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1.
Pediatr Int ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32009273

RESUMO

BACKGROUND: The challenges associated with the activity limitation and participation constraints of children with cerebral palsy may increase their parents' stress. The present study aims to identify the factors associated with parenting stress in mothers of children with cerebral palsy (CP) and to test the multidimensional assumptions of the condition, focusing on the relationship between stress, self-esteem, and depression among parents and the activity limitation of their children. METHODS: We used structural equation modeling (SEM) to examine the relationships between activity limitation (gross and fine motor, and communication function) in children with CP and their mothers' depression, self-esteem, and parenting stress. The participants were 217 children with CP (123 boys; 94 girls). The mean age of the children involved in the study was 6.61 (SD = 2.76). The types of CP were spastic (71.0%), dyskinetic/athetotic (7.8%), ataxic (4.6%), and mixed (5.5%). We further used SEM to investigate the mediating influence of depression and self-esteem on parent-child relationships, as well as the direct effects on parenting stress. RESULTS: The proposed model showed excellent fit indices. Activity limitation had an indirect effect and depression had a direct effect on self-esteem. Activity limitation and depression had effects on parenting stress both directly and indirectly, while self-esteem had only a direct effect on parenting stress. CONCLUSIONS: The results highlight the importance of identifying parental depression and self-esteem as predictive variables for parenting stress among parents of children with CP, as well as children's activity limitation.

2.
J Steroid Biochem Mol Biol ; 198: 105615, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32014605

RESUMO

Adrenal steroids are generated in the adrenal cortex and metabolized by various enzymes such as hydroxylases, dehydrogenases, and reductases. Determining the comprehensive metabolic signatures of adrenal steroids can provide insight into their metabolic functions and roles in the pathophysiology of adrenal diseases, including Cushing's syndrome (CS) and congenital adrenal hyperplasia (CAH). To this end, we developed an advanced quantitative profiling method of serum adrenal steroids with liquid chromatography-mass spectrometry (LC-MS) under molecular-specific scan modes. Twenty-seven steroids were separated on a 1.9-µm particle C18 column (50 × 2.1 mm) at a flow rate of 250 µL/min and quantified via triple-quadrupole MS with electrospray ionization. During validation, linearities ( r2) were higher than 0.940 with a limit of quantification of 0.1-5.0 ng/mL, and precision (coefficient of variation) and accuracy (%bias) of 3.7-14.3 % and 96.3-113.1 %, respectively. In contrast with the significantly increased serum levels of mineralocorticoids (P <  0.001), the present LC-MS assay revealed remarkably decreased levels of all glucocorticoids and androgens in a patient diagnosed with 17α-hydroxylase deficiency CAH (P <  0.001) compared to those of age- and sex-matched healthy and CS subjects. In the CAH patient, the metabolic ratios for 17α-hydroxylase were significantly decreased, whereas there was no reduction in the metabolic ratio of 17-hydroxyprogesterone to androstenedione, indicating 17,20-lyase activity. In particular, both pregnenolone and dehydroepiandrosterone sulfates, and their metabolic ratio, were identified as potential biomarkers for 17α-hydroxylase deficiency (all P <  0.001), which were also distinct from those of CS patients. The devised LC-MS assay clearly revealed the metabolic signatures of 17α-hydroxylase deficiency, as a rare phenotype of CAH, compared to both healthy and CS subjects, indicating its utility for screening adrenal diseases.

3.
Urol J ; 17(1): 91-96, 2020 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-31912478

RESUMO

PURPOSE: Ischemia-reperfusion (IR) causes various damage in renal tissues. The aim of the present study was to evaluate the renoprotective effect of phosphodiesterase 5 inhibitor (PDE5I) on IR induced renal injury in a rat model. MATERIALS AND METHODS: Thirty adult male, 12-week-old, Sprague-Dawley rats were divided into three groups. Renal IR injury was induced by occlusion of the bilateral renal pedicle for 45 min followed by reperfusion for 24 h. The rats were sacrificed for collecting blood and tissue specimens. IR rats were administered daily oral Tadalafil (group I) or no pills (group II), while sham-operated animals were treated with no pills (sham group). The pill was diluted with distilled water and administered to rats for 15 days, orally. Renal histopathology, function, pro-inflammatory and inflammatory cytokines and mediators were assessed by serum creatinine, western blot assay and immunohistochemistry. RESULTS: Compared with sham group, rats that underwent renal IR operation exhibited a significant increase in concentration in serum creatinine (p< .01) and tissue pro-inflammatory and inflammatory mediators. In group I, however, tadalafil significantly suppressed elevation of the serum creatinine and increased the levels of endothelial nitric oxide synthase and decreased the level of intercellular adhesion molecule-1 (ICAM-1) than group II (p< .05). Moreover, tadalafil prevented IR-induced expression of pro-inflammatory mediators such as monocyte chemotactic protein-1 (MCP-1) (p< .05). CONCLUSION: Tadalafil significantly promotes functional recovery after renal IR injury and effectively inhibits the induction of pro-inflammatory and inflammatory mediators. The results substantiate Tadalafil as a protective agent against IR-induced renal injury.

4.
Nanoscale ; 12(4): 2773-2786, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31957767

RESUMO

Until now, magnetic hyperthermia was used to remove solid tumors by targeting magnetic nanoparticles (MNPs) to tumor sites. In this study, leukemia cells in the bloodstream were directly removed by whole-body hyperthermia, using leukemia cell-specific MNPs. An epithelial cellular adhesion molecule (EpCAM) antibody was immobilized on the surface of MNPs (EpCAM-MNPs) to introduce the specificity of MNPs to leukemia cells. The viability of THP1 cells (human monocytic leukemia cells) was decreased to 40.8% of that in control samples by hyperthermia using EpCAM-MNPs. In AKR mice, an animal model of lymphoblastic leukemia, the number of leukemia cells was measured following the intravenous injection of EpCAM-MNPs and subsequent whole-body hyperthermia treatment. The result showed that the leukemia cell number was also decreased to 43.8% of that without the treatment of hyperthermia, determined by Leishman staining of leukemia cells. To support the results, simulation analysis of heat transfer from MNPs to leukemia cells was performed using COMSOL Multiphysics simulation software. The surface temperature of leukemia cells adhered to EpCAM-MNPs was predicted to be increased to 82 °C, whereas the temperature of free cells without adhered MNPs was predicted to be 38 °C. Taken together, leukemia cells were selectively removed by magnetic hyperthermia from the bloodstream, because EpCAM-modified magnetic particles were specifically attached to leukemia cell surfaces. This approach has the potential to remove metastatic cancer cells, and pathogenic bacteria and viruses floating in the bloodstream.

5.
J Neurosurg ; : 1-9, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31978882

RESUMO

OBJECTIVE: In this double-blind randomized trial, the necessity of preoperative steroid administration in patients without adrenal insufficiency (AI) undergoing endoscopic transsphenoidal surgery (ETSS) for pituitary adenoma was evaluated. METHODS: Forty patients with and without AI, defined as a peak cortisol level > 18 µg/dl on the insulin tolerance test or rapid adrenocorticotropic hormone (ACTH) test, undergoing ETSS for nonfunctioning pituitary adenomas were randomly allocated to treatment with either 100 mg of preoperative hydrocortisone (group HC, n = 20) or normal saline (group C, n = 20). The patients with pituitary apoplexy, the use of a drug within the last 3 months that could affect the hypothalamic-pituitary-adrenal axis, or a previous history of brain or adrenal surgery were excluded. Intraoperative cortisol and ACTH levels were measured after anesthesia induction, dura incision, and tumor removal, and at the end of surgery. Intraoperative hypotension, early postoperative AI, and postoperative 3-month pituitary function were investigated. RESULTS: Intraoperative serum cortisol levels were significantly higher in the HC group than in the C group after anesthesia induction (median 69.0 µg/dl [IQR 62.2-89.6 µg/dl] vs 12.7 µg/dl [IQR 8.4-18.2 µg/dl], median difference 57.5 µg/dl [95% CI 33.0-172.9 µg/dl]), after dura incision (median 53.2 µg/dl [IQR 44.9-63.8 µg/dl] vs 6.4 [IQR 4.8-9.2 µg/dl], median difference 46.6 µg/dl [95% CI 13.3-89.2 µg/dl]), after tumor removal (median 49.5 µg/dl [IQR 43.6-62.4 µg/dl] vs 9.2 µg/dl [IQR 5.75-16.7 µg/dl], median difference 39.4 µg/dl [95% CI 0.3-78.1 µg/dl]), and at the end of surgery (median 46.9 µg/dl [IQR 40.1-63.4 µg/dl] vs 16.9 µg/dl [IQR 12.1-23.2 µg/dl], median difference 32.2 µg/dl [95% CI -42.0 to 228.1 µg/dl]). Serum ACTH levels were significantly lower in group HC than in group C after anesthesia induction (median 3.9 pmol/L [IQR 1.7-5.2 pmol/L] vs 6.9 pmol/L [IQR 3.9-11.9 pmol/L], p = 0.007). No patient showed intraoperative hypotension due to AI. Early postoperative AI was observed in 3 and 5 patients in groups HC and C, respectively. The postoperative 3-month pituitary hormone outcomes including ACTH deficiency were not different between groups. CONCLUSIONS: Preoperative steroid administration may be unnecessary in patients without AI undergoing ETSS for nonfunctioning pituitary adenomas. However, a further large-scale study is needed to determine whether preoperative steroid administration has a significant impact on clinically meaningful events such as perioperative AI and postoperative 3-month ACTH deficiency in these patients.Korean Clinical Trial Registry no.: KCT0002426 (https://cris.nih.go.kr/cris/).

6.
J Clin Lab Anal ; 34(1): e23015, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31423640

RESUMO

BACKGROUNDS: Shortening of primary cilia in kidney epithelial cells is associated with kidney injury and involved with the induced level of α-tubulin in urine. Therefore, rapid detection and quantification of α-tubulin in the urine samples could be used to the preliminary diagnosis of kidney injury. METHODS: Cellulose-based nanobeads modified with α-tubulin were used for the detection probe of competitive immunochromatographic (IC) assay. The concentration of α-tubulin in the urine samples was determined by IC assay and compared with the amount determined by Western blotting analysis. RESULTS: The relationship between α-tubulin concentration and the colorimetric intensity resulted from IC assay was determined by logistic regression, and the correlation coefficient (R2 ) was 0.9948. When compared to the amount determined by Western blotting analysis, there was a linear relationship between the α-tubulin concentrations measured by the two methods and the R2 value was 0.823. CONCLUSIONS: This method is simple, rapid, and adequately sensitive to detect α-tubulin in patient urine samples, which could be used for the clinical diagnosis of kidney injury.

7.
World Neurosurg ; 133: e211-e217, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31493596

RESUMO

BACKGROUND: Craniopharyngiomas show a high recurrence rate despite their pathologically benign nature. Thus, we analyzed the clinical features to elucidate the prognostic factors for the recurrence of craniopharyngiomas in adults with long-term follow-up. METHODS: This retrospective study reviewed and analyzed the preoperative features, surgical results, and tumor recurrence of patients who underwent an operation at a single institution from 2004 to 2013. RESULTS: This study analyzed the results of 64 consecutive adult patients, and the median follow-up period was 83.5 months (range 9-163 months). Ten patients had a history of surgery, whereas 4 had a history of adjuvant radiation. Retrochiasmatic tumors (n = 51, 79.7%) were more common than prechiasmatic tumors. Operations were performed via the transcranial approach in 31 (48.4%) patients and transsphenoidal approach in 33. Gross total removal was achieved in 44 (68.8%) patients, and the transsphenoidal approach showed a greater gross total removal rate than the transcranial approach did (97.0% vs. 38.7%, P < 0.001). Adjuvant radiotherapy was performed in 8 patients, and radiosurgery was performed in 2. Recurrence was identified in 25 (39.1%) patients in 45.0 months of the median time to recurrence. The overall actuarial 5- and 7-year progression-free survival rates were 71.8% and 63.6%, respectively. Multivariate analysis revealed that supra- and subdiaphragmatic tumor locations and subtotal removal were risk factors for long-term tumor recurrence. CONCLUSIONS: The long-term recurrence rate of craniopharyngiomas was high; therefore, long-term regular follow-up is mandatory. Adjuvant irradiation for remnant tumors showed a long-term tumor control rate comparable to that of completely removed tumors.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31816662

RESUMO

BACKGROUND AND AIM: This study aimed to investigate the effect of acute kidney injury (AKI) on long-term mortality of spontaneous bacterial peritonitis (SBP) in cirrhotic patients using International Club of Ascites (ICA)-AKI criteria. METHODS: A total of 157 cirrhotic patients with a first episode of SBP between 2007 and 2016 were analyzed. We investigated the long-term mortality with related risk factors of SBP in cirrhosis including the ICA-AKI criteria. The ICA-AKI stage at SBP diagnosis is evaluated by stages 0-3. Stage progression was defined as a progression of AKI to a higher stage. RESULTS: The ICA-AKI stage at the diagnosis of SBP was stage 0 in 91 (58%), stage 1 in 33 (21%), stage 2 in 19 (12%), and stage 3 in 14 patients (9%). Stage progression within 48 h after SBP diagnosis was noted in 18 patients (12%). Multivariable analysis showed that the risk factors for overall survival were age ≥ 60 years (hazard ratio [HR] 1.74, P = 0.029), serum sodium ≤ 130 mmol/L (HR 1.3, P = 0.017), ICA-AKI stage 1 (HR 2.51, P = 0.003), ICA-AKI stage 2 or 3 (HR 3.36, P < 0.001), and stage progression at 48 h after SBP diagnosis (HR 2.57, P = 0.004). The differences in overall survival using the ICA-AKI in patients without AKI using the conventional criteria were significantly different (P = 0.019). CONCLUSION: Acute kidney injury and its progression are significant risk factors for mortality in cirrhotic patients with SBP. The application of the ICA-AKI criteria is important and advantageous for early evaluation and intervention for a better prognosis in cirrhotic patients with SBP.

9.
Occup Ther Int ; 2019: 7058415, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819741

RESUMO

Background: It is reported that hopeful thinking plays a positive role in encouraging patients to achieve functional goals during the rehabilitation process. Hope is a key concept in evaluating stroke outcomes in research and rehabilitation practice. Aims: The purpose of this study was to investigate the psychometric properties of the Korean Dispositional Hope Scale (K-DHS) using the Rasch analysis in patients with hemiplegic stroke. Methods: The K-DHS was completed by 166 community-dwelling hemiplegic stroke patients in Korea. Data were analyzed according to item fit, item difficulty, and the appropriateness of the rating scale using the Rasch analysis. Results: Item fit analysis showed that 8 items of the K-DHS are appropriate because the infit MSNQ was between 0.7 and 1.3. Item difficulty results revealed that there is a difference in distribution between personal attributes and item difficulty. It shows that the item fit statistics of the 4-point Likert scale of K-DHS are all good. The person separation index demonstrated that the K-DHS could differentiate two or three hope status strata in stroke patients. The item separation index indicated that the items were useful with high reliability. Conclusion: The K-DHS comprises appropriate items for measuring the hope of stroke patients living in the community, and the rating scale of the K-DHS is also appropriate. This study is the first to conduct an analysis of the rating scale and its appropriateness, as well as the difficulty of items based on item response theory, and offers new insights for enhancing hope and improving well-being following stroke.

10.
Nanomedicine (Lond) ; 14(24): 3143-3158, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31855122

RESUMO

Aim: To mitigate the side effects of medical treatment by Prussian blue (PB), a well-known adsorbent for radioactive cesium (Cs), PB-deposited magnetic nanoparticles (MNPs), were prepared and analyzed on the adsorbent capacity for Cs removal. Materials & methods: The PB-deposited MNPs were prepared by photo-deposition method and investigated for their Cs adsorption properties in vitro and in vivo. The distribution of the adsorbents was also evaluated in C57BL/6 mice. Results: PB-deposited MNPs provided an improved adsorbent capacity for Cs removal and reduced toxicity to blood cells compared with those of bulk PB. Conclusion: PB-deposited MNPs could be considered as an alternative of PB-based medicine to reduce the possible hazards caused by high dose of PB intake.

11.
Sci Rep ; 9(1): 18149, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31776443

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31704444

RESUMO

Among the most critical needs of natural product chemistry is a complete library of pure reference substances. Some khellactone-type isomers of pharmacological importance are either still lacking reference substances or references are only available in limited amounts. To address this need, a recycling high-performance liquid chromatography (R-HPLC) strategy was adopted to improve the isomer separation efficiency from Peucedanum japonicum. Under the optimal isolation conditions, we obtained isomerically pure substances, particularly khellactone coumarins with different substituent groups. Isolated compounds attained purities greater than 98% as determined by ultra-performance liquid chromatography-charged aerosol detector (UPLC-CAD) and photodiode array (PDA). The structures of these compounds were identified according to their mass patterns and 2D NMR spectra. The proposed methods of single-column recycling obtained the same amount of product as conventional systems while being simple, increasing efficiency and reducing cost.


Assuntos
Apiaceae/química , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/normas , Cumarínicos/análise , Cumarínicos/química , Camundongos , Extratos Vegetais/normas , Extratos Vegetais/toxicidade , Raízes de Plantas/química , Células RAW 264.7
13.
Acute Crit Care ; 34(1): 38-45, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31723903

RESUMO

Background: Critical illness-related corticosteroid insufficiency (CIRCI) and adrenocorticotropic hormone (ACTH)-cortisol dissociation are hormonal conditions frequently observed in patients in the intensive care unit (ICU). The aim of this study was to evaluate the association between ACTH-cortisol dissociation and clinical outcomes of critically ill patients. Methods: We retrospectively reviewed the medical records of 94 ICU patients who underwent two rapid cosyntropin tests during hospital admission and compared the clinical aspects of patients with and without ACTH-cortisol dissociation. ACTH-cortisol dissociation was defined as plasma ACTH and serum cortisol concentrations of <22 pmol/L and >600 nmol/L, respectively. Results: Dissociation was present in 30 of the 94 patients (31.9%). Patients with ACTH-cortisol dissociation in the initial test had significantly higher hospital mortality rate than those in the control group (55% vs. 25.7%, P=0.013) There was no difference in hospital mortality between patients classified as having CIRCI and those who were not. In multivariate adjusted Cox regression analysis, the mortality risk was higher in the group with ACTH-cortisol dissociation (hazard ratio, 2.98; 95% confidence interval, 1.34 to 6.63; P=0.007). Patients with dissociation in two consecutive stimulation tests showed the highest hospital mortality rate among groups classified according to stimulation test results (100% vs. 31.3%). Conclusions: The hospital mortality was higher in ICU patients diagnosed with ACTH-cortisol dissociation. It is clinically feasible to evaluate the presence of ACTH-cortisol dissociation by analyzing rapid ACTH stimulation test results in critically ill patients.

15.
BMC Geriatr ; 19(1): 281, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640593

RESUMO

BACKGROUND: Given the theoretical and methodological limitations, there is insufficient knowledge about the psychometric properties and internal structure of quality of life (QOL) measurements for patients with dementia living in nursing homes. The present study aimed to confirm the validity and reliability of the Geriatric Quality of Life-Dementia scale (GQOL-D) to measure the QOL of patients with dementia in nursing homes and analyze their QOL based on the validated GQOL-D factor structure. METHODS: The GQOL-D was used to assess QOL. A convenience sampling method was used to recruit patients with dementia or mild cognitive impairment from six nursing homes in two cities. In order to confirm the validity and factor structure of the scale, both exploratory factor analysis and confirmatory factor analysis were employed. An independent t-test and a one-way analysis of variance were performed to examine the difference in the QOL across general characteristics. RESULTS: The original factor model was not appropriate to assess the QOL of dementia patients living in nursing homes because the models did not show adequate fit indices. The results support a two-factor structure: environmental and personal factors. Our findings suggest that the internal consistency and construct validity of the proposed two-factor model are adequate, and the GQOL-D is a useful tool for assessing the QOL of dementia patients living in nursing homes. CONCLUSIONS: This factor structure model of environmental and personal aspects is a useful theoretical framework for designing and evaluating interventions for people with dementia and providing integrated person-centered care for people with dementia in nursing homes.

16.
Korean J Intern Med ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31564086

RESUMO

Background/Aims: Body mass index (BMI) is positively associated with bone mineral density and type 2 diabetes. We investigated an optimal BMI range for osteoporosis and type 2 diabetes. Methods: This cross-sectional study used data from the Korea National Health and Nutrition Examination Survey (KNHANES), 2008 to 2011. We included 3,774 men aged > 50 years and 4,982 postmenopausal women. Logistic regression models were applied to elucidate each BMI category's osteoporosis and diabetes risks. Results: The prevalence of osteoporosis was 9.0% for men and 40.8% for women. The prevalence of type 2 diabetes in men was 19.7% and in women was 15.5%. In men with BMI > 25 kg/m2, the osteoporosis risk did not further increase as BMI increased. In women, BMI was linearly associated with osteoporosis risk without a plateau. In both men and women, higher BMI was associated with a higher type 2 diabetes risk. Men with a BMI of 23.0 to 24.9 kg/m2 harbored about a 30% lower osteoporosis risk than and a similar diabetes risk to those with a BMI of 21.0 to 22.9 kg/m2. In women with a BMI of 23.0 to 24.9 kg/m2, the adjusted odds ratio for osteoporosis was 0.72 (95% confidence interval, 0.59 to 0.87); the diabetes risk was not higher than in those with a BMI of 21.0 to 22.9 kg/m2. Conclusions: For Korean men aged > 50 years and postmenopausal women, a BMI of 23.0 to 24.9 kg/m2 was the optimal range for minimizing osteoporosis and type 2 diabetes risks simultaneously.

17.
Endocrinol Metab (Seoul) ; 34(3): 314-322, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31565884

RESUMO

BACKGROUND: Invasive nonfunctioning pituitary adenomas (NFPAs) remain challenging due to their high complication rate and poor prognosis. We aimed to identify the distinctive molecular signatures of invasive NFPAs, compared with noninvasive NFPAs, using gene expression profiling by RNA sequencing. METHODS: We obtained frozen fresh tissue samples from 14 patients with NFPAs who underwent primary transsphenoidal surgery. Three non-invasive and 11 invasive NFPAs were used for RNA sequencing. The bioinformatics analysis included differential gene expression, gene ontology analysis, and pathway analysis. RESULTS: A total of 700 genes were differentially expressed (59 up-regulated and 641 down-regulated genes) between invasive and non-invasive NFPAs (false discovery rate <0.1, and |fold change| ≥2). Using the down-regulated genes in invasive NFPAs, gene ontology enrichment analyses and pathway analyses demonstrated that the local immune response was attenuated and that transforming growth factor-ß (TGF-ß) RII-initiated TGF-ß signaling was down-regulated in invasive NFPAs. The overexpression of claudin-9 (CLDN9) and the down-regulation of insulin-like growth factor-binding protein 5 (IGFBP5), death-associated protein kinase 1 (DAPK1), and tissue inhibitor of metalloproteinase-3 (TIMP3) may be related with invasiveness in NFPAs. CONCLUSION: Invasive NFPAs harbor different gene expression profiles relative to noninvasive NFPAs. In particular, local suppression of the immune response and TGF-ß signaling can make PAs prone to invasiveness.

18.
Cells ; 8(10)2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31547195

RESUMO

The loss of mitochondrial function impairs intracellular energy production and potentially results in chronic liver disease. Increasing evidence suggests that mitochondrial dysfunction in hepatocytes contributes to the activation of hepatic stellate cells (HSCs), thereby resulting in hepatic fibrogenesis. High-temperature requirement protein A2 (HtrA2/Omi), a mitochondrial serine protease with various functions, is responsible for quality control in mitochondrial homeostasis. However, little information is available regarding its role in mitochondrial damage during the development of liver fibrosis. This study examined whether HtrA2/Omi regulates mitochondrial homeostasis in hepatocyte during the development of hepatic fibrogenesis. In this study, we demonstrated that HtrA2/Omi expression considerably decreased in liver tissues from the CCl4-induced liver fibrotic mice model and from patients with liver cirrhosis. Knockdown of HtrA2/Omi in hepatocytes induced the accumulation of damaged mitochondria and provoked mitochondrial reactive oxygen species (mtROS) stress. We further show that the damaged mtDNA isolated from HtrA2/Omi-deficient hepatocytes as a form of damage-associated molecular patterns can induce HSCs activation. Moreover, we found that motor neuron degeneration 2-mutant mice harboring the missense mutation Ser276Cys in the protease domain of HtrA2/Omi displayed altered mitochondrial morphology and function, which increased oxidative stress and promoted liver fibrosis. Conversely, the overexpression of HtrA2/Omi via hydrodynamics-based gene transfer led to the antifibrotic effects in CCl4-induced liver fibrosis mice model through decreasing collagen accumulation and enhancing anti-oxidative activity by modulating mitochondrial homeostasis in the liver. These results suggest that suppressing HtrA2/Omi expression promotes hepatic fibrogenesis via modulating mtROS generation, and these novel mechanistic insights involving the regulation of mitochondrial homeostasis by HtrA2/Omi may be of importance for developing new therapeutic strategies for hepatic fibrosis.

19.
BMC Psychiatry ; 19(1): 219, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31299921

RESUMO

BACKGROUND: Virtual Reality (VR) is increasingly used in health-related fields and interventions using VR have the potential to be powerful tools in patient management. The aim of this study was to synthesize the effects of VR interventions for people with mild cognitive impairment (MCI) or dementia. METHODS: Electronic databases were searched to identify studies that used an experimental design to investigate VR intervention outcomes for patients with MCI or dementia. Studies were excluded if the intervention did not focus on VR, if relevant quantitative outcomes were not reported, or if the intended study purpose was assessment or diagnosis. Data were extracted and analyzed from studies that met criteria. To synthesize the intervention effect sizes (ES), we used random effects models to accommodate heterogeneity in the main effect and sub-group analyses. To identify the potential reason for heterogeneity and compare ES according to the moderator variables, subgroup analyses were conducted based on study characteristics and intervention outcomes. RESULTS: Data from eleven studies that met eligibility criteria were analyzed. VR intervention delivered to participants with MCI or dementia produced small to medium effects (ES = 0.29, CI = 0.16, 0.42). The ES for studies using semi-immersive technology (ES = 0.37, CI = 0.25, 0.49) was greater than the studies using full-immersive VR (ES = 0.03, CI = -0.14, 0.21). The results showed small-to-medium effects for VR interventions affecting key outcome variables such as cognition (ES = 0.42, CI = 0.24, 0.60) and physical fitness (ES = 0.41, CI = 0.16, 0.65). CONCLUSION: VR interventions, particularly of the semi-immersive type, are useful for people with MCI or dementia. These results should contribute to the establishment of practical guidelines for VR interventions for patients with cognitive decline.

20.
Exp Ther Med ; 18(1): 833-840, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31281457

RESUMO

Cedrela odorata L. is a native plant of the Amazon region. The bark is used in folk remedies for the treatment of diarrhea, vomiting, fever and inflammation. Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease accompanied by itching. It is a complex disease involving environmental factors and genetic factors. In the present study, the anti-inflammatory and anti-allergic effects of C. odorata L. methanol extract (COEE) on tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated HaCaT keratinocyte cells were investigated. ELISA and RT-PCR analysis revealed that the extract had anti-inflammatory effects, and reduced the interleukin (IL)-6 and IL-8 levels of the HaCaT cells. In addition, COEE exhibited anti-allergic effects, comprising a reduction in the thymus and activation-regulated chemokine and macrophage-derived chemokine levels. In addition, pathway analysis and comparison with Bay11-7082 indicated that these effects are due to the inhibition of nuclear factor (NF)-κB in TNF-α/IFN-γ-induced HaCaT cells. Therefore, the results of the present study suggest that COEE has anti-inflammatory and anti-allergic properties in TNF-α and IFN-γ-stimulated HaCaT cells, which are associated with the inhibition of pro-inflammatory cytokines and chemokines via the NF-κB pathway.

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