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1.
Pediatr Nephrol ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38926177

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is a prevalent health issue that can have detrimental effects on the quality of life (QoL) of children. Nevertheless, with adequate management and support, many children with CKD can have satisfying lives. The study aimed to investigate the effect of muscle stretching and isometric exercises on QoL of children undergoing hemodialysis. METHODS: Sixty-eight children aged 6-18 years with kidney failure undergoing hemodialysis at Assiut University Children Hospital were included. They were randomly assigned to two groups. The study group received a 40-min exercise program three times per week for 2 months, while the control group received routine hospital care. For outcome measures, two tools were used: a simple questionnaire sheet for personal and medical data and PedsQL™ scale. RESULTS: After 2 months of exercise, it was shown that most children in the study group (66.7%) had good QoL, in contrast to only 3.3% in the control group, with a highly statistically significant variation between the two examined groups pertaining to the health-related QoL scale (P value = 0.001) after exercise. CONCLUSION: The intensity of care for children on hemodialysis has a distinguished impact upon their quality of life. The implementation of muscle stretching and isometric exercises during hemodialysis represents an important aspect of such care that may be associated with significant improvement in all domains of QoL. Children undergoing hemodialysis need well-organized programs that cover all physical and psychological aspects with smart time manipulation and increased attention from their staff.

2.
Proc Natl Acad Sci U S A ; 121(15): e2321502121, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38564636

RESUMO

The release of paused RNA polymerase II (RNAPII) from promoter-proximal regions is tightly controlled to ensure proper regulation of gene expression. The elongation factor PTEF-b is known to release paused RNAPII via phosphorylation of the RNAPII C-terminal domain by its cyclin-dependent kinase component, CDK9. However, the signal and stress-specific roles of the various RNAPII-associated macromolecular complexes containing PTEF-b/CDK9 are not yet clear. Here, we identify and characterize the CDK9 complex required for transcriptional response to hypoxia. Contrary to previous reports, our data indicate that a CDK9 complex containing BRD4 but not AFF1/4 is essential for this hypoxic stress response. We demonstrate that BRD4 bromodomains (BET) are dispensable for the release of paused RNAPII at hypoxia-activated genes and that BET inhibition by JQ1 is insufficient to impair hypoxic gene response. Mechanistically, we demonstrate that the C-terminal region of BRD4 is required for Polymerase-Associated Factor-1 Complex (PAF1C) recruitment to establish an elongation-competent RNAPII complex at hypoxia-responsive genes. PAF1C disruption using a small-molecule inhibitor (iPAF1C) impairs hypoxia-induced, BRD4-mediated RNAPII release. Together, our results provide insight into potentially targetable mechanisms that control the hypoxia-responsive transcriptional elongation.


Assuntos
Proteínas Nucleares , Fatores de Transcrição , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Regulação da Expressão Gênica , Quinases Ciclina-Dependentes/metabolismo , Quinase 9 Dependente de Ciclina/genética , Quinase 9 Dependente de Ciclina/metabolismo , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , Fosforilação , Hipóxia , Transcrição Gênica , Fator B de Elongação Transcricional Positiva/genética , Fator B de Elongação Transcricional Positiva/metabolismo , Proteínas que Contêm Bromodomínio , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo
3.
Microorganisms ; 9(6)2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070716

RESUMO

Tumorigenesis due to viral infection accounts for a high fraction of the total global cancer burden (15-20%) of all human cancers. A comprehensive understanding of the mechanisms by which viral infection leads to tumor development is extremely important. One of the main mechanisms by which viruses induce host cell proliferation programs is through controlling the host's epigenetic machinery. In this review, we dissect the epigenetic pathways through which oncogenic viruses can integrate their genome into host cell chromosomes and lead to tumor progression. In addition, we highlight the potential use of drugs based on histone modifiers in reducing the global impact of cancer development due to viral infection.

4.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21250226

RESUMO

COVID-19 pandemic raises an extraordinary challenge to the healthcare systems globally. The governments are taking key measures to constrain the corresponding health, social, and economic impacts, however, these measures vary depending on the nature of the crisis and country-specific circumstances. ObjectivesConsidering different incidence and mortality rates across different countries, we aimed at explaining variance of these variables by performing accurate and precise multivariate analysis with aid of suitable predictors, accordingly, the model would proactively guide the governmental responses to the crisis. MethodsUsing linear and exponential time series analysis, this research aimed at studying the incidence and mortality rates of COVID-19 in 18 countries during the first six months of the pandemic, and further utilize multivariate techniques to explain the variance in monthly exponential growth rates of cases and deaths with aid of a set of different predictors: the recorded Google mobility trends towards six categories of places, daily average temperature, daily humidity, and key socioeconomic attributes of each country. ResultsThe analysis showed that changes in mobility trends were the most significant predictors of the incidence and mortality rates, temperature and humidity were also significant but to a much lesser extent, on the other hand, the socioeconomic attributes did not contribute significantly to explaining different incidence and mortality rates across countries. ConclusionChanges in mobility trends across countries dramatically affected the incidence and mortality rates across different countries, thus, it might be used as a proxy measure of contact frequency.

5.
J Hematol Oncol ; 12(1): 114, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31744508

RESUMO

Clonal evolution of chronic lymphocytic leukemia (CLL) often follows chemotherapy and is associated with adverse outcome, but also occurs in untreated patients, in which case its predictive role is debated. We investigated whether the selection and expansion of CLL clone(s) precede an aggressive disease shift. We found that clonal evolution occurs in all CLL patients, irrespective of the clinical outcome, but is faster during disease progression. In particular, changes in the frequency of nucleotide variants (NVs) in specific CLL-related genes may represent an indicator of poor clinical outcome.


Assuntos
Biomarcadores Tumorais/genética , Aberrações Cromossômicas , Evolução Clonal , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Mutação , Progressão da Doença , Humanos , Estudos Longitudinais , Prognóstico , Taxa de Sobrevida
6.
Iran J Kidney Dis ; 13(2): 129-131, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30988250

RESUMO

Acute kidney injury is manifested by sudden deterioration of kidney functions, with or without reduction of urine output. The spectrum of injury ranges from mild to severe, sometimes requires renal replacement therapy. The initial workup includes a patient history to identify the use of nephrotoxic medications or systemic illnesses that may cause poor renal perfusion or directly impair renal function. Formaldehyde which present in cosmetic products; is toxic to many parts including respiratory, renal, and neurologic systems. Here, we have reported 2 cases of acute kidney injury (AKI) after using formaldehyde free hair straightening protein presented with acute tubular injury, responded to corticosteroid therapy.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Corticosteroides/uso terapêutico , Preparações para Cabelo/química , Adolescente , Criança , Feminino , Formaldeído , Humanos , Rim/fisiopatologia
7.
Gene ; 702: 114-122, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-30902789

RESUMO

AIM: Diabetic peripheral neuropathy (DPN) is a frequent and debilitating complication of diabetes mellitus. The low-density lipoprotein receptor-related protein-1 (LRP-1) is a multifunctional cell surface receptor playing critical roles in lipoprotein metabolism and several cell signaling processes. C/EBP homologous protein (CHOP) is a main conduit to endoplasmic reticulum stress-induced apoptosis. We aimed to investigate LRP1 and CHOP gene expression in peripheral blood cells of type 2 diabetes mellitus (T2DM) subjects to clarify its possible relation to DPN pathogenesis. METHOD: The study included 20 non-complicated T2DM subjects, 20 subjects with DPN and 20 healthy controls. Quantitative real time PCR was used to study gene expression. RESULTS: There was a significant reduction in LRP1 mRNA expression and a significant increase in CHOP mRNA expression in subjects with DPN compared to non-complicated group and healthy controls. Both LRP1 and CHOP expression levels were inversely correlated, and both showed significant correlation with HbA1c, hyperlipidemia, hs-CRP, and different electrophysiological parameters. Receiver operating characteristics (ROC) analysis suggested that both LRP1 and CHOP mRNA expression and hs-CRP levels had great potential advantages to predict the progression of DPN. CONCLUSION: LRP1 and CHOP might be involved in DPN pathogenesis and progression, thus providing opportunities for early detection and treatment.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/sangue , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/sangue , Fator de Transcrição CHOP/sangue , Adulto , Células Sanguíneas/metabolismo , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/genética , Neuropatias Diabéticas/fisiopatologia , Feminino , Expressão Gênica , Humanos , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Masculino , Pessoa de Meia-Idade , Condução Nervosa , RNA Mensageiro/metabolismo , Fator de Transcrição CHOP/genética
8.
Crit Rev Oncol Hematol ; 98: 1-11, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26476748

RESUMO

No international guidelines are available for the treatment of oral tongue cancer during pregnancy. Six patients with tongue cancer during pregnancy were identified by a retrospective chart review. In three of the cases we did not follow the standard treatment, the women had disease progression, and two of them died after a short time. A multidisciplinary discussion and literature review suggest that following the standard surgical procedure could be the optimal treatment to ensure mother and baby health in tongue cancer. Nonetheless choosing between maternal advantage and potential fetal damage should not be an individual medical decision. Treatment "customization" is a possibility. Patients and their families should be provided with comprehensive information and appropriate support in order to fully participate in the decision-making process. The patient's care may be improved if carried out in a specialized maternity center where the surgical oncologic treatment is managed together with the obstetric aspects.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Complicações Neoplásicas na Gravidez/cirurgia , Neoplasias da Língua/cirurgia , Feminino , Humanos , Gravidez , Estudos Retrospectivos
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