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1.
Allergy Asthma Proc ; 45(2): 128-136, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38449018

RESUMEN

Background: Oral immunotherapy (OIT) can impose psychological burdens on patients and their parents due to the necessary preparations and repeated adverse reactions. Objective: To investigate changes in quality of life (QoL) and psychological burden in parents of children receiving OIT for food allergy (FA). Methods: Children aged 3-13 years with FA were enrolled. Parents were asked to fill out the Korean versions of the Food Allergy Quality of Life-Parental Burden (FAQL-PB), the Korean versions of the Food Allergy Quality of Life-Parental Form (K-FAQLQ-PF), the Korean versions of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Patient Health Questionnaire-9 (PHQ-9) for depression before OIT (T1), after 2 months of updosing (T2), and after the end of the updosing phase (T3). Results: A total of 111 parents were enrolled. The total FAQL-PB scores were decreased at T2 and T3 compared with those at T1 (all p < 0.001). Greater improvement in the total FAQL-PB score at T2 was noted in parents with a higher parental burden (FAQL-PB score ≥ 74 points) at baseline than in those with a lower parental burden (p = 0.001). Among the K-FAQLQ-PF domains, "food anxiety" scores were decreased at T2 and T3 compared with those at T1 (p = 0.049 and p = 0.030, respectively), whereas there was no change in "social and dietary limitation" and "emotional impact" scores between T1 and T2 and between T1 and T3. However, no differences were observed in K-BAI and PHQ-9 scores between T1 and T2 and between T1 and T3. Conclusion: Our results suggest that OIT improves parental burden and QoL in parents of children with FA.


Asunto(s)
Hipersensibilidad a los Alimentos , Calidad de Vida , Niño , Humanos , Hipersensibilidad a los Alimentos/terapia , Alimentos , Difenhidramina , Inmunoterapia , Padres
3.
Foods ; 12(8)2023 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-37107470

RESUMEN

The study investigated the effects of Petasites japonicus (Siebold & Zucc.) Maxim. extract (PJE) and fenofibrate on diet-induced obesity (DIO) in mice. PJE was found to contain various bio-active polyphenolic compounds, including kaempferol, p-hydroxybenzoic acid, ferulic acid, gallic acid, chlorogenic acid, 3,4-dicaffeoylquinic acid, caffeic acid, quercetin, rutin, protocatechuic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, p-coumaric acid, apigenin, and 1,3-dicaffeoylquinic acid. The results showed that PJE treatment up to 1000 µg/mL did not affect the viability of 3T3-L1 cell line, and it reduced the feed efficiency ratio in DIO mice. PJE administration also resulted in a significant reduction in body weight gain and fat accumulation in the liver compared to the DIO control group. Additionally, PJE administration improved the levels of lipid and related parameters, including total cholesterol, triacylglycerol, low-density lipoprotein, very low-density lipoprotein, glucose, insulin, insulin resistance, leptin, and atherogenic or cardiac indexes compared to the DIO control group. The study suggested that PJE may have a beneficial effect on insulin resistance, lipid profiles, atherogenesis, adipokines, and cardiac risk associated with diet-induced obesity.

4.
Biomedicines ; 10(8)2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-36009398

RESUMEN

Cilostazol is a selective inhibitor of phosphodiesterase type 3 (PDE3) that increases intracellular cyclic adenosine monophosphate (cAMP), which plays a critical role in the development of the beige phenotype and the activation of its thermogenic program in white adipose tissue (WAT). We investigated the metabolic effects of PDE3B inhibition with cilostazol treatment in the adipose tissue of high-fat diet (HFD)-fed mice. Seven-week-old male C57BL/6J mice were randomly assigned to either the cilostazol or control group. The control group was divided into two groups: the chow diet and HFD. The expression of uncoupling Protein 1 (UCP1) and other brown adipocyte markers was compared. In the HFD-fed cilostazol group, C57BL/6J mice displayed improvements in systemic metabolism, including improved glucose tolerance and lipid profile, but only modest effects on body weight were observed. In the visceral WAT of HFD-fed cilostazol-treated mice, cAMP/protein kinase A (PKA) signaling pathways were activated, resulting in the "browning" phenotype, smaller fat deposits, and enhanced mRNA expression of UCP1 and other brown adipocyte markers. PDE3B appears to be an important regulator of lipid metabolism, insulin sensitivity, and thermogenic programs in adipose tissues. An increase in intracellular cAMP via PDE3B inhibition with cilostazol treatment promoted the browning of visceral WAT.

5.
Antioxidants (Basel) ; 11(2)2022 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-35204264

RESUMEN

Previously, we reported the anti-diabetic effect of Morus alba root bark and the compounds therein. In our continuous study of other parts of this plant, the ability of the branch of Morus alba to inhibit α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), and advanced glycation end products (AGEs) formation was evaluated. Moreover, there are no previous studies that have performed enzyme kinetics and molecular docking analyses, along with assessments of peroxynitrite (ONOO-) inhibitory activities. Since the Morus alba branch exhibited favorable inhibitory effects, repeated column chromatography was performed to obtain eight compounds, including four flavonoids (1, 3, 6, 8), one arylbenzofuran (2), one stilbene (5), one Diels-Alder-type adduct (7), and one sterol (4). Among them, compounds 1-3 and 5-7 were mixed-type inhibitors of α-glucosidase, sharing the same catalytic residues with acarbose and the same allosteric sites with (Z)-3-bytylidenephthalide. On the other hand, kuwanon C (1) and oxyresveratrol (5) interacted with residues of the allosteric site (α3 and α6 helices) of PTP1B, indicating their use as non-competitive inhibitors. Interestingly, kuwanon G (7) directly bound the catalytic site, or interrupted the binding between the substrate and the active site, as a mixed-type inhibitor. Moreover, most of the compounds exhibited greater activity against AGE formation and ONOO- than positive controls. The IC50 values required to inhibit ONOO- using compounds 1, 3, 5, 6, and 7 were reported for the first time, and range from 1.08 to 12.92 µM. Based on the structure-activity relationship, the presence of hydroxyl, resorcinol, and prenyl moieties was important in the prevention of diabetes' pathological mechanisms, and these findings have been further supported by molecular docking analysis. These computational and experimental results will be useful in the development of therapeutic candidates to prevent/treat diabetes and its complications.

6.
Nanomaterials (Basel) ; 11(10)2021 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-34684955

RESUMEN

The selective control of halide ion exchange in metal halide perovskite quantum dots (PQDs) plays an important role in determining their band gap and composition. In this study, CsPbX3 (X = Cl-, Br-, and I-) PQDs were self-assembled with PbSO4-oleate to form a peapod-like morphology to selectively control halide ion exchange. Considering the distinct absorption and bright luminescence characteristics of these PQDs, in situ UV-Vis. absorption and fluorescence spectroscopies were employed to monitor the time-dependent band gap and compositional changes of the PQDs. We determined that the halide exchange in the capped PQDs is hindered-unlike the rapid anion exchange in noncapped PQDs-by a reduction in the halide exchange kinetic rate depending on the extent of coverage of the PQDs. Thus, we tracked the halide ion exchange kinetics between CsPbBr3 and CsPbI3 PQDs, depending on the coverage, using in situ UV-Vis. absorption/photoluminescence spectroscopy. We regulated the halide exchange reaction rate by varying the capping reaction temperature of the PQDs. The capping hindered the halide exchange kinetics and increased the activation energy. These results will enable the development of white LEDs, photovoltaic cells, and photocatalysts with alternative structural designs based on the divalent composition of CsPbX3 PQDs.

7.
J Clin Med ; 10(18)2021 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-34575189

RESUMEN

To investigate the effect of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists on glycemic variability (GV), the mean amplitude of glucose excursion (MAGE), mean blood glucose (MBG) levels, and percentage of time maintaining euglycemia were evaluated. Randomized controlled trials evaluating the efficacy of SGLT-2 inhibitors and GLP-1 agonists for treating people with diabetes were selected through searches of PubMed, EMBASE, and other databases. Sixteen studies were finally analyzed. There were no differences in the reductions in MAGE after treatment with SGLT-2 inhibitors or GLP-1 agonists (standardized mean difference (SMD) = -0.59, 95% CI = -0.82 to -0.36 vs. SMD = -0.43, 95% CI = -0.51 to -0.35, respectively), and treatment with SGLT-2 inhibitors was associated with an increased reduction in MBG levels (SMD = -0.56, 95% CI = -0.65 to -0.48, p < 0.00001). Monotherapy and add-on therapy with medications were correlated with MAGE and MBG level reductions. In conclusion, SGLT-2 inhibitors and GLP-1 agonists were associated with a reduction in GV and could be alternatives for treating people with diabetes.

8.
J Food Biochem ; : e13838, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-34212412

RESUMEN

We found that the fermented Lentinula edodes (FLE) products exhibited various differences in terms of proximate composition, free sugar, and amino acid. In particular, there were higher levels of ergosterol, and ergothioneine in FLE-Pediococcus pentosaceus (PP) and -Lactobacillus acidophilus (LA) than in the L. edodes (LE) products. The survival rates of lactic acid bacteria (LAB) strains on artificial gastric juice, artificial bile, or heat (50-60°C) were observed to vary from 60%-66%, 60%-66%, to 42%-79%, respectively. The FLE products up to 300 µg/ml had no cytotoxicity on RAW264.7, AGS, and RBL-2H3 cells, but inhibited the activities of α-amylase, α-glucosidase, and pancreatic lipase, as well as the production of nitrite, IL-1ß, IL-4, TNF-α, and prostaglandin E2 (PGE2) from lipopolysaccharide (LPS)-induced inflammatory response. Our findings suggest that FLE products have metabolic enzyme inhibitory and anti-inflammatory effects. PRACTICAL APPLICATIONS: Fermentation plays a critical role in improving the functional and nutritional properties of food. In addition, lactobacteria are the main microorganisms involved in the fermentation of food known to have a variety of biological activities. Therefore, the utilization of lactobacteria for research and development of mushroom food materials can be used as a key strategy to improve the biological activity characteristics of mushroom food materials and to increase their active ingredient content. The present results show that FLE products had promising inhibitory efficacies against the activities of obesity-related metabolic enzymes and LPS-induced inflammatory response. These suggest that FLE products have the potential to be developed as functional probiotic dietary supplements or food products.

9.
Nat Biotechnol ; 39(11): 1426-1433, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34211162

RESUMEN

Adenine base editors (ABEs) catalyze specific A-to-G conversions at genomic sites of interest. However, ABEs also induce cytosine deamination at the target site. To reduce the cytosine editing activity, we engineered a commonly used adenosine deaminase, TadA7.10, and found that ABE7.10 with a D108Q mutation in TadA7.10 exhibited tenfold reduced cytosine deamination activity. The D108Q mutation also reduces cytosine deamination activity in two recently developed high-activity versions of ABE, ABE8e and ABE8s, and is compatible with V106W, a mutation that reduces off-target RNA editing. ABE7.10 containing a P48R mutation displayed increased cytosine deamination activity and a substantially reduced adenine editing rate, yielding a TC-specific base editing tool for TC-to-TT or TC-to-TG conversions that broadens the utility of base editors.


Asunto(s)
Citosina , Edición Génica , Adenina , Sistemas CRISPR-Cas/genética , Edición de ARN/genética
10.
Foods ; 11(1)2021 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-35010171

RESUMEN

This study focuses on developing a quantification method for phosphatidylcholine (PC) and total phospholipid (PL) in krill oil using Fourier-transform infrared (FT-IR) spectroscopy. Signals derived from the choline and phosphate groups were selected as indicator variables for determining PC and total PL content; calibration curves with a correlation coefficient of >0.988 were constructed with calibration samples prepared by mixing krill oil raw material and fish oil in different ratios. The limit of detection (LOD, 0.35-3.29%) of the method was suitable for the designed assay with good accuracy (97.90-100.33%). The relative standard deviations for repeatability (0.90-2.31%) were acceptable. Therefore, both the methods using absorbance and that using second-derivative were confirmed to be suitable for quantitative analysis. When applying this method to test samples, including supplements, the PC content and total PL content were in good agreement with an average difference of 2-3% compared to the 31P NMR method. These results confirmed that the FT-IR method can be used as a convenient and rapid alternative to the 31P NMR method for quantifying PLs in krill oil.

11.
Foods ; 9(9)2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32899648

RESUMEN

Vinegar has been found to have in vitro improvement effect on inflammatory biomarkers, and clinically used to improve inflammation and obesity-related diseases. This study was designed to analyze in vitro anti-inflammatory effects of Cudrania tricuspidata fruits vinegar (CTFV) in a co-culture system with macrophages and adipocytes. We analyzed the physicochemical properties and polyphenolic ingredients of CTFV, and investigated in vitro anti-inflammatory effects of CTFV in a co-culture system with macrophages and adipocytes. The cells were cultured in the presence of CTFV for 24 h in contact with each other, then, harvested. The levels of monocyte chemoattractant protein (MCP)-1, tumour necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), nitric oxide (NO), and interleukin (IL)-6 were evaluated by using the Griess reagent, western blot, or enzyme-linked immunosorbent assay assays. We found that increasing levels for NO, iNOS, TNF-α, IL-6 and MCP-1 were caused by LPS treatment and co-culture using the contact method, whereas CTFV efficaciously attenuated inflammatory response by improving inflammatory parameters including NO, iNOS, TNF-α, IL-6 and MCP-1. The present study indicates that CTFV might provide a nutraceutical product or functional food resource for improving inflammation processed via the interaction of adipocytes and macrophages.

12.
PLoS One ; 15(7): e0235276, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32673331

RESUMEN

Smoking cessation reduces the cardiovascular risk but increases body weight. We investigated the risk of subsequent myocardial infarction and ischemic stroke according to weight gain after smoking cessation, using a nationwide population based cohort. We enrolled 3,797,572 Korean adults aged over 40 years who participated in national health screenings between 2009 and 2010. Subjects who quit smoking were classified into three subgroups according to the weight change between baseline and 4 years prior. Myocardial infarctions and ischemic strokes were followed until the end of 2015. We compared the hazard ratios among smoking cessation subgroups, non-smokers, and current smokers. The mean changes in weight (1.5 ± 3.9 kg) of the smoking cessation group were higher than those of the other groups (p < 0.0001). A total of 31,277 and 46,811 subjects were newly diagnosed with myocardial infarction and ischemic stroke, respectively. Regardless of weight change, all subgroups of smoking cessation had significantly less risk than current smokers. The subgroup of smoking cessation with weight gain over 4kg showed the lowest risk for myocardial infarctions (hazard ratio 0.646, 95% confidence interval 0.583-0.714, p < 0.0001) and ischemic strokes (hazard ratio 0.648, 95% confidence interval 0.591-0.71, p < 0.0001) after multivariable adjustment. In conclusion, weight gain after smoking cessation did not adversely affect the cardiovascular protective effect.


Asunto(s)
Infarto Encefálico/epidemiología , Infarto del Miocardio/epidemiología , Cese del Hábito de Fumar/estadística & datos numéricos , Fumar/efectos adversos , Aumento de Peso , Adulto , Anciano , Infarto Encefálico/etiología , Infarto Encefálico/prevención & control , Ex-Fumadores/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Infarto del Miocardio/prevención & control , No Fumadores/estadística & datos numéricos , Modelos de Riesgos Proporcionales , República de Corea/epidemiología , Factores de Riesgo , Fumadores/estadística & datos numéricos
13.
Diabetes Care ; 43(9): 2169-2175, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32611610

RESUMEN

OBJECTIVE: Previous studies have suggested that diabetes increases the risk of Parkinson disease (PD); however, this has not been conclusively established. We analyzed the risk of PD based on baseline glucose tolerance status in a large-scale cohort representative of the general Korean population. RESEARCH DESIGN AND METHODS: This analysis was performed in a cohort of 15,168,021 adults aged ≥40 years who underwent health checkups under the National Health Insurance Service between January 2009 and December 2010. The clinical course of subjects was monitored until December 2016. Subjects were classified into the following groups: no diabetes, impaired fasting glucose (IFG), diabetes duration <5 years, and diabetes duration ≥5 years. We analyzed the adjusted hazard ratio of PD for each group. RESULTS: During the observation period of 49,076,148.74 person-years, PD occurred in 31,577 patients. Compared with the nondiabetes group, the adjusted hazard ratio was 1.038 (95% CI, 1.009-1.067) in the IFG group, 1.185 (95% CI, 1.143-1.229) in the diabetes duration <5 years group, and 1.618 (95% CI, 1.566-1.672) in the diabetes duration ≥5 years group. These results were consistent with those of the subgroup analysis, and the presence of diabetes further increased the risk of PD regardless of comorbidities such as cardiovascular, cerebrovascular, and chronic kidney diseases. CONCLUSIONS: This population-based cohort study suggests that diabetes is an independent risk factor for PD.


Asunto(s)
Glucemia/metabolismo , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/etiología , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/análisis , Estudios de Cohortes , Comorbilidad , Complicaciones de la Diabetes/sangre , Complicaciones de la Diabetes/epidemiología , Complicaciones de la Diabetes/psicología , Diabetes Mellitus/sangre , Diabetes Mellitus/epidemiología , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Estado Prediabético/sangre , Estado Prediabético/complicaciones , Estado Prediabético/epidemiología , República de Corea/epidemiología , Factores de Riesgo
14.
Bioorg Med Chem Lett ; 30(8): 127049, 2020 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-32111435

RESUMEN

One achiral tetra-aryl cyclobutane [rheundulin A (1)] and three stilbene glycosides [rheundulins B-D (2-4)] were isolated from the methanol extract of Rheum undulatum L., along with eight known compounds (5-12). Structural determination of the new compounds (1-4) was accomplished using comprehensive spectroscopic methods. Compound 1 represents the first example of a dimeric stilbene linked via a cyclobutane ring from the Rheum genus. All isolates were screened for their inhibition against α-glucosidase. Among them, stilbene derivatives (5 and 6) showed strong inhibitory effects on α-glucosidase with IC50 values of 0.5 and 15.4 µM, respectively, which were significantly higher than that of the positive control, acarbose (IC50 = 126.8 µM). Rheundulin A (1) showed moderate α-glucosidase inhibition with an IC50 value of 80.1 µM. In addition, kinetic analysis and molecular docking simulation of the most active compound (5) with α-glucosidase were performed for the first time. Kinetic studies revealed that compound 5 competitively inhibited the active site of α-glucosidase (Ki = 0.40 µM), while 6 had a mixed-type inhibitory effect against α-glucosidase (Ki = 15.34 µM). Molecular docking simulations of 5 and 6 demonstrated negative-binding energies, indicating high proximity to the active site and tight binding to α-glucosidase enzyme.


Asunto(s)
Ciclobutanos/farmacología , Inhibidores de Glicósido Hidrolasas/farmacología , Extractos Vegetales/farmacología , Rheum/química , Rizoma/química , Estilbenos/farmacología , alfa-Glucosidasas/metabolismo , Ciclobutanos/química , Ciclobutanos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Humanos , Cinética , Simulación del Acoplamiento Molecular , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Estilbenos/química , Estilbenos/aislamiento & purificación , Relación Estructura-Actividad
15.
J Nat Prod ; 83(2): 323-332, 2020 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-31944695

RESUMEN

Seven new stilbene glycosides including three dimers (1-3) and four monomers (4-7) were isolated from the roots of Polygonum multiflorum along with nine previously identified stilbenes (8-16). In addition, two deglucosylated stilbenes, 2a and 3a, were also obtained as new dimeric stilbenes. The structures of the purified phytochemicals were elucidated by interpreting their spectroscopic data (NMR, HRMS, and ECD). To the best of our knowledge, this represents the first isolation of a phenylpropanoid (C6-C3) substituted with a stilbene unit (7) from the Polygonaceae family. In an in vitro enzyme assay with human recombinant protein tyrosine phosphatase-1B (PTP1B), compounds 2-5 showed weak PTP1B inhibition with an IC50 value range of 27.4-37.6 µM, while three deglucosylated stilbenes 2a, 3a, and 8a exhibited IC50 values of 2.1, 1.9, and 12.1 µM, respectively. The inhibition modes and binding mechanism of selected inhibitors (2a and 3a) were investigated using kinetic methods and molecular docking simulations.


Asunto(s)
Inhibidores Enzimáticos/química , Fallopia multiflora/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Estilbenos/química , Inhibidores Enzimáticos/aislamiento & purificación , Glicósidos/química , Humanos , Simulación del Acoplamiento Molecular , Fitoquímicos , Raíces de Plantas/química , Polygonaceae/química , Polygonum/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Proteína Tirosina Fosfatasa no Receptora Tipo 1/química , Estilbenos/aislamiento & purificación
16.
Clin Infect Dis ; 69(Suppl 6): S459-S465, 2019 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-31665774

RESUMEN

BACKGROUND: There are limited data on typhoid fever cost of illness (COI) and economic impact from Africa. Health economic data are essential for measuring the cost-effectiveness of vaccination or other disease control interventions. Here, we describe the protocol and methods for conducting the health economic studies under the Severe Typhoid Fever in Africa (SETA) program. METHODS: The SETA health economic studies will rely on the platform for SETA typhoid surveillance in 4 African countries-Burkina Faso, Ethiopia, Ghana, and Madagascar. A COI and long-term socioeconomic study (LT-SES) will be its components. The COI will be assessed among blood culture-positive typhoid fever cases, blood culture-negative clinically suspected cases (clinical cases), and typhoid fever cases with pathognomonic gastrointestinal perforations (special cases). Repeated surveys using pretested questionnaires will be used to measure out-of-pocket expenses, quality of life, and the long-term socioeconomic impact. The cost of resources consumed for diagnosis and treatment will be collected at health facilities. RESULTS: Results from these studies will be published in peer-reviewed journals and presented at scientific conferences to make the data available to the wider health economics and public health research communities. CONCLUSIONS: The health economic data will be analyzed to estimate the average cost per case, the quality of life at different stages of illness, financial stress due to illness, and the burden on the family due to caregiving during illness. The data generated are expected to be used in economic analysis and policy making on typhoid control interventions in sub-Saharan Africa.


Asunto(s)
Costo de Enfermedad , Análisis Costo-Beneficio , Salud Pública/economía , Factores Socioeconómicos , Fiebre Tifoidea/economía , Burkina Faso/epidemiología , Diseño de Investigaciones Epidemiológicas , Etiopía/epidemiología , Estudios de Seguimiento , Ghana/epidemiología , Humanos , Madagascar/epidemiología , Salud Pública/estadística & datos numéricos , Calidad de Vida , Fiebre Tifoidea/epidemiología
17.
Mol Ther ; 27(8): 1364-1371, 2019 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-31164261

RESUMEN

A nonsense mutation is a substitutive mutation in a DNA sequence that causes a premature termination during translation and produces stalled proteins, resulting in dysfunction of a gene. Although it usually induces severe genetic disorders, there are no definite methods for inducing read through of premature termination codons (PTCs). Here, we present a targeted tool for bypassing PTCs, named CRISPR-pass, that uses CRISPR-mediated adenine base editors. CRISPR-pass, which should be applicable to 95.5% of clinically significant nonsense mutations in the ClinVar database, rescues protein synthesis in patient-derived fibroblasts, suggesting potential clinical utility.


Asunto(s)
Adenina , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Codón sin Sentido , Edición Génica , Línea Celular , Bases de Datos Genéticas , Fibroblastos , Genes Reporteros , Humanos , Biosíntesis de Proteínas/genética , ARN Mensajero/genética
18.
J Clin Hypertens (Greenwich) ; 20(10): 1417-1426, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30315696

RESUMEN

The presence of abdominal obesity and lack of physical activity are both risk factors for the development of hypertension. The aim of this study was to analyze the risk of developing hypertension according to baseline waist circumference (WC). In total, 16 312 476 non-hypertensive participants who were covered by the National Health Insurance Service (NHIS) from 2009 to 2012 in Korea were included in the study. The participants were divided into six groups according to the level of baseline WC with a 5-cm interval starting from 80 cm in men and 75 cm in women. The risk for the future development of hypertension was assessed in 2015 using the claims data on the diagnosis of hypertension and prescription of anti-hypertensive medications. Approximately 7.8% of the participants developed hypertension over a median follow-up of 5.48 years. The proportion of participants who developed hypertension significantly increased from 4.2% in the WC level 1% to 17.5% in the WC level 6. After adjusting for confounding factors, level 6 of the baseline WC had a higher hazard ratio (HR) for the development of hypertension among the 6 levels of baseline with level 3 as the reference (1736; 95% confidence interval [95% CI]: 1.72-1.753). The participants with abdominal obesity had a significantly higher HR than those without abdominal obesity regardless of whether they engage in high- or moderate-intensity physical intensity (1.741; 95% CI: 1.718-1.764). WC had a linear association with the development of hypertension based on this large nationwide population-based cohort study, which was not influenced by physical activity.


Asunto(s)
Ejercicio Físico/fisiología , Hipertensión/diagnóstico , Obesidad Abdominal/complicaciones , Obesidad Abdominal/epidemiología , Adulto , Antropometría/métodos , Antihipertensivos/uso terapéutico , Estudios de Cohortes , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Factores de Riesgo , Circunferencia de la Cintura
19.
Elife ; 62017 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-28483042

RESUMEN

Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Näsström et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics.


Asunto(s)
Metabolómica/métodos , Plasma/química , Salmonella typhi/crecimiento & desarrollo , Salmonella typhi/metabolismo , Fiebre Tifoidea/diagnóstico , Fiebre Tifoidea/patología , Bangladesh , Humanos , Espectrometría de Masas , Senegal
20.
Biol Pharm Bull ; 39(6): 1060-8, 2016 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-27040904

RESUMEN

Alopecia is an important issue that can occur in people of all ages. Recent studies show that bee venom can be used to treat certain diseases including rheumatoid arthritis, neuralgia, and multiple sclerosis. In this study, we investigated the preventive effect of bee venom on alopecia, which was measured by applying bee venom (0.001, 0.005, 0.01%) or minoxidil (2%) as a positive control to the dorsal skin of female C57BL/6 mice for 19 d. Growth factors responsible for hair growth were analyzed by quantitative real-time PCR and Western blot analysis using mice skins and human dermal papilla cells (hDPCs). Bee venom promoted hair growth and inhibited transition from the anagen to catagen phase. In both anagen phase mice and dexamethasone-induced catagen phase mice, hair growth was increased dose dependently compared with controls. Bee venom inhibited the expression of SRD5A2, which encodes a type II 5α-reductase that plays a major role in the conversion of testosterone into dihydrotestosterone. Moreover, bee venom stimulated proliferation of hDPCs and several growth factors (insulin-like growth factor 1 receptor (IGF-1R), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)2 and 7) in bee venom-treated hDPCs dose dependently compared with the control group. In conclusion, bee venom is a potentially potent 5α-reductase inhibitor and hair growth promoter.


Asunto(s)
Inhibidores de 5-alfa-Reductasa/farmacología , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Alopecia/tratamiento farmacológico , Venenos de Abeja/farmacología , Venenos de Abeja/uso terapéutico , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/genética , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/metabolismo , Alopecia/metabolismo , Animales , Línea Celular , Proliferación Celular/efectos de los fármacos , Femenino , Factor 2 de Crecimiento de Fibroblastos/genética , Factor 7 de Crecimiento de Fibroblastos/genética , Cabello/efectos de los fármacos , Cabello/crecimiento & desarrollo , Humanos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones Endogámicos C57BL , Receptor IGF Tipo 1/genética , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo
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