Effect of Purified Resveratrol Butyrate Ester Monomers against Hypertension after Maternal High-Fructose Intake in Adult Offspring.

BACKGROUND: Offspring hypertension arising from adverse maternal conditions can be mitigated through dietary nutritional supplementation, including resveratrol. Previously, we identified derivatives of resveratrol butyrate ester (RBE), specifically 3,4'-di-O-butanoylresveratrol (ED2) and 3-O-butanoylresveratrol (ED4), demonstrating their superior antioxidant capabilities compared to RBE itself. This study sought to assess the protective impact of maternal supplementation with ED2 or ED4 on offspring hypertension in a rat model subjected to a high-fructose (HF) diet during pregnancy and lactation. METHODS: Female Sprague-Dawley rats were distributed into distinct dietary groups throughout pregnancy and lactation: (1) standard chow; (2) HF diet (60%); (3) HF diet supplemented with ED2 (25 mg/L); and (4) HF diet supplemented with ED4 (25 mg/L). Male offspring were euthanized at the age of 12 weeks. RESULTS: The maternal HF diet induced hypertension in the offspring, which was mitigated by perinatal supplementation with either ED2 or ED4. These protective effects were attributed to the antioxidant properties of ED2 and ED4, resulting in an increased availability of nitric oxide (NO). Additionally, supplementation with ED2 was connected to an increased abundance of Bifidobacterium and Clostridium genera, which was accompanied by a decrease in Angelakisella and Christensenella. On the other hand, ED4 supplementation shielded rat offspring from hypertension by elevating concentrations of short-chain fatty acids (SCFAs) and their receptors while reducing trimethylamine-N-oxide (TMAO) levels. CONCLUSIONS: These findings highlight the potential of purified RBE monomers, ED2 and ED4, as preventive measures against hypertension resulting from a maternal high-fructose diet. Further research is warranted to explore their clinical applications based on these promising results.

The Impact of Maternal Nanoplastic and Microplastic Particle Exposure on Mammal's Offspring.

The issue of environmental nanoplastic (NPl) particle and microplastic (MPl) particle pollution is becoming increasingly severe, significantly impacting ecosystems and biological health. Research shows that NPl/MPl can penetrate the placental barrier and enter the fetus, leading to transgenerational effects. This review integrates the existing literature on the effects of prenatal NPl/MPl exposure on mammalian offspring, focusing particularly on its negative impacts on the central nervous system, liver, intestinal health, reproductive function, and skeletal muscles. The vast majority of previous studies on prenatal NPl/MPl in mammals have used polystyrene material. Future research should explore the effects of other prenatal NPl/MPl materials on offspring to better reflect the realities of the human environment. It is also essential to investigate the potential harm and underlying mechanisms associated with prenatal NPl/MPl exposure to offspring in greater depth. This will aid in developing appropriate prevention and treatment strategies in the future.

Association of Perinatal Cardiovascular Features with Angiotensin System Expressions in Maternal Preeclampsia.

We hypothesized and investigated whether prenatal exposure to preeclampsia (PE) would simultaneously affect perinatal cardiovascular features and angiotensin system expressions. This prospective study was composed of mother-neonate dyads with (n = 49) and without maternal preeclampsia (n = 48) in a single tertiary medical center. The neonates exposed to PE had significantly larger relative sizes for the left and right coronary arteries and a higher cord plasma level of aminopeptidase-N, which positively correlated with the maternal diastolic blood pressures and determined the relative sizes of the left and right coronary arteries, whereas the encoding aminopeptidase-N (ANPEP) mRNA level in the PE cord blood leukocytes was significantly decreased, positively correlated with the neonatal systolic blood pressures (SBPs), and negatively correlated with the cord plasma-induced endothelial vascular cell adhesion molecule-1 mRNA levels. The PE cord plasma significantly induced higher endothelial mRNA levels of angiotensin II type 1 receptor (AT1R) and AT4R, whereas in the umbilical arteries, the protein expressions of AT2R and AT4R were significantly decreased in the PE group. The endothelial AT1R mRNA level positively determined the maternal SBPs, and the AT4R mRNA level positively determined the neonatal chamber size and cardiac output. In conclusion, PE may influence perinatal angiotensin system and cardiovascular manifestations of neonates across placentae. Intriguing correlations between these two warrant further mechanistic investigation.

Exosomes Secreted by Wharton's Jelly-Derived Mesenchymal Stem Cells Promote the Ability of Cell Proliferation and Migration for Keratinocyte.

Mesenchymal stem cells (MSCs) isolated from Wharton's jelly (WJ-MSCs) and adipose tissue (AD-MSCs) are alternative sources for bone marrow-derived MSCs. Owing to their multiple functions in angiogenesis, immune modulation, proliferation, migration, and nerve regeneration, MSC-derived exosomes can be applied in "cell-free cell therapy". Here, we investigated the functional protein components between the exosomes from WJ-MSCs and AD-MSCs to explain their distinct functions. Proteins of WJ-MSC and AD-MSC exosomes were collected and compared based on iTRAQ gel-free proteomics data. Results: In total, 1695 proteins were detected in exosomes. Of these, 315 were more abundant (>1.25-fold) in AD-MSC exosomes and 362 kept higher levels in WJ-MSC exosomes, including fibrinogen proteins. Pathway enrichment analysis suggested that WJ-MSC exosomes had higher potential for wound healing than AD-MSC exosomes. Therefore, we treated keratinocyte cells with exosomes and the recombinant protein of fibrinogen beta chain (FGB). It turned out that WJ-MSC exosomes better promoted keratinocyte growth and migration than AD-MSC exosomes. In addition, FGB treatment had similar results to WJ-MSC exosomes. The fact that WJ-MSC exosomes promoted keratinocyte growth and migration better than AD-MSC exosomes can be explained by their higher FGB abundance. Exploring the various components of AD-MSC and WJ-MSC exosomes can aid in their different clinical applications.

Carbohydrate-Mediated Pregnancy Gut Microbiota and Neonatal Low Birth Weight.

The effects of gut microbiota on the association between carbohydrate intake during pregnancy and neonatal low birth weight (LBW) were investigated. A prospective cohort study was conducted with 257 singleton-born mother-child pairs in Taiwan, and maternal dietary intake was estimated using a questionnaire, with each macronutrient being classified as low, medium, or high. Maternal fecal samples were collected between 24 and 28 weeks of gestation, and gut microbiota composition and diversity were profiled using 16S rRNA amplicon gene sequencing. Carbohydrates were the major source of total energy (56.61%), followed by fat (27.92%) and protein (15.46%). The rate of infant LBW was 7.8%, which was positively correlated with maternal carbohydrate intake. In the pregnancy gut microbiota, Bacteroides ovatus and Dorea spp. were indirectly and directly negatively associated with fetal growth, respectively; Rosenburia faecis was directly positively associated with neonatal birth weight. Maternal hypertension during pregnancy altered the microbiota features and was associated with poor fetal growth. Microbiota-accessible carbohydrates can modify the composition and function of the pregnancy gut microbiota, thus providing a potential marker to modulate deviations from dietary patterns, particularly in women at risk of hypertension during pregnancy, to prevent neonatal LBW.

Post COVID-19 condition and behavioral manifestations in Taiwanese children.

BACKGROUND: This study investigated the prevalence of post COVID-19 condition (PCC) in Taiwanese children, explored common symptoms and behavioral manifestations in children with PCC, and examined potential associations with parental stress and family functioning. METHODS: A total of 116 children who had contracted COVID-19 and their parents participated. At 1 month after the confirmed COVID-19 infection (baseline), the parents were asked to complete a questionnaire about the post COVID-19 symptoms, the child behavior checklist (CBCL) based on the child's situation, also the impact event scale of COVID-19 (IES-C) and family APGAR based on the parents' own situation. Three months after the confirmed COVID-19 infection, parents were again asked to complete the same questionnaires as they did at baseline. RESULTS: Results showed that 44.8% of the children met the criteria for PCC, with the most common symptoms being sputum/nasal congestion, tiredness and decreased concentration. Children without PCC exhibited a significant decrease in CBCL scores during the 2-month follow-up, while no such decrease was observed in children with PCC. However, no significant correlations were found between the number of post COVID-19 symptoms, behavioral manifestations, parental stress levels, and family functioning. CONCLUSIONS: Children with PCC have a less favorable trajectory in improving their behavioral manifestations. Additionally, in the post-pandemic era, post COVID-19 symptoms in children are not necessarily correlated with parental stress and family functioning. Further research is needed to better understand the long-term implications of PCC in children and its impact on their mental well-being, as well as their families.

Prenatal High-Fat Diet Combined with Microplastic Exposure Induces Liver Injury via Oxidative Stress in Male Pups.

Prenatal high-fat diet (HFD) or exposure to microplastics can affect the accumulation of liver fat in offspring. We sought to determine the effects of maternal HFD intake and microplastic exposure on fatty liver injury through oxidative stress in pups. Pregnant female Sprague-Dawley rats were randomly divided into maternal HFD (experimental group) or normal control diet (NCD; control group) groups with or without microplastic exposure. As a result, the following groups were established: HFD-L (HFD + microplastics, 5 µm, 100 µg/L), HFD-H (HFD + microplastics, 5 µm, 1000 µg/L), NCD-L (NCD + microplastics, 5 µm, 100 µg/L), and NCD-H (NCD + microplastics, 5 µm, 1000 µg/L). The pups were sacrificed on postnatal day 7 (PD7). Liver histology revealed increased hepatic lipid accumulation in pups in the HFD-L and HFD-H groups compared to those in the HFD, NCD-L, NCD-H, and NCD groups on PD7. Similarly, liver TUNEL staining and cellular apoptosis were found to increase in pups in the HFD-L and HFD-H groups compared to those in the HFD, NCD-L, NCD-H, and NCD groups. The expression levels of malondialdehyde, a lipid peroxidation marker, were high in the HFD, HFD-L, and HFD-H groups; however, the highest expression was observed in the HFD-H group (p < 0.05). The levels of glutathione peroxidase, an antioxidant enzyme, decreased in the HFD, HFD-L, and HFD-H groups (p < 0.05). Overall, oxidative stress with cellular apoptosis plays a vital role in liver injury in offspring after maternal intake of HFD and exposure to microplastic; such findings may shed light on future therapeutic strategies.

Association between prenatal and neonatal risk factors and development of bronchiolitis in early life.

Bronchiolitis is the most common seasonal viral respiratory disorder in infants. However, risk factors for the development of bronchiolitis, particularly during pregnancy, remain unclear. Methods: A questionnaire was administered to the parents of the hospitalized infants with acute bronchiolitis to obtain information regarding patients' medical, family, and prenatal exposure history. Logistic regression with adjustment was performed to evaluate risk factors associated with bronchiolitis in the infants. Results: Among the enrolled patients, 55 (36.7%) were diagnosed as having bronchiolitis, and the majority (89%) of the patients had moderate-to-severe bronchiolitis. The bronchiolitis group had lower C-reactive protein levels than did the control group. Fewer patients in the bronchiolitis group developed fever. However, hospital stays were longer in the bronchiolitis group than in the control group. Respiratory syncytial virus was the most detected virus (23/26, 88.6%) in the bronchiolitis group. Male sex (odds ratio [OR], 5.71; 95% confidence interval [CI], 2.02-16.12; P < 0.001), antibiotic usage during pregnancy (OR, 27.2; 95% CI, 1.12-660.84; P = 0.04), and viral infection (OR, 49.3; 95% CI, 9.01-270.26; P < 0.001) during the postnatal period were significantly associated with hospitalization for acute bronchiolitis in the infants. By contrast, pet exposure during the perinatal period was significantly and negatively associated with acute bronchiolitis (OR = 0.21, 95% CI = 0.07-0.69, P < 0.01). Conclusion: Environmental exposures during pregnancy may affect respiratory health in offspring, and effective strategies should be developed to prevent bronchiolitis in early life.

Impact of Protein Binding Capacity and Daily Dosage of a Drug on Total Serum Bilirubin Levels in Susceptible Infants.

Hyperbilirubinemia is a common pathological condition in neonates. Free bilirubin can penetrate the blood-brain barrier (BBB), which can lead to bilirubin neurotoxicity. In the context of predicting the risk of bilirubin neurotoxicity, although the specificity and sensitivity of free bilirubin levels are higher than those of total serum bilirubin (TSB), free bilirubin is not widely monitored in clinical practice. The threshold TSB levels at which phototherapy must be administered have been established previously. However, TSB levels are not well correlated with neurodevelopmental outcomes. Currently, TSB levels are commonly used to guide phototherapy for neonatal hyperbilirubinemia. Some clinical drugs can displace bilirubin from its albumin-binding sites, and consequently upregulate plasma bilirubin. Daily dosages play a vital role in regulating bilirubin levels. A drug with both a high protein binding capacity and high daily dosage significantly increases bilirubin levels in infants. Premature or very low birth weight (VLBW) infants are vulnerable to the upregulation of bilirubin levels as they exhibit the lowest reserve albumin levels and consequently the highest bilirubin toxicity index. Because bilirubin is involved in maintaining the balance between pro-oxidant and antioxidant agents, the downregulation of bilirubin levels is not always desirable. This review provides insights into the impact of protein binding capacity and daily dosage of drugs on the bilirubin levels in susceptible infants.

A Higher Abundance of Actinomyces spp. in the Gut Is Associated with Spontaneous Preterm Birth.

Preterm birth is a major challenge in pregnancy worldwide. Prematurity is the leading cause of death in infants and may result in severe complications. Nearly half of preterm births are spontaneous, but do not have recognizable causes. This study investigated whether the maternal gut microbiome and associated functional pathways might play a key role in spontaneous preterm birth (sPTB). Two hundred eleven women carrying singleton pregnancies were enrolled in this mother-child cohort study. Fecal samples were freshly collected at 24-28 weeks of gestation before delivery, and the 16S ribosomal RNA gene was sequenced. Microbial diversity and composition, core microbiome, and associated functional pathways were then statistically analyzed. Demographic characteristics were collected using records from the Medical Birth Registry and questionnaires. The result showed that the gut microbiome of mothers with over-weight (BMI ≥ 24) before pregnancy have lower alpha diversity than those with normal BMI before pregnancy. A higher abundance of Actinomyces spp. was filtered out from the Linear discriminant analysis (LDA) effect size (LEfSe), Spearman correlation, and random forest model, and was inversely correlated with gestational age in sPTB. The multivariate regression model showed that the odds ratio of premature delivery was 3.274 [95% confidence interval (CI): 1.349; p = 0.010] in the group with over-weight before pregnancy with a cutoff Hit% > 0.022 for Actinomyces spp. The enrichment of Actinomyces spp. was negatively correlated with glycan biosynthesis and metabolism in sPTB by prediction from the Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) platform. Maternal gut microbiota showing a lower alpha diversity, increased abundance of Actinomyces spp., and dysregulated glycan metabolism may be associated with sPTB risk.

Salivary Biomarkers to Differentiate between Streptococcus pneumoniae and Influenza A Virus-Related Pneumonia in Children.

Community-acquired pneumonia (CAP) is common among children and can be fatal in certain conditions. In children, CAP can be caused by viral or bacterial infections. Identification of pathogens can help select appropriate therapeutic strategies. Salivary analysis may be a potential diagnostic tool because it is noninvasive, patient-friendly, and easy to perform in children. A prospective study was conducted in children with pneumonia admitted to a hospital. Salivary samples from patients with definite Streptococcus pneumoniae and influenza A strains were used for gel-free (isobaric tag for relative and absolute quantitation (iTRAQ)) proteomics. No statistically significant difference was detected in salivary CRP levels between Streptococcus pneumoniae and influenza A pneumonia in children. Several potential salivary biomarkers were identified using gel-free iTRAQ proteomics to differentiate pneumonia from Streptococcus pneumoniae or influenza A virus infections in pediatric patients. ELISA validated that Streptococcus pneumoniae group has a higher abundance of salivary alpha 1-antichymotrypsin than those in the influenza A group. Whether these salivary biomarkers can be used to distinguish other bacteria from viral pneumonia requires further verification.

Use of Machine Learning to Differentiate Children With Kawasaki Disease From Other Febrile Children in a Pediatric Emergency Department.

Importance: Early awareness of Kawasaki disease (KD) helps physicians administer appropriate therapy to prevent acquired heart disease in children. However, diagnosing KD is challenging and relies largely on subjective diagnosis criteria. Objective: To develop a prediction model using machine learning with objective parameters to differentiate children with KD from other febrile children. Design, Setting, and Participants: This diagnostic study included 74 641 febrile children younger than 5 years who were recruited from 4 hospitals, including 2 medical centers and 2 regional hospitals, between January 1, 2010, and December 31, 2019. Statistical analysis was performed from October 2021 to February 2023. Main Outcomes and Measures: Demographic data and laboratory values from electronic medical records, including complete blood cell count with differential, urinalysis, and biochemistry, were collected as possible parameters. The primary outcome was whether the febrile children fulfilled the diagnostic criteria of KD. The supervised eXtreme Gradient Boosting (XGBoost) machine learning method was applied to establish a prediction model. The confusion matrix and likelihood ratio were used to evaluate the performance of the prediction model. Results: This study included a total of 1142 patients with KD (mean [SD] age, 1.1 [0.8] years; 687 male patients [60.2%]) and 73 499 febrile children (mean [SD] age, 1.6 [1.4] years; 41 465 male patients [56.4%]) comprising the control group. The KD group was predominantly male (odds ratio, 1.79; 95% CI, 1.55-2.06) with younger age (mean difference, -0.6 years [95% CI, -0.6 to -0.5 years]) compared with the control group. The prediction model's best performance in the testing set was able to achieve 92.5% sensitivity, 97.3% specificity, 34.5% positive predictive value, 99.9% negative predictive value, and a positive likelihood ratio of 34.0, which indicates outstanding performance. The area under the receiver operating characteristic curve of the prediction model was 0.980 (95% CI, 0.974-0.987). Conclusions and Relevance: This diagnostic study suggests that results of objective laboratory tests had the potential to be predictors of KD. Furthermore, these findings suggested that machine learning with XGBoost can help physicians differentiate children with KD from other febrile children in pediatric emergency departments with excellent sensitivity, specificity, and accuracy.

Reprogramming Effects of Postbiotic Butyrate and Propionate on Maternal High-Fructose Diet-Induced Offspring Hypertension.

Maternal nutrition has a key role in the developmental programming of adult disease. Excessive maternal fructose intake contributes to offspring hypertension. Newly discovered evidence supports the idea that early-life gut microbiota are connected to hypertension later in life. Short-chain fatty acids (SCFAs), butyrate, and propionate are microbiota-derived metabolites, also known as postbiotics. The present study aimed to determine whether maternal butyrate or propionate supplementation can protect offspring from hypertension using a maternal high-fructose (HF) diet rat model. Female Sprague Dawley rats were allocated during pregnancy and lactation to (1) regular chow (ND); (2) 60% high-fructose diet (HF); (3) HF diet plus butyrate (HFB, 400 mg/kg/day); and (4) HF diet plus propionate (HFP, 200 mmol/L). Male offspring were sacrificed at 12 weeks of age. The maternal HF diet impaired the offspring's BP, which was prevented by perinatal butyrate or propionate supplementation. Both butyrate and propionate treatments similarly increased plasma concentrations of propionic acid, isobutyric acid, and valeric acid in adult offspring. Butyrate supplementation had a more profound impact on trimethylamine N-oxide metabolism and nitric oxide parameters. Whilst propionate treatment mainly influenced gut microbiota composition, it directly altered the abundance of genera Anaerovorax, Lactobacillus, Macellibacteroides, and Rothia. Our results shed new light on targeting gut microbiota through the use of postbiotics to prevent maternal HF intake-primed hypertension, a finding worthy of clinical translation.

Comparison of glucocorticoids and painkiller prescribed days between rheumatoid arthritis patients receiving early and late treatment with a biological agent via a population-based cohort study.

Comparison between early biologics treatment and late biologics treatment of rheumatoid arthritis (RA) patients in decreasing prescription days of glucocorticoids and painkillers by using the Taiwan National Health Insurance Research database from January 1, 1997 to December 31, 2013. We defined early use of biologics as biologics prescribed within 2.24 years after the RA diagnosis, and the late use of biologics was defined as those prescribed after 2.24 years of the RA diagnosis. These definitions are based on previous studies defining early arthritis as arthritis within 2 years of diagnosis, while we needed another 3 months for application biologics here in Taiwan, which equals a total of 2.24 years. Among the 821 patients, 410 patients (50%) were classified in the Early group, and the other 411 patients (50%) were classified in the Late group. The use of any of these 3 types of medication, including steroids, disease modifying antirhuematic drugs, and nonsteroid anti-inflammatory drug (NSAID) was changed significantly after biologics treatment. Comparing between before and after biologics treatment, oral medication was significantly tapered (all P < .0001). The results show that men are 1.81 times more likely than women to taper oral glucocorticoids and NSAIDs. Younger age (<45) patients are 1.91 times more likely to taper steroids and NSAIDs than those aged over 65 years old. Both gender and age were found to be independent factors that could decrease days of prescription of both steroids and NSAIDs in early use of biologics agents. This study indicates that younger patients only need short-term (2.53 ±â€…1.92 years, P = .03) and early treatment with biologics (within 2.24 years of diagnosis of RA), just in order to taper steroids and NSAIDs to less than 50% compared to the steroids and NSAIDs doses before biologics treatment.

Vinpocetine Ameliorates Metabolic-Syndrome-Associated Bladder Overactivity in Fructose-Fed Rats by Restoring Succinate-Modulated cAMP Levels and Exerting Anti-Inflammatory Effects in the Bladder Detrusor Muscle.

Succinate and its receptor, the G protein-coupled receptor 91 (GPR91), have pathological implications in metabolic syndrome (MetS) and its associated bladder dysfunction, particularly in decreasing bladder cAMP levels and promoting proinflammation. Using fructose-fed rats (FFRs), a rat model of MetS, we investigate the effects of vinpocetine (a phosphodiesterase-1 inhibitor) and celecoxib (a selective cyclooxygenase-2 inhibitor) on MetS-associated bladder overactivity. Phenotypes of the overactive bladder, including increased micturition frequency and a shortened intercontractile interval in cystometry, were observed in FFRs, together with elevated succinate levels in the liver and serum and the downregulation of GPR91 in the liver and urinary bladder. Treatments with vinpocetine and celecoxib improved tissue fibrosis and ameliorated the overexpression of the inflammatory cytokines, such as IL-1ß, in the liver and bladder. In bladder organ bath studies, vinpocetine, but not celecoxib, treatment restored the contraction and relaxation responses of the detrusor muscle strip in response to KCl, carbachol, and forskolin stimulation. At a molecular level, vinpocetine and celecoxib treatments modulated the downstream messengers of GPR91 (i.e., ERK1/2 and JNK), suppressed NF-κB and IL-1ß expressions in the bladder, and prevented the fibrogenesis observed in FFRs. The exogenous application of succinate to a bladder organ bath significantly reduced the forskolin-induced cAMP production by the detrusor muscle, which was notably restored in the presence of vinpocetine. Together, these results suggest that vinpocetine may alleviate the MetS-associated bladder overactivity by restoring the succinate-modulated detrusor cAMP production and exerting the anti-inflammatory effects in the bladder detrusor muscle.

Maternal Metformin Treatment Reprograms Maternal High-Fat Diet-Induced Hepatic Steatosis in Offspring Associated with Placental Glucose Transporter Modifications.

Maternal high-fat (HF) diet exposure in utero may affect fetal development and cause metabolic problems throughout life due to lipid dysmetabolism and oxidative damage. Metformin has been suggested as a potential treatment for body weight reduction and nonalcoholic fatty liver disease, but its reprogramming effect on offspring is undetermined. This study assesses the effects of maternal metformin treatment on hepatic steatosis in offspring caused by maternal HF diet. Female rats were fed either a control or an HF diet before conception, with or without metformin treatment during gestation, and placenta and fetal liver tissues were collected. In another experiment, the offspring were fed a control diet until 120 d (adult stage). Metformin treatment during pregnancy ameliorates placental oxidative stress and enhances placental glucose transporter 1 (GLUT1), GLUT3, and GLUT4 expression levels through 5' adenosine monophosphate-activated protein kinase (AMPK) activation. Maternal metformin treatment was shown to reprogram maternal HF diet-induced changes in offspring fatty liver with the effects observed in adulthood as well. Further validation is required to develop maternal metformin therapy for clinical applications.

Effects of Maternal Gut Microbiota-Targeted Therapy on the Programming of Nonalcoholic Fatty Liver Disease in Dams and Fetuses, Related to a Prenatal High-Fat Diet.

Metabolic disorders can start in utero. Maternal transmission of metabolic phenotypes may increase the risks of adverse metabolic outcomes, such as nonalcoholic fatty liver disease (NAFLD); effective intervention is essential to prevent this. The gut microbiome plays a crucial role in fat storage, energy metabolism, and NAFLD. We investigated the therapeutic use of probiotic Lactobacillus reuteri and postbiotic butyrate gestation in the prevention of perinatal high-fat diet-induced programmed hepatic steatosis in the offspring of pregnant Sprague-Dawley rats who received regular chow or a high-fat (HF) diet 8 weeks before mating. L. reuteri or sodium butyrate was administered via oral gavage to the gestated rats until their sacrifice on day 21 of gestation. Both treatments improved liver steatosis in pregnant dams; L. reuteri had a superior effect. L. reuteri ameliorated obesity and altered the metabolic profiles of obese gravid dams. Maternal L. reuteri therapy prevented maternal HF diet-induced fetal liver steatosis, and reformed placental remodeling and oxidative injury. Probiotic therapy can restore lipid dysmetabolism in the fetal liver, modulate nutrient-sensing molecules in the placenta, and mediate the short-chain fatty acid signaling cascade. The therapeutic effects of maternal L. reuteri on maternal NAFLD and NAFLD reprogramming in offspring should be validated for further clinical translation.

Protection by -Biotics against Hypertension Programmed by Maternal High Fructose Diet: Rectification of Dysregulated Expression of Short-Chain Fatty Acid Receptors in the Hypothalamic Paraventricular Nucleus of Adult Offspring.

The role of short-chain fatty acids (SCFAs) in the brain on the developmental programming of hypertension is poorly understood. The present study explored dysregulated tissue levels of SCFAs and expression of SCFA-sensing receptors in the hypothalamic paraventricular nucleus (PVN), a key forebrain region engaged in neural regulation of blood pressure of offspring to maternal high fructose diet (HFD) exposure. We further investigated the engagement of SCFA-sensing receptors in PVN in the beneficial effects of -biotics (prebiotic, probiotic, synbiotic, and postbiotic) on programmed hypertension. Maternal HFD during gestation and lactation significantly reduced circulating butyrate, along with decreased tissue level of butyrate and increased expression of SCFA-sensing receptors, GPR41 and olfr78, and tissue oxidative stress and neuroinflammation in PVN of HFD offspring that were rectified by oral supplement with -biotics. Gene silencing of GPR41 or olfr78 mRNA in PVN also protected adult HFD offspring from programmed hypertension and alleviated the induced oxidative stress and inflammation in PVN. In addition, oral supplement with postbiotic butyrate restored tissue butyrate levels, rectified expressions of GPR41 and olfr78 in PVN, and protected against programmed hypertension in adult HFD offspring. These data suggest that alterations in tissue butyrate level, expression of GPR41 and olfr78, and activation of SCFA-sensing receptor-dependent tissue oxidative stress and neuroinflammation in PVN could be novel mechanisms that underlie hypertension programmed by maternal HFD exposure in adult offspring. Furthermore, oral -biotics supplementation may exert beneficial effects on hypertension of developmental origin by targeting dysfunctional SCFA-sensing receptors in PVN to exert antioxidant and anti-inflammatory actions in the brain.

The Clinical Implication of Serogroup Distribution and Drug Resistance of Non-Typhoidal Salmonella in Children: A Single Center Study in Southern Taiwan during 2004-2019.

Background: A regional antibiotic susceptibility database of certain pathogens is crucial for first-line physicians in terms of providing clinical judgement and appropriate selection of antimicrobial agents. The aim of this study is to update the epidemiological data of Salmonella serogroups and drug resistance in pediatric patients. Methods: This is a single-center retrospective study enrolling patients aged from 0 to 18 years who were hospitalized with cultured proven non-typhoidal Salmonella (NTS) infection from 2004 to 2019. The isolates were collected and the demographic data, serogroups of Salmonella and antimicrobial susceptibilities were further analyzed. Results: A total of 1583 isolates of NTS were collected. Serogroup C2 was prone to cause invasive non-typhoidal salmonellosis (iNTS), especially bacteremia. Patients aged < 2 years were associated with serogroups B and C2 infection, while those aged ≥ 2 years were associated with serogroups D and E infection. The prevalence of serogroup B declined with simultaneous increase in prevalence of serogroups D and E. Serogroups B and E were associated with ceftriaxone resistance, while Serogroup D was less drug-resistant than the others. The prevalence of ceftriaxone-resistant Salmonella had not increased, although more ciprofloxacin-resistant isolates were found in iNTS infection. Conclusions: Age < 2 years is a risk factor of iNTS for children, and the distribution of serogroup changes should be closely monitored. Ceftriaxone is still the drug of choice for treating pediatric iNTS infection, and although no increase was observed in the prevalence of ceftriaxone-resistant strains in this study, continuing surveillance of such cases is warranted.