RESUMO
The CRISPR/Cas system, an innovative gene-editing tool, is emerging as a promising technique for genome modifications. This straightforward technique was created based on the prokaryotic adaptive immune defense mechanism and employed in the studies on human diseases that proved enormous therapeutic potential. A genetically unique patient mutation in the process of gene therapy can be corrected by the CRISPR method to treat diseases that traditional methods were unable to cure. However, introduction of CRISPR/Cas9 into the clinic will be challenging because we still need to improve the technology's effectiveness, precision, and applications. In this review, we first describe the function and applications of the CRISPR-Cas9 system. We next delineate how this technology could be utilized for gene therapy of various human disorders, including cancer and infectious diseases and highlight the promising examples in the field. Finally, we document current challenges and the potential solutions to overcome these obstacles for the effective use of CRISPR-Cas9 in clinical practice.
Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Humanos , Edição de Genes/métodos , Sistemas CRISPR-Cas/genética , Terapia Genética/métodosRESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a growing chronic disease that can lead to disability and early death. This study aimed to establish a predictive model for the 10-year incidence of T2DM based on novel anthropometric indices. METHODS: This was a prospective cohort study comparing people with (n = 1256) and without (n = 5193) diabetes mellitus in phase II of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. The association of several anthropometric indices in phase I, including Body Mass Index (BMI), Body Adiposity Index (BAI), Abdominal Volume Index (AVI), Visceral Adiposity Index (VAI), Weight-Adjusted-Waist Index (WWI), Body Roundness Index (BRI), Body Surface Area (BSA), Conicity Index (C-Index) and Lipid Accumulation Product (LAP) with T2DM incidence (in phase II) were examined; using Logistic Regression (LR) and Decision Tree (DT) analysis. RESULTS: BMI followed by VAI and LAP were the best predictors of T2DM incidence. Participants with BMI < 21.25 kg/m2 and VAI ≤ 5.9 had a lower chance of diabetes than those with higher BMI and VAI levels (0.033 vs. 0.967 incident rate). For BMI > 25 kg/m2, the chance of diabetes rapidly increased (OR = 2.27). CONCLUSIONS: BMI, VAI, and LAP were the best predictors of T2DM incidence.
Assuntos
Índice de Massa Corporal , Diabetes Mellitus Tipo 2 , Aprendizado de Máquina , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Masculino , Irã (Geográfico)/epidemiologia , Feminino , Pessoa de Meia-Idade , Incidência , Estudos Prospectivos , Antropometria/métodos , Idoso , Adulto , Adiposidade/fisiologia , Fatores de RiscoRESUMO
Studies indicated that imbalance of proinflammatory and anti-inflammatory cytokines may contribute to development of type 2 diabetes mellitus (T2DM). We hypothesized that sitagliptin and VitD3 may exert more anti-inflammatory effects on the regulation of cytokine balance in T2DM. Nonnephropathic and nephropathic T2DM patients were divided into the subgroups, based on treatments. The effect of 8 months sitagliptin, alone or together with 2 months of VitD3, on serum IFN-γ, IL-4, IL-17, IL-6, IL-21, TGF-ß, and IL-37 levels was determined using enzyme-linked immunosorbent assay. Increased levels of interferon (IFN)-γ and IL-17 in untreated (without sitagliptin and VitD3) nephropathic and nonnephropathic patients and decreased levels of IL-37 in untreated nephropathic patients were observed compared with healthy controls. Treatment with sitagliptin plus VitD3 reduced the levels of IFN-γ and IL-17 in both nonnephropathic and nephropathic patients compared with untreated patients. The level of IL-37 was enhanced in patients treated with sitagliptin or sitagliptin plus VitD3, compared with untreated patients. Sitagliptin plus VitD3 treatment increased the levels of IL-4 in nonnephropathic patients. These findings indicated that the sitagliptin plus VitD3 was more effective to reduce the increased proinflammatory IFN-γ and IL-17 cytokines in T2DM patients.
Assuntos
Anti-Inflamatórios/uso terapêutico , Colecalciferol/uso terapêutico , Citocinas/sangue , Citocinas/imunologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/imunologia , Fosfato de Sitagliptina/uso terapêutico , Adulto , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/imunologia , Combinação de Medicamentos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Uranium(VI) biosorption from aqueous solutions containing 60 mg l(-1) metal concentration by Ca-pretreated Cystoseira indica alga was studied in a packed bed column with 1.5 cm internal diameter. The effect of bed height and flow rate on biosorption process was investigated and the experimental breakthrough curves were obtained. Results showed that by increasing the bed height, the breakthrough and exhaustion times increased and the slope of breakthrough curves decreased. Also, it was observed that the controlled-rate step shifted from external to internal mass transfer limitations, as the flow rate increased. The maximum uptake capacity, 318.15 mg g(-1), and total metal removal, 59.32%, were obtained at flow rate of 2.3 ml min(-1) and bed height of 6 cm. The column was regenerated using 0.1M HCl solution and sorption-desorption studies were carried out for three cycles. The obtained results confirmed that reusability of this biosorbent is possible. The results obtained agreed well with the bed depth service time model. In addition, for estimations of the parameters necessary for the design of a large-scale packed bed column, the experimental data were also fitted to the Thomas, Yan and Belter models and were found to agree with the experimental data fairly well.