Biosynthetic Pathways of Tryptophan Metabolites in Saccharomyces cerevisiae Strain: Insights and Implications.

Tryptophan metabolites, such as 5-hydroxytryptophan (5-HTP), serotonin, and melatonin, hold significant promise as supplements for managing various mood-related disorders, including depression and insomnia. However, their chemical production via chemical synthesis and phytochemical extraction presents drawbacks, such as the generation of toxic byproducts and low yields. In this study, we explore an alternative approach utilizing S. cerevisiae STG S101 for biosynthesis. Through a series of eleven experiments employing different combinations of tryptophan supplementation, Tween 20, and HEPES buffer, we investigated the production of these indolamines. The tryptophan metabolites were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Notably, setups replacing peptone in the YPD media with tryptophan (Run 3) and incorporating tryptophan along with 25 mM HEPES buffer (Run 4) demonstrated successful biosynthesis of 5-HTP and serotonin. The highest 5-HTP and serotonin concentrations were 58.9 ± 16.0 mg L-1 and 0.0650 ± 0.00211 mg L-1, respectively. Melatonin concentrations were undetected in all the setups. These findings underscore the potential of using probiotic yeast strains as a safer and conceivably more cost-effective alternative for indolamine synthesis. The utilization of probiotic strains presents a promising avenue, potentially offering scalability, sustainability, reduced environmental impact, and feasibility for large-scale production.

Mercury abatement in the environment: Insights from industrial emissions and fates in the environment.

Mercury's neurotoxic effects have prompted the development of advanced control and remediation methods to meet stringent measures for industries with high-mercury feedstocks. Industries with significant Hg emissions, including artisanal and small-scale gold mining (ASGM)-789.2 Mg year-1, coal combustion-564.1 Mg year-1, waste combustion-316.1 Mg year-1, cement production-224.5 Mg year-1, and non-ferrous metals smelting-204.1 Mg year-1, use oxidants and adsorbents capture Hg from waste streams. Oxidizing agents such as O3, Cl2, HCl, CaBr2, CaCl2, and NH4Cl oxidize Hg0 to Hg2+ for easier adsorption. To functionalize adsorbents, carbonaceous ones use S, SO2, and Na2S, metal-based adsorbents use dimercaprol, and polymer-based adsorbents are grafted with acrylonitrile and hydroxylamine hydrochloride. Adsorption capacities span 0.2-85.6 mg g-1 for carbonaceous, 0.5-14.8 mg g-1 for metal-based, and 168.1-1216 mg g-1 for polymer-based adsorbents. Assessing Hg contamination in soils and sediments uses bioindicators and stable isotopes. Remediation approaches include heat treatment, chemical stabilization and immobilization, and phytoremediation techniques when contamination exceeds thresholds. Achieving a substantially Hg-free ecosystem remains a formidable challenge, chiefly due to the ASGM industry, policy gaps, and Hg persistence. Nevertheless, improvements in adsorbent technologies hold potential.

Perinatal Use of Citrulline Rescues Hypertension in Adult Male Offspring Born to Pregnant Uremic Rats.

The growing recognition of the association between maternal chronic kidney disease (CKD) and fetal programming highlights the increased vulnerability of hypertension in offspring. Potential mechanisms involve oxidative stress, dysbiosis in gut microbiota, and activation of the renin-angiotensin system (RAS). Our prior investigation showed that the administration of adenine to pregnant rats resulted in the development of CKD, ultimately causing hypertension in their adult offspring. Citrulline, known for enhancing nitric oxide (NO) production and possessing antioxidant and antihypertensive properties, was explored for its potential to reverse high blood pressure (BP) in offspring born to CKD dams. Male rat offspring, both from normal and adenine-induced CKD models, were randomly assigned to four groups (8 animals each): (1) control, (2) CKD, (3) citrulline-treated control rats, and (4) citrulline-treated CKD rats. Citrulline supplementation successfully reversed elevated BP in male progeny born to uremic mothers. The protective effects of perinatal citrulline supplementation were linked to an enhanced NO pathway, decreased expression of renal (pro)renin receptor, and changes in gut microbiota composition. Citrulline supplementation led to a reduction in the abundance of Monoglobus and Streptococcus genera and an increase in Agothobacterium Butyriciproducens. Citrulline's ability to influence taxa associated with hypertension may be linked to its protective effects against maternal CKD-induced offspring hypertension. In conclusion, perinatal citrulline treatment increased NO availability and mitigated elevated BP in rat offspring from uremic mother rats.

Advanced Nanomaterial-Based Biosensors for N-Terminal Pro-Brain Natriuretic Peptide Biomarker Detection: Progress and Future Challenges in Cardiovascular Disease Diagnostics.

Cardiovascular diseases (CVDs) represent a significant challenge in global health, demanding advancements in diagnostic modalities. This review delineates the progressive and restrictive facets of nanomaterial-based biosensors in the context of detecting N-terminal pro-B-type natriuretic peptide (NT-proBNP), an indispensable biomarker for CVD prognosis. It scrutinizes the escalation in diagnostic sensitivity and specificity attributable to the incorporation of novel nanomaterials such as graphene derivatives, quantum dots, and metallic nanoparticles, and how these enhancements contribute to reducing detection thresholds and augmenting diagnostic fidelity in heart failure (HF). Despite these technological strides, the review articulates pivotal challenges impeding the clinical translation of these biosensors, including the attainment of clinical-grade sensitivity, the substantial costs associated with synthesizing and functionalizing nanomaterials, and their pragmatic deployment across varied healthcare settings. The necessity for intensified research into the synthesis and functionalization of nanomaterials, strategies to economize production, and amelioration of biosensor durability and ease of use is accentuated. Regulatory hurdles in clinical integration are also contemplated. In summation, the review accentuates the transformative potential of nanomaterial-based biosensors in HF diagnostics and emphasizes critical avenues of research requisite to surmount current impediments and harness the full spectrum of these avant-garde diagnostic instruments.

Unlocking Catalytic Potential: Exploring the Impact of Thermal Treatment on Enhanced Electrocatalysis of Nanomaterials.

In the evolving field of electrocatalysis, thermal treatment of nano-electrocatalysts has become an essential strategy for performance enhancement. This review systematically investigates the impact of various thermal treatments on the catalytic potential of nano-electrocatalysts. The focus encompasses an in-depth analysis of the changes induced in structural, morphological, and compositional properties, as well as alterations in electro-active surface area, surface chemistry, and crystal defects. By providing a comprehensive comparison of commonly used thermal techniques, such as annealing, calcination, sintering, pyrolysis, hydrothermal, and solvothermal methods, this review serves as a scientific guide for selecting the right thermal technique and favorable temperature to tailor the nano-electrocatalysts for optimal electrocatalysis. The resultant modifications in catalytic activity are explored across key electrochemical reactions such as electrochemical (bio)sensing, catalytic degradation, oxygen reduction reaction, hydrogen evolution reaction, overall water splitting, fuel cells, and carbon dioxide reduction reaction. Through a detailed examination of the underlying mechanisms and synergistic effects, this review contributes to a fundamental understanding of the role of thermal treatments in enhancing electrocatalytic properties. The insights provided offer a roadmap for future research aimed at optimizing the electrocatalytic performance of nanomaterials, fostering the development of next-generation sensors and energy conversion technologies.

Protective Role of Taurine on Rat Offspring Hypertension in the Setting of Maternal Chronic Kidney Disease.

Taurine is a natural antioxidant with antihypertensive properties. Maternal chronic kidney disease (CKD) has an impact on renal programming and increases the risk of offspring hypertension in later life. The underlying mechanisms cover oxidative stress, a dysregulated hydrogen sulfide (H2S) system, dysbiotic gut microbiota, and inappropriate activation of the renin-angiotensin-aldosterone system (RAAS). We investigated whether perinatal taurine administration enables us to prevent high blood pressure (BP) in offspring complicated by maternal CKD. Before mating, CKD was induced through feeding chow containing 0.5% adenine for 3 weeks. Taurine was administered (3% in drinking water) during gestation and lactation. Four groups of male offspring were used (n = 8/group): controls, CKD, taurine-treated control rats, and taurine-treated rats with CKD. Taurine treatment significantly reduced BP in male offspring born to mothers with CKD. The beneficial effects of perinatal taurine treatment were attributed to an augmented H2S pathway, rebalance of aberrant RAAS activation, and gut microbiota alterations. In summary, our results not only deepen our knowledge of the mechanisms underlying maternal CKD-induced offspring hypertension but also afford us the impetus to consider taurine-based intervention as a promising preventive approach for future clinical translation.

Plasma and Urinary Platelet Factor 4 as Biomarkers for Cardiovascular Risk in Children with Chronic Kidney Disease.

Children suffering from chronic kidney disease (CKD) have a high risk of cardiovascular disease (CVD). The early detection and diagnosis of subclinical CVD in pediatric CKD can reduce mortality later in life. Plasma factor 4 (PF4) is a chemokine released by activated platelets. We examined whether or not PF4 in the plasma and urine, its kidney function normalized ratio, and fractional excretion have differential associations with CVD risk markers in 139 youths aged 3 to 18 years old with CKD stages G1-G4. Significant negative correlations were observed between plasma PF4 and cardiovascular surrogate markers, such as the left ventricular mass index (LVMI), carotid intima-media thickness (cIMT), and pulse wave velocity (PWV). The plasma PF4/creatinine (Cr) ratio was lower in CKD children with a high daytime BP and 24 h BP, high BP load, and nocturnal non-dipping status. After adjusting for confounders, the plasma PF4 and plasma PF4/Cr ratio still independently predicted an abnormal ABPM profile. In addition, both the plasma PF4 and plasma PF4/Cr ratio presented a negative correlation with the L-arginine and asymmetric dimethylarginine ratio. These findings provide convincing evidence supporting the link between PF4 and CVD markers in pediatric CKD. Our study highlights the importance of further research to assess the performance of PF4-related biomarkers in predicting CVD events and CKD progression in children with CKD.

Renoprotective Effects of Solid-State Cultivated Antrodia cinnamomea in Juvenile Rats with Chronic Kidney Disease.

Antrodia cinnamomea (AC), a medicinal mushroom, has multiple beneficial actions, such as acting as a prebiotic. The incidence of chronic kidney disease (CKD) in children has steadily increased year by year, and CKD is related to gut microbiota dysbiosis. Herein, we investigated the renoprotection of solid-state cultivated AC in adenine-induced CKD juvenile rats. CKD was induced in 3-week-old male rats by feeding with adenine (0.5%) for three weeks. Treated groups received oral administration of AC extracts at either a low (10 mg/kg/day) or high dose (100 mg/kg/day) for six weeks. At nine weeks of age, the rats were sacrificed. Renal outcomes, blood pressure, and gut microbiome composition were examined. Our results revealed that AC treatment, either low- or high-dose, improved kidney function, proteinuria, and hypertension in CKD rats. Low-dose AC treatment increased plasma concentrations of short-chain fatty acids (SCFAs). Additionally, we observed that AC acts like a prebiotic by enriching beneficial bacteria in the gut, such as Akkermansia and Turicibacter. Moreover, the beneficial action of AC against CKD-related hypertension might also be linked to the inhibition of the renin-angiotensin system. This study brings new insights into the potential application of AC as a prebiotic dietary supplement in the prevention and treatment of pediatric CKD.

Protection by Means of Perinatal Oral Sodium Thiosulfate Administration against Offspring Hypertension in a Rat Model of Maternal Chronic Kidney Disease.

Hydrogen sulfide (H2S) and related reactive sulfur species are implicated in chronic kidney disease (CKD) and hypertension. Offspring born to CKD-afflicted mothers could develop hypertension coinciding with disrupted H2S and nitric oxide (NO) signaling pathways as well as gut microbiota. Thiosulfate, a precursor of H2S and an antioxidant, has shown anti-hypertensive effects. This study aimed to investigate the protective effects of sodium thiosulfate (STS) in a rat model of maternal CKD-induced hypertension. Before mating, CKD was induced through feeding 0.5% adenine chow for 3 weeks. Mother rats were given a vehicle or STS at a dosage of 2 g/kg/day in drinking water throughout gestation and lactation. Perinatal STS treatment protected 12-week-old offspring from maternal CKD-primed hypertension. The beneficial effects of STS could partially be explained by the enhancement of both H2S and NO signaling pathways and alterations in gut microbiota. Not only increasing beneficial microbes but maternal STS treatment also mediates several hypertension-associated intestinal bacteria. In conclusion, perinatal treatment with STS improves maternal CKD-primed offspring hypertension, suggesting that early-life RSS-targeting interventions have potential preventive and therapeutic benefits, awaiting future translational research.

The Fabrication of a La2Sn2O7/f-HNT Composite for Non-Enzymatic Electrochemical Detection of 3-Nitro-l-tyrosine in Biological Samples.

Reactive oxygen and nitrogen species (RONS), including 3-nitro-l-tyrosine, play a dual role in human health, inducing oxidative damage and regulating cellular functions. Early and accurate detection of such molecules, such as L-tyrosine in urine, can serve as critical biomarkers for various cancers. In this study, we aimed to enhance the electrochemical detection of these molecules through the synthesis of La2Sn2O7/f-HNT nanocomposites via a simple hydrothermal method. Detailed structural and morphological characterizations confirmed successful synthesis, consistent with our expected outcomes. The synthesized nanocomposites were utilized as nanocatalysts in electrochemical sensors, showing a notable limit of the detection of 0.012 µM for the real-time detection of 3-nitro-l-tyrosine. These findings underscore the potential of nanomaterial-based sensors in advancing early disease detection with high sensitivity, furthering our understanding of cellular oxidative processes.

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.

Dietary Resveratrol Butyrate Monoester Supplement Improves Hypertension and Kidney Dysfunction in a Young Rat Chronic Kidney Disease Model.

Chronic kidney disease (CKD) remains a public health problem. Certain dietary supplements can assist in the prevention of CKD progression. In this regard, resveratrol is a polyphenol and has a potential therapeutic role in alleviating CKD. We previously utilized butyrate in order to improve the bioavailability of resveratrol via esterification and generated a resveratrol butyrate monoester (RBM). In this study, the hypothesis that RBM supplementation is able to protect against kidney dysfunction and hypertension was tested by using an adenine-induced CKD model. For this purpose, three-week-old male Sprague Dawley rats (n = 40) were equally categorized into: group 1-CN (sham control); group 2-CKD (adenine-fed rats); group 3-REV (CKD rats treated with 50 mg/L resveratrol); group 4-MEL (CKD rats treated with 25 mg/L RBM); and group 5-MEH (CKD rats treated with 50 mg/L RBM). At the end of a 12-week period, the rats were then euthanized. The adenine-fed rats displayed hypertension and kidney dysfunction, which were attenuated by dietary supplementation with RBM. The CKD-induced hypertension coincided with: decreased nitric oxide (NO) bioavailability; augmented renal protein expression of a (pro)renin receptor and angiotensin II type 1 receptor; and increased oxidative stress damage. Additionally, RBM and resveratrol supplementation shaped distinct gut microbiota profiles in the adenine-treated CKD rats. The positive effect of high-dose RBM was shown together with an increased abundance of the genera Duncaniella, Ligilactobacillus, and Monoglobus, as well as a decrease in Eubacterium and Schaedierella. Importantly, the mechanism of action of the RBM supplementation may be related to the restoration of NO, rebalancing of the RAS, a reduction in oxidative stress, and alterations to the gut microbiota. Moreover, RBM supplementation shows promise for the purposes of improving CKD outcomes and hypertension. As such, further translation to human studies is warranted.

Resveratrol Butyrate Ester Supplementation Blunts the Development of Offspring Hypertension in a Maternal Di-2-ethylhexyl Phthalate Exposure Rat Model.

Resveratrol (REV) is a plant polyphenol with a plethora of beneficial properties. We previously enhanced the efficacy of REV via esterification of REV with butyrate to form resveratrol butyrate ester (RBE). Compared with REV, RBE exhibits higher bioavailability and better antioxidant effects. Hypertension can originate in early life because of maternal toxic chemical exposure. This study aims to examine the effectiveness of RBE in the protection of offspring hypertension induced by maternal di-2-ethylhexylphthalate (DEHP) exposure and to explore the underlying mechanisms. DEHP (10 mg/kg/day) was used as oral gavage to pregnant rats during gestation and lactation. The control group received the vehicle. Three groups of DEHP-exposed dams received REV (6.67 mg/kg/day), or low-dose (3.33 mg/kg/day) or high-dose (6.67 mg/kg/day) RBE in drinking water during gestation and lactation. Perinatal DEHP exposure resulted in hypertension and bodyweight gain in adult male offspring, which was prevented by high-dose RBE. REV supplementation attenuated DEHP exposure-induced increases in blood pressure but not bodyweight. High-dose RBE decreased renal oxidative damage, increased plasma butyrate concentrations, and altered short chain fatty acid receptor (SCFA) expression. Low-dose RBE treatment reduced downstream mediators of the acryl hydrocarbon receptor (AHR) signaling pathway. Moreover, DEHP exposure, REV and RBE treatment differentially shaped the offspring's gut microbiota. In particular, high-dose RBE increased the abundance of the genus Duncaniella. The beneficial effects of RBE treatment were related to reducing oxidative damage, increasing plasma butyrate concentrations, downregulating SCFA receptor expression, antagonizing AHR signaling, and altering the gut microbiota. This study provides the first evidence of RBE as a novel plant polyphenol bioproduct targeting the oxidative stress and gut microbiota to protect against maternal DEHP exposure-primed offspring hypertension.

Anti-Hypertensive Property of an NO Nanoparticle in an Adenine-Induced Chronic Kidney Disease Young Rat Model.

Hypertension is the most common complication of chronic kidney disease (CKD) in children but is still poorly controlled. Nitric oxide (NO) deficiency plays a pivotal role in CKD and hypertension. NO is known to have health benefits, while NO typically has a short half-life and is not specifically targeted. In this study, we used a pediatric CKD model, which was induced in young rats by feeding them 0.25% adenine. We investigated two different NO donors, namely S-nitrosoglutathione (GSNO) and diethylenetriamine/NO adduct (DETA NONOate) via intraperitoneal injection at 10 mg/kg/day daily for 3 weeks. GSNO was delivered by Cu2+-doped zeolitic imidazolate framework (Cu/ZIF-8) nanoparticles to generate NO. As a result, we observed Cu/ZIF-8 nanoparticles were successfully loaded with GSNO and were able to release NO. Young rats fed with adenine displayed kidney dysfunction and hypertension at 9 weeks of age, which were prevented by GSNO-loaded nanoparticle or DETA NONOate treatment. GSNO-loaded nanoparticles reduced CKD-induced hypertension, which was related to an enhanced endogenous NO-generating system, reduced renal oxidative stress, and downregulated several components belonging to the classic renin-angiotensin (RAS) system. Our results cast new light on targeting NO delivery through the use of nanoparticles aiming to improve child-focused outcomes related to CKD worthy of clinical translation.

Iodomethylcholine Inhibits Trimethylamine-N-Oxide Production and Averts Maternal Chronic Kidney Disease-Programmed Offspring Hypertension.

Chronic kidney disease (CKD) affects 10% of the global population, including pregnant women. Adverse maternal conditions determine the developmental programming of many diseases later in life. We previously demonstrated that adult rat offspring born to dams with CKD developed hypertension and renal hypertrophy. Trimethylamine-N-oxide (TMAO), a uremic toxin derived from the gut microbiota, has been linked to hypertension. This study assesses the effects of TMAO inhibition by iodomethylcholine (IMC) treatment on offspring hypertension programmed by maternal CKD. Female rats were fed either a control or a 0.5% adenine diet before conception, with or without IMC treatment during pregnancy and lactation. Maternal IMC treatment averted maternal CKD-primed offspring hypertension and renal hypertrophy in 12-week-old offspring. Offspring hypertension is associated with increases in the plasma TMAO concentration and oxidative stress and shifts in gut microbiota. The beneficial effects of IMC are related to a reduction in TMAO; increases in genera Acetatifactor, Bifidobacterium, and Eubacterium; and decreases in genera Phocacecola and Bacteroides. Our findings afford insights into the targeting of the gut microbiota to deplete TMAO production, with therapeutic potential for the prevention of offspring hypertension programmed by maternal CKD, although these results still need further clinical translation.

Mixture analysis on associations between semen quality and sperm DNA integrity and occupational exposure to polycyclic aromatic hydrocarbons.

The objective of this study was to assess relationships between exposure to PAHs at occupational levels and outcomes of human semen quality and sperm DNA integrity. Personal breathing zone air samples were collected to quantify exposure of 16 targeted PAHs to coke-oven workers at a steel company in southern Taiwan. Semen quality, including concentration, motility, morphology, and viability, were assessed. Sperm DNA fragmentation, 8-oxodGuo, bulky PAH adducts, and benzo[a]pyrene diol epoxide-DNA adducts served as biomarkers for assessment of sperm DNA integrity. The Bayesian Kernel Machine Regression modeling was employed to estimate mixture effects of the PAH mixture on the outcomes of semen quality and sperm DNA integrity and to identify individual compounds of PAH mixtures associated with the mixture effects. Exposure to the PAH mixture was inversely associated with sperm viability, while benzo(b)fluoranthene (B[b]F) was identified as the main predictor for sperm viability. Exposure to the PAH mixture also exhibited a positive trend with sperm DNA fragmentation. B[b]F and benzo(a)anthracene (B[a]A) were identified as individual PAH compounds associated with increased sperm DNA fragmentation.

Perinatal Garlic Oil Supplementation Averts Rat Offspring Hypertension Programmed by Maternal Chronic Kidney Disease.

Garlic (Allium sativum) is a functional food, having hydrogen sulfide (H2S)-releasing capacity, which exhibits considerable effects on hypertension and gut microbiota. H2S is strongly associated with hypertension and chronic kidney disease (CKD). Maternal CKD leads to hypertension in adult rat progeny, which was linked to disruption of the gut microbiota. This study validated the benefits of perinatal garlic oil supplementation against offspring hypertension induced by maternal CKD via modulation of H2S signaling, nitric oxide (NO), and the gut microbiota. Before pregnancy, female rats received a 0.5% adenine diet for 3 weeks to develop an animal model to mimic human CKD. Garlic oil (100 mg/kg/day) or vehicle was administered to pregnant rats by oral gavage during gestation and lactation. Perinatal garlic oil supplementation protected against maternal CKD-induced hypertension in offspring at 12 weeks of age. The beneficial effects of garlic oil are associated with enhanced H2S signaling, increased NO bioavailability, and shifts in gut microbiota. Perinatal garlic oil supplementation reduces abundance of genera Variovorax, Nocardia, Sphingomonas, and Rhodococcus. Our findings provide insight into the role of early H2S-targeted intervention as a preventive strategy in hypertension for further translational research.

Perinatal Propionate Supplementation Protects Adult Male Offspring from Maternal Chronic Kidney Disease-Induced Hypertension.

Emerging evidence supports that early-life disturbance of gut microbiota has an impact on adult disease in later life. Offspring hypertension can be programmed by maternal chronic kidney disease (CKD). Conversely, perinatal use of gut microbiota-targeted therapy has been implemented to reverse programming processes and prevent hypertension. Short-chain fatty acids (SCFAs), the major gut microbiota-derived metabolites, can be applied as postbiotics. Propionate, one of predominant SCFAs, has been shown to have antihypertensive property. We examined whether perinatal propionate supplementation can prevent offspring hypertension induced by maternal CKD. CKD was induced by chow supplemented with 0.5% adenine for 3 weeks before pregnancy. Propionate (P) was supplemented at 200 mmol/L in drinking water during pregnancy and lactation. Male offspring were divided into four groups (n = 7-8/group): control, CKD, control+propionate (CP), and CKD+propionate (CKDP). Maternal CKD-induced offspring hypertension was reversed by perinatal propionate supplementation. The protective effects of perinatal propionate treatment were related to increased propionate-generating bacteria Clostridium spp. and plasma propionate level, increased expression of renal G protein-coupled receptor 41 (GPR41, a SCFA receptor), augmentation of α-diversity, and shifts in gut microbiota composition. In summary, our results highlight that maternal CKD-induced offspring hypertension can be prevented by the use of gut microbial metabolite SCFAs in early life, which could shed light on the prevention of the current hypertension pandemic.

Hydrogen Sulfide-to-Thiosulfate Ratio Associated with Blood Pressure Abnormalities in Pediatric CKD.

Identifying children with chronic kidney disease (CKD) at high risk of cardiovascular disease (CVD) and ensuring they receive appropriate treatment can prevent CVD events and mortality later in life. Hydrogen sulfide (H2S) is a gaseous signaling molecule participating in CVD and CKD. Thiosulfate is not only an oxidation product of H2S but is also a H2S donor. We examined whether H2S, thiosulfate, and their combined ratio have differential associations with CVD risk markers in 56 children and adolescents aged 6-18 years with CKD stages G1-G4. Up to two-thirds of CKD children showed higher BP load on 24 h ambulatory blood pressure monitoring (ABPM), even in the early stage. CKD children with ABPM abnormalities had a higher H2S-to-thiosulfate ratio, while H2S-related parameters were not affected by the severity of CKD. The H2S-to-thiosulfate ratio was positively correlated with 24 h systolic BP (SBP), nighttime SBP, and carotid artery intima-media thickness (cIMT). After adjusting for confounders, H2S was negatively associated with LV mass, thiosulfate was positively associated with 24-DBP, and the H2S-to-thiosulfate ratio was positively correlated with nighttime SBP and cIMT. Our data demonstrate differential associations in circulating H2S, thiosulfate, and their combined ratio with CVD risk in childhood CKD. Further studies are required to determine whether targeting the H2S signaling pathway can develop novel therapeutic strategies against CVD in this high-risk population.

Maternal Acetate Supplementation Reverses Blood Pressure Increase in Male Offspring Induced by Exposure to Minocycline during Pregnancy and Lactation.

Emerging evidence supports that hypertension can be programmed or reprogrammed by maternal nutrition. Maternal exposures during pregnancy, such as maternal nutrition or antibiotic use, could alter the offspring's gut microbiota. Short-chain fatty acids (SCFAs) are the major gut microbiota-derived metabolites. Acetate, the most dominant SCFA, has shown its antihypertensive effect. Limited information exists regarding whether maternal acetate supplementation can prevent maternal minocycline-induced hypertension in adult offspring. We exposed pregnant Sprague Dawley rats to normal diet (ND), minocycline (MI, 50 mg/kg/day), magnesium acetate (AC, 200 mmol/L in drinking water), and MI + AC from gestation to lactation period. At 12 weeks of age, four groups (n = 8/group) of male progeny were sacrificed. Maternal acetate supplementation protected adult offspring against minocycline-induced hypertension. Minocycline administration reduced plasma acetic acid level, which maternal acetate supplementation prevented. Additionally, acetate supplementation increased the protein level of SCFA receptor G protein-coupled receptor 41 in the offspring kidneys. Further, minocycline administration and acetate supplementation significantly altered gut microbiota composition. Maternal acetate supplementation protected minocycline-induced hypertension accompanying by the increases in genera Roseburia, Bifidobacterium, and Coprococcus. In sum, our results cast new light on targeting gut microbial metabolites as early interventions to prevent the development of hypertension, which could help alleviate the global burden of hypertension.