Butyrate ameliorates maternal high-fat diet-induced fetal liver cellular apoptosis.

A maternal high-fat diet (HFD) can impact the offspring's development of liver steatosis, with fetal development in utero being a crucial period. Therefore, this study investigated the mechanism and whether butyrate can rescue liver injury caused by maternal HFD in the fetus. Pregnant female Sprague Dawley rats were randomly divided into two groups, prenatal HFD (58% fat) exposure or normal control diet (4.5% fat). The HFD group was fed an HFD 7 weeks before mating and during gestation until sacrifice at gestation 21 days. After confirmation of mating, the other HFD group was supplemented with sodium butyrate (HFSB). The results showed that maternal liver histology showed lipid accumulation with steatosis and shortened ileum villi in HFD, which was ameliorated in the HFSB group (P<0.05). There was increased fetal liver and ileum TUNEL staining and IL-6 expression with increased fetal liver TNF-α and malondialdehyde expression in the HFD group (P<0.05), which decreased in the HFSB group (P<0.05). The fetal liver expression of phospho-AKT/AKT and GPX1 decreased in the HFD group but increased in the HFSB group (P<0.05). In conclusion that oxidative stress with inflammation and apoptosis plays a vital role after maternal HFD in the fetus liver that can be ameliorated with butyrate supplementation.

Resveratrol intake during pregnancy and lactation re-programs adiposity and ameliorates leptin resistance in male progeny induced by maternal high-fat/high sucrose plus postnatal high-fat/high sucrose diets via fat metabolism regulation.

BACKGROUND: Maternal obesity is an emerging problem in the modern world. Growing evidence suggests that intrauterine high-fat (HF) exposure may predispose progeny to subsequent metabolic challenges. Progeny born to mothers who ate an HF diet also tends to eat an HF diet when growing and aggravate metabolic issues. Thus, the generational transmission of obesity is cyclical. Developing a strategy to prevent the occurrence of metabolic syndrome related to prenatal and/or postnatal HF diet is important. In this study, the reprogramming effects of maternal resveratrol treatment for the progeny with maternal HF/postnatal HF diets were investigated. METHODS: Sprague-Dawley dams were fed either a control or a high-fat/high sucrose diet (HFHS) from mating to lactation. After weaning, the progeny was fed chow or an HF diet. Four experimental groups were yielded: CC (maternal/postnatal control diet), HC (maternal HF/postnatal control diet), CH (maternal control/postnatal HFHS diet), and HH (maternal/postnatal HFHS diet). A fifth group (HRH) received a maternal HFHS diet plus maternal resveratrol treatment and a postnatal chow diet to study the effects of maternal resveratrol therapy. RESULTS: Maternal resveratrol treatment lessened the weight and adiposity of progeny that were programmed by combined prenatal and postnatal HFHS diets. Maternal resveratrol therapy ameliorated the decreased abundance of the sirtuin 1 (SIRT1) enzyme in retroperitoneal tissue and the altered leptin/soluble leptin receptor ratio of progeny. Maternal resveratrol therapy also decreased lipogenesis and increased lipolysis for progeny. CONCLUSIONS: Maternal resveratrol intervention can prevent adiposity programmed by maternal and postnatal HFHS diets by inducing lipid metabolic modulation. This study offers a novel reprogramming role for the effect of maternal resveratrol supplements against obesity.

Maternal Tryptophan Supplementation Protects Adult Rat Offspring against Hypertension Programmed by Maternal Chronic Kidney Disease: Implication of Tryptophan-Metabolizing Microbiome and Aryl Hydrocarbon Receptor.

Hypertension and chronic kidney disease (CKD) can originate during early-life. Tryptophan metabolites generated by different pathways have both detrimental and beneficial effects. In CKD, uremic toxins from the tryptophan-generating metabolites are endogenous ligands of the aryl hydrocarbon receptor (AHR). The interplay between AHR, nitric oxide (NO), the renin-angiotensin system (RAS), and gut microbiota is involved in the development of hypertension. We examined whether tryptophan supplementation in pregnancy can prevent hypertension and kidney disease programmed by maternal CKD in adult offspring via the aforementioned mechanisms. Sprague-Dawley (SD) female rats received regular chow or chow supplemented with 0.5% adenine for 3 weeks to induce CKD before pregnancy. Pregnant controls or CKD rats received vehicle or tryptophan 200 mg/kg per day via oral gavage during pregnancy. Male offspring were divided into four groups (n = 8/group): control, CKD, tryptophan supplementation (Trp), and CKD plus tryptophan supplementation (CKDTrp). All rats were sacrificed at the age of 12 weeks. We found maternal CKD induced hypertension in adult offspring, which tryptophan supplementation prevented. Maternal CKD-induced hypertension is related to impaired NO bioavailability and non-classical RAS axis. Maternal CKD and tryptophan supplementation differentially shaped distinct gut microbiota profile in adult offspring. The protective effect of tryptophan supplementation against maternal CKD-induced programmed hypertension is relevant to alterations to several tryptophan-metabolizing microbes and AHR signaling pathway. Our findings support interplay among tryptophan-metabolizing microbiome, AHR, NO, and the RAS in hypertension of developmental origins. Furthermore, tryptophan supplementation in pregnancy could be a potential approach to prevent hypertension programmed by maternal CKD.

Mitochondrial Transfer from Wharton's Jelly Mesenchymal Stem Cell to MERRF Cybrid Reduces Oxidative Stress and Improves Mitochondrial Bioenergetics.

Myoclonus epilepsy associated with ragged-red fibers (MERRF) is a maternally inherited mitochondrial disease affecting neuromuscular functions. Mt.8344A>G mutation in mitochondrial DNA (mtDNA) is the most common cause of MERRF syndrome and has been linked to an increase in reactive oxygen species (ROS) level and oxidative stress, as well as impaired mitochondrial bioenergetics. Here, we tested whether WJMSC has therapeutic potential for the treatment of MERRF syndrome through the transfer of mitochondria. The MERRF cybrid cells exhibited a high mt.8344A>G mutation ratio, enhanced ROS level and oxidative damage, impaired mitochondrial bioenergetics, defected mitochondria-dependent viability, exhibited an imbalance of mitochondrial dynamics, and are susceptible to apoptotic stress. Coculture experiments revealed that mitochondria were intercellularly conducted from the WJMSC to the MERRF cybrid. Furthermore, WJMSC transferred mitochondria exclusively to cells with defective mitochondria but not to cells with normal mitochondria. MERRF cybrid following WJMSC coculture (MF+WJ) demonstrated improvement of mt.8344A>G mutation ratio, ROS level, oxidative damage, mitochondrial bioenergetics, mitochondria-dependent viability, balance of mitochondrial dynamics, and resistance against apoptotic stress. WJMSC-derived mitochondrial transfer and its therapeutic effect were noted to be blocked by F-actin depolymerizing agent cytochalasin B. Collectively, the WJMSC ability to rescue cells with defective mitochondrial function through donating healthy mitochondria may lead to new insights into the development of more efficient strategies to treat diseases related to mitochondrial dysfunction.

Epidemiological features of infantile hypertrophic pyloric stenosis in Taiwan: a national study 1996-2004.

BACKGROUND AND AIM: The incidence of infantile hypertrophic pyloric stenosis (IHPS) varies among different countries and is supposed to be lower in Asian countries than in Western countries. However, the incidence of IHPS in Taiwan has not been well investigated. METHODS: The National Health Insurance (NHI) program was implemented in Taiwan in 1995 and covers most of the population (>99%). We used the NHI database to investigate the epidemiological features of IHPS in Taiwan and to compare the data with that of other countries. RESULTS: We identified 962 new IHPS cases during the period from 1996 to 2004. The overall incidence of IHPS was 0.39 (0.34-0.50) cases per 1000 live births. The estimation was 0.39-0.59 per 1000 live births after adjustment for the misdiagnosis rate. The peak incidence (0.58 per 1000 live births) occurred in winter in 1999. Rates were consistently higher in male subjects. The 1-year survival rate was not significantly different in the patients receiving pyloromyotomy in medical centers, regional hospitals, and district hospitals (P=0.389). CONCLUSIONS: Taiwan had the second lowest incidence of IHPS reported in the medical literature. IHPS patients can be successfully treated in district and general hospitals with good prognosis.

Pediatric small bowel intussusception disease: feasibility of screening for surgery with early computed tomographic evaluation.

BACKGROUND: This study investigated the feasibility of early computed tomographic (CT) evaluation and the operative results of pediatric small bowel intussusception with deteriorating ischemic or obstructive symptoms, so-called small bowel intussusception disease (SBID). METHODS: Between 1988 and 1999, among 18 patients surgically proven SBID (conventional group), 12 mimicked ileocolic intussusception and were conventionally managed with abdominal radiography, ultrasonography, reduction enema, and eventually operation. Between 2000 and 2008, we applied a modified approach with inclusion of early CT evaluation if ultrasonography showed a target lesion suspicious for SBID (diameter

Melatonin ameliorates bile duct ligation-induced systemic oxidative stress and spatial memory deficits in developing rats.

Bile duct ligation (BDL) induces primary biliary cirrhosis characterized by cholestasis, impaired liver function, and cognition. Young male Sprague-Dawley rats were used: rats underwent laparotomy without BDL [sham-control (SC) group]; rats had restricted diets supply [diet-control (DC) group]; rats underwent BDL for 2 wk (BDL group); BDL rats with melatonin (500 microg/kg/d) intraperitoneally for 2 wk [melatonin (500 microg/kg/d) (M500) group]; and BDL rats with melatonin (1000 microg/kg/d/intraperitoneally) for 2 wk [melatonin (1000 microg/kg/d) (M1000) group]. All the surviving rats were assessed for spatial memory and blood was tested for biochemical study. Liver, brain cortex, and hippocampus were collected for determination of malondialdehyde (MDA) and glutathione (GSH)/oxidized glutathione (GSSG) ratios. BDL group rats had significantly higher plasma direct/total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), MDA values and higher liver MDA values and lower GSH/GSSG ratios when compared with SC group. In addition, BDL group rats had impaired spatial performance. After melatonin treatment, cholestatic rats' plasma MDA levels, liver MDA levels, and liver GSH/GSSG ratios approached to the values of SC group. Only high dose of melatonin improved spatial performance. Results of this study indicate cholestasis in the developing rats increase oxidative stress and cause spatial memory deficits, which are prevented by melatonin treatment.

Association of bladder cancer with residential exposure to petrochemical air pollutant emissions in Taiwan.

To investigate the relationship between petrochemical air pollution and risk of death due to bladder cancer, studies were conducted using a matched cancer case-control model based upon deaths that occurred in Taiwan from 1995 through 2005. Data on all eligible bladder cancer deaths were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. The control group consisted of individuals who died from causes other than neoplasms or diseases associated with genitourinary problems. The controls were pair matched to the cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. The proportion of a municipality's total population employed in the petrochemical industry in a municipality was used as an indicator of a resident's exposure to air emissions from the petrochemical industry. The subjects were divided into three levels (< or =25th percentile; 25th-50th percentile; >50th percentile). Subjects who lived in the group of municipalities characterized by the high levels of petrochemical air pollution had a significantly higher risk of death attributed to bladder cancer than subjects in the group that lived in municipalities with the lowest petrochemical air pollution levels, after controlling for possible confounders. The findings of this study warrant further investigation of the role of petrochemical air pollution in the etiology of bladder cancer.

Small bowel intussusception in symptomatic pediatric patients: experiences with 19 surgically proven cases.

Nineteen cases of surgically proven symptomatic pediatric small bowel intussusceptions (SBI) were retrospectively reviewed. Clinical presentations included vomiting (89.5%), abdominal pain and/or irritable crying (89.5%), fever (52.6%), bloody stools (26.3%), palpable abdominal masses (15.8%), hematemesis (10.5%), jaundice (5.3%), and seizures (5.3%). The duration between symptom onset and hospitalization ranged between 20 and 336 hours (average 75.8 hours). Two patients with suspected appendicitis and small bowel obstruction were operated on promptly. Sonograms revealed target lesions (average diameter 2.9 cm) suggestive of intussusception in 13 out of 17 patients, with 10 lesions located in the paraumbilical or left abdominal regions. Barium enemas in 12 of these 13 patients demonstrated no colonic lesions. Diagnosis and surgery were delayed in 16 patients (average delay = 32 hours). The remaining 1 patient with positive sonographic findings underwent early surgery after computed tomographic (CT) confirmation of SBI. Surgery revealed ileoileal intussusceptions in 11 patients, jejunojejunal in 4, jejunoileal in 3, and duodenojejunal in 1. Eight patients had lead points. Bowel complications (ischemia, necrosis, or perforation) occurred in 8 patients. The duration between symptom onset and surgery in patients with bowel complications was significantly longer than for patients without complications (p = 0.0026). In conclusion, delayed diagnosis and surgical treatment in symptomatic pediatric patients with SBI were common, leading to a high rate (42%) of bowel complications. Sonographic demonstration of a 2-3 cm target lesion, especially if paraumbilical or left abdominal, is suggestive of SBI and may obviate the need for a barium enema; however, CT is helpful for confirming SBI. In symptomatic SBI, once diagnosed, early surgical referral is strongly recommended.