellular redox and scavenges reactive oxygen species through the function of glutathione reductase (GR) enzyme, NADPH and reduced glutathione (GSH). This study was performed to investigate potential changes in GR gene expression and activity as well as GSH level, and their association with the viral load in HTLV-1 infection. Forty HTLV-1 seropositive patients divided into two groups: asymptomatic carriers (N = 20) and HAM/TSP (N = 20) with the same number of age and sex-matched healthy controls were recruited in this study. GR cellular gene expression and viral load in PBMCs were determined using Real-time PCR Technique. Enzyme activity and GSH level in sera were measured by commercial kits based on manufacturer's provided protocols. GR gene expression and GR enzyme activity, as well as GSH level, were significantly lower in HTLV-1 patients. A negative correlation between viral load and GR gene expression/enzyme activity was observed in HAM/TSP group. Similarly, a negative relationship between viral load and GSH levels was observed in both carrier and HAM/TSP groups. We also found that in profound complicated condition of HTLV-1 infection, HAM/TSP, Grx system components activity was significantly decreased compared to the controls. Such observation was not the case in clinically healthy HTLV-1 carriers. These findings may shed a light on the conditions contributing in pathogenesis of the complications and exacerbation of the disease in the HAM/TSP cases. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-022-00758-y.
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OBJECTIVES: Irritable bowel syndrome (IBS) is known as one of the most common irritating gastrointestinal disorders. The mechanism behind IBS is still under investigation and it is thought that it may arose from multi factors among which free radicals have been previously mentioned. Studies have found an association between oxidative stress and IBS; however, little is known about the mechanisms and oxidative stress components status during IBS. One of the key factors playing a central role in oxidative stress network is glutathione reductase (GR). Here we report the GR activity in colon tissue samples during IBS to explore a part of contributing components in IBS pathogenesis. METHODS: The GR enzyme activity was measured in 15 active IBS colon biopsy samples and was compared to our best available age and sex matched colorectal tissue samples from normal marginal tissue of resected colon cancers (n=15). The enzyme activity in the two groups was determined and compared using a commercial GR Assay Kit (Cayman chemical). RESULTS: A significant decrease in GR activity among IBS tissue samples was observed compared to anatomically normal marginal colon tissue samples (p=0.007). CONCLUSIONS: Lower GR activity may increase oxidized glutathione there by in turn could contribute as a main component in oxidative stress network. The lower GR activity results in hampered defense mechanism against produced free radical species. This finding may clarify a part of IBS pathogenesis.
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Glutationa Redutase/metabolismo , Síndrome do Intestino Irritável/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Colo/metabolismo , Colo/patologia , Feminino , Glutationa Redutase/análise , Humanos , Síndrome do Intestino Irritável/patologia , Masculino , Pessoa de Meia-Idade , Estresse OxidativoRESUMO
Colorectal cancer (CRC) is a noticeable reason of cancer-associated deaths with a high incidence and mortality rate. Countless effort have been put into the improving clinical management of CRC patients including more effective tools and a wide variety of biomarkers for diagnostic, prognostic or predictive purposes. In recent years, dysregulated miRNAs have been emerged as highly sensitive and specific markers to manage CRC in an effective way. They can play key roles in carcinogenesis as potential oncogenes, tumor suppressors or regulators of cancer network. Therefore, miRNAs may serve as molecular tools that can be quantified and used in diagnostic and prognostic approaches. Growing evidence also suggests that forced expression of tumor suppressor miRNAs or inhibiting the oncogene ones, can be used as a novel treatment strategy. In this review, we focus on the clinical applications of miRNAs as promising biomarkers of early cancer detection, prognosis and treatment.
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Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , MicroRNAs/metabolismo , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Prognóstico , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
The antagonists of the neurokinin-1 receptor (NK1R) are known for their anti-inflammatory, anxiolytic, antiemetic, and anticancer activities. Aprepitant, a nonpeptide NK1R antagonist, is used in nausea and vomiting, the most common side effects of cancer chemotherapy in patients. It has been established that NK1R activation by substance P (SP), which links cancer promotion and progression to a neurokinin-mediated environment, became one mechanism that corresponds to the mitogenesis of tumor cells. Therefore, this study is aimed at explaining and evaluating the anticancer impacts of aprepitant on esophageal squamous cancer cell (ESCC) spheres by using in vitro experiments, such as resazurin, ROS, annexin-V binding, RT-PCR, and Western blot analysis. As a result, we showed that aprepitant had strong antiproliferative and cytotoxic effects on ESCC cell spheres. Also, aprepitant caused significant G2-M cell cycle arrest depending on concentration increase. Further, exposure of cells to this agent resulted in caspase -8/-9-dependent apoptotic pathway activation by modifying the expression of genes involved in apoptosis. Besides, treatment of the cells by aprepitant abrogates of the PI3K/Akt pathway, as shown by reducing the level of Akt, induces apoptotic cell death. In summary, pharmacological inhibition of NK1R with aprepitant seems to have a significant chance of treating ESCC as a single agent or in conjunction with other chemotherapeutic drugs.
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Apoptose/efeitos dos fármacos , Aprepitanto/farmacologia , Morte Celular/efeitos dos fármacos , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/farmacologia , Caspases/metabolismo , Linhagem Celular Tumoral , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Humanos , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores da Neurocinina-1/metabolismoRESUMO
Motexafin gadolinium (MGd) is an expanded porphyrin anticancer agent which selectively targets tumor cells and works as a radiation enhancer, with promising results in clinical trials. Its mechanism of action is oxidation of intracellular reducing molecules and acting as a direct inhibitor of mammalian ribonucleotide reductase (RNR). This paper focuses on the mechanism of inhibition of RNR by MGd. Our experimental data present at least two pathways for inhibition of RNR; one precluding subunits oligomerization and the other direct inhibition of the large catalytic subunit of the enzyme. Co-localization of MGd and RNR in the cytoplasm particularly in the S-phase may account for its inhibitory properties. These data can elucidate an important effect of MGd on the cancer cells with overproduction of RNR and its efficacy as an anticancer agent and not only as a general radiosensitizer.
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Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Metaloporfirinas/farmacologia , Ribonucleotídeo Redutases/antagonistas & inibidores , Animais , Antineoplásicos/metabolismo , Inibidores Enzimáticos/metabolismo , Células HeLa , Humanos , Metaloporfirinas/metabolismo , Camundongos , Estresse Oxidativo , Subunidades Proteicas/antagonistas & inibidores , Subunidades Proteicas/metabolismo , Ribonucleotídeo Redutases/metabolismoRESUMO
INTRODUCTION: Contrast-induced nephropathy (CIN) is the most common cause of iatrogenic acute kidney injury. It is happened more commonly in patients with underlying kidney diseases. It is appeared that the oxidative stress is the main mechanism of contrast nephropathy. Curcumin is suggested as an herbal antioxidant agent, so we decided to assess the effect of curcumin in preventing of this complication in patients with underlying chronic kidney disease (CKD) who need coronary angiography. METHODS AND MATERIALS: We conducted double blind, placebo-controlled clinical trial in 60 moderate to severe CKD patients who underwent coronary angiography or angioplasty. Adjusted dose of Iodixanol was used as contrast agent in all of them. Curcumin or placebo administered orally, 1.5 g daily from 2 days before procedure to 3 days after it. CIN was defined by an increased serum creatinine level≥0.3mg/dl or an increase to ≥1.5 times of the baseline within 48 hours after procedure. Urinary NGAL test was also done the next day after angiography. RESULTS: CIN occurred in 12(20%) of patients, 5(16.7%) in Curcumin group and 7(23.3%) in placebo group (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.18 to 2.36; P0.51). Serum Creatinine was increased after72 hours of intervention from 1.65±0.26 mg/dl to 1.79±0.33 mg/dl in Curcumin group and from 1.61±0.23 mg/dl to 1.86±0.35 in placebo group. There is no significant difference between the mean increase in serum creatinine concentration in the placebo group and Curcumin group (difference of 0.006 mg/dL; 95% CI, - 0.06 to 0.08; P0.85). Urinary NGAL test was significantly higher in patients with AKI (p=0.000), but there weren't differences in its level in two groups (p=0.761) Conclusion: It is appeared prophylactic oral Curcumin hasn't protective effects on CIN in high risk patients who have undergone coronary procedure.
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Injúria Renal Aguda/induzido quimicamente , Antioxidantes/administração & dosagem , Meios de Contraste/efeitos adversos , Curcumina/administração & dosagem , Ácidos Tri-Iodobenzoicos/efeitos adversos , Injúria Renal Aguda/prevenção & controle , Administração Oral , Angioplastia/efeitos adversos , Angiografia Coronária/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/prevenção & controle , Insuficiência Renal Crônica/complicaçõesRESUMO
Human T-cell lymphotropic virus type 1 (HTLV-1) infection is linked to adult T-cell leukemia-lymphoma (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and several other disorders. ATLL occurs in approximately 5% of the 15-20 million people infected by HTLV-1 in the world. In general, ATLL is resistant to chemotherapy, which underlines the need for new and effective therapeutic strategies. Previous studies highlighted the role of viral enzymes, responsible for viral replication, and regulatory proteins such as Tax and HBZ in the progression of HTLV-1-associated diseases. There are conflicting reports on the efficacy of current enzyme inhibitors, mainly developed against human immunodeficiency virus (HIV), for treatment of HTLV-1 infection. New treatment approaches including monoclonal antibodies show promising results and exert significant cytotoxic effects on ATLL cells. This manuscript reviews the recent developments in molecular targeting for treatment of HTLV-1 infection.
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Infecções por HTLV-I/tratamento farmacológico , Infecções por HTLV-I/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Terapia de Alvo Molecular/métodos , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/administração & dosagem , Inibidores Enzimáticos/administração & dosagem , Vírus Linfotrópico T Tipo 1 Humano/química , Humanos , Terapia de Alvo Molecular/tendências , Estrutura Secundária de Proteína , Resultado do TratamentoRESUMO
BACKGROUND: Until recently, a gene polymorphism in the promoter region of endothelial nitric oxide synthase has been suggested as a risk factor for thromboangiitis obliterans (TAO) development. The aim of this study was to compare the metabolites of nitric oxide (NO) and its backup, heme-oxygenase-1 (HMOX1), between TAO patients and those of a smoking control group matched by race, age, sex, and smoking habits. METHODS: Twenty-four male Caucasian TAO patients and 20 male Caucasian controls enrolled in the study. Their smoking habits were matched based on the serum cotinine levels of 17 of the TAO patients and the 20 controls. A colorimetric kit was used to measure NO, and an enzyme-linked immunosorbent assay kit was used to measure cotinine and HMOX1 levels. RESULTS: The mean serum level of NO metabolites in the TAO group was significantly less than in the controls (p = 0.03) and also significantly less in the patients with below-knee amputations than in non-amputees (p= 0.018). Also, HMOX1 was significantly greater in the TAO patients than in the controls (p= 0.01). No significant correlation was found between NO and HMOX1 (p = 0.054). CONCLUSION: Nitric oxide may play a pivotal role in TAO development and its outcome. However, the intact HMOX1 pathway may demonstrate the unique role of NO, which cannot be compensated for by HMOX1 and whose absence may make patients susceptible to developing TAO. In addition, another pathway besides NO, with influence on vascular tone and hemostasis, might be involved in TAO development, such as the autonomic nervous system. Further studies are suggested regarding these issues.
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Objective: Schizophrenia is a disease with unknown etiology. There is evidence suggesting that oxidative damage occurs in schizophrenia. Oxidative damage may arouse from imbalance between oxidant and anti-oxidant factors in cellular and tissue environment. Although it may not be the primary cause, it can worsen the disease and may be a reason of poor response to therapy in these patients. The present study aimed at evaluating the pro-oxidant antioxidant balance (PAB) and total antioxidant capacity (TAC) in serum of schizophrenia patients. PAB is an assay to determine the pro-oxidant load and antioxidant capacity in a single measurement. Method : In this cross- sectional study, patients with diagnosis of schizophrenia, who referred to a psychiatry university hospital (Ibn-e-Sina Hospital) affiliated to Mashhad University of Medical Sciences, were enrolled. Patients' demographic characteristics and laboratory data were recorded from patients' files. Serum PAB and TAC were measured using a special PAB assay and commercial kit, respectively. Data were analyzed using SPSS 16. Results: A total of 84 individuals (42 schizophrenia cases and 42 healthy controls) participated in this study. Controls were age and sex-matched with the patients' group. The mean TAC in the patient and control groups was 0.49±0.04 and 0.51±0.04 nmol/L, respectively (p = 0.16). PAB was higher in patients' group than in controls (127.36±36.44 vs. 118.93±52.34 HK), however, this difference was not statistically significant (p = 0.09). The change was correlated with the chronicity of the disease. Conclusion: Pro-oxidant antioxidant balance was elevated in serum of patients with schizophrenia. These data suggested the occurrence of oxidative stress during the progression of the disease. Lower antioxidant capacity might suggest that patients with schizophrenia could be more susceptible to oxidative stress damage.
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BACKGROUND & OBJECTIVE: Globally, breast cancer is the most common malignancy among females. Prohibition (PHB)-I, a homologous protein, was initially introduced as a suppressor gene for amplification process. Further, the protein has a key role in the cell cycle and is capable of inhibiting DNA transcription in many cell types. Therefore, its possible role in different types of human malignancies is of interest.The current study aimed at examining the relationship between the tissue distribution of PHB-I and prognostic factors of breast cancer. METHODS: Paraffin-embedded tissue specimens of 33 patients diagnosed with breast cancer at Omid teaching Hospital, Mashhad, Iran were studied and a commercial monoclonal antibody was used to perform immunohistochemistry (IHC). The relationship between PHB-I tissue expression with age, disease stage, tumor grade and size, as well as hormone receptor status including estrogen (ER) and progesterone (PR) receptors, and Her-2 receptor were evaluated. RESULTS: The Immunohistochemical analysis showed a relative increase in PHB-I tissue expression along with higher tumor grade (P=0.057). In addition, higher expression of ER and PR were observed (P=0.027 and 0.009, respectively). The age of patients and other prognostic factors including Her-2 receptor status and disease stage did not statistically correlate with PHB-I expression. CONCLUSION: An increased expression of PHB-I was observed in the breast cancer tumors of the current study patients compared with the anatomically healthy margin. Its coloration with some prognostic factors such as disease grade and expression of ER and PR might indicate the PHB-I potential application for diagnostic and patient management purposes.
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ST2 is a member of IL-1 receptor family expressed on Th2 cells and regulates Th2 responces. The gene of ST2 encodes soluble ST2 (sST2) and the transmembrane ST2 (ST2L) isoforms through alternative mRNA splicing. The discovery of IL33/ ST2 signaling pathway, has drawn a great scientific attention to this system. sST2 has been shown to be an indacating factor in various infl ammatory conditions. This study aims to evaluate serum sST2 levels in HTLV-1 infected patients. This study included 49 HTLV-1 seropositive cases of which 14 were sympthomatic. Controls consisted of 30 healthy volunteers. sST2 level was measured using a quantitative ELISA assay and the results of the study groups were compared. Corroborating the previous reports, sST2 was lower in females (P = 0.003). The sST2 levels was slightly increased in HTLV-1 patients, though such increase was not statistically significant (P = 0.91), in addition sST2 level did not correlate significantly to the disease duration (P = 0.78). Despite some other chronic viral infection, HTLV-1 seems not to induce high serum sST2. However owing to relatively high normal variation of sST2 levels and rather small sample size, we stongly recommend further reseach with preferably larger sample size to evalute sST2 in HTLV-1 infected patients.
Assuntos
Infecções por HTLV-I/metabolismo , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Receptores de Superfície Celular/sangue , Adulto , Idoso , Feminino , Infecções por HTLV-I/sangue , Infecções por HTLV-I/virologia , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1 , Masculino , Pessoa de Meia-Idade , Transdução de SinaisRESUMO
Ribonucleotide reductase (RNR) catalyzes the rate-limiting step in deoxyribonucleotide synthesis essential for DNA replication and repair. RNR in S phase mammalian cells comprises a weak cytosolic complex of the catalytic R1 protein containing redox active cysteine residues and the R2 protein harboring the tyrosine free radical. Each enzyme turnover generates a disulfide in the active site of R1, which is reduced by C-terminally located shuttle dithiols leaving a disulfide to be reduced. Electrons for reduction come ultimately from NADPH via thioredoxin reductase and thioredoxin (Trx) or glutathione reductase, glutathione, and glutaredoxin (Grx), but the mechanism has not been clarified for mammalian RNR. Using recombinant mouse RNR, we found that Trx1 and Grx1 had similar catalytic efficiency (k(cat)/K(m)). With 4 mm GSH, Grx1 showed a higher affinity (apparent K(m) value, 0.18 microm) compared with Trx1 which displayed a higher apparent k(cat), suggesting its major role in S phase DNA replication. Surprisingly, Grx activity was strongly dependent on GSH concentrations (apparent K(m) value, 3 mm) and a Grx2 C40S mutant was active despite only one cysteine residue in the active site. This demonstrates a GSH-mixed disulfide mechanism for glutaredoxin catalysis in contrast to the dithiol mechanism for thioredoxin. This may be an advantage with the low levels of RNR for DNA repair or in tumor cells with high RNR and no or low Trx expression. Our results demonstrate mechanistic differences between the mammalian and canonical Escherichia coli RNR enzymes, which may offer an explanation for the nonconserved shuttle dithiol sequences in the C terminus of the R1.
Assuntos
Glutarredoxinas/química , Hidrogênio/química , Ribonucleotídeo Redutases/química , Fase S/fisiologia , Tiorredoxinas/química , Animais , Catálise , Domínio Catalítico/fisiologia , Replicação do DNA/fisiologia , Desoxirribonucleotídeos/biossíntese , Desoxirribonucleotídeos/química , Escherichia coli/enzimologia , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Glutarredoxinas/metabolismo , Hidrogênio/metabolismo , Camundongos , Ribonucleotídeo Redutases/metabolismo , Tiorredoxinas/metabolismoRESUMO
Glutaredoxin 2 (Grx2) is a glutathione-dependent oxidoreductase involved in the maintenance of mitochondrial redox homeostasis. Grx2 was first characterized as mitochondrial protein, but alternative mRNA variants lacking the transit peptide-encoding first exon were demonstrated for human and proposed for mouse. We systematically screened for alternative transcript variants of mouse Grx2. We identified a total of six exons, three constitutive (II, III, and IV), two alternative first exons (exons Ia and Ic), and one single-cassette exon (exon IIIb) located between exons III and IV. Exons Ic and IIIb are not present in the human genome; mice lack human exon Ib. The six exons give rise to five transcript variants that encode three protein isoforms: mitochondrial Grx2a, a cytosolic isoform that is homologous to the cytosolic/nuclear human Grx2c and present in specific cells of many tissues and the testis-specific isoform Grx2d that is unique to mice. Mouse Grx2c can form an iron/sulfur cluster-bridged dimer, is enzymatically active as a monomer, and can donate electrons to ribonucleotide reductase. Testicular cells lack mitochondrial Grx2a but contain cytosolic Grx2. Prominent immunostaining was detected in spermatogonia and spermatids. These results provide evidence for additional functions of Grx2 in the cytosol, in cell proliferation, and in cellular differentiation.