The Epigenetic Legacy of Maternal Protein Restriction: Renal Ptger1 DNA Methylation Changes in Hypertensive Rat Offspring.

Nutrient imbalances during gestation are a risk factor for hypertension in offspring. Although the effects of prenatal nutritional deficiency on the development of hypertension and cardiovascular diseases in adulthood have been extensively documented, its underlying mechanisms remain poorly understood. In this study, we aimed to elucidate the precise role and functional significance of epigenetic modifications in the pathogenesis of hypertension. To this end, we integrated methylome and transcriptome data to identify potential salt-sensitive hypertension genes using the kidneys of stroke-prone spontaneously hypertensive rat (SHRSP) pups exposed to a low-protein diet throughout their fetal life. Maternal protein restriction during gestation led to a positive correlation between DNA hypermethylation of the renal prostaglandin E receptor 1 (Ptger1) CpG island and high mRNA expression of Ptger1 in offspring, which is consistently conserved. Furthermore, post-weaning low-protein or high-protein diets modified the Ptger1 DNA hypermethylation caused by fetal malnutrition. Here, we show that this epigenetic variation in Ptger1 is linked to disease susceptibility established during fetal stages and could be reprogrammed by manipulating the postnatal diet. Thus, our findings clarify the developmental origins connecting the maternal nutritional environment and potential epigenetic biomarkers for offspring hypertension. These findings shed light on hypertension prevention and prospective therapeutic strategies.

3D-Printed river-type thick carbon electrodes for docking possible practical application-level capacitive deionization.

The low carbon mass loading along with serious imbalance between the carbon mass loading and the electrode performance greatly hinders practical applications of capacitive deionization (CDI). Traditional thick bulk-type (BT) carbon electrodes often suffer from extremely limited active sites, thereby being vital to explore a basic strategy to unlock the performance. Herein, 3D-printed thick carbon electrodes were utilized for CDI desalination for the first time. The experimental outcomes revealed that BT electrodes existed a serious salt adsorption capacity (SAC) drop under variable mass loading of 3-30 mg/cm2. In contrary, 3D-printed river-type (RT) electrodes acquired a superior SAC of 10.67 mg/g and achieved 54.1 % SAC rise compared with that of BT electrodes (500 mg/L; 1.0 V; 30 mg/cm2). Meanwhile, RT electrodes took only 12 min to reach the equilibrium SAC of BT electrodes, being 44 min faster. Further, RT electrodes with diverse mass loading of 30-45 mg/cm2 were investigated, and it still kept 7.13 mg/g SAC under ultrahigh mass loading of 45 mg/cm2. This strategy has been successfully extended and carbons with proper micro-meso pore distribution, high specific capacitances and low resistance may be a better selection. Besides, the impact of electrode channel structure on the desalting performance was investigated, and the influence mechanism was revealed via COMSOL simulation. Overall, this work demonstrates the splendid feasibility of utilizing 3D-printed thick carbon electrodes for possible practical application-level CDI desalination.

Multiple-statistical genome-wide association analysis and genomic prediction of fruit aroma and agronomic traits in peaches.

'Chinese Cling' is an important founder in peach breeding history due to the pleasant flavor. Genome-wide association studies (GWAS) combined with genomic selection are promising tools in fruit tree breeding, as there is a considerable time lapse between crossing and release of a cultivar. In this study, 242 peaches from Shanghai germplasm were genotyped with 145 456 single-nucleotide polymorphisms (SNPs). The six agronomic traits of fruit flesh color, fruit shape, fruit hairiness, flower type, pollen sterility, and soluble solids content, along with 14 key volatile odor compounds (VOCs), were recorded for multiple-statistical GWAS. Except the reported candidate genes, six novel genes were identified as associated with these traits. Thirty-nine significant SNPs were associated with eight VOCs. The putative candidate genes were confirmed for VOCs by RNA-seq, including three genes in the biosynthesis pathway found to be associated with linalool, soluble solids content, and cis-3-hexenyl acetate. Multiple-trait genomic prediction enhanced the predictive ability for γ-decalactone to 0.7415 compared with the single-trait model value of 0.1017. One PTS1-SSR marker was designed to predict the linalool content, and the favorable genotype 187/187 was confirmed, mainly existing in the 'Shanghai Shuimi' landrace. Overall, our findings will be helpful in determining peach accessions with the ideal phenotype and show the potential of multiple-trait genomic prediction to improve accuracy for highly correlated genetic traits. The diagnostic marker will be valuable for the breeder to bridge the gap between quantitative trait loci and marker-assisted selection for developing strong-aroma cultivars.

Construction of ACNF/Polypyrrole/MIL-100-Fe composites with exceptional removal performance for ceftriaxone and indomethacin inspired by "Ecological Infiltration System".

Developing advanced adsorbents for removing the alarming level of pharmaceuticals active compounds (PhACs) pollution is an urgent task for environmental treatment. Herein, a novel acid-treated carbon nanofiber/polypyrrole/MIL-100-Fe (ACNF/PPy/MIL-100-Fe) with stable 3D-supporting skeleton and hierarchical porous structure had been fabricated to erasure ceftriaxone (CEF) and indomethacin (IDM) from aqueous solution. ACNF as scaffold achieved the highly uniform growth of MIL-100-Fe and PPy. Viewing the large BET surface area (SBET, 999.7 m2/g), highly exposed accessible active sites and copious functional groups, ACNF/PPy/MIL-100-Fe separately showed an excellent adsorption capacity for CEF (294.7 mg/g) and IDM (751.8 mg/g), outstripping the most previously reported adsorbents. Moreover, ACNF/PPy/MIL-100-Fe reached rapid adsorption kinetics and standout reusability property. Further, the redesigned easy-to-recyclable ACF/PPy/MIL-100-Fe inspired by the electrode formation craft achieved prominent adsorption capacity and good reusability property. The adsorption mechanism was evaluated via Fourier transformed infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS). The outcomes revealed that the splendid adsorption capability mainly depended on the electrostatic interactions, hydrogen bonding and π-π interactions. This work sheds light on one facile practical strategy to exploit advanced materials in water environmental remediation.

Identification of the Light-Harvesting Chlorophyll a/b Binding Protein Gene Family in Peach (Prunus persica L.) and Their Expression under Drought Stress.

In higher plants, light-harvesting chlorophyll a/b binding (Lhc) proteins play a vital role in photosynthetic processes and are widely involved in the regulation of plant growth, development, and response to abiotic stress. However, the Lhc gene family has not been well identified in peaches (Prunus persica L.). In this study, 19 PpLhc genes were identified in the peach genome database, which were unevenly distributed on all chromosomes. Phylogenetic analysis demonstrated that PpLhc proteins could be divided into three major subfamilies, each of whose members had different exon-intron structures but shared similar conserved motifs. A total of 17 different kinds of cis-regulatory elements were identified in the promoter regions of all PpLhc genes, which could be classified into three categories: plant growth and development, stress response, and phytohormone response. In addition, transcriptomic data analysis and RT-qPCR results revealed that the expression profiles of some PpLhc genes changed under drought treatment, suggesting the crucial roles of Lhc genes in the regulation of plant tolerance to drought stress. Taken together, these findings will provide valuable information for future functional studies of PpLhc genes, especially in response to drought stress.

Effects of Heat-Moisture-Treated High-Amylose Rice Flour on Body Weight, Lipid Metabolism, and Gut Microbiome Composition in Obese Rats.

The rising prevalence of lifestyle diseases, such as type 2 diabetes, cardiovascular diseases, and metabolic syndrome, has increased the need for effective dietary interventions. This study aimed to evaluate the effects of heat-moisture-treated high-amylose rice (HA-HMT) on body weight, lipid metabolism, and gut microbiome composition in a rat model of obesity. Starch digestibility-specifically, resistant starch-has been shown to provide various health benefits, including improved metabolic health and gut microbiome composition. We employed a sequential approach: firstly, utilizing diet-induced obesity rat models fed with HMT-processed and HMT-non-processed low- or high-amylose rice to investigate the potential of amylose content or HMT to alter phenotypic characteristics and lipid metabolism; and secondly, using the optimal rice flour identified in the previous step to explore the underlying mechanisms. Our findings indicate that heat-moisture treatment, rather than the level of the amylose content of the rice, contributes to the observed anti-obesity and cholesterol-lowering effects. We identified candidate genes contributing to the cholesterol-regulating potential and demonstrated that HMT rice flour could influence the gut microbiome, particularly the Ruminococcus taxa. This study provides valuable insights into the health benefits of HA-HMT rice and supports its potential as a functional food ingredient in the management of obesity and cholesterol-related disorders.

Effects of Thyme (Thymus vulgaris L.) Essential Oil on Aging-Induced Brain Inflammation and Blood Telomere Attrition in Chronologically Aged C57BL/6J Mice.

Chronological aging is commonly accompanied by chronic low-grade inflammation (or "inflammaging"), a contributor to the development of age-related chronic diseases. Aging increases oxidative stress that accelerates telomere shortening, leading to cell senescence and the generation of senescence-associated secretory phenotype (SASP) that exacerbates inflammation. Dietary antioxidants may help protect telomeres and attenuate inflammation. Thyme essential oil (TEO), reported for its potency against neuroinflammation, was fed to chronologically aged C57BL/6J mice for 24 weeks. The TEO diet showed notable impacts on the hippocampus, indicated by lower expression of the aging-related gene p16INK4A (p = 0.0783) and significantly lower expression of cyclin D kinase Cdk4 and Cdk6 (p < 0.05) compared to the age-matched control mice. The TEO group also showed significantly lower gene expression of the pro-inflammatory cytokine Il6 (p < 0.05) in the hippocampus and lower Il1b expression in the liver and cerebellum (p < 0.05). In vitro experiments conducted on NIH-3T3 cells expressing SASP revealed the dose-dependent anti-inflammatory activity of TEO. Remarkably, TEO diet-fed mice showed higher survival rates and significantly longer blood telomere lengths than the control mice. Monoterpene antioxidants in TEO, particularly thymol and p-cymene, may primarily contribute to the anti-inflammatory and telomere-protecting activities of TEO.

Postnatal nutrition environment reprograms renal DNA methylation patterns in offspring of maternal protein-restricted stroke-prone spontaneously hypertensive rats.

Maternal malnutrition hampers the offspring health by manipulating the epigenome. Recent studies indicate that the changes in DNA methylation could be reversed by afterbirth nutrition supplementation. In this study, we used DNA methylation arrays to comprehensively investigate the DNA methylation status of the renal promoter regions and the effects of postnatal protein intake on DNA methylation. We fed stroke-prone spontaneously hypertensive (SHRSP) rat dams a normal diet or a low-protein diet during pregnancy, and their 4-week-old male offspring were fed a normal diet or a high-/low-protein diet for 2 weeks. We found that the methylation status of 2,395 differentially methylated DNA regions was reprogrammed, and 34 genes were reset by different levels of postnatal protein intake in the offspring. Among these genes, Adora2b, Trpc5, Ar, Xrcc2, and Atp1b1 are involved in renal disease and blood pressure regulation. Our findings indicate that postnatal nutritional interventions can potentially reprogram epigenetic changes, providing novel therapeutic and preventive epigenetic targets for salt-sensitive hypertension.

Effects of Turmeric Extract on Age-Related Skeletal Muscle Atrophy in Senescence-Accelerated Mice.

Muscle atrophy is one of the main causes of sarcopenia-the age-related loss of skeletal muscle. In this study, we investigated the effect of turmeric (Curcuma longa) extract (TE) supplementation on age-related muscle atrophy in a senescence-accelerated mouse model and explored the underlying mechanisms. Twenty-six-week-old male, senescence-accelerated mouse resistant (SAMR) mice received the AIN-93G basal diet, while twenty-six-week-old male, senescence-accelerated mouse prone 8 (SAMP8) mice received the AIN-93G basal diet or a 2% TE powder-supplemented diet for ten weeks. Our findings revealed that TE supplementation showed certain effects on ameliorating the decrease in body weight, tibialis anterior weight, and mesenteric fat tissue weight in SAMP8 mice. TE improved gene expression in the glucocorticoid receptor-FoxO signaling pathway in skeletal muscle, including redd1, klf15, foxo1, murf1, and mafbx. Furthermore, TE might have the certain potential on improving the dynamic balance between anabolic and catabolic processes by inhibiting the binding of glucocorticoid receptor or FoxO1 to the glucocorticoid response element or FoxO-binding element in the MuRF1 promoter in skeletal muscle, thereby promoting muscle mass and strength, and preventing muscle atrophy and sarcopenia prevention. Moreover, TE may have reduced mitochondrial damage and maintained cell growth and division by downregulating the mRNA expression of the genes mfn2 and tsc2. Thus, the results indicated TE's potential for preventing age-related muscle atrophy and sarcopenia.

Association between Dietary Behaviors and BMI Stratified by Sex and the ALDH2 rs671 Polymorphism in Japanese Adults.

The rs671 polymorphism, unique to East Asians, is well known to change the sensitivity to alcohol. Moreover, this polymorphism is associated not only with alcohol intake but also with several dietary behaviors (DBs), chronic diseases, and BMI, but the triadic association among the rs671 genotype, DBs, and BMI is unclear. This study included 12,271 Japanese subjects and aimed to observe this three-way association using the rs671 polymorphism, data of 56 DBs, and BMI. All analyses were stratified by participant sex. First, linear regression analyses resulted in significant associations between 18 and 21 DBs and BMI in males and females, respectively. Next, genetic heterogeneity was observed in all sub-groups via interaction analysis of the rs671 genotype stratified by drinking habits. Finally, we observed the characteristics of BMI-related DBs based on the rs671 genotype via stepwise regression analyses stratified by the rs671 genotype and drinking habits. Notably, positive associations were observed between lactobacillus beverage intake and BMI among participants with the rs671 polymorphism AA genotype in both sexes. This study suggests that the rs671 polymorphism modifies the association between DBs and BMI independently of drinking habits, providing evidence for the potential use of rs671 polymorphism information for precision nutrition with East Asians.

Transcriptome and Methylome Profiling in Rat Skeletal Muscle: Impact of Post-Weaning Protein Restriction.

Skeletal muscle is programmable, and early-life nutritional stimuli may form epigenetic memory in the skeletal muscle, thus impacting adult muscle function, aging, and longevity. In the present study, we designed a one-month protein restriction model using post-weaning rats, followed by a two-month rebound feeding, to investigate how early-life protein restriction affects overall body growth and muscle development and whether these influences could be corrected by rebound feeding. We observed comprehensive alterations immediately after protein restriction, including retarded growth, altered biochemical indices, and disturbed hormone secretion. Transcriptome profiling of the gastrocnemius muscle followed by gene ontology analyses revealed that "myogenic differentiation functions" were upregulated, while "protein catabolism" was downregulated as a compensatory mechanism, with enhanced endoplasmic reticulum stress and undesired apoptosis. Furthermore, methylome profiling of the gastrocnemius muscle showed that protein restriction altered the methylation of apoptotic and hormone secretion-related genes. Although most of the alterations were reversed after rebound feeding, 17 genes, most of which play roles during muscle development, remained altered at the transcriptional level. In summary, early-life protein restriction may undermine muscle function in the long term and affect skeletal muscle development at the both transcriptional and methylation levels, which may hazard future muscle health.

Suppressive Effects of Turmeric Extract on Muscle Atrophy in Dexamethasone-Treated Mice and Myotubes.

Sarcopenia is the decline in skeletal muscle mass, strength, and functions, which decreases the quality of life in elderly people. This study investigated the suppressive effect of turmeric (Curcuma longa) extract (TE) on muscle atrophy in dexamethasone (DEX)-treated mice and C2C12 myotubes. DEX treatment significantly decreased the muscle weight and significantly increased Fbxo32 and Murf1 expression in mice, and these changes were suppressed by the supplementation of an AIN-93 based diet with 2% TE. A similar pattern was observed in FBXO32 and MuRF1 protein expression. In C2C12 myotubes, DEX treatment significantly increased FBXO32 and MuRF1 gene and protein expression, and these increases were significantly suppressed by TE supplementation at a concentration of 200 µg/mL. Furthermore, one of the five TE fractions, which were separated by high-performance liquid chromatography had a similar effect with TE supplementation. The present study proposes the suppressive effect of turmeric on sarcopenia.

Effect of ozonated water, mancozeb, and thiophanate-methyl on the phyllosphere microbial diversity of strawberry.

Phyllosphere microorganisms are closely linked to plant health. This study investigated the effect of ozonated water, mancozeb, and thiophanate-methyl on phyllosphere microorganisms in strawberry plants of the "Hongyan" variety. Sequencing analysis of the phyllosphere bacterial and fungal communities was performed using 16S rRNA gene fragment and ITS1 region high-throughput sequencing after spraying ozonated water, mancozeb, thiophanate-methyl, and clear water. Proteobacteria, Actinobacteria, and Firmicutes were the dominant bacterial phyla in strawberry. The relative abundance of Proteobacteria (82.71%) was higher in the ozonated water treatment group than in the other treatment groups, while the relative abundance of Actinobacteria (9.38%) was lower than in the other treatment groups. The strawberry phyllosphere fungal communities were mainly found in the phyla Basidiomycota and Ascomycota. The relative abundance of Basidiomycota was highest in the ozonated water treatment group (81.13%), followed by the mancozeb treatment group (76.01%), while the CK group only had an abundance of 43.38%. The relative abundance of Ascomycota was lowest in the ozonated water treatment group (17.98%), 23.12% in the mancozeb treatment group, 43.39% in the thiophanate-methyl treatment group, and 55.47% in the CK group. Pseudomonas, Halomonas, and Nesterenkonia were the dominant bacterial genera on strawberry surfaces, while Moesziomyces, Aspergillus, and Dirkmeia were the dominant fungal genera. Ozonated water was able to significantly increase the richness of bacteria and fungi and decrease fungal diversity. However, bacterial diversity was not significantly altered. Ozonated water effectively reduced the relative abundance of harmful fungi, such as Aspergillus, and Penicillium, and enriched beneficial bacteria, such as Pseudomonas and Actinomycetospora, more effectively than mancozeb and thiophanate-methyl. The results of the study show that ozonated water has potential as a biocide and may be able to replace traditional agents in the future to reduce environmental pollution.

Zeolitic Imidazole Framework-90-Based Pesticide Smart-Delivery System with Enhanced Antimicrobial Performance.

Multimodal antimicrobial technology is regarded as a promising strategy for controlling plant diseases because it enhances antimicrobial efficacy by blocking multiple pesticide-resistance pathways. In this work, a pH-responsive multimodal antimicrobial system was constructed based on ZIF-90 for the controlled release of kasugamycin (KSM). A series of physicochemical characterizations confirmed the successful fabrication of ZIF-90-KSM. The results indicated that the loading capacity of ZIF-90-KSM for KSM was approximately 6.7% and that the ZIF-90 nanocarriers could protect KSM against photodegradation effectively. The acid pH at the site of disease not only decompose the Schiff base bonds between KSM and ZIF-90, but also completely dissolved the nanocarriers. The simultaneous release of KSM and Zn2+ ions was able to achieve multimodal antimicrobial functions during disease occurs. A bioactivity survey indicated that ZIF-90-KSM had superior fungicidal activity and longer duration against Magnaporthe oryzae than KSM aqueous solution. In addition, the phytotoxicity assessment of ZIF-90-KSM on rice plants did not reveal any adverse effects. Therefore, ZIF-90-KSM prepared by Schiff base reaction has great potential for achieving synergistic antifungal functions and provides an eco-friendly approach to manage rice diseases.

Pectin functionalized metal-organic frameworks as dual-stimuli-responsive carriers to improve the pesticide targeting and reduce environmental risks.

Encapsulation of active ingredients into intelligent response controlled release carriers has been recognized as a promising approach to enhance the utilization efficiency and reduce the environmental risks of pesticides. In this work, an intelligent redox and pectinase dual stimuli-responsive pesticide delivery system was constructed by bonding pectin with metal-organic frameworks (FeMOF nanoparticles) which were loaded with pyraclostrobin (PYR@FeMOF-pectin nanoparticles). The successful fabrication of PYR@FeMOF-pectin nanoparticles was proved by a series of physicochemical characterizations. The results indicated that the loading capacity of PYR@FeMOF-pectin nanoparticles for pyraclostrobin was approximately 20.6%. The pectin covered on the surface of PYR@FeMOF nanoparticles could protect pyraclostrobin from photolysis and improve their spreadability on rice blades effectively. Different biological stimuli associated with Magnaporthe oryzae could trigger the release of pyraclostrobin from the pesticide-loaded core-shell nanoparticles, resulting in the death of pathogens. The bioactivity survey determined that PYR@FeMOF-pectin nanoparticles had a superior fungicidal activity and a longer duration against Magnaporthe oryzae than pyraclostrobin suspension concentrate. In addition, the FeMOF-pectin nanocarriers showed no obvious phytotoxicity and could enhance the shoot length and root length of rice plants. More importantly, PYR@FeMOF-pectin nanoparticles had an 8-fold reduction in acute toxicity to zebrafish than that of pyraclostrobin suspension concentrate. Therefore, the dual-responsive FeMOF-pectin nanocarriers have great potential for realizing site-specific pesticide delivery and promoting plant growth.

Characterization of volatile constituents and odorous compounds in peach (Prunus persica L) fruits of different varieties by gas chromatography-ion mobility spectrometry, gas chromatography-mass spectrometry, and relative odor activity value.

The aim of this study is to acquire information for future breeding efforts aimed at improving fruit quality via effects on aroma by comparing the diversity of Chinese local peach cultivars across 10 samples of three varieties (honey peach, yellow peach, and flat peach). The volatile components of peach fruits were analyzed and identified by gas chromatography-ion mobility spectrometry (GC-IMS) combined with gas chromatography-mass spectrometry (GC-MS), and the main flavor components of peach fruit were determined by relative odor activity value (ROAV) and principal component analysis (PCA). A total number of 57 volatile components were detected by GC-IMS, including eight aldehydes, nine alcohols, eight ketones, 22 esters, two acids, two phenols, two pyrazines, one thiophene, one benzene, and two furans. The proportion of esters was up to 38.6%. A total of 88 volatile components were detected by GC-MS, among which 40 were key aroma compounds, with an ROAV ≥ 1. The analysis results showed that alcohols, ketones, esters, and aldehydes contributed the most to the aroma of peach fruit. PCA demonstrated that (E,E)-2, 6-non-adienal, γ-decalactone, ß-ionone, and hexyl hexanoate were the key contributors to the fruit aroma. A reference for future directional cultivation and breeding could be provided by this study through evaluating the aroma quality of the peach at the cultivar level. The possible reasonable application of these peach fruits pulp will be guided through these research.

Activating transcription factor 4-dependent hsa-miR-663a transcription mediates mTORC1/p70S6K1 signaling underleucine deprivation.

The mechanistic target of rapamycin complex 1 (mTORC1) is involved in nutrient-induced signaling and is a master regulator of cell growth and metabolism. Amino acid-deficient conditions affect mTORC1 activity; however, its upstream regulators warrant further investigation. MicroRNAs are key regulators of nutrient-related responses; therefore, the present study aimed to assess the leucine starvation-induced microRNA profile and its impact on mTORC1 activity. Transcriptome analysis of human hepatocellular carcinoma cells (HepG2) under leucine deprivation revealed that hsa-miR-663a and hsa-miR-1469 were altered in a transcription factor 4-dependent manner. Overexpression of these microRNAs induced phosphorylation of the ribosomal protein S6 kinase beta-1, a mTORC1 downstream target. Furthermore, hsa-miR-663a downregulated proline-rich Akt1 substrate of 40 kDa (PRAS40), one of the mTORC1 components. In summary, this study provides new insights into the regulatory role of microRNAs in amino acid metabolism and demonstrates alterations in microRNA profile under leucine deprivation in human hepatocytes.

Dietary Eggshell Membrane Powder Improves Survival Rate and Ameliorates Gut Dysbiosis in Interleukin-10 Knockout Mice.

Inflammatory bowel disease (IBD) is known to be associated with compositional and metabolic changes in the gut microbiota. The aim of this study was to investigate whether dietary eggshell membrane (ESM) improves survival rate or ameliorates gut dysbiosis in a spontaneous IBD model of interleukin-10 knockout (IL10-/-) mice. Female C57BL/6J wild-type (WT) and IL10-/- mice (KO) were fed an AIN-93G basal diet or an ESM diet (KOE) for 19 weeks. Gut microbiota profiles were analyzed via 16S rRNA sequencing, and short-chain fatty acids in cecal content were analyzed with high-performance liquid chromatography. The results demonstrated that ESM supplementation significantly improved the survival rate and body composition in KO mice. Alpha diversity analysis of the microbiota revealed that ESM supplementation significantly increased gut microbial diversity, which was decreased in IL10-/- mice. The Firmicutes/Bacteroidetes ratio was recovered to a normal level by ESM supplementation, suggesting that ESM helps maintain the compositional balance of the gut microbiota. ESM increased relative abundance of commensal bacterial Ruminococcus and Bacteroidales S24-7 and reduced the abundance of the proinflammatory-related bacterium, Enterobacteriaceae. Additionally, ESM supplementation promoted the production of butyrate in cecal contents and downregulated the expression of proinflammatory genes, including interleukin-1ß (Il-1ß) and tumor necrosis factor-α (Tnf-α) in IL10-/- mice colon, indicating anti-inflammatory functions. These findings suggest that ESM may be used as a beneficial dietary intervention for IBD.

Eggshell membrane modulates gut microbiota to prevent murine pre-cachexia through suppression of T helper cell differentiation.

BACKGROUND: Cachexia is a life-threatening condition observed in several pathologies, such as cancer or chronic diseases. Interleukin 10 (Il10) gene transfer is known to improve cachexia by downregulating Il6. Here, we used an IL10-knockout mouse model to simulate cachexia and investigate the effects of eggshell membrane (ESM), a resistant protein, on general pre-cachexia symptoms, which is particularly important for the development of cachexia therapeutics. METHODS: Five-week-old male C57BL6/J mice were fed an AIN-93G powdered diet (WT), and 5-week-old male B6.129P2-Il10 < tm1Cgn>/J (IL10-/- ) mice were fed either the AIN-93G diet (KO) or an 8% ESM-containing diet (KOE) for 28 weeks. The tissue weight and levels of anaemia-, blood glucose-, lipid metabolism-, and muscular and colonic inflammation-related biochemical markers were measured. Transcriptomic analysis on liver and colon mucus and proteomic analysis on skeletal muscle were performed. Ingenuity Pathway Analysis was used to identify molecular pathways and networks. Caecal short-chain fatty acids (SCFAs) were identified using HPLC, and caecal bacteria DNA were subjected to metagenomic analysis. Flow cytometry analysis was performed to measure the CD4+ IL17+ T cells in mesenteric lymph nodes. RESULTS: The body weight, weight of gastrocnemius muscle and fat tissues, colon weight/length ratio, plasma HDL and NEFA, muscular PECAM-1 levels (P < 0.01), plasma glucose and colonic mucosal myeloperoxidase activity (P < 0.05) and T helper (Th) 17 cell abundance (P = 0.071) were improved in KOE mice over KO mice. Proteomic analysis indicated the protective role of ESM in muscle weakness and maintenance of muscle formation (>1.5-fold). Transcriptomic analysis revealed that ESM supplementation suppressed the LPS/IL1-mediated inhibition of RXR function pathway in the liver and downregulated the colonic mucosal expression of chemokines and Th cell differentiation-related markers (P < 0.01) by suppressing the upstream BATF pathway. Analysis of the intestinal microenvironment revealed that ESM supplementation ameliorated the microbial alpha diversity and the abundance of microbiota associated with the degree of inflammation (P < 0.05) and increased the level of total organic acids, particularly of SCFAs such as butyrate (2.3-fold), which could inhibit Th1 and Th17 production. CONCLUSIONS: ESM supplementation ameliorated the chief symptoms of cachexia, including anorexia, lean fat tissue mass, skeletal muscle wasting and reduced physical function. ESM also improved colon and skeletal muscle inflammation, lipid metabolism and microbial dysbiosis. These results along with the suppressed differentiation of Th cells could be associated with the beneficial intestinal microenvironment and, subsequently, attenuation of pre-cachexia. Our findings provide insights into the potential of ESM in complementary interventions for pre-cachexia prevention.

Laurel Attenuates Dexamethasone-Induced Skeletal Muscle Atrophy In Vitro and in a Rat Model.

Prevention of muscle atrophy contributes to improved quality of life and life expectancy. In this study, we investigated the effects of laurel, selected from 34 spices and herbs, on dexamethasone (DEX)-induced skeletal muscle atrophy and deciphered the underlying mechanisms. Co-treatment of C2C12 myotubes with laurel for 12 h inhibited the DEX-induced expression of intracellular ubiquitin ligases-muscle atrophy F-box (atrogin-1/MAFbx) and muscle RING finger 1 (MuRF1)-and reduction in myotube diameter. Male Wistar rats were supplemented with 2% laurel for 17 days, with DEX-induced skeletal muscle atrophy occurring in the last 3 days. Laurel supplementation inhibited the mRNA expression of MuRF1, regulated DNA damage and development 1 (Redd1), and forkhead box class O 1 (Foxo1) in the muscles of rats. Mechanistically, we evaluated the effects of laurel on the cellular proteolysis machinery-namely, the ubiquitin/proteasome system and autophagy-and the mTOR signaling pathway, which regulates protein synthesis. These data indicated that the amelioration of DEX-induced skeletal muscle atrophy induced by laurel, is mainly mediated by the transcriptional inhibition of downstream factors of the ubiquitin-proteasome system. Thus, laurel may be a potential food ingredient that prevents muscle atrophy.