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1.
Genes (Basel) ; 12(10)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34680942

RESUMO

Nasopharyngeal carcinoma (NPC) and alcohol flush syndrome are thought to be strongly influenced by genetic factors and are highly prevalent amongst East Asians. Diminished activity of aldehyde dehydrogenase (ALDH), a major enzyme in the alcohol-metabolizing pathway, causes the flushing syndrome associated with alcoholic consumption. The genetic effect of ALDH isoforms on NPC is unknown. We therefore investigated the association between the genetic polymorphisms of all 19 ALDH isoforms and NPC among 458 patients with NPC and 1672 age- and gender-matched healthy controls in Taiwan. Single-nucleotide polymorphisms (SNPs) located between the 40,000 base pairs upstream and downstream of the 19 ALDH isoform coding regions were collected from two genome-wise association studies conducted in Taiwan and from the Taiwan Biobank. Thirteen SNPs located on ALDH4A1, ALDH18A1, ALDH3B2, ALDH1L2, ALDH1A2, and ALDH2 Glu487Lys (rs671) were associated with NPC susceptibility. Stratification by alcohol status revealed a cumulative risk effect for NPC amongst drinkers and non-drinkers, with odds ratios of 4.89 (95% confidence interval 2.15-11.08) and 3.57 (1.97-6.47), respectively. A synergistic effect was observed between SNPs and alcohol. This study is the first to report associations between genetic variants in 19 ALDH isoforms, their interaction with alcohol consumption and NPC in an East Asian population.

2.
Cancers (Basel) ; 13(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34439303

RESUMO

Colorectal cancer is the second most common cancer and the third cancer-associated death in Taiwan. Currently used serum markers for detecting colorectal cancer lack excellent diagnostic accuracy, which results in colorectal cancer being often recognized too late for successful therapy. Mitophagy is the selective autophagic degradation of damaged or excessive mitochondria. DJ-1 is an antioxidant protein that attenuates oxidative stress and maintains mitochondrial quality through activating mitophagy. Mitophagy activation contributes to anti-cancer drug resistance. However, the role of DJ-1-induced mitophagy in colorectal cancer progression remains unclear. In the present study, we collected matched tumor and adjacent normal tissues and serum from patients and cancer cells to demonstrate the clinical value and physiological function of DJ-1 in colorectal cancer. We found that DJ-1 increased in tumor tissues and serum; it was positively correlated with TNM (tumor-node-metastasis) stages of colorectal cancer patients. Through stable knockdown DJ-1 expression in metastatic colorectal adenocarcinoma cells SW620, DJ-1 knockdown inhibited cancer cell survival, migration, and colony formation. In SW620 cells, DJ-1 knockdown induced an incomplete autophagic response that did not affect ATP production; DJ-1 knockdown enhanced intracellular reactive oxygen species generation and damaged mitochondrial accumulation and mitophagy inhibition. It suggests that DJ-1 knockdown inhibits mitophagy that causes metastatic colorectal adenocarcinoma cells to be unable to remove damaged mitochondria and further enhance cancer cell apoptosis. Our data indicate that DJ-1 might be clinically valuable as serum and tissue biomarkers for predicting the TNM stage in colorectal cancer patients. Since DJ-1-induced mitophagy promotes tumor progression, DJ-1 inhibition is a potential therapeutic strategy for colorectal cancer treatment.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34335824

RESUMO

This study investigated the effect and mechanism of electroacupuncture (EA) on the contralesional hemisphere in rats with ischemic stroke. EA of 2 Hz was applied on the contralesionally Luoque (BL8) and Tongtian (BL7) acupoints of the scalp to investigate the neurological status and mechanism in ischemia-reperfusion injury rats. The differences in the neurological deficit score and Rotarod test time between days 3 and 15 after reperfusion were significantly lower in the sham group (0.00 (-1.00, 0.00) and 3.53 (-0.39, 7.48) second, respectively) than in the EA group (-4.00 (-4.00, -3.00) and 44.80 (41.69, 54.13) second, respectively, both p < 0.001). The ratio of infarction volume was 0.19 ± 0.04 in the sham group greater than 0.07 ± 0.04 in the EA group (p < 0.001). On day 15, in the cerebral cortex of the lesioned hemisphere, the gamma-aminobutyric acid (GABA)-A/actin ratio in the normal group (1.11 ± 0.36) was higher than that in the sham group (0.38 ± 0.07, p < 0.05) and similar to that in the EA group (0.69 ± 0.18, p > 0.05); the difference between the EA and sham groups was significant (p < 0.05). EA of 2 Hz on the BL8 and BL7 acupoints on the contralesional scalp can improve motor function and also can reduce infarction volume, and this effect of EA, and that GABA-A, plays at least a partial role in ischemia-reperfusion injury rats.

4.
Sci Rep ; 11(1): 14843, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290337

RESUMO

Aromatase inhibitors (AIs) are standard adjuvant therapy for postmenopausal women with oestrogen receptor-positive, early-stage, and metastatic breast cancer. Although effective, the risk of falls due to AI-associated knee joint pain significantly increased. The aim of this study was to evaluate the therapeutic effects of yoga and massage on AI-associated knee joint pain. Breast cancer survivors were randomly assigned to a 6-week yoga intervention-2-week rest-6-week massage exposure (Yoga first, n = 30) or a 6-week massage intervention-2-week rest-6-week yoga exposure (Massage first, n = 30). Evaluations of the treatment efficacy were made at baseline, post-intervention, and post-exposure using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale, plasma cytokine levels, and changes in meridian energy. The results showed that yoga, superior to massage intervention, significantly reduced AI-associated knee joint pain, as demonstrated by the WOMAC pain score. The yoga intervention improvements were also associated with changes in plasma cytokine levels and meridian energy changes. In conclusion, this study provides scientific evidence that yoga was more effective than massage for reducing AI-associated knee joint pain. Meridian energy changes may provide another scientific, objective, non-invasive way to monitor the therapeutic effects of yoga and investigate another alternative, complementary medicine.


Assuntos
Antineoplásicos/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Artralgia/terapia , Neoplasias da Mama/tratamento farmacológico , Sobreviventes de Câncer , Articulação do Joelho , Massagem , Ioga , Adulto , Idoso , Artralgia/induzido quimicamente , Neoplasias da Mama/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Receptores de Estrogênio/metabolismo
5.
Medicina (Kaunas) ; 57(6)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072817

RESUMO

Background and Objectives: To regain the ability of community ambulation is a meaningful goal for stroke patients. Recent research recommended that the distance accomplished during the six-minute walk test (≥205 m in 6MWT) is the fittest for defining community ambulation. Until now, there are few studies that have used the updated definition to investigate the related predictors. The aim of this study was to investigate the association between the admission clinical parameters and community ambulation measured by the 6MWT at discharge. The other aim was to find the admission Berg Balance Scale (BBS) cut-off score to discriminate between household or community ambulators. Materials and Methods: This cohort study collected the data of patients who entered the post-acute Care Cerebrovascular Diseases program. Multivariate logistic regression was used to identify significant predictors measured at admission that are associated with community ambulation, and a receiver operating characteristic was adopted to calculate the cut-off value for admission status. There were 120 participants included in this study, and 25% (n = 30) of them regained the ability of community ambulation at discharge. The BBS on admission was identified as the only significant predictor for community ambulation (odds ratio 1.06). Results: The optimal cut-off score for the BBS at admission was 29, and the area under the curve for BBS scores on admission when discriminating between household and community ambulators at discharge was 0.74. Conclusions: The admission BBS scores could be used to predict household and community ambulators at discharge in stroke patients. The results of this study could help clinical physicians set appropriate discharge goals early.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estudos de Coortes , Humanos , Alta do Paciente , Equilíbrio Postural , Caminhada
6.
Cancers (Basel) ; 13(11)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070538

RESUMO

Elevated expression of C-X-C motif chemokine receptor 4 (CXCR4) correlates with chemotaxis, invasion, and cancer stem cell (CSC) properties within several solid-tumor malignancies. Recent studies reported that microRNA (miRNA) modulates the stemness of embryonic stem cells. We aimed to investigate the role of miRNA, via CXCR4-modulation, on CSC properties in breast cancer using cell lines and xenotransplantation mouse model and evaluated miR-193 levels in 191 patients with invasive ductal carcinoma. We validated miR-139 directly targets the 3'-untranslated region of CXCR4. Hoechst 33342 fluorescence-activated cell sorting (FACS) and sphere-forming assay were used to identify CSCs. MiR-139 suppressed breast CSCs with mesenchymal traits; led to decreased migration and invasion abilities through down-regulating CXCR4/p-Akt signaling. In lung cancer xenograft model of nude mice transplanted with human miR-139-carrying MDA-MB-231 cells, metastatic lung nodules were suppressed. Clinically, microdissected breast tumor tissues showed miR-139 reduction, compared to adjacent non-tumor tissues, that was significantly associated with worse clinicopathological features, including larger tumor size, advanced tumor stage and lymph node metastasis; moreover, reduced miR-139 level was predominately occurred in late-stage HER2-oreexpression tumors. Collectively, our findings highlight miR-139-mediated suppression of CXCR4/p-Akt signaling and thereby affected mesenchymal stem-cell genesis, indicating its potential as a therapeutic target for invasive breast cancer.

7.
Obes Surg ; 31(8): 3707-3714, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34033013

RESUMO

BACKGROUND: Taking advantage of isomeric form of vitamin E in the supplement, adherence to supplement could be evaluated by changes in circulating α- and γ-tocopherol concentrations. Accordingly, effects of supplementation on postoperative nutrition and bone metabolism were studied in terms of adherence. METHODS: Thirty-eight SG patients were all prescribed a postoperative nutritional supplement containing a low dose of vitamin D (600 IU) and calcium (200 mg). Blood samples were collected prior to (M0) and 6 months after (M6) surgery and concentrations of nutrients and C-terminal telopeptide of type I collage (CTX), a marker of bone resorption, were measured. Adherence and non-adherence were stratified according to change (△, M6-M0) in serum α-tocopherol concentrations (> 0 vs. ≤ 0, respectively). RESULTS: When M0 and M6 were compared, there were significant increases in serum concentrations of 25(OH)D, α-tocopherol and selenium, whereas there were reductions in parathyroid hormone, ferritin, and γ-tocopherol. At M6, the prevalence of vitamin D insufficiency (25(OH)D < 30 ng/mL) and high CTX were 72 and 26%, respectively. When comparison was made between adherence and non-adherence, only △25(OH)D concentrations, but no other nutrients nor postoperative CTX differed. Multiple linear regression demonstrated that postoperative vitamin D status was independently associated with its preoperative concentrations (ß = 0.85, p < 0.001) and adherence (ß = 0.52, p < 0.05). CONCLUSION: SG patients' adherence to supplementation, even with a low dose of vitamin D and calcium, determined vitamin D status but not bone resorption marker concentrations, at least within 6 months after surgery.


Assuntos
Reabsorção Óssea , Obesidade Mórbida , Deficiência de Vitamina D , Suplementos Nutricionais , Gastrectomia , Humanos , Obesidade Mórbida/cirurgia , Hormônio Paratireóideo , Vitamina D
9.
J Proteome Res ; 20(5): 2953-2963, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33780252

RESUMO

Urothelial carcinoma (UC) is the ninth most prevalent malignancy worldwide. Noninvasive and efficient biomarkers with high accuracy are imperative for the surveillance and diagnosis of UC. CKD patients were enrolled as a control group in this study for the discovery of highly specific urinary protein markers of UC. An iTRAQ-labeled quantitative proteomic approach was used to discover novel potential markers. These markers were further validated with 501 samples by ELISA assay, and their diagnostic accuracies were compared to those of other reported UC markers. BRDT, CYBP, GARS, and HDGF were identified as novel urinary UC biomarkers with a high discrimination ability in a population comprising CKD and healthy subjects. The diagnostic values of the four novel UC markers were better than that of a panel of well-known or FDA-approved urinary protein markers CYFR21.1, Midkine, and NUMA1. Three of our discovered markers (BRDT, HDGF, GARS) and one well-known marker (CYFR21.1) were finally selected and combined as a marker panel having AUC values of 0.962 (95% CI, 0.94-0.98) and 0.860 (95% CI, 0.83-0.89) for the discrimination between UC and normal groups and UC and control (healthy + CKD) groups, respectively.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Biomarcadores , Biomarcadores Tumorais , Proteínas de Ciclo Celular , Humanos , Proteômica
10.
BMC Geriatr ; 20(1): 530, 2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33297982

RESUMO

BACKGROUND: This study aims to identify the age trajectories of disability in instrumental activities of daily life (IADLs) over 11 years and their correlates, and to estimate disability-free life expectancy for identified trajectory groups in middle-aged and older adults. METHODS: We included 3118 participants aged 50 and over without IADL limitations at baseline from the Taiwan Longitudinal Study in Aging, followed across 1996-2007. We used group-based trajectory models to identify age trajectories of IADL disability, and multiple logistic regressions to examine their correlates. Sullivan method was used to compute IADL disability-free life expectancy for trajectory groups at different ages. RESULTS: We identified two trajectories groups: 67.7% of participants classified as the late-onset group and 32.3% as the early-onset group. Female (adjusted odds ratio [aOR]: 1.93, 95% confidence interval [95% CI]: 1.54, 2.41), not being employed (aOR: 1.30, 95% CI: 1,08, 1,56), poor/fair self-rated health (aOR: 1.31, 95% CI:1.09, 1.58), hypertension (aOR: 1.32, 95% CI: 1.07, 1.63), diabetes mellitus (aOR: 2.29, 95% CI: 1.72, 3.07), arthritis (aOR: 1.42, 95% CI: 1.11, 1.81), stroke (aOR: 2.21, 95% CI: 1.04, 4.70), and one-point increase in a 10-item depression scale (aOR: 1.04, 95% CI: 1.02, 1.06) were associated with early-onset of disability, whereas higher education (aOR: 0.59, 95% CI: 0.42, 0.81), regular exercise (aOR: 0.76, 95% CI: 0.62, 0.93), and participating voluntary or club activities (aOR: 0.78, 95% CI: 0.65, 0.93) related to the late-onset. IADL disability-free life expectancies at 65 years old in the late-onset group were 15.6 years for women and 14.4 for men, respectively, comprising 56.6 and 64.2% of their remaining life, whereas those of the early-onset group were 4.8 and 4.6 years for women and men respectively, comprising 22.5 and 27.2% of remaining life. CONCLUSIONS: Early-onset of IADLs disability may correlate to chronic conditions, and engagement in employment, exercise, and social participation were associated with a reduced risk of early disability in IADLs.


Assuntos
Atividades Cotidianas , Pessoas com Deficiência , Idoso , Teorema de Bayes , Avaliação da Deficiência , Feminino , Humanos , Expectativa de Vida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Taiwan/epidemiologia
11.
Genes (Basel) ; 12(1)2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33374471

RESUMO

Adiponectin (APN) is suggested to be a potential biomarker for predicting diabetic retinopathy (DR) risk, but the association between APN and DR has been inconsistent in observational studies. We used a Mendelian randomization (MR) analysis to evaluate if circulating APN levels result in DR. We applied three different genetic risk scores (GRS): GRSAll combined all 47 single nucleotide polymorphisms (SNPs), which from a genome-wide association study (GWAS) database-catalog reach significance level; GRSLimited comprised 16 GRSAll-SNPs with a rigorous threshold (p < 5.0 × 10-8 for GWAS), and GRSAPN combined 5 SNPs significantly associated with APN level. The MR-inverse-variance weighted method analysis showed that for each 1-SD increase in genetically induced increase in plasma APN, the OR of having DR was ß = 0.20 (95% CI: -0.46-0.85, p = 0.553) for GRSAPN, 0.61 (95% CI: 0.10-1.13, p = 0.020) for GRSAll, and 0.57 (95% CI: -0.06 to 1.20, p = 0.078) for GRSLimited. Sensitivity analysis, including MR-egger regression and the weighted-median approach, did not provide evidence of the pleiotropic effect of IVs. Limited evidence for the causal role of APN in DR risk among Taiwanese diabetic patients was shown based on MR analysis in the present study.


Assuntos
Adiponectina/sangue , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/epidemiologia , Adiponectina/genética , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Retinopatia Diabética/sangue , Retinopatia Diabética/genética , Feminino , Pleiotropia Genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Medição de Risco/métodos , Taiwan/epidemiologia
12.
Sci Rep ; 10(1): 16087, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999320

RESUMO

Epigenetics alternation of non-genetic variation and genome-wide association study proven allelic variants may associate with insulin secretion in type 2 diabetes (T2D) development. We analyzed promoter DNA methylation array to evaluate the associated with increased susceptibility to T2D (30 cases, 10 controls) and found 1,091 gene hypermethylated in promoter regions. We performed the association study of T2D and found 698 single nucleotide polymorphisms in exon and promoter sites by using 2,270 subjects (560 cases, 1,710 controls). A comparison of DNA hypermethylation and gene silencing of mouse T2D results in our T2D patients' results showed that the 5'-nucleotidase, cytosolic II (NT5C2) and fucosyltransferase 8 (FUT8) genes were strongly associated with increased susceptibility to T2D. DNA hypermethylation in promoter regions reduced NT5C2 gene expression, but not FUT8 in T2D patients. NT5C2 protein expression was decreased in pancreatic ß-cells from T2D mice. Transient transfection NT5C2 into RIN-m5F cells down-regulated DNA methyltransferase I (DNMT1) expression and up-regulation of the insulin receptor. Moreover, NT5C2 knockdown induced in DNMT1 overexpression and insulin receptor inhibition. Taken together, these results showed that NT5C2 epigenetically regulated insulin receptor in patients and mice with T2D, and maybe provide for T2D therapy strategy.


Assuntos
5'-Nucleotidase/genética , Antígenos CD/genética , DNA (Citosina-5-)-Metiltransferase 1/genética , Metilação de DNA , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Receptor de Insulina/genética , Adulto , Idoso , Animais , Estudos de Casos e Controles , Epigênese Genética , Feminino , Fucosiltransferases/genética , Regulação da Expressão Gênica , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , RNA Mensageiro/sangue , RNA Mensageiro/genética , Transdução de Sinais
13.
Obes Surg ; 30(10): 3940-3946, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32638247

RESUMO

BACKGROUND: This is the first report from Taiwan using laboratory tests to assess nutritional status of patients with obesity before bariatric-metabolic surgery. Moreover, the 25(OH)D threshold for maximal suppression of parathyroid hormone (PTH) was evaluated to offer a reference value for preoperative nutritional care. METHODS: Inclusion criteria were Taiwanese, 18-65 years old, and with BMI ≥ 27.5 kg/m2 awaiting bariatric-metabolic surgery. Anthropometric data and blood samples were collected before surgery. Serum concentrations of protein; vitamins B1, B12, folate, A, D, and E; calcium; iron; zinc; copper; selenium; PTH; and erythrocyte glutathione reductase activity coefficient (vitamin B2 status) were measured. RESULTS: For 52 participants with a mean BMI 37.6 ± 6.4 kg/m2, vitamin D deficiency (25(OH)D < 20 ng/mL) and insufficiency (20 < 25(OH)D < 30 ng/mL) were at 73 and 22% prevalence, respectively. Secondary hyperparathyroidism (PTH â‰§ 65 pg/mL) was 24% and hypocalcemia was 50% (ionized Ca < 4.5 mg/dL). Deficiency of other nutrients was sporadic (< 10%) or nil. When participants were stratified according to 25(OH)D concentrations (< 10, 10-15, 15-20, and ≥ 20 ng/mL), PTH increased at 25(OH)D < 10 ng/mL (ß = 48.34, p = 0.001) after adjusting for age, gender, and BMI. CONCLUSION: For patients with obesity before bariatric-metabolic surgery, vitamin D/calcium deficiency was the only nutritional issue that needs to be addressed in Taiwan. However, a lower cutoff point of 25(OH)D, i.e., 10 ng/mL, for vitamin D deficiency may be considered for patients before surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03915158.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida , Deficiência de Vitamina D , Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Estado Nutricional , Obesidade/complicações , Obesidade/cirurgia , Obesidade Mórbida/cirurgia , Hormônio Paratireóideo , Taiwan/epidemiologia , Vitamina D/análogos & derivados , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Adulto Jovem
14.
Artigo em Inglês | MEDLINE | ID: mdl-32419820

RESUMO

Glaucoma is characterized by the degeneration of retinal ganglion cells that cause progressive optic neuropathy, finally resulting in changes to the optic nerve head. Lowering intraocular pressure (IOP) is the only method proven for treating glaucoma. Several studies have discovered that acupuncture can reduce IOP and also increase ocular perfusion and ocular blood flow. Therefore, the present study investigated the effect of acupuncture on IOP in glaucoma patients. We conducted a single-blinded, randomized, controlled trial involving 45 glaucoma patients. The results indicated that the difference between the IOP 60 min after the intervention and IOP immediately before the intervention was greater in the acupuncture group (AG) and electroacupuncture group (EG) than in the sham group (SG) for all four of the interventions performed and in both eyes (all p < 0.05). The IOP difference between immediately before the first intervention and after finishing the final intervention was also greater in the AG and EG than in the SG in both eyes (all p < 0.05). In conclusion, IOP was reduced at 60 min after acupuncture or electroacupuncture was performed at BL1 and EX-HN7. Additionally, IOP was reduced after finishing four acupuncture or electroacupuncture sessions. Therefore, our results suggest that acupuncture and electroacupuncture are beneficial for lowering IOP in glaucoma patients. This trial is registered with NCT04157530.

16.
Nutrients ; 12(2)2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32093185

RESUMO

Our objective was to determine how docosahexaenoic acid (DHA) proportions in human milk are modulated by maternal FADS gene variants and dietary intake in Taiwanese women. Inclusion criteria included being healthy, 20-40 y old, having had a full-term baby that they intended to breast feed for at least 1 month, and willingness to participate in this study. Intake of DHA was assessed by food frequency questionnaire and fatty acids were analyzed in human milk samples collected 3-4 weeks postpartum. Based on multiple linear regression of data from 164 mothers that completed this study, there was 0.28% (FA%) reduction in milk DHA in high versus low genetic risk (stratified by whether minor allele numbers were ≥ 3 in rs1535 and rs174448) and 0.45% reduction in low versus high intake (stratified by whether DHA intake reached 200 mg/d). There was a significant gene-diet interaction; mothers with low genetic risk only had high milk DHA proportions with high DHA intake, whereas for mothers with high genetic risk, dietary effects were quite limited. Therefore, for FADS single nucleotide polymorphism in Taiwanese women, increasing DHA intake did not correct low milk DHA proportions in those with a high-risk genotype. Diet only conferred benefits to those with a low-risk genotype. Trial registration: This trial was retrospectively registered (Feb 12, 2019) in ClinicalTrials.gov (No. NCT03842891, https://clinicaltrials.gov/ct2/show/NCT03842891).


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Ácidos Docosa-Hexaenoicos/análise , Ingestão de Alimentos/genética , Ácidos Graxos Dessaturases/genética , Leite Humano/química , Adulto , Alelos , Aleitamento Materno , Inquéritos sobre Dietas , Feminino , Genótipo , Humanos , Recém-Nascido , Fenômenos Fisiológicos da Nutrição Materna/genética , Mães , Polimorfismo de Nucleotídeo Único/genética , Período Pós-Parto , Gravidez , Taiwan , Adulto Jovem
17.
Artigo em Inglês | MEDLINE | ID: mdl-31958309

RESUMO

OBJECTIVE: Diabetic nephropathy (DN) and diabetic retinopathy (DR) comprise major microvascular complications of diabetes that occur with a high concordance rate in patients and are considered to potentially share pathogeneses. In this case-control study, we sought to investigate whether DR-related single nucleotide polymorphisms (SNPs) exert pleiotropic effects on renal function outcomes among patients with diabetes. RESEARCH DESIGN AND METHODS: A total of 33 DR-related SNPs were identified by replicating published SNPs and via a genome-wide association study. Furthermore, we assessed the cumulative effects by creating a weighted genetic risk score and evaluated the discriminatory and prediction ability of these genetic variants using DN cases according to estimated glomerular filtration rate (eGFR) status along with a cohort with early renal functional decline (ERFD). RESULTS: Multivariate logistic regression models revealed that the DR-related SNPs afforded no individual or cumulative genetic effect on the nephropathy risk, eGFR status or ERFD outcome among patients with type two diabetes in Taiwan. CONCLUSION: Our findings indicate that larger studies would be necessary to clearly ascertain the effects of individual genetic variants and further investigation is also required to identify other genetic pathways underlying DN.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/genética , Retinopatia Diabética/genética , Marcadores Genéticos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/patologia , Retinopatia Diabética/etiologia , Retinopatia Diabética/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taiwan
18.
J Formos Med Assoc ; 119(1 Pt 2): 254-259, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31147198

RESUMO

BACKGROUND: Functional impairment is frequently seen in patients with stroke. Although the progression of functional recovery after stroke has been proposed, the recovery profile after acute stroke is not well described. The objective of this study is to investigate functional recovery in stroke patients entering post-acute rehabilitation care. METHODS: A retrospective cohort study collected the data of patients who entered the stroke Post-acute Care (PAC) programs. Ninety-five patients after stroke with a modified Ranking Scale (mRS) score of 3-4 who were referred to a post-acute care unit for intensive rehabilitation were recruited. The patients underwent functional, quality of life, and neuropsychological evaluation tests at admission and before discharge. The test scores before discharge were used as outcome variables and were compared with the test scores at admission to show functional recovery. RESULTS: The average length of stay was 58.15 days. After an intensive rehabilitation intervention, significant improvements were observed in all test scores. Additionally, a significant removal rate for nasogastric tubes (p = 0.000) and Foley catheters (p = 0.003) was found at discharge. CONCLUSION: This study showed that the PAC rehabilitation unit was beneficial for patients with acute stroke who had functional impairments. The study results may call for further investigation to identify and develop better models for the delivery of rehabilitation in the stroke PAC unit.


Assuntos
Recuperação de Função Fisiológica , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/terapia , Cuidados Semi-Intensivos/métodos , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Avaliação da Deficiência , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Taiwan
19.
Int J Mol Sci ; 21(1)2019 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-31881805

RESUMO

The anti-tumor activity of diosgenin, a new steroidal constituent present in fenugreek, on two human breast cancer cell lines, MCF-7 and Hs578T, was studied. Diosgenin treatment resulted in cell growth inhibition, cell cycle arrest, and apoptosis in concentration- and time-dependent manners in both cell lines. Western blot analyses of whole cell lysates for cell cycle proteins showed that diosgenin altered phosphorylated cyclin checkpoint1 (p-Chk1Ser345) and cyclin B expression, which resulted in G2/M phase blockade. Mechanistically, Cdc25C-Cdc2 signaling was involved in inactivating Chk1Ser345 by p53-dependence in MCF-7 cells and p21-dependence in Hs578T cells that are p53-deficient. Moreover, diosgenin induced a significant loss of the mitochondrial membrane potential in breast cancer cells, and prominently affected cell death through down-regulation of the anti-apoptotic protein, Bcl-2. This released cytochrome c and activated the caspase signaling cascade. Taken together, these findings reveal that the anti-proliferative activity of diosgenin involves the induction of G2/M phase arrest via modulating the Cdc25C-Cdc2-cyclin B pathway and mitochondria-mediated apoptosis in human breast cancer cell lines. This suggests the potential usefulness of diosgenin in treating breast cancer.


Assuntos
Apoptose/efeitos dos fármacos , Quinase 1 do Ponto de Checagem/metabolismo , Diosgenina/farmacologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Fosfatases cdc25/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Ciclina B/metabolismo , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos
20.
J Biomed Sci ; 26(1): 91, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699087

RESUMO

BACKGROUND: Genetic factors, dysregulation in the endocrine system, cytokine and paracrine factors are implicated in the pathogenesis of familial short stature (FSS). Nowadays, the treatment choice for FSS is limited, with only recombinant human growth hormone (rhGH) being available. METHODS: Herein, starting from the identification of 122 genetic loci related to FSS, we adopted a genetic-driven drug discovery bioinformatics pipeline based on functional annotation to prioritize crucial biological FSS-related genes. These genes were suggested to be potential targets for therapeutics. RESULTS: We discovered five druggable subnetworks, which contained seven FSS-related genes and 17 druggable targerts. CONCLUSIONS: This study provides a valuable drug repositioning accompanied by corresponding targetable gene clusters for FSS therapy.


Assuntos
Estatura/genética , Descoberta de Drogas , Reposicionamento de Medicamentos , Predisposição Genética para Doença/genética , Adolescente , Criança , Pré-Escolar , Biologia Computacional , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
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