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1.
Sci Total Environ ; 730: 138987, 2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32428804

RESUMO

BACKGROUND: A large number of studies have found a positive association between diurnal temperature range (DTR) and cardiovascular diseases (CVDs) incidence and mortality. Few studies regarding the effects of DTR on blood pressure (BP) are available. OBJECTIVE: To investigate the effects of DTR on BP in Jinchang, northwestern China. METHODS: Based on a prospective cohort research, a total of 46,609 baseline survey data were collected from 2011 to 2015. The meteorological observation data and environmental monitoring data were collected in the same period. The generalized additive model (GAM) was used to estimate the relationship between DTR and BP after adjusting for confounding variables. RESULTS: Our study found that there was a positive linear correlation between DTR and systolic blood pressure (SBP) and plus pressure (PP), and a negative linear correlation between DTR and diastolic blood pressure (DBP). With a 1 °C increase of DTR, SBP and PP increased 0.058 mmHg (95%CI: 0.018-0.097) and 0.114 mmHg (95%CI: 0.059-0.168) respectively, and DBP decreased 0.039 mmHg (95%CI:-0.065 ~ -0.014). There was a significant interaction between season and DTR on SBP and PP. DTR had the greatest impact on SBP and PP in hot season. The association between DTR and BP varied significantly by education level. CONCLUSION: There was a significant association between DTR and BP in Jinchang, an area with large temperature change at high altitudes in northwestern China. These results provide new evidence that DTR is an independent risk factor for BP changes among general population. Therefore, effective control and management of BP in the face of temperature changes can help prevent CVDs.

2.
J Pediatr Surg ; 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32234318

RESUMO

PURPOSE: Butyrate is a short-chain fatty acid produced in the intestine. It is controversial whether butyrate is protective or destructive for the intestinal epithelium in the development of diseases like necrotizing enterocolitis (NEC), and its mechanism of action remains unclear. We aimed to determine the effect of butyrate on the intestinal epithelium by studying its effects on intestinal epithelial cells (IEC-18) exposed to injury and in vivo by investigating the effects on the intestine in an experimental model of NEC. METHODS: A) In vitro study: Butyrate was given to normal IEC-18 to determine the dose triggering injury. Based on above results, low dose butyrate (1 mM) was given to H2O2-injured cells to determine its effect against inflammation. B) In vivo study: NEC was induced by hypoxia and gavage feeding between postnatal day P5 and P9 (n = 8). Breastfed mice were used as control (n = 7). Butyrate (150 mM) was administered by enema on P6 in NEC (n = 6). Distal ileum was harvested on P9. RESULTS: High dose (16 mM) butyrate upregulated inflammatory marker IL-6, while low dose butyrate protected cells from injury by reducing IL-6 expression. Similarly, compared with NEC alone, NEC mice who received butyrate had reduced intestinal damage, reduced IL-6 and NF-ĸB expression, and increased intestinal tight junction marker Claudin-7. CONCLUSION: Butyrate has opposite effects depending on the dose administered. Butyrate can protect cells from H2O2-induced injury and can in vivo protect the intestine from NEC. This beneficial effect is because of downregulation of inflammation and enhancement of intestinal barrier.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(2): 629-635, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32319407

RESUMO

OBJECTIVE: To assess the coagulation state of patients with abnormal coagulation function by thrombelastography (TEG) and conventional coagulation tests (CCT) and to estimate their correlations in determining the blood coagulation. METHODS: A total of 150 patients with abnormal coagulation function were enrolled, standard coagulation tests were assessed for the patients. At the same time, the thrombelastographic test was performed with TEG after sample recalcification with kaolin activator. RESULTS: There were correlations between the TEG and CCT. PT and APTT positively correlated with the R time (r=0.296, r=0.369, P<0.01), the R time negatively correlated with the Fib (r=-0.257, P<0.01), K negatively correlated with the Fib (r=0.509, P<0.01), K positively correlated with the TT (r=0.318, P<0.01), Angle positively correlated with the Fib (r=0.506, P<0.01) and negatively correlated with the TT (r=-0.237, P<0.05). CI negatively correlated with the PT (r=-0.236, P<0.05). The sensitivity to detect hypocoagulable state estimated with TEG parameter R was higher than that with PT and Fib (P<0.01), respectively. The sensitivity to hypocoagulable state estimated with K and Angle was higher than that with Fib and TT, respectively (P<0.01). CONCLUSION: There are significant correlation between some parameters of the TEG and conventionnal coagulation tests, however, the consistency and sensitivity of the two methods are poor, two methods can not be replaced by each other.

4.
Microbiologyopen ; : e1031, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32180355

RESUMO

The shallow Caroline Seamount is located in the tropical western Pacific Ocean. Its summit is 57 m below the surface and penetrates the euphotic zone. Therefore, it is ideal for the study of the influence of seamount on plankton distribution. Here, virioplankton abundance and distribution were investigated by flow cytometry (FCM) in the Caroline Seamount in August and September 2017. The total abundance of virus-like particles (VLP) was in the range of 0.64 × 106 -18.77 × 106  particles/ml and the average was 5.37 ± 3.75 × 106  particles/ml. Three to four distinct viral subclusters with similar side scatter but different green fluorescence intensities were identified. Above the deep chlorophyll maximum (DCM), two medium fluorescence virus (MFV) subclusters were discriminated. Between the DCM and the deeper layers, only one MFV subcluster was resolved. In general, low fluorescence viruses (LFV) comprised the most abundant subclusters. In the 75-150 m water column, however, the MFV abundance was higher than the LFV abundance. High fluorescence viruses (HFV) constituted the least abundant subcluster throughout the entire water column. Virioplankton abundance was significantly enhanced at the seamount stations. Environmental factors including water temperature and nitrate concentration were the most correlated with the variation in virioplankton abundance at the seamount stations. Interactions between shallow seamounts and local currents can support large virus standing stocks, causing a so-called indirect "seamount effect" on the virioplankton.

5.
Eur J Med Chem ; 193: 112178, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32171154

RESUMO

Based on our previous finding that the titled compound possesses anti-tuberculosis activity, a series of novel ((4-methoxyphenyl)carbamoyl) (5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazol-2-yl)amide analogues have been synthesized. Amongst the 22 compounds synthesized and tested, 5b, 5c and 6c showed potent inhibitory activity with Ki values of 2.02, 5.48 and 4.72 µM for their target, Mycobacterium tuberculosis (Mt) ketol-acid reductoisomerase (KARI). In addition, these compounds have excellent in vitro activity against Mt H37Rv with MIC values as low as 1 µM. The mode of binding for these compounds to Mt KARI was investigated through molecular docking and dynamics simulations. Furthermore, these compounds were evaluated for their activity in Mt infected macrophages, and showed inhibitory activities with up to a 1.9-fold reduction in growth (at 10 µM concentration). They also inhibited Mt growth in a nutrient starved model by up to 2.5-fold. In addition, these compounds exhibited low toxicity against HEK 293T cell lines. Thus, these compounds are promising Mt KARI inhibitors that can be further optimized into anti-tuberculosis agents.

6.
Pediatr Dermatol ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32212177

RESUMO

We present a retrospective case series of 3 patients with retroperitoneal kaposiform hemangioendothelioma (KHE) complicated by Kasabach-Merritt phenomenon (KMP) and biliary obstruction. We found sirolimus to be a safe and effective treatment for these patients who were refractory to other treatment modalities. However, our patients were slow to respond in comparison to published reports of sirolimus use for KHE without biliary obstruction. We postulate that therapeutic serum levels of sirolimus may be affected by biliary obstruction and improved with surgical alleviation of the obstruction.

7.
J Ovarian Res ; 13(1): 19, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059683

RESUMO

BACKGROUND: The aim of this study was to explore the clinicopathological characteristics of recurrent adult-type granulosa cell tumor of the ovary (AGCOT) and evaluated the treatment results to define the prognostic parameters for survival after recurrence. RESULTS: A retrospective review of 40 patients with recurrent AGCOT, who were treated in the Cancer Hospital at the Chinese Academy of Medical Sciences from 2000 to 2015 was conducted. The impact of clinical and pathological characteristics, progression-free survival (PFS), and post-recurrence therapeutic approaches on prognosis were analyzed. Among the 40 recurrent patients, there were 10 cases where the relapse was uncontrolled, 24 cases had second relapses, and 6 cases without further relapses at the time of our follow-up. The median PFS was 61 months (range, 7-408 months), and the median time interval between the first and the second relapses (R-PFS) was 25 months (range, 0-94 months). The median time interval between the first relapse and death (R-OS) was 90 months (range, 2-216 months). PFS ≥ 61 months (P = 0.004) and post-recurrence therapeutic approach (P < 0.001) were independent risk factors for repeated recurrences. The age at recurrence (P = 0.031) and post-recurrence therapeutic approach (P = 0.001) were independent risk factors for death after recurrence. CONCLUSION: Among patients with recurrent AGCOT, those with long PFS had good prognoses. Maximal cytoreductive effort should be made after recurrence. Complete resection and postoperative adjuvant chemotherapy may improve the prognosis of patients with recurrent AGCOT.

8.
Neurotoxicol Teratol ; 78: 106856, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31923456

RESUMO

Fetal and neonatal exposure to propofol can lead to neuronal death and long-term neurobehavioral deficiencies in both rodents and nonhuman primates. Zebrafish embryo, which is fertilized ex-utero, has provided us a new model species to study the effects of general anesthetics on developing brain. Inhibited electron transport chain leads to mitochondrial dysfunction and insufficient energy production. The aim of this study was to dissect the role of electron transport chain in propofol-induced neurotoxicity. 6 h post fertilization (hpf) zebrafish embryos were exposed to control or 1, 2 or 4 µg/ml propofol until 48hpf. Acridine orange staining was used to assess cell apoptosis in the brain of zebrafish embryos. The activity of mitochondrial electron transport chain complex was assessed using colorimetric method. Expression of key subunit of cytochrome c oxidase was assessed by western blot and transcription level of cox4i1 was assessed by quantitative real time-PCR. The mitochondrial membrane potential and ATP content were assessed. Exposure to 1, 2 and 4 µg/ml propofol induced significant increases in cell apoptosis in the brain of zebrafish embryos in a dose-dependent manner and led to significant decreases in electron transport chain complex IV activity from (0.161 ± 0.023)µmol/mg/min in blank control-treated group to (0.096 ± 0.015)µmol/mg/min, (0.083 ± 0.013)µmol/mg/min and (0.045 ± 0.014)µmol/mg/min respectively, accompanied by decreased expression of key regulatory subunit of cytochrome c oxidase-subunit IV and decreased transcription level of cox4i1. Propofol exposure also decreased the mitochondrial membrane potential and ATP content. Our findings demonstrate that inhibition of the electron transport chain is involved in the mechanisms by which propofol induces neurotoxicity in the developing brain.

9.
Dermatology ; 236(3): 262-270, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31896113

RESUMO

BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors have been shown to have excellent effects in the management of kaposiform hemangioendothelioma (KHE); however, the mechanism of action is unclear. This study identified the expressions of mTOR pathway-related proteins in different vascular tumors to provide insight into the pathogenesis of KHE. METHODS: We retrospectively reviewed the pathologic specimens of 30 patients (KHE, 15; tufted angioma [TA], 5; infantile hemangioma [IH], 5; and lymphatic malformation [LM], 5). The immunohistochemical expression of mTOR-related proteins tuberous sclerosis complex 2 (TSC2), phosphatase and tensin homologue (PTEN), phosphorylated eukaryotic translation initiation factor 4E binding protein 1 (p-4EBP1), phosphorylated mTOR (p-mTOR), and phosphorylated ribosomal protein S6 kinase B1 (p-P70S6K) were analyzed using Image-Pro Plus software. KHE had the following pattern of expression in the spindle vascular endothelial cells: TSC2 (-); PTEN (-); p-4EBP1 (+); p-mTOR (+); and p-P70S6K (+). RESULTS: All 3 patients treated with sirolimus had good responses. The TA results were similar to KHE with no significant differences (p-4EBP1: p = 0.0687; p-mTOR: p = 0.0832). The expressions of TSC2, PTEN, p-4EBP1, p-mTOR, and p-P70S6K were negative or weakly positive in IH with a statistically significant difference compared to KHE (p-4EBP1: p < 0.001; p-mTOR: p < 0.001; p-P70S6K: p < 0.001). LM had no significant differences when compared to KHE. CONCLUSIONS: The absence of TSC2 and PTEN caused abnormal activation of the mTOR signaling pathway and may be involved in the pathogenesis of KHE. The expression of mTOR-related proteins in TA and LM was similar to KHE, unlike IH. The KHE pattern of expression [PTEN (-), TSC2 (-), p-mTOR (+), p-P70S6K (+), and p-4EBP1 (+)] suggested that sirolimus may be a good therapeutic choice.

10.
J Appl Toxicol ; 40(6): 855-863, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31998977

RESUMO

Prenatal propofol exposure induced neurotoxicity in the developing brains and led to persistent learning deficits in the offspring. Our goal was to use zebrafish to explore whether the decline in learning and memory was correlated with inhibition of neuronal growth after propofol exposure. Zebrafish embryos at 6 hours postfertilization (hpf) were exposed to control or 1, 2 or 4 µg/mL propofol until 48 hpf. Spontaneous locomotor activity and swimming behavior in response to dark-to-light photoperiod stimulation were studied in zebrafish larvae at 6 days postfertilization (dpf). The adaptability to repeated stimulation was used to indicate learning and memory function of larvae. Transgenic NBT line zebrafish was used to quantitate the effect of propofol on motor neuronal growth of embryos in vivo. Six dpf transgenic zebrafish larvae went through photoperiod stimulation after their neuronal length had been analyzed during the embryonic period. Our data indicate that embryonic exposure to 1, 2 and 4 µg/mL propofol had no adverse effect on spontaneous movement in zebrafish larvae, but 2 and 4 µg/mL propofol significantly impaired the learning and memory function of larvae. Moreover, propofol significantly inhibited axonal growth of motor neurons during the embryonic stage, which was correlated with learning and memory deficiency in larvae. Our findings demonstrate that the neuronal growth was correlated with learning and memory function, indicating the relevance of zebrafish as a new model to explore the mechanisms through which propofol induces long-term learning and memory impairment.

11.
Sci Total Environ ; 713: 136357, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31962241

RESUMO

Microplastic (MP) ingestion has been recorded in 39 zooplankton species from 28 taxonomic orders, and marine zooplankton are the organisms most susceptible to MPs. However, few field studies have examined the characteristics and major influencing factors of MPs in marine zooplankton. The present study investigated the shape, color, size, chemical composition and quantity of MPs in zooplankton in the rainy and dry seasons in the Bohai Sea. Furthermore, the relationship between the MPs in zooplankton and the MPs in seawater was studied. The results showed that the MPs in zooplankton of the Bohai Sea were dominated by blue fibers. In the rainy and dry seasons, fibers accounted for 92% and 93%, respectively, of all ingested MPs, while 50% and 55%, respectively, of ingested MPs were blue. The average size of MPs in zooplankton was 1300 ± 1520 µm in the rainy season and 1040 ± 1060 µm in the dry season. Regarding the MP chemical composition, in the rainy and dry seasons, the ingested MPs were dominated by cellophane, which accounted for 53% and 68%, respectively, of MPs, followed by polyester (PET), which accounted for 18% and 20%, respectively, of MPs. The composition of MPs in zooplankton was mainly affected by the composition of MPs in seawater. No significant difference in the MP composition was observed between the two seasons or among the different zooplankton groups. The MP number was significantly higher in individual medusa than in individuals of other zooplankton groups. The mean quantity of MPs in the Bohai Sea zooplankton community in the rainy season was 2.03 ± 2.87 piece/m3, which was significantly higher than that in the dry season, 0.41 ± 0.38 piece/m3. The above results will provide a reference for marine ecological risk assessments based on the characteristics of MPs in natural seas.


Assuntos
Microplásticos , Zooplâncton , Animais , China , Monitoramento Ambiental , Oceanos e Mares , Poluentes Químicos da Água
12.
J Gastroenterol Hepatol ; 35(2): 334-342, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31271681

RESUMO

BACKGROUND AND AIM: Biliary atresia (BA) is a progressive fibro-inflammatory cholangiopathy with an unclear etiology. Various liver disorders are associated with an altered microbiome. However, gut microbiome in BA remains unknown. Here, we performed a case-control study to investigate the gut microbiota in BA. METHODS: A cross-sectional analysis was first conducted for 34 BA patients and 34 healthy controls. Then we investigated the shift in gut microbiota 2 weeks after the Kasai procedure in 16 BA patients. Gut microbiome was initially analyzed using 16S ribosome RNA gene sequencing and further validated by metagenomic sequencing. Fecal bile acids were determined using ultra-high performance liquid chromatography. RESULTS: Compared with healthy controls, BA showed lower diversity and significant structural segregation in the microbiome. At phylum level, Proteobacteria numbers increased, whereas those of Bacteroidetes decreased in BA. At genus level, several potential pathogens such as Streptococcus and Klebsiella thrived in BA, while numbers for Bifidobacterium and several butyrate-producing bacteria declined. The microbiome was also disturbed after the Kasai procedure. Operational taxonomic units responding to BA showed significant correlation with liver function. Furthermore, the abundance ratio of Streptococcus/Bacteroides showed great promise in distinguishing BA from healthy controls. Intestinal bile acids were dramatically decreased in BA, and Clostridium XIVa positively correlated with the ratio of primary/secondary bile acids. CONCLUSIONS: Gut microbial dysbiosis, may be caused by decreased bile acids, was associated with liver function and had a good diagnostic potential for BA. Therefore, further exploration of gut microbiota may provide important insights into their potential diagnostic and therapeutic benefits.

13.
Eur J Pediatr Surg ; 30(1): 90-95, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31344710

RESUMO

INTRODUCTION: Necrotizing enterocolitis (NEC) is a devastating intestinal illness in premature infants characterized by severe intestinal inflammation. Despite medical interventions, NEC mortality remains alarmingly high, which necessitates improved therapies. Lactoferrin is among the most abundant proteins in human milk and has important immunomodulatory functions. While previous studies have indicated protective effects of lactoferrin against neonatal sepsis and NEC, the underlying mechanism remains unclear. We hypothesize that lactoferrin downregulates inflammation and upregulates proliferation in intestinal epithelium during NEC injury. MATERIALS AND METHODS: NEC was induced by hypoxia, gavage feeding of hyperosmolar formula and lipopolysaccharide between postnatal day P5 and P9 (n = 8). Breastfed mice were used as control (n = 7). Lactoferrin (0.3 g/kg/day) was administered once daily by gavage from P6 to P8 in both NEC (NEC + Lac; n = 9) and control mice (Cont + Lac; n = 5). Distal ileum was harvested on P9 and analyzed for disease severity, inflammation, and proliferation. Groups were compared using one-way ANOVA and t-test appropriately; p < 0.05 was considered significant. RESULTS: Compared to NEC group, lactoferrin-treated NEC mice had reduced disease severity, reduced inflammation markers IL-6 and TNF-α expression and increased intestinal stem cell marker Lgr5 + expression. Lactoferrin-treated NEC mice exhibited increased nuclear ß-catenin, indicating upregulated Wnt pathway, and increased Ki67 positivity, suggesting enhanced proliferation. Furthermore, lactoferrin administration to control mice did not affect intestinal inflammation as well as Lgr5 + stem cell expression and epithelial proliferation. This supports the safety of lactoferrin administration and indicates that the beneficial effects of lactoferrin are present when intestinal injury such as NEC is present. CONCLUSION: Lactoferrin administration reduces the intestinal injury in experimental NEC by downregulating inflammation and upregulating cell proliferation. This beneficial effect of lactoferrin in stimulating cell proliferation is mediated by the Wnt pathway. This experimental study provides insights on the mechanism of action of lactoferrin in NEC and the role of lactoferrin in enteral feeding.

14.
CNS Neurosci Ther ; 26(1): 14-20, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31875482

RESUMO

AIM: Previous studies have found significant differences in clinical characteristics between pediatric and adult moyamoya disease (MMD) patients, but few studies have focused on the factors underlying these differences. We aimed to investigate the differences in leptomeningeal collateral (LMC) status between pediatric and adult MMD patients and to analyze the effects of LMCs on clinical characteristics and therapeutic prognosis. METHODS: We retrospectively analyzed 214 MMD patients from January 2014 to January 2016. Clinical characteristics and LMC status were compared between the pediatric and adult patients. LMC status was graded as good or poor depending on the retrograde flow from the posterior cerebral artery (PCA) on digital subtraction angiography (DSA). RESULTS: A total of 83 pediatric and 131 adult (1:1.6) MMD patients were analyzed. Pediatric patients were more likely to experience a transient ischemic attack (81%), whereas adult patients were more likely to experience infarction (51%). Regarding the different MMD stages (the early, medium, and advanced stages corresponded to Suzuki stages 1-2, 3-4, and 5-6, respectively), the prevalence of good LMC status was higher for pediatric patients than for adult patients in the early stage (P = 0.047) and the medium stage (P = 0.001), but there were no differences between these patient groups in the advanced stage (P = 0.547). Worse postoperative angiographic outcomes (P = 0.017) were found in adult patients than in pediatric patients in the medium stage. Poor LMC status had strong correlations with infarction (P < 0.001 and P = 0.017) and poor postoperative outcomes (P = 0.003 and P = 0.043) in both pediatric and adult patients. CONCLUSIONS: Pediatric MMD patients have greater patency and a greater ability to establish good LMC status than adult patients, and poor LMC status has a strong correlation with severe clinical symptoms and poor postoperative outcomes. LMC status may be an important factor in the differences in clinical characteristics and prognosis between pediatric and adult MMD patients.

15.
Gastroenterol Res Pract ; 2019: 4621372, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781188

RESUMO

Objectives: To detail the effects of vitamin D (VD) deficiency and assess the relationships between VD deficiency and liver function and liver fibrosis in patients with biliary atresia (BA). Methods: In this study, BA patients confirmed by intraoperative cholangiography were enrolled between January 2017 and February 2019. Preoperative serum 25-(OH)D level, liver function, serum biomarker levels of liver fibrosis, and histopathologic features were recorded. Deficiency, insufficiency, and sufficiency of VD were defined as serum 25-(OH)D concentrations of <10, 10-20, and >20 ng/ml, respectively. Associations between serum 25-(OH)D level and liver function and liver fibrosis were analyzed. Results: A total of 161 BA infants were included. The median (interquartile range (IQR)) serum 25-(OH)D level in all patients was 7.56 (IQR: 4.48-11.40) ng/ml. The rates of 25-(OH)D deficiency, insufficiency, and sufficiency were 67.1% (108/161), 29.2% (47/161), and 3.7% (6/161), respectively. Serum 25-(OH)D level was negatively correlated with alkaline phosphatase (r = -0.232, P = 0.003). After adjusting for age, a decrease in serum 25-(OH)D level was correlated with the increase of the Batts-Ludwig stage score (odds ratio (OR): 0.94, 95% confidence interval (CI): 0.88-0.99; P = 0.028). Serum 25-(OH)D level was also correlated with the N-terminal propeptide of type III procollagen (PIIINP) (r = -0.246, P = 0.002). Additionally, PIIINP (P = 0.038) and ALP (P = 0.031) were independently associated with serum 25-(OH)D level. Conclusions: VD deficiency was common and inversely correlated with liver fibrosis in BA patients. Furthermore, VD was not correlated with liver function except alkaline phosphatase.

16.
J Pediatr Surg ; 54(12): 2509-2513, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31668400

RESUMO

PURPOSE: Lactoferrin has been used as a milk supplement to prevent disease progression in necrotizing enterocolitis. However, the underlying mechanism is still unclear. We hypothesize that lactoferrin administration can modulate intestinal epithelial cell injury. METHODS: We established an in vitro model of epithelial cell injury by treating rat intestinal epithelial cells IEC-18 and human Caco-2 cells with hydrogen peroxide (H2O2), while lactoferrin was added as treatment at the same time. Live/dead cells were detected by immunofluorescence. Gene expression of inflammatory markers interleukin-6 (IL-6), intestinal stem cells (Lgr5), and proliferation marker (Wnt/ß-catenin) were measured. Data was presented as mean ±â€¯SEM and compared using one-way ANOVA. A p-value <0.05 was considered significant. RESULTS: Compared to control cells, H2O2 induced cell death in both IEC-18 and Caco-2 cells, whereas treatment with lactoferrin maintained cell viability. In addition, lactoferrin reduced gene expression of IL-6, while it increased gene expression of Lgr5 and Wnt/ß-catenin. CONCLUSIONS: Intestinal cell injury can be induced by exposure to H2O2, mimicking epithelial damage during intestinal injury. This damage can be reversed by lactoferrin administration by reducing inflammation and inducing cell proliferation. Lactoferrin can be a potential pharmacological intervention for the prevention and recovery of intestinal epithelial injury.

17.
J Pediatr Surg ; 54(12): 2559-2564, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31668401

RESUMO

PURPOSE: Cholangitis after Kasai procedure has been previously shown to be related to poor prognosis in Biliary Atresia (BA). To investigate the risk factors and clinical outcomes of cholangitis, we did a retrospective study in post-Kasai BA patients. METHODS: Two-year follow-up data of 180 type-III BA patients after Kasai procedure in 2016 in our hospital were analyzed, including 119 cholangitis patients (66.11%). Among the cholangitis group, patients were further divided into early vs late cholangitis and single vs recurrent cholangitis groups. Liver pathology, liver function, cholangitis occurrence and frequency, jaundice clearance, and survival rates were examined. RESULTS: Higher gamma-glutamyl transferase level before Kasai is a risk factor for cholangitis (p = 0.0393). Older age and higher liver fibrosis score at Kasai are risk factors for recurrent cholangitis (p < 0.05). Shorter prophylactic intravenous antibiotics usage may contribute to early cholangitis, which may lead to higher cholangitis frequency (p < 0.0001). Recurrent cholangitis is associated with earlier cholangitis onsets (p < 0.0001). Cholangitis patients have a relatively delayed jaundice clearance, while early and recurrent cholangitis may contribute to lower overall survival. CONCLUSIONS: Personalized treatment considering risk factors in individual BA patients is needed to prevent cholangitis, especially early onsets, and to improve postoperative outcomes. LEVEL OF EVIDENCE: III.

18.
Pediatrics ; 144(5)2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604829

RESUMO

BACKGROUND: The overlapping features of biliary atresia (BA) and other neonatal cholestasis with alternative causes (non-BA) have posed challenges for diagnosis. Matrix metalloproteinase-7 (MMP-7) has been reported to be promising in diagnosing BA. We aimed to validate the diagnostic accuracy of MMP-7 for BA in a large population sample. METHODS: We enrolled 288 patients with neonatal obstructive jaundice from March 2017 to October 2018. Serum MMP-7 levels were measured by using an enzyme-linked immunosorbent assay. Receiver operating characteristic curves were constructed, and decision curve analysis was done. A Pearson correlation coefficient test was conducted to assess the correlation between MMP-7 levels and other characteristics. RESULTS: The median serum MMP-7 levels were 38.89 ng/mL (interquartile range: 22.96-56.46) for the BA group and 4.4 ng/mL (interquartile range: 2.73-6.56) for the non-BA group (P < .001). The area under the receiver operating characteristic curve value was 0.9829 for MMP-7, and the sensitivity, specificity, positive predictive value, and negative predictive value were 95.19%, 93.07%, 97.27%, and 91.43%, respectively, at a cutoff value of 10.37 ng/mL. When MMP-7 was combined with γ glutamyl transferase, the diagnostic accuracy was slightly improved without significance when compared with MMP-7 alone and had an area under the curve of 0.9880 (P = .08). Decision curve analysis also showed potential for MMP-7 to be used for clinical applications. A significant correlation was found with fibrosis stage from liver biopsy (R = 0.47; P < .001). CONCLUSIONS: MMP-7 demonstrated good accuracy in diagnosing BA and holds promise for future clinical application. Furthermore, its correlation with liver fibrosis indicated its potential use as a therapeutic target or prognostic biomarker.


Assuntos
Atresia Biliar/diagnóstico , Icterícia Neonatal/sangue , Metaloproteinase 7 da Matriz/sangue , Área Sob a Curva , Atresia Biliar/sangue , Atresia Biliar/complicações , Biomarcadores/sangue , Biópsia , Coleta de Amostras Sanguíneas/métodos , Coleta de Amostras Sanguíneas/normas , Técnicas de Apoio para a Decisão , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Icterícia Neonatal/etiologia , Fígado/patologia , Masculino , Curva ROC , Sensibilidade e Especificidade
19.
Pediatr Surg Int ; 35(12): 1363-1368, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31576466

RESUMO

AIM OF THE STUDY: Human breast milk reduces the risk and severity of necrotizing enterocolitis (NEC). Exosomes are extracellular vesicles (EVs) found in high concentrations in milk, and they mediate intercellular communication and immune responses. The aim of this study is to compare the protective effects of exosomes that are derived from different time periods of breast milk production against intestinal injury using an ex vivo intestinal organoid model. METHODS: Colostrum, transitional and mature breast milk samples from healthy lactating mothers were collected. Exosomes were isolated using serial ultracentrifugation and filtration. Exosomes' presence was confirmed using transmission electron microscopy (TEM) and western blot. To form the intestinal organoids, terminal ileum was harvested from neonatal mice pups at postnatal day 9, crypts were isolated and organoids were cultured in matrigel. Organoids were either cultured with exposure to lipopolysaccharide (LPS), or in treatment groups where both LPS and exosomes were added in the culturing medium. Inflammatory markers and organoids viability were evaluated. MAIN RESULTS: Human milk-derived exosomes were successfully isolated and characterized. LPS administration reduced the size of intestinal organoids, induced inflammation through increasing TNFα and TLR4 expression, and stimulated intestinal regeneration. Colostrum, transitional and mature human milk-derived exosome treatment all prevented inflammatory injury, while exosomes derived from colostrum were most effective at reducing inflammatory cytokine. CONCLUSIONS: Human breast milk-derived exosomes were able to protect intestine organoids against epithelial injury induced by LPS. Colostrum exosomes offer the best protective effect among the breast-milk derived exosomes. Human milk exosomes can be protective against the development of intestinal injury such as that seen in NEC.


Assuntos
Colostro/metabolismo , Enterocolite Necrosante/prevenção & controle , Exossomos/metabolismo , Mucosa Intestinal/metabolismo , Leite Humano/metabolismo , Organoides/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Humanos , Lactação , Camundongos , Camundongos Endogâmicos C57BL
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