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BACKGROUND: Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has shown results in slowing estimated glomerular filtration rate (eGFR) decline and reducing proteinuria in adult patients with chronic kidney disease. This retrospective study examines dapagliflozin's effects in 22 children with kidney disease and proteinuria. METHODS: Children with a median age of 15.6 years were treated with dapagliflozin for > 3 months between July 2022 and December 2023. All children had been treated with either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for at least 1 month before starting dapagliflozin. RESULTS: The most common kidney disease diagnoses in this study included Alport syndrome (n = 7) and medication-resistant nephrotic syndrome or focal segmental glomerulosclerosis (n = 7). After 6.1 months of treatment, dapagliflozin treatment did not result in significant changes in eGFR or proteinuria. However, at the latest follow-up, a statistically significant decrease in eGFR was noted (65.5 compared to the baseline 71.1 mL/min/1.73 m2, P = 0.003). Proteinuria remained stable between baseline and the last follow-up (final spot urine protein/creatinine ratio (uPCR) 0.7 vs. baseline uPCR 0.6 mg/mg, P = 0.489). In the subgroup analysis of children treated for > 8 months, the eGFR decline post-treatment changed from - 0.5 to - 0.2 ml/min/1.73 m2 per month (P = 0.634). Only two children discontinued dapagliflozin due to suspected adverse events. CONCLUSIONS: Dapagliflozin has not been associated with serious side effects. Further prospective clinical trials are needed to confirm the efficacy and safety of dapagliflozin in children with kidney disease.
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PURPOSE: Strabismus in patients with craniosynostosis is common, but surgical correction of strabismus in these patients remains challenging. We report our findings in six patients (four of whom were Korean) with craniosynostosis who underwent strabismus surgery to specifically address V-pattern horizontal strabismus with moderate-to-severe inferior oblique (IO) overaction, using IO myectomy at a single tertiary hospital between 2005 and 2016. METHODS: We recorded preoperative characteristics including sex, age, type of strabismus, versions grading, refractive error, and visual acuity. The grading of cyclorotation of horizontal rectus muscles by V-pattern categorized using coronal computed tomography imaging. RESULTS: Of the six patients, exodeviation was found in four patients and vertical deviation in two patients in primary position. One patient had both horizontal and vertical strabismus. Available computed tomography imaging showed that V-patterns were category 1 (mild) in two patients, category 2 (moderate) in one patient, and category 3 (severe) in two patients. Complete success was defined as absence of IO overaction any more. Overall complete success rate of IO myectomy was 83.3%. CONCLUSIONS: IO myectomy appeared to have some benefits in V-pattern horizontal strabismus with moderate-to-severe IO overaction in patients with craniosynostosis.
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Craniossinostoses , Movimentos Oculares , Músculos Oculomotores , Procedimentos Cirúrgicos Oftalmológicos , Estrabismo , Tomografia Computadorizada por Raios X , Humanos , Craniossinostoses/cirurgia , Craniossinostoses/complicações , Masculino , Músculos Oculomotores/cirurgia , Músculos Oculomotores/fisiopatologia , Feminino , Procedimentos Cirúrgicos Oftalmológicos/métodos , Estrabismo/cirurgia , Estrabismo/fisiopatologia , Estrabismo/etiologia , Estudos Retrospectivos , Movimentos Oculares/fisiologia , Pré-Escolar , Resultado do Tratamento , Lactente , Acuidade Visual , Visão Binocular/fisiologia , Seguimentos , CriançaRESUMO
BACKGROUND: Ibuprofen and acetaminophen are widely used as adjuvant analgesics for postoperative pain. This meta-analysis compared the effects of intravenous (IV) ibuprofen and acetaminophen on postoperative opioid consumption and pain intensity after general anesthesia. METHODS: PubMed/MEDLINE, EMBASE, and Cochrane Library databases were searched to identify relevant studies published up to May 2023. Randomized controlled trials comparing the effects of perioperative IV ibuprofen and acetaminophen on postoperative opioid consumption and pain after general anesthesia were included in the meta-analysis and trial sequential analysis (TSA). RESULTS: Eight studies with 494 participants were included. Compared to IV acetaminophen, IV ibuprofen significantly reduced 24 h opioid consumption, presented as morphine equivalents (mean difference [MD]: -6.01 mg, 95% CI [-8.60, -3.42], P < 0.00001, I2 = 55%), and pain scores (on a scale of 0-10) at 4-6 h (MD: -0.83, 95% CI [-1.29, -0.37], P = 0.0004, I2 = 65%) and 12 h (MD: -0.38, 95% CI [-0.68, -0.08], P = 0.01, I2 = 11%) postoperatively. These results were statistically significant in TSA. Pain scores at 24 h postoperatively and side effects were not significantly different between the two groups in the meta-analysis, and TSA revealed that the sample size was too small to adequately evaluate the effects, requiring further studies for conclusive results. CONCLUSIONS: Perioperative IV ibuprofen reduced 24 h opioid consumption and pain severity up to 12 h postoperatively compared to acetaminophen. Additional research is required to assess pain intensity beyond 12 h and side effects.
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Acetaminofen , Analgésicos não Narcóticos , Analgésicos Opioides , Anestesia Geral , Ibuprofeno , Dor Pós-Operatória , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Ibuprofeno/administração & dosagem , Acetaminofen/administração & dosagem , Analgésicos Opioides/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Anestesia Geral/métodos , Anestesia Geral/efeitos adversos , Analgésicos não Narcóticos/administração & dosagem , Administração IntravenosaRESUMO
The transgene toggling device is recognized as a powerful tool for gene- and cell-based biological research and precision medicine. However, many of these devices often operate in binary mode, exhibit unacceptable leakiness, suffer from transgene silencing, show cytotoxicity, and have low potency. Here, we present a novel transgene switch, SIQ, wherein all the elements for gene toggling are packed into a single vector. SIQ has superior potency in inducing transgene expression in response to tebufenozide compared with the Gal4/UAS system, while completely avoiding transgene leakiness. Additionally, the ease and versatility of SIQ make it possible with a single construct to perform transient transfection, establish stable cell lines by targeting a predetermined genomic locus, and simultaneously produce adenovirus for transduction into cells and mammalian tissues. Furthermore, we integrated a cumate switch into SIQ, called SIQmate, to operate a Boolean AND logic gate, enabling swift toggling-off of the transgene after the removal of chemical inducers, tebufenozide and cumate. Both SIQ and SIQmate offer precise transgene toggling, making them adjustable for various researches, including synthetic biology, genome engineering, and therapeutics.
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OBJECTIVE: This study examines associations between sleep apnea risk and hypertension in a sample of immigrant Chinese and Korean Americans. DESIGN: The dataset included Chinese and Korean patients ages 50-75 recruited from primary care physicians' offices from April 2018 to June 2020 in the Baltimore-Washington DC Metropolitan Area (n = 394). Hypertension risk was determined using a combination of blood pressure measurements, self-reported diagnosis of hypertension by a medical professional, and/or self-reported use of antihypertensive medications. Linear regression models examined the associations between sleep apnea risk and blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]). Poisson regression models examined associations sleep apnea risk and hypertension. Models controlled for body mass index (BMI), demographic, and socioeconomic risk factors. We further examined models for potential effect modification by age, gender, Asian subgroup, and obesity, as well as effect modification of daytime sleepiness on the association between snoring and hypertension risk. RESULTS: High risk of sleep apnea appeared to be associated positively with SBP (ß = 6.77, 95% CI: 0.00-13.53), but not with DBP. The association was positive for hypertension, but it was not statistically significant (PR = 1.11, 95% CI: 0.87-1.41). We did not find effect modification of the associations between sleep apnea and hypertension risk, but we did find that daytime sleepiness moderated the effect of snoring on SBP. Snoring was associated with higher SBP, primarily in the presence of daytime sleepiness, such that predicted SBP was 133.27 mmHg (95% CI: 126.52, 140.02) for someone with both snoring and daytime sleepiness, compared to 123.37â mmHg (95% CI: 120.40, 126.34) for someone neither snoring nor daytime sleepiness. CONCLUSION: Chinese and Korean immigrants living in the U.S. who are at high risk of sleep apnea have higher SBP on average, even after accounting for sociodemographic characteristics and BMI. CLINICAL TRAIL REGISTRATION: : NCT03481296, date of registration: 3/29/2018.
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Distúrbios do Sono por Sonolência Excessiva , Hipertensão , Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Humanos , Asiático , Pressão Sanguínea/fisiologia , Distúrbios do Sono por Sonolência Excessiva/complicações , Hipertensão/epidemiologia , Polissonografia , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/complicações , Apneia Obstrutiva do Sono/complicações , Ronco/complicações , Emigrantes e ImigrantesRESUMO
BACKGROUND AND AIM: Although obesity is a known risk factor for colorectal neoplasms, the correlation between weight change and colorectal neoplasm is unclear. Thus, we aim to evaluate the association between weight change and advanced colorectal neoplasm (ACRN) recurrence during post-polypectomy surveillance colonoscopy. METHODS: This retrospective cohort study included 7473 participants diagnosed with colorectal neoplasms between 2003 and 2010 who subsequently underwent surveillance colonoscopies until 2020. We analyzed the association between the risk of metachronous ACRN and weight change, defining stable weight as a weight change of <3% and weight gain as a weight increase of ≥3% from baseline during the follow-up period. RESULTS: During a median 8.5 years of follow-up, 619 participants (8.3%) developed ACRN. Weight gain was reported as an independent risk factor for metachronous ACRN in a time-dependent Cox analysis. A weight gain of 3-6% and ≥6% had adjusted hazard ratios (AHRs) of 1.48 (95% confidence interval [CI]: 1.19-1.84) and 2.14 (95% CI: 1.71-2.69), respectively. Participants aged 30-49 and 50-75 years with weight gain of ≥6% showed AHRs of 2.88 (95% CI: 1.96-4.21) and 1.90 (95% CI: 1.43-2.51), respectively. In men and women, weight gain of ≥3% was significantly correlated with metachronous ACRN. CONCLUSIONS: Weight gain is associated with an increased risk of metachronous ACRN. Furthermore, weight gain is associated with the recurrence of ACRN in both men and women regardless of age.
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Pólipos do Colo , Neoplasias Colorretais , Segunda Neoplasia Primária , Masculino , Humanos , Feminino , Pólipos do Colo/epidemiologia , Estudos Retrospectivos , Recidiva Local de Neoplasia/complicações , Colonoscopia/efeitos adversos , Fatores de Risco , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Aumento de Peso , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologiaRESUMO
BACKGROUND & AIMS: Although non-alcoholic fatty liver disease (NAFLD) is becoming a leading cause of hepatocellular carcinoma (HCC), HCC risk in non-cirrhotic NAFLD received little attention. We aimed to develop and validate an HCC risk prediction model for non-cirrhotic NAFLD. METHODS: A nationwide cohort of non-cirrhotic NAFLD patients in Korea was recruited to develop a risk prediction model and validate it internally (n = 409 088). A model using a simplified point system was developed by Cox proportional hazard model. K-fold cross-validation assessed the accuracy, discrimination and calibration. The model was validated externally using a hospital cohort from Asan Medical Center (n = 8721). RESULTS: An 11-point HCC risk prediction model for non-cirrhotic NAFLD was developed using six independent factors of age, sex, diabetes, obesity, serum alanine aminotransferase level and gamma-glutamyl transferase level (c-index 0.75). The average area under receiver operating curves (AUROCs) of the model was 0.72 at 5 years and 0.75 at 10 years. In the external validation cohort, the AUROCs were 0.79 [95% confidence interval [CI], 0.59-0.95] at 5 years and 0.84 (95% CI, 0.73-0.94) at 10 years. The calibration plots showed the expected risks corresponded well with the observed risks. Risk stratification categorized patients into the low (score 0-6), moderate (7, 8) and high (9-11; estimated incidence rate >0.2%/year) risk groups. CONCLUSIONS: A novel HCC risk prediction model for non-cirrhotic NAFLD patients was developed and validated with fair performance. The model is expected to serve as a simple and reliable tool to assess HCC risk and assist precision screening of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Estudos Retrospectivos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Fatores de Risco , FibroseRESUMO
Tight regulation of Toll-like receptor (TLR)-mediated inflammatory responses is important for innate immunity. Here, we show that T-cell death-associated gene 51 (TDAG51/PHLDA1) is a novel regulator of the transcription factor FoxO1, regulating inflammatory mediator production in the lipopolysaccharide (LPS)-induced inflammatory response. TDAG51 induction by LPS stimulation was mediated by the TLR2/4 signaling pathway in bone marrow-derived macrophages (BMMs). LPS-induced inflammatory mediator production was significantly decreased in TDAG51-deficient BMMs. In TDAG51-deficient mice, LPS- or pathogenic Escherichia coli infection-induced lethal shock was reduced by decreasing serum proinflammatory cytokine levels. The recruitment of 14-3-3ζ to FoxO1 was competitively inhibited by the TDAG51-FoxO1 interaction, leading to blockade of FoxO1 cytoplasmic translocation and thereby strengthening FoxO1 nuclear accumulation. TDAG51/FoxO1 double-deficient BMMs showed significantly reduced inflammatory mediator production compared with TDAG51- or FoxO1-deficient BMMs. TDAG51/FoxO1 double deficiency protected mice against LPS- or pathogenic E. coli infection-induced lethal shock by weakening the systemic inflammatory response. Thus, these results indicate that TDAG51 acts as a regulator of the transcription factor FoxO1, leading to strengthened FoxO1 activity in the LPS-induced inflammatory response.
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Escherichia coli , Lipopolissacarídeos , Camundongos , Animais , Proteínas 14-3-3 , Fatores de Transcrição/genética , Mediadores da InflamaçãoRESUMO
Little is known about the prevalence of chronic kidney disease (CKD) during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to investigate the long-term trends in CKD prevalence from South Korea including the early pandemic. We used data from 108,152 Korean adults from 2007 to 2020 obtained from a representative longitudinal serial study. We defined CKD as a condition when the participant's estimated glomerular filtration rate was < 60 mL/min/1.73 m2, or one-time spot proteinuria was ≥ 1 +, and then examined the overall trends in the prevalence of CKD. Among the included adults (n = 80,010), the overall national prevalence of CKD was 6.2%. The trend slope gradually increased from 2007 to 2019, however, there was a sudden decrease in 2020 (2007-2010, 5.1% [95% confidence interval (CI) 4.7-5.5]; 2017-2019, 7.1% [95% CI 6.6-7.6]; pandemic period, 6.5% [95% CI 5.7-7.3]; and ßdiff, - 0.19; 95% CI - 0.24 to - 0.13). The prevalence of CKD among younger adults and those with poor medical utilization significantly decreased during the early pandemic. This study was the first large-scale study to investigate the longitudinal prevalence of CKD from 2007 to 2020. Further research is needed to fully understand the exact causes for this decline and to identify healthcare policy strategies for preventing and managing CKD.
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COVID-19 , Insuficiência Renal Crônica , Adulto , Humanos , Prevalência , COVID-19/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Taxa de Filtração Glomerular , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
INTRODUCTION: Abdominal obesity increases the risk of gastroesophageal reflux disease (GERD). This study aimed to determine the association between GERD and abdominal fat area quantified by computed tomography (CT). METHODS: We analyzed the effect of abdominal fat area on gastroesophageal reflux symptoms and erosive esophagitis using logistic regression models in 5,338 participants who underwent abdominal fat measurement CT and screening esophagogastroduodenoscopy. RESULTS: Participants with reflux symptoms and erosive esophagitis were diagnosed in 1,168 (21.9%) and 671 (12.5%), respectively. Multivariate analysis showed that subcutaneous and visceral fat areas were significantly associated with reflux symptoms and erosive esophagitis. The adjusted odds ratio (OR) in the fourth quartile of visceral fat area compared with that in the lowest quartile was 1.98 (95% confidence interval (CI) 1.63-2.39) for reflux symptoms and 2.33 (95% CI 1.80-3.01) for erosive esophagitis. Visceral fat area had a stronger effect in the younger age-group. In the group <50 years, the adjusted OR in fourth quartile of visceral fat area was 2.70 (95% CI 1.86-3.94) for reflux symptoms and 3.59 (95% CI 2.22-5.80) for erosive esophagitis. High visceral-to-subcutaneous fat ratio (VSR) increased the risk of reflux symptoms and erosive esophagitis in participants with body mass index <25 kg/m2 and normal waist circumference. CONCLUSION: Subcutaneous and visceral fat areas were associated with an increased risk of reflux symptoms and erosive esophagitis. High VSR increased the risk of reflux symptoms and erosive esophagitis in participants with normal body weight and waist circumference.
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Esofagite , Refluxo Gastroesofágico , Adulto , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Fatores de Risco , Refluxo Gastroesofágico/complicações , Esofagite/complicações , Gordura Subcutânea/diagnóstico por imagemRESUMO
BACKGROUND: Growing evidence suggests an association between the vitamin D levels and respiratory outcomes of preterm infants. The objective of this systematic review and meta-analysis was to explore whether premature neonates with a vitamin D deficiency have an increased risk of respiratory distress syndrome (RDS). METHODS: We searched PubMed, EMBASE, and the Cochrane Library up through July 20, 2021. The search terms were 'premature infant', 'vitamin D', and 'respiratory distress syndrome'. We retrieved randomized controlled trials and cohort and case-control studies. For statistical analysis, we employed the random-effects model in Comprehensive Meta-Analysis Software ver. 3.3. We employed the Newcastle-Ottawa Scales for quality assessment of the included studies. RESULTS: A total of 121 potentially relevant studies were found, of which 15 (12 cohort studies and 3 case-control studies) met the inclusion criteria; the studies included 2,051 preterm infants. We found significant associations between RDS development in such infants and vitamin D deficiency within 24 h of birth based on various criteria, thus vitamin D levels < 30 ng/mL (OR 3.478; 95% CI 1.817-6.659; p < 0.001), < 20 ng/mL (OR 4.549; 95% CI 3.007-6.881; p < 0.001), < 15 ng/mL (OR 17.267; 95% CI 1.084-275.112; p = 0.044), and < 10 ng/ml (OR 1.732; 95% CI 1.031-2.910; p = 0.038), and an even lower level of vitamin D (SMD = -0.656; 95% CI -1.029 to -0.283; p = 0.001). CONCLUSION: Although the vitamin D deficiency definitions varied and different methods were used to measure vitamin D levels, vitamin D deficiency or lower levels of vitamin D within 24 h of birth were always associated with RDS development. Monitoring of neonatal vitamin D levels or the maintenance of adequate levels may reduce the risk of RDS.
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Síndrome do Desconforto Respiratório do Recém-Nascido , Deficiência de Vitamina D , Lactente , Feminino , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/complicações , Vitamina D , Deficiência de Vitamina D/complicações , VitaminasRESUMO
BACKGROUND: Studies generally show that higher acculturation is associated with greater cardiovascular disease (CVD) risk among immigrants in the United States (US). However, few studies have compared how proxies of acculturation are differentially associated with metabolic abnormalities measured using objective biomarkers, self-reported diagnosis, and medication use, particularly among East Asian Americans. METHODS: Survey data and biomarker measurements collected from random (non-fasting) blood samples of Chinese and Korean immigrants in the US (n = 328) were used to examine the associations between two proxies for acculturation (years living in the US and English speaking proficiency) with three cardiometabolic abnormalities (high triglyceride levels, diabetes, and hypercholesterolemia). Poisson regression models estimated prevalence ratios adjusted for demographic characteristics, socioeconomic factors, and body mass index. Gender, Asian subgroup, and household income were tested as potential effect modifiers. RESULTS: Living longer in the US was associated with greater likelihood of having high triglycerides. In addition, living longer in the US was associated with greater likelihood of diabetes for people with lower household income and greater likelihood of hypercholesterolemia for people with higher household income. Higher level of English proficiency was less consistently associated with higher cardiometabolic risk, although there was a significant association with greater likelihood of hypercholesterolemia. CONCLUSIONS: Longer time lived in the US is associated with higher risk of cardiometabolic abnormalities among Chinese and Korean Americans. Future studies of acculturation and cardiometabolic risk should carefully consider potential mechanisms and what proxy measures of acculturation capture. TRIAL REGISTRATION NUMBER: NCT03481296, date of registration: 3/29/2018.
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Aculturação , Asiático , Doenças Cardiovasculares , Diabetes Mellitus , Hipercolesterolemia , Hiperlipidemias , Humanos , Asiático/etnologia , Asiático/estatística & dados numéricos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etnologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etnologia , População do Leste Asiático , Hipercolesterolemia/epidemiologia , Hipercolesterolemia/etnologia , Hiperlipidemias/epidemiologia , Hiperlipidemias/etnologia , Estados Unidos/epidemiologia , Emigrantes e Imigrantes/estatística & dados numéricos , Fatores de TempoRESUMO
Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a group of chronic inflammatory diseases of the gastrointestinal tract. Although the multifactorial etiology of IBD pathogenesis is relatively well documented, the regulatory factors that confer a risk of IBD pathogenesis remain less explored. In this study, we report that T-cell death-associated gene 51 (TDAG51/PHLDA1) is a novel regulator of the development of dextran sulfate sodium (DSS)-induced colitis in mice. TDAG51 expression was elevated in the colon tissues of DSS-induced experimental colitis mice. TDAG51 deficiency protected mice against acute DSS-induced lethality and body weight changes and disease severity. DSS-induced structural damage and mucus secretion in colon tissues were significantly reduced in TDAG51-deficient mice compared with wild-type mice. We observed similar results in a DSS-induced chronic colitis mouse model. Finally, we showed that the production of inflammatory mediators, including proinflammatory enzymes, molecules and cytokines, was decreased in DSS-treated TDAG51-deficient mice compared with DSS-treated wild-type mice. Thus, we demonstrated that TDAG51 deficiency plays a protective role against DSS-induced colitis by decreasing the production of inflammatory mediators in mice. These findings suggest that TDAG51 is a novel regulator of the development of DSS-induced colitis and is a potential therapeutic target for IBD.
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Besouros , Colite , Doenças Inflamatórias Intestinais , Camundongos , Animais , Sulfato de Dextrana/toxicidade , Colite/induzido quimicamente , Mediadores da InflamaçãoRESUMO
Osteoclasts (OCs) are clinically important cells that resorb bone matrix. Accelerated bone destruction by OCs is closely linked to the development of metabolic bone diseases. In this study, we screened novel chemical inhibitors targeting OC differentiation to identify drug candidates for metabolic bone diseases. We identified that 1,3-dibenzyl-5-fluorouracil, also named OCI-101, is a novel inhibitor of osteoclastogenesis. The formation of multinucleated OCs is reduced by treatment with OCI-101 in a dose-dependent manner. OCI-101 inhibited the expression of OC markers via downregulation of receptor activator of NF-κB ligand and M-CSF signaling pathways. Finally, we showed that OCI-101 prevents ovariectomy-induced bone loss by suppressing OC differentiation in mice. Hence, these results demonstrated that OCI-101 is a good drug candidate for treating metabolic bone diseases.
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The aim of this meta-analysis was to determine the incidence and risk factors of early pulmonary hypertension (PHT) in preterm infants and evaluate the association of early PHT with morbidities such as bronchopulmonary dysplasia (BPD), late PHT, and in-hospital mortality. We searched the PubMed (1980-2021), Embase (1968-2021), CINAHL (2002-2021), Cochrane library (1989-2021), and KoreaMed (1993-2021). Observational studies on the association between early PHT diagnosed within the first 2 weeks after birth and its clinical outcomes in preterm infants born before 37 weeks of gestation or with very low birth weight (< 1500 g) were included. Two authors independently extracted the data and assessed the quality of each study using a modified Newcastle-Ottawa Scale. We performed meta-analysis using Comprehensive Meta-Analysis version 3.3. A total of 1496 potentially relevant studies were found, of which 8 studies (7 cohort studies and 1 case-control study) met the inclusion criteria comprising 1435 preterm infants. The event rate of early PHT was 24% (95% confidence interval [CI] 0.174-0.310). The primary outcome of our study was moderate to severe BPD at 36 weeks postmenstrual age, and it was associated with early PHT (6 studies; odds ratio [OR] 1.682; 95% CI 1.262-2.241; P < 0.001; heterogeneity: I2 = 0%; P = 0.492). Preterm infants with early PHT had higher OR of in-hospital mortality (6 studies; OR 2.372; 95% CI 1.595-3.528; P < 0.001; heterogeneity: I2 = 0%; P = 0.811) and developing late PHT diagnosed after 4 weeks of life (4 studies; OR 2.877; 95% CI 1.732-4.777; P < 0.001; heterogeneity: I2 = 0%; P = 0.648). Infants with oligohydramnios (4 studies; OR 2.134; 95% CI 1.379-3.303; P = 0.001) and those who were small-for-gestational-age (5 studies; OR 1.831; 95% CI 1.160-2.890; P = 0.009) had an elevated risk of developing early PHT. This study showed that early PHT is significantly associated with mortality and morbidities, such as BPD and late PHT. Preterm infants with a history of oligohydramnios and born small-for-gestational-age are at higher risk for developing early PHT; however, high-quality studies that control for confounders are necessary.
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Displasia Broncopulmonar , Hipertensão Pulmonar , Oligo-Hidrâmnio , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/etiologia , Estudos de Casos e Controles , Feminino , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/epidemiologia , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Gravidez , Fatores de RiscoRESUMO
This study was conducted to evaluate the protective effect of Juglans regia (walnut, Gimcheon 1ho cultivar, GC) on high-fat diet (HFD)-induced cognitive dysfunction in C57BL/6 mice. The main physiological compounds of GC were identified as pedunculagin/casuariin isomer, strictinin, tellimagrandin I, ellagic acid-O-pentoside, and ellagic acid were identified using UPLC Q-TOF/MS analysis. To evaluate the neuro-protective effect of GC, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 2',7'-dichlorodihydrofluorecein diacetate (DCF-DA) analysis were conducted in H2O2 and high glucose-induced neuronal PC12 cells and hippocampal HT22 cells. GC presented significant cell viability and inhibition of reactive oxygen species (ROS) production. GC ameliorated behavioral and memory dysfunction through Y-maze, passive avoidance, and Morris water maze tests. In addition, GC reduced white adipose tissue (WAT), liver fat mass, and serum dyslipidemia. To assess the inhibitory effect of antioxidant system deficit, lipid peroxidation, ferric reducing antioxidant power (FRAP), and advanced glycation end products (AGEs) were conducted. Administration of GC protected the antioxidant damage against HFD-induced diabetic oxidative stress. To estimate the ameliorating effect of GC, acetylcholine (ACh) level, acetylcholinesterase (AChE) activity, and expression of AChE and choline acetyltransferase (ChAT) were conducted, and the supplements of GC suppressed the cholinergic system impairment. Furthermore, GC restored mitochondrial dysfunction by regulating the mitochondrial ROS production and mitochondrial membrane potential (MMP) levels in cerebral tissues. Finally, GC ameliorated cerebral damage by synergically regulating the protein expression of the JNK signaling and apoptosis pathway. These findings suggest that GC could provide a potential functional food source to improve diabetic cognitive deficits and neuronal impairments.
Assuntos
Disfunção Cognitiva , Juglans , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Dieta Hiperlipídica , Ácido Elágico/farmacologia , Peróxido de Hidrogênio/farmacologia , Juglans/metabolismo , MAP Quinase Quinase 4/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Estresse Oxidativo , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Background/Aims: Dietary factors can aggravate the symptoms of irritable bowel syndrome (IBS). Many IBS patients try restrictive diets to relieve their symptoms, but the types of diets with an exacerbating factor are unknown. Therefore, this paper reports the results of a systematic review and network meta-analysis of randomized-controlled trials (RCTs) reviewing the efficacy of food restriction diets in IBS. Methods: The MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov databases were searched until July 21, 2021, to retrieve RCTs assessing the efficacy of restriction diets in adults with IBS. Two independent reviewers performed the eligibility assessment and data abstraction. RCTs that evaluated a restriction diet versus a control diet and assessed the improvement in global IBS symptoms were included. These trials reported a dichotomous assessment of the overall response to therapy. Results: A total of 1,949 citations were identified. After full-text screening, 14 RCTs were considered eligible for the systematic review and network meta-analysis. A starch- and sucrose-reduced diet and a diet with low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) showed significantly better results than a usual diet. Symptom flare-ups in patients on a gluten- free diet were also significantly lower than in those on high-gluten diets. Conclusions: These findings showed that the starch- and sucrose-reduced, low FODMAP, and gluten-free diets had superior effects in reducing IBS symptoms. Further studies, including head-to-head trials will be needed to establish the effectiveness of dietary restrictions on IBS symptoms.
Assuntos
Síndrome do Intestino Irritável , Adulto , Dieta , Dieta com Restrição de Carboidratos , Dieta Livre de Glúten , Fermentação , Humanos , Síndrome do Intestino Irritável/terapia , Monossacarídeos , Metanálise em Rede , Oligossacarídeos , Amido , SacaroseRESUMO
Idiopathic pneumoperitoneum has an unknown etiology despite exploratory laparotomy. However, it may occur without definite abdominal symptoms; thus, adequate management could be in clinical dilemma. We experienced three cases of idiopathic nonsurgical pneumoperitoneum in healthy individuals during a health check-up. Their cases were not accompanied by any relevant etiology or definite abdominal symptoms. All of the three cases exhibited a benign clinical course. The three patients underwent an abdominal computed tomography (CT) scan as part of a health check-up program, which incidentally revealed free air in the right paracolic gutter without evidence of visceral perforation or inflammation. Among the three cases, two patients underwent colonoscopy before abdominal CT, whereas one patient did not. Two cases were completely asymptomatic and were observed without any treatment in the outpatient clinic. Only the third case with minimal symptoms was treated conservatively for a short time. If a small amount of free air typically located in the right paracolic gutter is detected in the absence of perforation during colonoscopy, close observation without unnecessary treatment would be sufficient.