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AIM: This study was carried out to investigate the perception of the main competencies of disaster management in Iranian emergency department nurses in 2023 in hospitals affiliated with Kermanshah University of Medical Sciences. The present study was conducted to explore the perceived core disaster competencies in nurses of hospitals affiliated with Kermanshah University of Medical Sciences in 2023. BACKGROUND: Due to the rise in natural disasters, their escalating severity and associated regulatory response necessitate a closer look at the preparedness and core competencies of nursing personnel. The main competencies of nurses are necessary to deal with disasters in unexpected events, and they are expected to use their professional expertise to provide the required nursing services to reduce the risks caused by disasters. METHODOLOGY: This descriptive-analytical study was conducted cross-sectionally between May and September 2023. In the study, a sample of 384 nurses working in the departments of four hospitals affiliated with Kermanshah University of Medical Sciences was selected through a random stratification. The data collection instrument was a 45-item scale of nurses' perceived core competencies (NPDCC) in handling disasters. The data were analyzed using the Mann-Whitney U-test, Kruskal-Wallis test, and independent samples t-test. The significance level was set at 5%. RESULTS: The mean total score of perceived core disaster competencies was 139.11 ± 37.65. The technical skills subscale got the highest score (51.81 ± 11.28) and critical thinking skills received the lowest (9.74 ± 3.92). Also, "technical skills" had the highest average and "critical thinking skills" had the lowest average in all three age groups. The results found a significant difference between the scores of nurses in perceived core disaster competencies in age groups, work environments, education degrees, marital statuses, and experiences of attending disaster workshops (p ≤ 0.05). CONCLUSIONS: The results showed that nurses had different levels of core disaster competencies in the department. There are gaps in the core disaster nursing competencies that need to be filled. Nursing managers should consistently evaluate the core nursing competencies to achieve efficacious disaster preparedness. To this aim, it is recommended that authorities implement training courses and programs to enhance the preparedness of nurses in responding to disasters.
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Non-small cell lung cancer (NSCLC) has constituted over 80% of the lung cancer population with a poor prognosis. Over the past decade, immunotherapy has been constructed in the enlargement of immune checkpoint inhibitors as a promising approach for NSCLC treatment. Evading the immune system using the PD-1/PD-L1 axis is an intelligent way for cancers, and T cells cannot respond fully and confront cancer. Recently, the miR-138 was reported as a PD-L1 regulator in NSCLC. However, its inhibitory impact on T-cell exhaustion has not been characterized. The present study aims to impair PD-L1 (B7-H1) expression in Adenocarcinoma cell lines using miR-138-5p and determines how it prevents Jurak cell exhaustion. To gain the purpose, first, 18 highly significant dysregulated miRNAs containing hsa-miR-138 and CD274-mRNA network were detected in NSCLC based on bioinformatics analysis. Moreover, our study revealed a high level of miR-138-5p could make significant changes like PDL1 downregulation, proliferation, and mortality rate in A549/Calu6 cells. We also simulate cancer environmental conditions by culturing Jurak cells and NSCLC cell lines under the influence of stimulator cytokines to show how miR-138-5p survives Jurak cells by targeting PD-L1/PD-1pathway.
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Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , MicroARNs , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Células Jurkat , Células A549 , Supervivencia Celular , Proliferación Celular , Línea Celular TumoralRESUMEN
Objective: Emerging evidence suggests that dietary interventions hold promise for promoting cognitive function and mental well-being in aging populations. This systematic review aimed to examine the potential relationship between Time-Restricted Eating (TRE) and Intermittent Fasting (IFA) with cognitive function and mental health in older adults. Methods: A thorough exploration was undertaken on electronic databases such as PubMed, Scopus, Web of Science, Science Direct, and Google Scholar, up to October 2023, following PRISMA standards. The evaluation of the quality and potential bias in the incorporated articles involved the use of the Newcastle-Ottawa Scale and Consolidated Standards of Reporting Trials (CONSORT). Results: From a total of 539 articles initially identified, eight studies met the eligibility criteria for inclusion in this review. Out of these eight studies, six focused on cognitive function, and 2 focused on mental health. The reviewed articles encompassed a wide range of population sizes, with the number of older adults studied varying from 10 to 1357, reflecting a diverse cohort of individuals. Conclusions.The findings suggest that TRE and IFA may have a positive impact on cognitive function and mental health in this population. However, additional research is needed to fully comprehend this relationship. Therefore, future research should specifically examine factors such as the duration and timing of the eating window in TRE, as well as the physical condition of older adults, to provide a more nuanced understanding of the cognitive and mental health benefits of TRE and IFA in older adults.
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Glycogen storage diseases (GSDs) are a group of rare inherited metabolic disorders characterized by clinical, locus, and allele heterogeneity. This study aims to investigate the phenotype and genotype spectrum of GSDs in a cohort of 14 families from Iran using whole-exome sequencing (WES) and variant analysis. WES was performed on 14 patients clinically suspected of GSDs. Variant analysis was performed to identify genetic variants associated with GSDs. A total of 13 variants were identified, including six novel variants, and seven previously reported pathogenic variants in genes such as AGL, G6PC, GAA, PYGL, PYGM, GBE1, SLC37A4, and PHKA2. Most types of GSDs observed in the cohort were associated with hepatomegaly, which was the most common clinical presentation. This study provides valuable insights into the phenotype and genotype spectrum of GSDs in a cohort of Iranian patients. The identification of novel variants adds to the growing body of knowledge regarding the genetic landscape of GSDs and has implications for genetic counseling and future therapeutic interventions. The diverse nature of GSDs underscores the need for comprehensive genetic testing methods to improve diagnostic accuracy. Continued research in this field will enhance our understanding of GSDs, ultimately leading to improved management and outcomes for individuals affected by these rare metabolic disorders.
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Background and aims: The occurrence of thiamine metabolism dysfunction syndrome (THMD), a rare autosomal recessive condition, may be linked to various mutations found in the TPK1 and SLC19A3 genes. The disease chiefly manifests through ataxia, muscle hypotonia, abrupt or subacute onset encephalopathy, and a decline in developmental milestones achieved during the early stages of infancy. We present findings from an investigation that involved two individuals from Iran, both of whom experienced seizures along with ataxia and hypotonia. The underlying genetic causes were found with the use of next-generation sequencing (NGS) technology, which has facilitated the detection of causal changes in a variety of genetic disorders. Material and methods: The selection of cases for this study was based on the phenotypic and genetic information that was obtainable from the Center for Comprehensive Genetic Services. The genetic basis for the problems observed among the participants was determined through the application of whole-exome sequencing (WES). Subsequently, sanger sequencing was employed as a means of validating any identified variations suspected to be causative. Results: The first patient exhibited a homozygous mutation in the TPK1 gene, NM_022445.4:c.224 T > A:p.I75 N, resulting in the substitution of isoleucine for asparagine at position 75 (p.I75 N). In our investigation, patient 2 exhibited a homozygous variant, NM_025243.4:c.1385dupA:pY462X, within the SLC19A3 gene. Conclusions: Collectively, when presented with patients showcasing ataxia, encephalopathy, and basal ganglia necrosis, it is essential to account for thiamine deficiency in light of the potential advantages of prompt intervention. At times, it may be feasible to rectify this deficiency through the timely administration of thiamine dosages. Accordingly, based on the results of the current investigation, these variations may be useful for the diagnosis and management of patients with THMD.
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Epilepsy is a neurological condition distinguished by recurrent and unexpected seizures. Astrocytic channels and transporters are essential for maintaining normal neuronal functionality. The astrocytic water channel, aquaporin-4 (AQP4), which plays a pivotal role in regulating water homeostasis, is a potential target for epileptogenesis. In present study, we examined the effect of different doses (10, 50, 100 µM and 5 mM) of AQP4 inhibitor, 2-nicotinamide-1, 3, 4-thiadiazole (TGN-020), during kindling acquisition, on seizure parameters and seizure-induced cognitive impairments. Animals were kindled by injection of pentylenetetrazole (PTZ: 37.5 mg/kg, i.p.). TGN-020 was administered into the right lateral cerebral ventricle 30 min before PTZ every alternate day. Seizure parameters were assessed 20 min after PTZ administration. One day following the last PTZ injection, memory performance was investigated using spontaneous alternation in Y-maze and novel object recognition (NOR) tests. The inhibition of AQP4 during the kindling process significantly decreased the maximal seizure stage and seizure duration (two-way ANOVA, P = 0.0001) and increased the latency of seizure onset and the number of PTZ injections required to induce different seizure stages (one-way ANOVA, P = 0.0001). Compared to kindled rats, the results of the NOR tests showed that AQP4 inhibition during PTZ-kindling prevented recognition memory impairment. Based on these results, AQP4 could be involved in seizure development and seizure-induced cognitive impairment. More investigation is required to fully understand the complex interactions between seizure activity, water homeostasis, and cognitive dysfunction, which may help identify potential therapeutic targets for these conditions.
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Acuaporina 4 , Disfunción Cognitiva , Excitación Neurológica , Niacinamida , Tiadiazoles , Animales , Ratas , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Niacinamida/administración & dosificación , Niacinamida/análogos & derivados , Pentilenotetrazol , Convulsiones/inducido químicamente , Convulsiones/complicaciones , Convulsiones/tratamiento farmacológico , Tiadiazoles/administración & dosificación , Agua/efectos adversos , Acuaporina 4/antagonistas & inhibidoresRESUMEN
PURPOSE: This study aims to assess the vision-related quality of life in patients with retinal vein occlusion (RVO) among those referred to Labbafinejad Medical Center and Imam Hossein Hospital between 2019 and 2021. METHODS: This comparative study included 37 eligible patients diagnosed with various types of RVO, with an average age of 61 ± 9. To ensure data validity, we included 74 age- and sex-matched healthy individuals. Only cases with a definitive diagnosis of RVO, confirmed by two retina specialists (ND and RN), were included. We assessed the vision-related quality of life of our participants using the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25). All participants underwent interviews. RESULTS: In our study, we examined the vision-related quality of life in different subgroups of RVO patients. Overall, RVO patients had a significantly lower total VRQoL score compared to healthy individuals (P < 0.001), except in the subscale analysis of specific factors such as ocular pain, color vision, and driving, where no statistically significant difference was observed. A statistically significant difference was found in the comparison of subgroups, indicating lower VRQoL in central retinal vein occlusion (CRVO) patients (P = 0.010). Furthermore, a significant correlation was observed between lower VRQoL and decreased vision (P = 0.009) as well as longer disease duration (P = 0.011). CONCLUSION: Retinal vein occlusion can significantly reduce vision-related quality of life, particularly in more severe cases.
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Calidad de Vida , Oclusión de la Vena Retiniana , Humanos , Persona de Mediana Edad , Anciano , Oclusión de la Vena Retiniana/diagnóstico , Dolor Ocular , Encuestas y CuestionariosRESUMEN
The present study aimed to investigate the effect of corticolimbic cannabinoid CB1 receptors activity on memory impairment in the intracerebroventricular (ICV)-streptozotocin (STZ) animal model of Alzheimer's like-disease. This study also assessed whether the corticolimbic overexpression of miRNA-137 or -let-7a could increase the endocannabinoids by inhibiting the monoglyceride lipase (MAGL) to ameliorate STZ response. The results showed that ICV microinjection of STZ (3 mg/kg/10 µl) impaired passive avoidance memory retrieval. The chronic microinjection of arachidonylcyclopropylamide (ACPA; 10 ng/0.5 µl), a selective cannabinoid CB1 receptor agonist, into the hippocampal CA1 region, the central amygdala (CeA) or the medial prefrontal cortex (mPFC) ameliorated the amnesic effect of ICV-STZ. Intra-CA1 or -CeA microinjection of ACPA alone did not affect memory retrieval, while its microinjection into the mPFC impaired memory formation. Based on bioinformatics analysis and verification of the MAGL gene, miRNA-137 and -let-7a were chosen to target the expression levels of MAGL in the corticolimbic regions. The chronic corticolimbic microinjection of lentiviral particles containing miRNA-137 or -let-7a ameliorated ICV-STZ-induced memory impairment. The high transfection efficiency was determined for each virus using comparing fluorescent and conventional vision. Corticolimbic overexpression of miRNA-137 or -let-7a decreased the MAGL gene expression that encodes the MAGL enzyme to increase the endocannabinoids. Thus, among the molecular mechanisms and signaling pathways involved in the pathophysiology of Alzheimer's disease (AD), it is worth mentioning the role of endocannabinoids in the corticolimbic regions. CB1 receptor agonists, miRNA-137 or -let-7a, may be potential therapeutic targets against cognitive decline in AD.
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Enfermedad de Alzheimer , Cannabinoides , Ratas , Animales , Estreptozocina , Ratas Wistar , Endocannabinoides/uso terapéutico , Endocannabinoides/metabolismo , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Microinyecciones , Receptor Cannabinoide CB1/uso terapéutico , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/metabolismo , Agonistas de Receptores de Cannabinoides/uso terapéutico , Cannabinoides/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
AIMS: Heart failure (HF) after myocardial infarction (MI) is a major cause of morbidity and mortality. We sought to investigate the functional importance of cardiac iron status after MI and the potential of pre-emptive iron supplementation in preventing cardiac iron deficiency (ID) and attenuating left ventricular (LV) remodelling. METHODS AND RESULTS: MI was induced in C57BL/6J male mice by left anterior descending coronary artery ligation. Cardiac iron status in the non-infarcted LV myocardium was dynamically regulated after MI: non-haem iron and ferritin increased at 4 weeks but decreased at 24 weeks after MI. Cardiac ID at 24 weeks was associated with reduced expression of iron-dependent electron transport chain (ETC) Complex I compared with sham-operated mice. Hepcidin expression in the non-infarcted LV myocardium was elevated at 4 weeks and suppressed at 24 weeks. Hepcidin suppression at 24 weeks was accompanied by more abundant expression of membrane-localized ferroportin, the iron exporter, in the non-infarcted LV myocardium. Notably, similarly dysregulated iron homeostasis was observed in LV myocardium from failing human hearts, which displayed lower iron content, reduced hepcidin expression, and increased membrane-bound ferroportin. Injecting ferric carboxymaltose (15 µg/g body weight) intravenously at 12, 16, and 20 weeks after MI preserved cardiac iron content and attenuated LV remodelling and dysfunction at 24 weeks compared with saline-injected mice. CONCLUSION: We demonstrate, for the first time, that dynamic changes in cardiac iron status after MI are associated with local hepcidin suppression, leading to cardiac ID long term after MI. Pre-emptive iron supplementation maintained cardiac iron content and attenuated adverse remodelling after MI. Our results identify the spontaneous development of cardiac ID as a novel disease mechanism and therapeutic target in post-infarction LV remodelling and HF.
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Insuficiencia Cardíaca , Deficiencias de Hierro , Infarto del Miocardio , Masculino , Ratones , Humanos , Animales , Hepcidinas/metabolismo , Hepcidinas/uso terapéutico , Hierro/metabolismo , Hierro/uso terapéutico , Ratones Endogámicos C57BL , Miocardio/metabolismo , Insuficiencia Cardíaca/metabolismo , Suplementos Dietéticos , Remodelación VentricularRESUMEN
BACKGROUND: Glioblastoma multiforme (GBM) is associated with remarkably poor prognosis, and its treatment is challenging. This investigation aimed to evaluate the safety of suicide gene therapy using allogeneic adipose tissue-derived mesenchymal stem cells (ADSCs) carrying herpes simplex virus-thymidine kinase (HSV-TK) gene for the first time in patients with recurrent GBM. METHODS: This study was a first-in-human, open-label, single-arm, phase I clinical trial with a classic 3 + 3 dose escalation design. Patients who did not undergo surgery for their recurrence were included and received this gene therapy protocol. Patients received the intratumoral stereotactic injection of ADSCs according to the assigned dose followed by prodrug administration for 14 days. The first dosing cohort (n = 3) received 2.5 × 105 ADSCs; the second dosing cohort (n = 3) received 5 × 105 ADSCs; the third dosing cohort (n = 6) received 10 × 105 ADSCs. The primary outcome measure was the safety profile of the intervention. RESULTS: A total of 12 patients with recurrent GBM were recruited. The median follow-up was 16 (IQR, 14-18.5) months. This gene therapy protocol was safe and well tolerated. During the study period, eleven (91.7%) patients showed tumor progression, and nine (75.0%) died. The median overall survival (OS) was 16.0 months (95% CI 14.3-17.7) and the median progression-free survival (PFS) was 11.0 months (95% CI 8.3-13.7). A total of 8 and 4 patients showed partial response and stable disease, respectively. Moreover, significant changes were observed in volumetric analysis, peripheral blood cell counts, and cytokine profile. CONCLUSIONS: The present clinical trial, for the first time, showed that suicide gene therapy using allogeneic ADSCs carrying the HSV-TK gene is safe in patients with recurrent GBM. Future phase II/III clinical trials with multiple arms are warranted to validate our findings and further investigate the efficacy of this protocol compared with standard therapy alone. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT), IRCT20200502047277N2. Registered 8 October 2020, https://www.irct.ir/ .
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Neoplasias Encefálicas , Glioblastoma , Trasplante de Células Madre Hematopoyéticas , Humanos , Glioblastoma/genética , Glioblastoma/terapia , Irán , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patología , Recurrencia Local de Neoplasia/terapia , Recurrencia Local de Neoplasia/patología , Terapia Genética/métodosRESUMEN
Introduction: The prognosis for glioblastoma multiforme (GBM), a malignant brain tumor, is poor despite recent advancements in treatments. Suicide gene therapy is a therapeutic strategy for cancer that requires a gene to encode a prodrug-activating enzyme which is then transduced into a vector, such as mesenchymal stem cells (MSCs). The vector is then injected into the tumor tissue and exerts its antitumor effects. Case presentation: A 37-year-old man presented to our department with two evident foci of glioblastoma multiforme at the left frontal and left parietal lobes. The patient received an injection of bone marrow-derived MSCs delivering the herpes simplex virus thymidine kinase (HSV-tk) gene to the frontal focus of the tumor, followed by ganciclovir administration as a prodrug for 14 days. For follow-up, the patient was periodically assessed using magnetic resonance imaging (MRI). The growth and recurrence patterns of the foci were assessed. After the injection on 09 February 2019, the patient's follow-up appointment on 19 December 2019 MRI revealed a recurrence of parietal focus. However, the frontal focus had a slight and unremarkable enhancement. On the last follow-up (18 March 2020), the left frontal focus had no prominent recurrence; however, the size of the left parietal focus increased and extended to the contralateral hemisphere through the corpus callosum. Eventually, the patient passed away on 16 July 2020 (progression-free survival (PFS) = 293 days, overall survival (OS) = 513 days). Conclusion: The gliomatous focus (frontal) treated with bone marrow-derived MSCs carrying the HSV-TK gene had a different pattern of growth and recurrence compared with the non-treated one (parietal). Trial registration: IRCT20200502047277N2. Registered 10 May 2020-Retrospectively registered, https://eng.irct.ir/trial/48110.
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Nanofibrous patches have attracted much attention as a solution to resolve drug delivery challenges. In this study, vitamin B12- loaded polyvinyl alcohol (PVA)/chitosan (Cs) nanofiber patch (NFP) was electrospun and cross-linked by glutaraldehyde (GA). The physicochemical properties of the nanofiber patches were assessed by morphological studies, FTIR analysis, hydrophilicity test, mechanical tests, and in-vitro evaluations including biodegradability, MTT assay, and cumulative release test of vitamin. In-vivo studies were also carried out by measuring vitamin B12 levels in the bloodstream and conducting histopathology studies on the animal models. The results showed that the mean diameter of Cs/PVA/B12 and cross-linked patch were approximately 207 and 256 nm, respectively. Cross-linking of NFP led to the lower, slower, and more continuous release of the vitamin with a slight decrease in biodegradability, and an increase in the mechanical properties of the nanofiber patches. Furthermore, the cytocompatibility assay, MTT, and in vivo results revealed no cytotoxicity of Cs/PVA/B12 NFP towards L929 cell line. No lesion or tissue damage was observed in the skin tissue of the animal models wearing these skin patches. Therefore, B12-loaded NFP can be introduced as a potential candidate for commercial transdermal routes.
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Quitosano , Nanofibras , Animales , Quitosano/química , Vitamina B 12 , Nanofibras/química , Alcohol Polivinílico/química , VitaminasRESUMEN
Coronavirus infectious disease-19 (COVID-19) usually alters the innate and adaptive immune setting by excessive production of proinflammatory cytokines, leading to a deviation in the natural course of simultaneous malignant disease. In the absence of disease-modifying therapy, complete remission of acute myeloid leukemia (AML) is an extraordinary event caused mainly by an immune-related mechanism secondary to a severe infectious process. We present a 57-year-old woman with a new diagnosis of AML associated with a 11q23/KMT2A abnormality who had achieved temporary spontaneous remission in the absence of disease-modifying therapy following the severe pulmonary infection with coronavirus lasting for six months. We review the literature and explain the potential impact of stimulated immune responses by COVID-19 on induction of remission in a patient with AML that could provide an excellent opportunity for new immune-based therapies to evolve for the hematologic malignancies. Despite the high ability of the immune process to destroy the malignant cells, the remission of duration is usually short. Therefore, it seems that continuing treatment after SR of AML by a consolidation regimen or bone marrow transplantation, based on a risk-adapted treatment approach, may reduce the recurrence risk.
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Objective: The aim of this study was to investigate the moderating role of job control in relation to mental workload and job satisfaction of healthcare workers. Methods: This cross-sectional study was carried out on 480 nurses, midwives, and administrative workers in four educational hospitals of Ardabil, Iran. Research tools were included demographic information questionnaire, NASA-TLX questionnaire, job description index (JDI) questionnaire and job control inquiry. Results: Compared with administrative workers, mental workload of nurses and midwives was significantly higher and likewise mental workload of nurses was significantly difference compared to midwives (P < 0.001). Nurses and midwives had substantially higher job satisfaction than administrative workers (P < 0.001). Also, nurses and midwives had higher job control than administrative workers (P < 0.001 and P = 0.002, respectively). Based on the designed model, the correlation between mental workload and job satisfaction was negative and significant (r = -0.22); which in the presence of job control, the relationship between the two variables of workload and job satisfaction slightly increased (r = -0.19, P < 0.001). These conditions were the same in the three job groups separately. Conclusion: Mental workload is inversely related to job satisfaction and job control. Job control plays an important role in improving working conditions in healthcare workers.
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Satisfacción en el Trabajo , Carga de Trabajo , Estudios Transversales , Personal de Salud , Humanos , Encuestas y CuestionariosRESUMEN
BACKGROUND: We performed a multicenter, randomized open-label trial in patients with moderate to severe Covid-19 treated with a range of possible treatment regimens. METHODS: Patients were randomly assigned to one of three regimen groups at a ratio of 1:1:1. The primary outcome of this study was admission to the intensive care unit. Secondary outcomes were intubation, in-hospital mortality, time to clinical recovery, and length of hospital stay (LOS). Between April 13 and August 9, 2020, a total of 336 patients were randomly assigned to receive one of the 3 treatment regimens including group I (hydroxychloroquine stat, prednisolone, azithromycin and naproxen; 120 patients), group II (hydroxychloroquine stat, azithromycin and naproxen; 116 patients), and group III (hydroxychloroquine and lopinavir/ritonavir (116 patients). The mean LOS in patients receiving prednisolone was 5.5 in the modified intention-to-treat (mITT) population and 4.4 days in the per-protocol (PP) population compared with 6.4 days (mITT population) and 5.8 days (PP population) in patients treated with Lopinavir/Ritonavir. RESULTS: The mean LOS was significantly lower in the mITT and PP populations who received prednisolone compared with populations treated with Lopinavir/Ritonavir (p = 0.028; p = 0.0007). We observed no significant differences in the number of deaths, ICU admission, and need for mechanical ventilation between the Modified ITT and per-protocol populations treated with prednisolone and Lopinavir/Ritonavir, although these outcomes were better in the arm treated with prednisolone. The time to clinical recovery was similar in the modified ITT and per-protocol populations treated with prednisolone, lopinavir/ritonavir, and azithromycin (P = 0.335; P = 0.055; p = 0.291; p = 0.098). CONCLUSION: The results of the present study show that therapeutic regimen (regimen I) with low dose prednisolone was superior to other regimens in shortening the length of hospital stay in patients with moderate to severe COVID-19. The steroid sparing effect may be utilized to increase the effectiveness of corticosteroids in the management of diabetic patients by decreasing the dosage.
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Tratamiento Farmacológico de COVID-19 , Glucocorticoides/uso terapéutico , Prednisolona/uso terapéutico , Adulto , Anciano , Antivirales/uso terapéutico , COVID-19/diagnóstico , COVID-19/mortalidad , COVID-19/virología , Quimioterapia Combinada , Femenino , Glucocorticoides/efectos adversos , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Intubación Intratraqueal , Irán , Tiempo de Internación , Masculino , Persona de Mediana Edad , Prednisolona/efectos adversos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
Colorectal cancer (CRC) with high metastasis rates has been known as a major cause of death worldwide. Lack of the specificity and insufficient concentrations of traditional chemotherapeutics at tumor site and their severe adverse effects necessitate development of new treatment strategies such as designing suitable nanocarriers for delivery of drugs, improving their pharmacological profiles and reducing adverse effects. We have developed a platform based on the poly-ursolic acid (poly-UA), a polymeric system with potential anticancer effect. Following the self-assembly of poly-UA into the nanoparticles (NPs), they were applied for delivery of mithramycin A (Mith-A), a promising candidate for CRC therapy, however, with some limitations such as rapid clearance and serious side effects. Mith-A-loaded poly-UA NPs with suitable physicochemical properties and efficient drug entrapment, released Mith-A in a controlled manner and provided suitable toxicity against the CT-26 colorectal cancer cells, increased accumulation in tumor, and protection against the detrimental features of the disease. Poly-UA NPs demonstrated therapeutic efficiency (in vivo and in vitro) by themselves. The prepared NPs induced no remarkable alteration of body weights or damages to the major organs in animals bearing tumor indicating the safety of NPs. The bioactive nanoformulation along with improving the pharmacological profile of Mith-A could provide a synergistic toxicity against the CRC.
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Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Animales , Antineoplásicos/administración & dosificación , Línea Celular , Composición de Medicamentos , Humanos , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
Widespread investigation has revealed the promising ability of suicidal genes in the treatment of glioma tumors; nevertheless, promoting their effects relies on the ability to apply suitable vehicles and techniques. In this study, the safety and feasibility of using bone marrow-derived mesenchymal stem cells (MSCs) in combination with prodrug for treatment of patients with primary and secondary glioblastoma multiform (GBM) was assessed. Five GBM patients were recruited. Following gross total resection of the tumor and adjuvant radiotherapy and chemotherapy, intracerebral injection of autologous MSCs transduced with lentivirus containing herpes simplex virus thymidine kinase (HSV-TK) was performed followed by intravenous administration of ganciclovir for 2 weeks. The treatment was well tolerated by all patients. Mild-to-moderate fever, headache, and cerebrospinal fluid leukocytosis were evident in three, two, and one patient, respectively. The progression-free survival (PFS) and overall survival (OS) of patients were 95.79 ± 51.40 and 128.85 ± 48.81 weeks, respectively. The 1-year PFS and OS were 60% and 100%, respectively, among our patients, and two patients had more than 3 years of OS and more than 2 years of PFS. It seems that intracerebral administration of bone marrow MSC containing the HSV-TK gene in combination with intravenous ganciclovir would be safe and feasible in the treatment of patients with GBM.
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Antineoplásicos/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Ganciclovir/administración & dosificación , Glioblastoma/tratamiento farmacológico , Células Madre Mesenquimatosas , Adulto , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Sistemas de Liberación de Medicamentos , Estudios de Factibilidad , Femenino , Ganciclovir/uso terapéutico , Glioblastoma/mortalidad , Glioblastoma/patología , Células HEK293 , Humanos , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
Nanotechnology-based approaches have enabled overcoming the challenging issues such as the rapid clearance, poor solubility, and non-specific action or cellular uptake of drugs. In this study, we have evaluated the therapeutic effects of the phenolic compound, ferulic acid (FA), in the acute pancreatitis (AP) as this phenolic compound has demonstrated promising effects against the oxidative stress and inflammatory reactions. In order to overcome the poor solubility and bioavailability of FA, it was entrapped into the nanoparticles (NPs) based on the silk fibroin (SF) as a biomimetic substance. Neutrophil membrane-coated SF-NPs with appropriate capacity of FA loading and physicochemical characteristics, released FA in a controlled fashion, selectively delivered FA into the inflammatory pancreas lesion, and demonstrated protective effects against the detrimental aspects of the disease. The prepared nanoformulation by improving the pharmacological profile of FA and targeted delivery could be of therapeutic importance against the AP via suppressing the inflammation and oxidative stress.
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Ácidos Cumáricos/farmacología , Neutrófilos/química , Pancreatitis/tratamiento farmacológico , Animales , Disponibilidad Biológica , Ácidos Cumáricos/química , Ácidos Cumáricos/metabolismo , Sistemas de Liberación de Medicamentos , Fibroínas/química , Fibroínas/metabolismo , Fibroínas/farmacología , Masculino , Nanopartículas/química , Neutrófilos/metabolismo , Pancreatitis/metabolismo , Tamaño de la Partícula , Ratas , Ratas WistarRESUMEN
AIM: In the current study, it was hypothesized that single nucleotide polymorphisms (SNPs) in the regulatory region of the IL-22 signaling pathway genes, including IL-22 and IL-22RA1 variants, may be associated with CRC susceptibility. BACKGROUND: The important role of pro-inflammatory cytokines during tumorigenesis is well-established. In recent years, IL-22 has been linked with colorectal cancer (CRC) through a number of mechanistic and observational studies. METHODS: The association of four polymorphisms in the IL-22 (rs1179251 and rs1179246) and IL-22RA1 (rs4648936 and rs10794665) genes with CRC risk were studied using a case-control design with 304 cases and 345 controls from the Iranian population. All 649 subjects were evaluated by PCR-RFLP method. RESULTS: No significant difference was found in genotype and allele frequencies between the cases and controls for either IL-22 and IL-22RA1 gene variants or CRC risk before or after adjusting for confounders. CONCLUSION: The current findings do not present any significant evidence for associations between variants in IL-22 signaling pathway genes and CRC. Complementary studies with greater sample sizes may be necessary to fully elucidate the nature of these associations.
RESUMEN
Recently, drug-eluting nanofibrous scaffolds have attracted a great attention to enhance the cell differentiation through biomimicking the extracellular matrix (ECM) in regenerative medicine. In this study, electrospun nanocomposite polycaprolactone (PCL)-based scaffolds containing synthesized graphene oxide (GO) nanosheets and osteogenic drugs, i.e. dexamethasone and simvastatin were fabricated. The physicochemical and surface properties of the scaffolds were investigated through FTIR, wettability, pH, and drug release studies. The cell viability, differentiation, and biomineralization were studied on mesenchymal stem cells (MSCs) by Alamar Blue, alkaline phosphatase (ALP) activity, and Alizarin Red-S staining, respectively. Uniformly distributed GO (thickness < 1 nm) in PCL nanofibers was observed by electron microscopy. It was revealed that the addition of GO and the drugs improved the hydrophilicity, cell viability, and osteogenic differentiation, in addition to pH changes, in comparison with PCL scaffolds. Despite the notable reduction in the cell viability, significant differentiation was revealed by ALP assay on PCL/GO-Dex scaffolds. Noteworthy, a twofold increase in the osteogenic differentiation was observed in comparison with the cells cultured in osteogenic differentiation medium, while a significant biomineralization was observed. The results of this study indicate the synergistic effect of GO and dexamethasone on improving osteogenic differentiation of drug-eluting nanocomposite scaffolds in bone tissue engineering applications.