Characterization of Eurotium cristatum Fermented Thinned Young Apple and Mechanisms Underlying Its Alleviating Impacts on Experimental Colitis.

A hundred million tons of young apples are thinned and discarded in the orchard per year, aiming to increase the yield and quality of apples. We fermented thinned young apples using a potential probiotic fungus, Eurotium cristatum, which notably disrupted the microstructure of raw samples, as characterized by the scanning electron microscope. Fermentation substantially altered the metabolite profiles of samples, which are predicted to alleviate colitis via regulating inflammatory response and response to lipopolysaccharide by using network pharmacology analysis. In vivo, oral gavage of water extracts of E. cristatum fermented young apples (E.YAP) effectively alleviated DSS-induced colitis, restored the histopathology damage, reduced the levels of inflammatory cytokines, and promoted colonic expressions of tight junction proteins. Moreover, E.YAP ameliorated gut dysbacteriosis by increasing abundances of Lactobacillus,Blautia, Muribaculaceae, and Prevotellaceae_UCG-001 while inhibiting Turicibacter, Alistipes, and Desulfovibrio. Importantly, E.YAP increased colonic bile acids, such as CA, TCA, DCA, TUDCA, and LCA, thereby alleviating colitis via PXR/NF-κB signaling. Furthermore, a synbiotic combination with Limosilactobacillus reuteri WX-94, a probiotic strain isolated from feces of healthy individuals with anti-inflammatory properties, augmented anticolitis capacities of E.YAP. Our findings demonstrate that E.YAP could be a novel, potent, food-based anti-inflammatory prebiotic for relieving inflammatory injuries.

Intermittent fasting, exercise, and dietary modification induce unique transcriptomic signatures of multiple tissues governing metabolic homeostasis during weight loss and rebound weight gain.

Obesity and its related metabolic diseases bring great challenges to public health. In-depth understanding on the efficacy of weight-loss interventions is critical for long-term weight control. Our study demonstrated the comparable efficacy of exercise (EX), intermittent fasting (IF), or the change of daily diet from an unhealthy to a normal chow (DR) for weight reduction, but largely divergently affected metabolic status and transcriptome of subcutaneous fat, scapular brown fat, skeletal muscles and liver in high-fat-high-fructose diet (HFHF) induced obese mice. EX and IF reduced systematic inflammation, improved glucose and lipid metabolism in liver and muscle, and amino acid metabolism and thermogenesis in adipose tissues. EX exhibited broad regulatory effects on TCA cycle, carbon metabolism, thermogenesis, propanoate-, fatty acid and amino acid metabolism across multiple tissues. IF prominently affected genes involved in mitophagy and autophagy in adipose tissues and core genes involved in butanoate metabolism in liver. DR, however, failed to improve metabolic homeostasis and biological dysfunctions in obese mice. Notably, by exploring potential inter-organ communication, we identified an obesity-resistant-like gene profile that were strongly correlated with HFHF induced metabolic derangements and could predict the degree of weight regain induced by the follow-up HFHF diet. Among them, 12 genes (e.g., Gdf15, Tfrc, Cdv3, Map2k4, and Nqo1) were causally associated with human metabolic traits, i.e., BMI, body fat mass, HbA1C, fasting glucose, and cholesterol. Our findings provide critical groundwork for improved understanding of the impacts of weight-loss interventions on host metabolism. The identified genes predicting weight regain may be considered regulatory targets for improving long-term weight control.

Mutations in the NUP93, NUP107 and NUP160 genes cause steroid-resistant nephrotic syndrome in Chinese children.

BACKGROUND: The variants of nucleoporins are extremely rare in hereditary steroid-resistant nephrotic syndrome (SRNS). Most of the patients carrying such variants progress to end stage kidney disease (ESKD) in their childhood. More clinical and genetic data from these patients are needed to characterize their genotype-phenotype relationships and elucidate the role of nucleoporins in SRNS. METHODS: Four patients of SRNS carrying biallelic variants in the NUP93, NUP107 and NUP160 genes were presented. The clinical and molecular genetic characteristics of these patients were summarized, and relevant literature was reviewed. RESULTS: All four patients in this study were female and initially presented with SRNS. The median age at the onset of the disease was 5.08 years, ranging from 1 to 10.5 years. Among the four patients, three progressed to ESKD at a median age of 7 years, ranging from 1.5 to 10.5 years, while one patient reached stage 3 chronic kidney disease (CKD3). Kidney biopsies revealed focal segmental glomerulosclerosis in three patients. Biallelic variants were detected in NUP93 in one patient, NUP107 in two patients, as well as NUP160 in one patient respectively. Among these variants, five yielded single amino acid substitutions, one led to nonsense mutation causing premature termination of NUP107 translation, one caused a single nucleotide deletion resulting in frameshift and truncation of NUP107. Furthermore, one splicing donor mutation was observed in NUP160. None of these variants had been reported previously. CONCLUSION: This report indicates that biallelic variants in NUP93, NUP107 and NUP160 can cause severe early-onset SRNS, which rapidly progresses to ESKD. Moreover, these findings expand the spectrum of phenotypes and genotypes and highlight the importance of next-generation sequencing in elucidating the molecular basis of SRNS and allowing rational treatment for affected individuals.

Polygonatum kingianum Polysaccharides Enhance the Preventive Efficacy of Heat-Inactivated Limosilactobacillus reuteri WX-94 against High-Fat-High-Sucrose-Induced Liver Injury and Gut Dysbacteriosis.

Limosilactobacillus reuteri (L. reuteri) is an efficacious probiotic that could reduce inflammation and prevent metabolic disorders. Here, we innovatively found that Polygonatum kingianum polysaccharides (PKP) promoted proliferation and increased stability of L. reuteri WX-94 (a probiotic strain showing anti-inflammation potentials) in simulated digestive fluids in vitro. PKP was composed of galactose, glucose, mannose, and arabinose. The cell-free supernatant extracted from L. reuteri cultured with PKP increased ABTS•+, DPPH•, and FRAP scavenging capacities compared with the supernatant of the medium without PKP and increased metabolites with health-promoting activities, e.g., 3-phenyllactic acid, indole-3-lactic acid, indole-3-carbinol, and propionic acid. Moreover, PKP enhanced alleviating effects of heat-inactivated L. reuteri on high-fat-high-sucrose-induced liver injury in rats via reducing inflammation and regulating expressions of protein and genes involved in fatty acid metabolism (such as HIF1-α, FAßO, CPT1, and AMPK) and fatty acid profiles in liver. Such benefits correlated with its prominent effects on enriching Lactobacillus and short-chain fatty acids while reducing Dubosiella, Fusicatenilacter, Helicobacter, and Oscillospira. Our work provides novel insights into the probiotic property of PKP and emphasizes the great potential of the inactivated L. reuteri cultured with PKP in contracting unhealthy diet-induced liver dysfunctions and gut dysbacteriosis.

'Nine Steaming Nine Sun-drying' processing enhanced properties of Polygonatum kingianum against inflammation, oxidative stress and hyperglycemia.

BACKGROUND: Polygonatum kingianum Coll. & Hemsl (PK), a prominent medicine and food homology plant, has been consumed as a decoction from boiling water for thousands of years. 'Nine Steaming Nine Sun-drying' processing has been considered an effective method for enriching tonic properties, but studies investigating such impacts on PK and underlying mechanisms are extremely rare. RESULTS: We first demonstrated substantial improvements in the anti-oxidative, anti-inflammatory and anti-hyperglycemia effects of the Nine Steaming Nine Sun-drying processed PK water extracts compared with crude PK in cell models (i.e., HepG2 and Raw 264.7 cells). We then integrated foodomics and network pharmacology analysis to uncover the key compounds responsible for the improved benefits. A total of 551 metabolites of PK extracts were identified, including polyphenols, flavonoids, alkaloids, and organic acids. During processing, 204 metabolites were enhanced, and 32 metabolites were recognized as key constituents of processed PK responsible for the improved health-promoting activities, which may affect PI3K-Akt-, MAPK-, and HIF-1 pathways. We further confirmed the high affinity between identified key constituents of processed PK and their predicted acting targets using molecular docking. CONCLUSION: Our results provide novel insights into bioactive compounds of processed PK, elaborating the rationality of processing from the perspective of tonic effects. Consuming processed PK could be an efficacious strategy to combat the high prevalence of metabolic diseases that currently affect millions of people worldwide. © 2023 Society of Chemical Industry.

Oat-based postbiotics ameliorate high-sucrose induced liver injury and colitis susceptibility by modulating fatty acids metabolism and gut microbiota.

High-sucrose (HS) consumption leads to metabolic disorders and increases susceptibility to colitis. Postbiotics hold great potentials in combating metabolic diseases and offer advantages in safety and processability, compared with living probiotics. We developed innovative oat-based postbiotics and extensively explored how they could benefit in rats with long-term high-sucrose consumption. The postbiotics fermented with Lactiplantibacillus plantarum (OF-1) and OF-5, the one fermented with the optimal selection of five probiotics (i.e., L. plantarum, Limosilactobacillus reuteri, Lacticaseibacillus rhamnosus, Lactobacillus acidophilus, and Bifidobacterium lactis) alleviated HS induced liver injury, impaired fatty acid metabolism and inflammation through activating AMPK/SREBP-1c pathways. Moreover, oat-based postbiotics restored detrimental effects of HS on fatty acid profiles in liver, as evidenced by the increases in polyunsaturated fatty acids and decreases in saturated fatty acids, with OF-5 showing most pronounced effects. Furthermore, oat-based postbiotics prevented HS exacerbated susceptibility to dextran sodium sulfate caused colitis and reconstructed epithelial tight junction proteins in colons. Oat-based postbiotics, in particular OF-5 notably remodeled gut microbiota composition, e.g., enriching the relative abundances of Akkermansia, Bifidobacterium, Alloprevotella and Prevotella, which may play an important role in the liver-colon axis responsible for improvements of liver functions and reduction of colitis susceptibility. The heat-inactivated probiotics protected against HS-induced liver and colon damage, but such effects were less pronounced compared with oat-based postbiotics. Our findings emphasize the great value of oat-based postbiotics as nutritional therapeutics to combat unhealthy diet induced metabolic dysfunctions.

Clinical, histological and molecular characteristics of Alport syndrome in Chinese children.

BACKGROUND: Alport syndrome is caused by COL4A3, COL4A4, or COL4A5 gene mutations. The present study aims to compare the clinicopathological features, gene mutations, and outcome of Chinese children with different forms of Alport syndrome. METHODS: One hundred twenty-eight children from 126 families diagnosed with Alport syndrome through pathological and genetic examination between 2003 and 2021 were included in this single-center retrospective study. The laboratory and clinicopathological features of the patients with different inheritance patterns were analyzed. The patients were followed-up for disease progression and phenotype-genotype correlation. RESULTS: Of the 126 Alport syndrome families, X-linked forms accounted for 77.0%, autosomal recessive for 11.9%, autosomal dominant for 7.1%, and digenic for 4.0%. Among the patients, 59.4% were males and 40.6% were females. Altogether, 114 different mutations were identified in 101 patients from 99 families by whole-exome sequencing, of which 68 have not been previously reported. The most prevalent type of mutation was glycine substitution, which was identified in 52.1%, 36.7%, and 60% of the patients with X-linked Alport syndrome, autosomal recessive and autosomal dominant Alport syndrome, respectively. At the end of a median follow up of 3.3 (1.8-6.3) years, Kaplan-Meier curves showed kidney survival was significantly lower in autosomal recessive compared to X-linked Alport syndrome (P = 0.004). Pediatric patients with Alport syndrome seldom presented extrarenal involvement. CONCLUSIONS: X-linked Alport syndrome is the most frequent form found in this cohort. Progression was more rapid in autosmal recessive than in X-linked Alport syndrome.

Clinical and Renal Histology Findings and Different Responses to Induction Treatment Affecting the Long-Term Renal Outcomes of Children With ANCA-Associated Vasculitis: a Single-Center Cohort Analysis.

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is relatively rare in children. This article aimed to analyze clinical and renal histology findings and different responses to induction treatment associated with the long-term renal outcomes in children with AAV in a single center. Methods: All pediatric patients with AAV admitted to Tongji Hospital from January 2002 to January 2021 were included in the study. The demographic, clinical, pathological, laboratory, and treatment data and outcomes were collected and analyzed to identify predictors associated with response to induction treatment and progression to end-stage renal disease (ESRD). Results: In total, 48 children with AAV were included in this cohort; 81.25% of them were women, and 91.7% were microscopic polyangiitis (MPA). Kidney involvement was found in 45 patients (93.75%). The most common histopathological subtype was crescentic form in this cohort according to Berden's classification. In total, 34 patients (70.8%) showed eGFR <60 ml/min/1.73 m2 at the time of diagnosis. Complete and partial remission was achieved in 8 patients (16.7%) and 19 patients (39.6%), respectively, following 6-month induction treatment. Half of the patients eventually progressed to ESRD at a mean time of (13.04 ± 15.83) months after diagnosis. The independent predictors of nonremission following induction treatment and progression to ESRD were baseline eGFR <60 ml/min/1.73 m2 and hypertension at diagnosis. Renal survival significantly decreased over time in patients with renal sclerotic subtypes or those with nonremission following induction treatment by Kaplan-Meier curve estimation. Conclusions: Our study demonstrates that women, MPA, and crescentic subtypes are predominant in pediatric AAV in China. Initial renal failure (eGFR <60 ml/min/1.73 m2), hypertension, sclerotic pathological subtype, and nonremission following induction treatment are predictive of long-term renal outcomes.