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BACKGROUND: Predictive and prognostic biomarkers to guide 2019 novel coronavirus disease (COVID-19) are critically evolving. Dysregulated immune responses are the pivotal cause of severity mainly mediated by neutrophil activation. Thus, we evaluated the association of calprotectin, neutrophil secretory protein, and other mediators of inflammation with the severity and outcomes of COVID-19. METHODS: This two-center prospective study focused on PCR-proven COVID-19 patients (n = 76) with different clinical presentations and SARS-CoV-2 negative control subjects (n = 24). Serum calprotectin (SC) was compared with IL-6 and other laboratory parameters. RESULTS: Median levels of SC were significantly higher in COVID-19 patients in comparison to the control group (3760 vs. 2100 ng/ml, p < 0.0001). Elevated SC was significantly respective of disease severity (3760 ng/ml in mild up to 5700 ng/ml in severe cases, p < 0.0001). Moreover, the significant positive and negative correlations of SC with disease severity and oxygenation status indicated disease progression and respiratory worsening, respectively. It was found that SC was high in severe patients during hospitalization and significantly declined to normal after recovery. The logistic analysis identified the independent predictive power of SC for respiratory status or clinical severity. Indeed, SC behaved as a better discriminator for both outcomes, as it exhibited the largest area under the curve (receiver operating curve analysis), with the highest specificity and sensitivity when the predictive value of inflammatory biomarkers was compared. CONCLUSION: Calprotectin can be used as a reliable prognostic tool to predict the poor clinical outcomes of COVID-19 patients.
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COVID-19 , Humanos , COVID-19/diagnóstico , Complexo Antígeno L1 Leucocitário , SARS-CoV-2 , Estudos Prospectivos , Biomarcadores , Índice de Gravidade de DoençaRESUMO
Today, growing evidence indicates that patients with type 2 diabetes (T2D) are at a higher risk of developing Alzheimer's disease (AD). Indeed, AD as one of the main causes of dementia in people aged more than 65 years can be aggravated by insulin resistance (IR) and other metabolic risk factors related to T2D which are also linked to the function of the brain. Remarkably, a new term called "type 3 diabetes" has been suggested for those people who are diagnosed with AD while also showing the symptoms of IR and T2D. In this regard, the role of genetic and epigenetic changes associated with AD has been confirmed by many studies. On the other hand, it should be noted that the insulin signaling pathway is highly regulated by various mechanisms, including epigenetic factors. Among these, the role of noncoding RNAs (ncRNAs), including microRNAs and long noncoding RNAs has been comprehensively studied with respect to the pathology of AD and the most well-known underlying mechanisms. Nevertheless, the number of studies exploring the association between ncRNAs and the downstream targets of the insulin signaling pathway in the development of AD has notably increased in recent years. With this in view, the present study aimed to review the interplay between different ncRNAs and the insulin signaling pathway targets in the pathogenesis of AD to find a new approach in the field of combining biomarkers or therapeutic targets for this disease.
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Doença de Alzheimer , Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Resistência à Insulina , Doença de Alzheimer/patologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Insulina/genética , Insulina/metabolismo , Resistência à Insulina/genética , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Transdução de Sinais/genéticaRESUMO
As healthcare systems transition into an era dominated by quantum technologies, the need to fortify cybersecurity measures to protect sensitive medical data becomes increasingly imperative. This paper navigates the intricate landscape of post-quantum cryptographic approaches and emerging threats specific to the healthcare sector. Delving into encryption protocols such as lattice-based, code-based, hash-based, and multivariate polynomial cryptography, the paper addresses challenges in adoption and compatibility within healthcare systems. The exploration of potential threats posed by quantum attacks and vulnerabilities in existing encryption standards underscores the urgency of a change in basic assumptions in healthcare data security. The paper provides a detailed roadmap for implementing post-quantum cybersecurity solutions, considering the unique challenges faced by healthcare organizations, including integration issues, budget constraints, and the need for specialized training. Finally, the abstract concludes with an emphasis on the importance of timely adoption of post-quantum strategies to ensure the resilience of healthcare data in the face of evolving threats. This roadmap not only offers practical insights into securing medical data but also serves as a guide for future directions in the dynamic landscape of post-quantum healthcare cybersecurity.
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Background: Sexual dysfunction is a common disorder among women, especially during menopause. Metabolic syndrome is a multifactorial disease that, according to previous studies, there is a relationship between the metabolic syndrome and sexual dysfunction among women. The aim of this systematic review and meta-analysis is to obtain the prevalence of Female Sexual Dysfunction (FSD) among women with metabolic syndrome, and to analyze available related evidence. Methods: In this systematic review and meta-analysis, the keywords of MeSH, female sexual dysfunction, FSD, metabolic syndrome were searched in PubMed, Web of Science, Scopus, Science Direct and Google Scholar. The searches were conducted without a lower time limit and until May 2022. Results: The prevalence of FSD among women with metabolic syndrome was found to be 39.3% (95% CI: 28.3-51.5). In the subgroup analysis and in the review of 4 studies, the prevalence of sexual dysfunction in postmenopausal women with metabolic syndrome was 49.8% (95% CI: 26.1-73.6). Analyzing the results of the meta-regression test in examining the effect of the three factors of sample size, year of the study, age, and BMI of the patients on the heterogeneity of the meta-analysis, showed that with the increase of the sample size, the prevalence of sexual dysfunction among women with metabolic syndrome decreases (p < 0.05). Moreover, the prevalence of sexual dysfunction among women with metabolic syndrome increases (p < 0.05) with the increase in the years of conducting studies and the mean of age of women with metabolic syndrome. Also, with increasing mean of BMI of female patients with metabolic syndrome, the prevalence of sexual dysfunction in these women also increases (p < 0.05). Conclusion: Female sexual dysfunction is a global health problem that can affect women's life to a great extent. Metabolic syndrome, which is a set of factors such as obesity, high blood pressure, and diabetes, affects sexual dysfunction in women. From this study, it can be concluded that there is a close relationship between metabolic syndrome and female sexual dysfunction.
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Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a highly pathogenic and transmissible virus. Infection caused by SARS-CoV-2 known as Coronavirus disease 2019 (COVID-19) can be severe, especially among high risk populations affected of underlying medical conditions. COVID-19 is characterized by the severe acute respiratory syndrome, a hyper inflammatory syndrome, vascular injury, microangiopathy and thrombosis. Antiviral drugs and immune modulating methods has been evaluated. So far, a particular therapeutic option has not been approved for COVID-19 and a variety of treatments have been studied for COVID-19 including, current treatment such as oxygen therapy, corticosteroids, antiviral agents until targeted therapy and vaccines which are diverse in each patient and have various outcomes. According to the findings of different in vitro and in vivo studies, some novel approach such as gene editing, cell based therapy, and immunotherapy may have significant potential in the treatment of COVID-19. Based on these findings, this paper aims to review the different strategies of treatment against COVID-19 and provide a summary from traditional and newer methods in curing COVID-19.
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COVID-19 , Vacinas , Antivirais/uso terapêutico , COVID-19/terapia , Terapia Genética , Humanos , Fatores Imunológicos , Imunoterapia , SARS-CoV-2RESUMO
Animal studies suggest that administration of vitamin A to rats with experimental urinary tract infection decreases the frequency of renal scars (Kavukçu et al., BJU Int 83(9):1055-1059, 1999). The aim of this study was to determine the effect of vitamin A on the rate of permanent renal damage in children with acute pyelonephritis. Fifty children, median age of 24 months (range 2-144), with first-time pyelonephritis verified by an uptake defect on acute dimercaptosuccinic acid (DMSA) scan were included in the study and randomly allocated to the case or control groups. All were given intravenous ceftriaxone for 10 days followed by oral cephalexin for 3 months. Cases in addition were given a single intramuscular dose of vitamin A, 25,000 U for infants below 1 year of age and 50,000 U for older children. At the repeat DMSA scan after 3 months, five of 25 cases (20%) and 17 of 25 controls (68%) had abnormal findings (p = 0.001). In conclusion, administration of vitamin A was associated with a significantly lower rate of permanent renal damage.
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Cicatriz/prevenção & controle , Rim/patologia , Pielonefrite/tratamento farmacológico , Vitamina A/uso terapêutico , Criança , Pré-Escolar , Cicatriz/etiologia , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Pielonefrite/complicações , Pielonefrite/patologia , SuccímeroRESUMO
Fabricating graphite electrode corrected with nanofiber by electrospinning as a considerable procedure for utilization in the fluid materials, milk, and syrup for detection of T2 mycotoxin is a significant technique. The modern biosensor was fabricated at normal degrees of room and utilized via buffer Britton-Robinson (B-R) in pH = 5 to refine the chemico-mechanical specifications. The electrochemical manner of the modified surface was surveyed using the scanning electron microscopy (SEM), cyclic voltammetry (CV), square wave voltammetry (SQWV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV). The corrected electrode displayed a linear reply to T2 toxin in two distinct concentration ranges of 30-100 nM with correlation coefficients of 0.99. The greatest signals in the square wave spectrums for the B-R buffer created on the uttermost signals of the obtained streams were pH = 5 and 0.5 M of KNO3 for T2 toxin. The modified electrode has a big signal, broad dynamic concentration and high sensitivity and selectivity.
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PURPOSE: To investigate the efficacy of short-term treatment with ciprofloxacin in alteration of gut microbiota pattern and reduction of seizure frequency in adult patients with drug-resistant epilepsy. METHODS: In a prospective study, we investigated the effect of a 5-day course of treatment with ciprofloxacin on gut microbiota pattern and seizure frequency of 23 adults with drug-resistant epilepsy. Fecal samples were collected before and after treatment and were analyzed for microbial load and species. Changes in seizure frequency were registered for 12 weeks. Responders were defined as patients who experienced ≥50 % seizure reduction in comparison to baseline. Outcome measures were specified as alteration in fecal microbial burden in days 5-7 and responder rate in 4th and 12th weeks. RESULTS: The mean baseline frequency of seizures was5.6 ±7.7 per week. All patients were on polytherapy with a mean of 3 ± 1.2 anti-seizure medications. Microbial analysis showed a considerable increase in Bacteroidetes/Firmicutes ratio after treatment. Seizure frequency significantly decreased at the end of first week and the therapeutic effect continued to week 12 (P < 0.001). The responder rate at 4th and 12th weeks were 69.6 % and 73.9 % respectively with a more prominent response in patients with symptomatic generalized epilepsy (P:0.06). CONCLUSION: Alteration of abnormal gut microbiota pattern by methods such as short-course antibiotic therapy, prescription of probiotics and fecal microbiota transplant might be effective in treatment of drug-resistant epilepsy.
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Epilepsia Resistente a Medicamentos , Epilepsia Generalizada , Adulto , Anticonvulsivantes/uso terapêutico , Ciprofloxacina/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Humanos , Estudos Prospectivos , Resultado do TratamentoRESUMO
Aspirin, as one of the most frequently prescribed drugs, can have therapeutic effects on different conditions such as cardiovascular and metabolic disorders and malignancies. The effects of this common cardiovascular drug are exerted through different molecular and cellular pathways. Altered noncoding RNA (ncRNA) expression profiles during aspirin treatments indicate a close relationship between these regulatory molecules and aspirin effects through regulating gene expressions. A better understanding of the molecular networks contributing to aspirin efficacy would help optimize efficient therapies for this very popular drug. This review is aimed at discussing and highlighting the identified interactions between aspirin and ncRNAs and their targeting pathways and better understanding pharmacogenetic responses to aspirin.
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Aspirina/farmacologia , Medicamentos sob Prescrição/farmacologia , RNA não Traduzido/genética , Animais , Fármacos Cardiovasculares/farmacologia , Expressão Gênica/genética , Humanos , Farmacogenética/métodosRESUMO
The proteins secreted by human tissues and blood cells, the secretome, are important both for the basic understanding of human biology and for identification of potential targets for future diagnosis and therapy. Here, a high-throughput mammalian cell factory is presented that was established to create a resource of recombinant full-length proteins covering the majority of those annotated as 'secreted' in humans. The full-length DNA sequences of each of the predicted secreted proteins were generated by gene synthesis, the constructs were transfected into Chinese hamster ovary (CHO) cells and the recombinant proteins were produced, purified and analyzed. Almost 1,300 proteins were successfully generated and proteins predicted to be secreted into the blood were produced with a success rate of 65%, while the success rates for the other categories of secreted proteins were somewhat lower giving an overall one-pass success rate of ca. 58%. The proteins were used to generate targeted proteomics assays and several of the proteins were shown to be active in a phenotypic assay involving pancreatic ß-cell dedifferentiation. Many of the proteins that failed during production in CHO cells could be rescued in human embryonic kidney (HEK 293) cells suggesting that a cell factory of human origin can be an attractive alternative for production in mammalian cells. In conclusion, a high-throughput protein production and purification system has been successfully established to create a unique resource of the human secretome.
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Ensaios de Triagem em Larga Escala , Animais , Células CHO , Cricetulus , DNA/biossíntese , DNA/genética , Células HEK293 , Humanos , Proteômica , Proteínas Recombinantes/análise , Proteínas Recombinantes/metabolismoRESUMO
AIMS: Osteoporosis is a common extra-hepatic complication in patients with chronic liver disease. Tumor necrosis factor related apoptosis-inducing ligand (TRAIL), sex hormones, adiponectin, and sclerostin are involved in the regulation of bone turnover but little is known about their role in the promotion of hepatic osteodystrophy. Endogenous opioids are reported to increase during cholestasis and may influence bone resorption. The purpose of this study was to investigate the circulating levels of these factors and their expression in the femur of bile duct ligated (BDL) rats, to evaluate the biomechanical bone strength, and the effect of naltrexone (NTX). MATERIALS AND METHODS: BDL and sham-operated (SO) rats received 10â¯mg/kg NTX as an opioid-receptors antagonist or saline once daily for 28â¯days intraperitoneally. Three-point bending test was performed on the right femurs and, plasma bone alkaline phosphatase (BALP), sex hormones, TRAIL, adiponectin, sclerostin, as well as the mRNA expression levels of the latter three proteins, were measured in the femur tissues. KEY FINDINGS: Plasma TRAIL, estrogen, adiponectin, sclerostin and, BALP levels increased in BDL animals when compared to the related controls, whereas testosterone level decreased and NTX reversed these effects significantly. Femur strength decreased in cirrhotic animals and interestingly, blocking opioid-receptors by NTX improved it significantly (pâ¯≤â¯0.05). SIGNIFICANCE: High levels of TRAIL, adiponectin and, sclerostin after bile duct ligation, suggest that these factors may have some roles in bone loss after cirrhosis. Administration of NTX improved all the mentioned factors except for bone strength. Effect of NTX on bone loss in BDL rats needs more study to clarify.
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Adiponectina/sangue , Ductos Biliares/cirurgia , Proteínas Morfogenéticas Ósseas/sangue , Reabsorção Óssea/patologia , Cirrose Hepática Biliar/patologia , Naltrexona/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Animais , Reabsorção Óssea/sangue , Marcadores Genéticos , Ligadura , Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/tratamento farmacológico , Cirrose Hepática Biliar/etiologia , Masculino , Antagonistas de Entorpecentes/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Opioides/químicaRESUMO
INTRODUCTION: Acetaminophen (APAP) as an analgesic and antipyretic drug can result to liver damages while using more than 4 g/day. Therefore, APAP toxicity causes the liver to dysfunction. This study aims to investigate the hepatoprotective and antioxidant activity of hydroalcoholic extract of watercress (WC) in APAP-induced hepatotoxicity in rats. MATERIALS AND METHODS: Randomly, twenty-four Wistar rats were divided into four groups of six each. Groups named as control, APAP, APAP + WC and APAP + S for group 1, 2, 3, and 4, respectively. Group 1 received distilled water 1 ml/kg for 7 days. In group 2, 3, and 4, rats pretreated by receiving distilled water (1 ml/kg), WC extract (500 mg/kg), silymarin extract (mg/kg) for 7 days, respectively. Of note, to induce acute hepatotoxicity in groups 2, 3, and 4, rats posttreated by orally intoxicated with single dose of APAP (2 g/kg) on the sixth day. The animals were sacrificed on the seventh day. Alanine amino transferase (ALT), aspartate amino transferase (AST), ferric reducing ability of plasma (FRAP), protein carbonyl (PCO), total thiol (T-SH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were measured in plasma. It should be noted that the chemical composition of WC extract was identified by GC-MS analysis. RESULTS: The results have shown that there was a significant increase in AST, ALT, FRAP and PCO content in APAP group in comparison to control. Also, there was a significant reduction in T-SH levels and GPx activity in APAP group compared to control. However, administration of WC extract and silymarin not only causes a significant decrease in AST activity, but they markedly increased T-SH content and GPx activity compared to APAP group. GC-MS analysis showed the major compositions were found to be benzenepropanenitrile (48.30 %), Phytol (10.10 %), α-cadinene (9.50%) and linolenic acid (8.0). CONCLUSIONS: It is concluded that the WC extract reduces APAP-induced toxicity through its hepatoprotective and antioxidant activity in rats.