Metabolic regulation of longevity and immune response in Caenorhabditis elegans by ingestion of Lacticaseibacillus rhamnosus IDCC 3201 using multi-omics analysis.

Probiotics, specifically Lacticaseibacillus rhamnosus, have garnered attention for their potential health benefits. This study focuses on evaluating the probiotics properties of candidate probiotics L. rhamnosus IDCC 3201 (3201) using the Caenorhabditis elegans surrogate animal model, a well-established in vivo system for studying host-bacteria interactions. The adhesive ability to the host's gastrointestinal tract is a crucial criterion for selecting potential probiotic bacteria. Our findings demonstrated that 3201 exhibits significantly higher adhesive capabilities compared with Escherichia coli OP50 (OP50), a standard laboratory food source for C. elegans and is comparable with the widely recognized probiotic L. rhamnosus GG (LGG). In lifespan assay, 3201 significantly increased the longevity of C. elegans compared with OP50. In addition, preconditioning with 3201 enhanced C. elegans immune response against four different foodborne pathogenic bacteria. To uncover the molecular basis of these effects, transcriptome analysis elucidated that 3201 modulates specific gene expression related to the innate immune response in C. elegans. C-type lectin-related genes and lysozyme-related genes, crucial components of the immune system, showed significant upregulation after feeding 3201 compared with OP50. These results suggested that preconditioning with 3201 may enhance the immune response against pathogens. Metabolome analysis revealed increased levels of fumaric acid and succinic acid, metabolites of the citric acid cycle, in C. elegans fed with 3201 compared with OP50. Furthermore, there was an increase in the levels of lactic acid, a well-known antimicrobial compound. This rise in lactic acid levels may have contributed to the robust defense mechanisms against pathogens. In conclusion, this study demonstrated the probiotic properties of the candidate probiotic L. rhamnosus IDCC 3201 by using multi-omics analysis.

Molecular characterization and environmental impact of newly isolated lytic phage SLAM_phiST1N3 in the Cornellvirus genus for biocontrol of a multidrug-resistant Salmonella Typhimurium in the swine industry chain.

Salmonella Typhimurium is a highly lethal pathogenic bacterium in weaned piglets, causing significant treatment costs and economic losses in the swine industry. Additionally, due to its ability to induce zoonotic diseases, resulting in harm to humans through the transmission of the pathogen from pork, it presents a serious public health issue. Bacteriophages (phages), viruses that infect specific bacterial strains, have been proposed as an alternative to antibiotics for controlling pathogenic bacteria. In this study, we isolated SLAM_phiST1N3, a phage infecting a multidrug-resistant (MDR) S. Typhimurium wild-type strain isolated from diseased pigs. First, comparative genomics and phylogenetic analysis revealed that SLAM_phiST1N3 belongs to the Cornellvirus genus. Moreover, utilizing a novel classification approach introduced in this study, SLAM_phiST1N3 was classified at the species level. Host range experiments demonstrated that SLAM_phiST1N3 did not infect other pathogenic bacteria or probiotics derived from pigs or other livestock. While complete eradication of Salmonella was not achievable in the liquid inhibition assay, surprisingly, we succeeded in largely eliminating Salmonella in the FIMM analysis, a gut simulation system using weaned piglet feces. Furthermore, using the C. elegans model, we showcased the potential of SLAM_phiST1N3 to prevent S. Typhimurium infection in living organisms. In addition, it was confirmed that bacterial control could be achieved when phage was applied to Salmonella-contaminated pork. pH and temperature stability experiments demonstrated that SLAM_phiST1N3 can endure swine industry processes and digestive conditions. In conclusion, SLAM_phiST1N3 demonstrates potential environmental impact as a substance for Salmonella prevention across various aspects of the swine industry chain.

Molecular characterization of Fusarium venenatum-based microbial protein in animal models of obesity using multi-omics analysis.

Microbial protein, produced by fermentation of Fusarium venenatum is a promising candidate alternative protein source. Previous study has demonstrated its ability to improve hyperlipidemia in rats, yet the related mechanism remains unclear. In this study, we aimed to evaluate the potential of F. venenatum as an alternative protein source and its impact on lipid metabolism using multi-omics analysis. Initial experiments with Caenorhabditis elegans revealed that F. venenatum enhanced longevity, improved immune responses, and reduced lipid metabolism by downregulating fat synthesis-related genes. Subsequently, we conducted experiments with mice on a high-fat diet to confirm the anti-obesity effects of F. venenatum. The groups fed F. venenatum showed improved lipid profiles and reduced hepatic fat accumulation. Furthermore, fecal metabolomic analysis showed higher excretion of primary bile acid and cholesterol in the groups fed F. venenatum which might lead to a decrease in lipid digestion and hepatic fat accumulation. Collectively, this series of experiments revealed the potential of F. venenatum as a sustainable alternative protein and its application as an anti-obesity supplement.

A postoperative in-hospital mortality risk model for elderly patients undergoing cardiac valvular surgery based on LASSO-logistic regression / 中国胸心血管外科临床杂志

@#Objective     To evaluate the risk factors for postoperative in-hospital mortality in elderly patients receiving cardiac valvular surgery, and develop a new prediction models using the least absolute shrinkage and selection operator (LASSO)-logistic regression. Methods     The patients≥65 years who underwent cardiac valvular surgery from 2016 to 2018 were collected from the Chinese Cardiac Surgery Registry (CCSR). The patients who received the surgery from January 2016 to June 2018 were allocated to a training set, and the patients who received the surgery from July to December 2018 were allocated to a testing set. The risk factors for postoperative mortality were analyzed and a LASSO-logistic regression prediction model was developed and compared with the EuroSCOREⅡ. Results     A total of 7 163 patients were collected in this study, including 3 939 males and 3 224 females, with a mean age of 69.8±4.5 years. There were 5 774 patients in the training set and 1 389 patients in the testing set. Overall, the in-hospital mortality was 4.0% (290/7 163). The final LASSO-logistic regression model included 7 risk factors: age, preoperative left ventricular ejection fraction, combined coronary artery bypass grafting, creatinine clearance rate, cardiopulmonary bypass time, New York Heart Association cardiac classification. LASSO-logistic regression had a satisfying discrimination and calibration in both training [area under the curve (AUC)=0.785, 0.627] and testing cohorts (AUC=0.739, 0.642), which was superior to EuroSCOREⅡ. Conclusion     The mortality rate for elderly patients undergoing cardiac valvular surgery is relatively high. LASSO-logistic regression model can predict the risk of in-hospital mortality in elderly patients receiving cardiac valvular surgery.

Alleviation of DSS-induced colitis via bovine colostrum-derived extracellular vesicles with microRNA let-7a-5p is mediated by regulating Akkermansia and ß-hydroxybutyrate in gut environments.

IMPORTANCE: Even though studying on the possible involvement of extracellular vesicles (EVs) in host-microbe interactions, how these relationships mediate host physiology has not clarified yet. Our current findings provide insights into the encouraging benefits of dietary source-derived EVs and microRNAs (miRNAs) on organic acid production and ultimately stimulating gut microbiome for human health, suggesting that supplementation of dietary colostrum EVs and miRNAs is a novel preventive strategy for the treatment of inflammatory bowel disease.

Remote Perimetry in a Virtual Reality Metaverse Environment for Out-of-Hospital Functional Eye Screening Compared Against the Gold Standard Humphrey Visual Fields Perimeter: Proof-of-Concept Pilot Study.

BACKGROUND: The growing global burden of visual impairment necessitates better population eye screening for early detection of eye diseases. However, accessibility to testing is often limited and centralized at in-hospital settings. Furthermore, many eye screening programs were disrupted by the COVID-19 pandemic, presenting an urgent need for out-of-hospital solutions. OBJECTIVE: This study investigates the performance of a novel remote perimetry application designed in a virtual reality metaverse environment to enable functional testing in community-based and primary care settings. METHODS: This was a prospective observational study investigating the performance of a novel remote perimetry solution in comparison with the gold standard Humphrey visual field (HVF) perimeter. Subjects received a comprehensive ophthalmologic assessment, HVF perimetry, and remote perimetry testing. The primary outcome measure was the agreement in the classification of overall perimetry result normality by the HVF (Swedish interactive threshold algorithm-fast) and testing with the novel algorithm. Secondary outcome measures included concordance of individual testing points and perimetry topographic maps. RESULTS: We recruited 10 subjects with an average age of 59.6 (range 28-81) years. Of these, 7 (70%) were male and 3 (30%) were female. The agreement in the classification of overall perimetry results was high (9/10, 90%). The pointwise concordance in the automated classification of individual test points was 83.3% (8.2%; range 75%-100%). In addition, there was good perimetry topographic concordance with the HVF in all subjects. CONCLUSIONS: Remote perimetry in a metaverse environment had good concordance with gold standard perimetry using the HVF and could potentially avail functional eye screening in out-of-hospital settings.

The colonic metabolism differences of main alkaloids in normal and colitis mice treated with Coptis chinensis Franch. and Sophora flavescens Ait. herbal pair using liquid chromatography-high resolution mass spectrometry method combined with chemometrics.

Coptis chinensis Franch. and Sophora flavescens Ait. is a herbal pair frequently used in treating ulcerative colitis. However, the bio-disposition profile of the major components in the inflamed gut remains unclear, which is essential to understand the pharmacological material basis of this herb pair. Here we established an integral quantitative and chemometric method to deduce the colonic metabolism differences of this herbal pair in normal and colitis mice. With this LC-MS method, a total of 41 components have been found in the Coptis chinensis Franch. and Sophora flavescens Ait. extract, and 28 metabolites were found in the colon after oral administration. Alkaloid and its phase I metabolites were the main components in the colon of normal and colitis mice. The results of principal component analysis at 6 h after oral administration showed significant colonic metabolism differences between normal and colitis mice. Heamap results showed that colitis induced significant changes in the colonic bio-disposition of this herbal pair extract. In particular, in the context of colitis, the phase I metabolism of berberine, coptisine, jatrorrhizine, palmatine,and epiberberine has been inhibited. These results may provide a basis for understanding the pharmacological material basis of Coptis chinensis Franch. and Sophora flavescens Ait. in treating ulcerative colitis.

Subvacuum environment-enhanced cell migration promotes wound healing without increasing hypertrophic scars caused by excessive cell proliferation.

Cell migration and proliferation are conducive to wound healing; however, regulating cell proliferation remains challenging, and excessive proliferation is an important cause of scar hyperplasia. Here, we aimed to explore how a subvacuum environment promotes wound epithelisation without affecting scar hyperplasia. Human immortalized keratinocyte cells and human skin fibroblasts were cultured under subvacuum conditions (1/10 atmospheric pressure), and changes in cell proliferation and migration, target protein content, calcium influx, and cytoskeleton and membrane fluidity were observed. Mechanical calcium (Ca2+ ) channel blockers were used to prevent Ca2+ influx for reverse validation. A rat wound model was used to elucidate the mechanism of the subvacuum dressing in promoting healing. The subvacuum environment was observed to promote cell migration without affecting cell proliferation; intracellular Ca2+ concentrations and PI3K, p-PI3K, AKT1, p-AKT 1 levels increased significantly. The cytoskeleton was depolymerized, pseudopodia were reduced or absent, and membrane fluidity increased. The use of Ca2+ channel blockers weakened or eliminated these changes. Animal experiments confirmed these phenomena and demonstrated that subvacuum dressings can effectively promote wound epithelisation. Our study demonstrates that the use of subvacuum dressings can enhance cell migration without affecting cell proliferation, promote wound healing, and decrease the probability of scar hyperplasia.

Integration of LC-LTQ-Orbitrap-MS and Network Pharmacology to Analyze the Active Components of Sijunzi Decoction and their Mechanism of Action Against Cytotoxicity-associated Premature Ovarian Insufficiency.

INTRODUCTION: Sijunzi Decoction (SJZD) is a classical prescription in traditional Chinese medicine that enhances neuroimmune endocrine function to alleviate inflammatory aging, a key pathogenic mechanism underlying premature ovarian insufficiency (POI). However, the mechanism through which SJZD alleviates POI remains unknown. Hence, we aimed to identify the active components of SJZD and its mechanism of therapeutic action against POI. METHODS: We identified compounds in SJZD using liquid chromatography-linear trap quadrupole- Orbitrap-mass spectrometry (LC-LTQ-Orbitrap-MS). Traditional Chinese Medicine Systems (TCMSP) and HERB databases were used to identify the ingredients and potential targets of SJZD. We analyzed Gene Ontology (GO) terms and enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using RStudio and constructed a visual network using Cytoscape3.9.1. RESULTS: We identified 98 compounds using LC-LTQ-Orbitrap-MS, among which 29 were bioactive. The screen outputted yielded 151 predicted targets of these compounds that were associated with POI. The results of the GO and KEGG analyses showed that these compounds play key roles in cell growth, division, migration, and survival signaling pathways. Therefore, phosphatidylinositol 3-kinase (PI3K)/AKT, mitogen-activated protein kinase (MAPK), and epidermal growth factor receptor (EGFR) pathways might be closely associated with the pharmacological effects of SJZD on the pathological processes of POI. CONCLUSION: Our findings provide a scientific basis for rapidly analyzing bioactive compounds in SJZD and their pharmacological mechanisms.

Omicron variants breakthrough infection elicited higher specific memory immunity than third dose booster in healthy vaccinees.

Homologous booster, heterologous booster, and Omicron variants breakthrough infection (OBI) could improve the humoral immunity against Omicron variants. Questions concerning about memory B cells (MBCs) and T cells immunity against Omicron variants, features of long-term immunity, after booster and OBI, needs to be explored. Here, comparative analysis demonstrate antibody and T cell immunity against ancestral strain, Delta and Omicron variants in Omicron breakthrough infected patients (OBIPs) are comparable to that in Ad5-nCoV boosted healthy volunteers (HVs), higher than that in inactivated vaccine (InV) boosted HVs. However, memory B cells (MBCs) immunity against Omicron variants was highest in OBIPs, followed by Ad5-nCoV boosted and InV boosted HVs. OBIPs and Ad5-nCoV boosted HVs have higher classical MBCs and activated MBCs, and lower naïve MBCs and atypical MBCs relative to both vaccine boosted HVs. Collectively, these data indicate Omicron breakthrough infection elicit higher MBCs and T cells against SARS-CoV-2 especially Omicron variants relative to homologous InV booster and heterologous Ad5-nCoV booster.

Platycodon grandiflorus root extract activates hepatic PI3K/PIP3/Akt insulin signaling by enriching gut Akkermansia muciniphila in high fat diet fed mice.

BACKGROUND: Increasing hepatic insulin signaling is found to be an important mechanism of Platycodon grandiflorus root to alleviate metabolic syndrome (MetS) symptoms such as insulin resistance, obesity, hyperlipidemia and hepatic steatosis, but the details are not yet clear. Since the main constituents of Platycodon grandiflorus root were hard to be absorbed by gastrointestinal tract, getting opportunity to interact with gut microbiota, we speculate the gut microorganisms may mediate its effect. PURPOSE: Our work aimed to confirm the critical role of gut microbes in the intervention of Platycodon grandiflorus root extract (PRE) on MetS, and investigate the mechanism. METHODS: Biochemical analyses, glucose tolerance test and hepatic lipidomics analysis were used to evaluate the anti-MetS effect of PRE on high fat diet (HFD) fed mice. Perform 16S rDNA analysis, qPCR analysis and in vitro co-incubation experiment to study its effect on gut microbes, followed by fecal microbiota transplantation (FMT) experiment and antibiotics intervention experiment. Also, the effect of Akkermansia muciniphila treatment on HFD mice was investigated. RESULTS: PRE alleviated lipid accumulation and insulin resistance in HFD mice and remodeled the fecal microbiome. It also increased the gene expression of colonic tight junction proteins, alleviated metabolic endotoxemia and inflammation, so that reduced TNF-α induced hepatic JNK-dependent IRS-1 serine phosphorylation and the impairment of PI3K/PIP3/Akt insulin signaling pathway. A. muciniphila was one of the most significantly enriched microbes by PRE treatment, and its administration to HFD mice showed similar effects to PRE, repairing the gut barrier and activating hepatic PI3K/PIP3/Akt pathway. Finally, anti-MetS effect of PRE could be delivered to FMT recipients, and PRE could not further attenuate MetS in gut microbiota depleted mice. CONCLUSION: We demonstrated for the first time that PRE alleviated MetS in a gut microbiota dependent manner, and found activation of hepatic insulin signaling mediated by gut A. muciniphila was a potential mechanism of it.

Non-targeted characteristic filter analysis combined with in silico prediction strategies to identify the chemical components and in vivo metabolites of Dalitong Granules by UPLC-Q-TOF/MS/MS.

Dalitong Granules, a potent gastrointestinal motility promoting traditional Chinese medicine, is used to treat functional dyspepsia clinically. It shows good effect on alleviating gastrointestinal motility disorders and has a broad prospect of clinical application. However, there is no comprehensive study on its in vivo and in vitro chemical analysis. UPLC-Q-TOF-MS combined with the non-targeted characteristic filter analysis and in silico prediction strategies (NCFS) were used to deduce and identify the chemical components and in vivo metabolites in the bio-samples of rats following oral administration of Dalitong Granules. In this study, 108 chemical components were identified in Dalitong granules, including 50 flavonoids, 22 alkaloids, 13 terpenes, 11 organic acids, 10 coumarins and 2 volatile oils. In the plasma, tissue, urine and fecal samples of rats after administration of Dalitong granules, a total of 147 compounds were speculated (60 prototype compounds and 87 metabolites). The main metabolic pathways in vivo include methylation, demethylation, deglycosylation, hydrogenation, hydroxylation, sulfonation and glucuronidation as there are many flavonoids existing in Dalitong Granules. In conclusion, the chemical components and metabolites of Dalitong Granules were comprehensively identified by using a rapid and accurate analysis method, which laid a foundation for dissecting its bioactive substances. In addition, it provides a scientific basis for the in-depth study of the material basis of Dalitong Granules efficacy and its further comprehensive development and utilization.

Ad5-nCoV booster and Omicron variant breakthrough infection following two doses of inactivated vaccine elicit comparable antibody levels against Omicron variants.

Little information is available for antibody levels against SARS-CoV-2 variants of concern induced by Omicron breakthrough infection and a third booster with an inactivated vaccine (InV) or Ad5-nCoV in people with completion of two InV doses. Plasma was collected from InV pre-vaccinated Omicron-infected patients (OIPs), unvaccinated OIPs between 0 and 22 days, and healthy donors (HDs) 14 days or 6 months after the second doses of an InV and 14 days after a homogenous booster or heterologous booster of Ad5-nCoV. Anti-Wuhan-, Anti-Delta-, and Anti-Omicron-receptor binding domain (RBD)-IgG titers were detected using enzyme-linked immunosorbent assay. InV pre-vaccinated OIPs had higher anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers compared to unvaccinated OIPs. Anti-Wuhan-RBD-IgG titers sharply increased in InV pre-vaccinated OIPs 0-5 days postinfection (DPI), while the geometric mean titers (GMTs) of anti-Delta- and anti-Omicron-RBD-IgG were 3.3-fold and 12.0-fold lower. Then, the GMT of anti-Delta- and anti-Omicron-RBD-IgG increased to 35 112 and 28 186 during 11-22 DPI, about 2.6-fold and 3.2-fold lower, respectively, than the anti-Wuhan-RBD-IgG titer. The anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers declined over time in HDs after two doses of an InV, with 25.2-fold, 5.6-fold, and 4.5-fold declination, respectively, at 6 months relative to the titers at 14 days after the second vaccination. Anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers elicited by a heterologous Ad5-nCoV booster were significantly higher than those elicited by an InV booster, comparable to those in InV pre-vaccinated OIPs. InV and Ad5-nCoV boosters could improve humoral immunity against Omicron variants. Of these, the Ad5-nCoV booster is a better alternative.

A Case Report of Fabry Disease Associated with Dermatomyositis / 罕见病研究

Fabry disease is an X-linked lysosomal storage disease, and its pathogenesis is the deficient of α-galactosidase A (α-Gal A) activity caused by GLA mutation, which leads to accumulation of the glycosphingolipid globotriaosylceramide (Gb-3) and other glycosphingolipids in the lysosome of cells, resulting in the dysfunction of relevant tissues and organs. We report the clinical characteristics of a case of Fabry disease with dermatomyositis. The patient, a 61-year-old male, presented with intermittent amaurosis, limb weakness and dyspnea on exertion. Based on the low α-Gal A activity and positive anti-myositis antibodies, diagnosis of Fabry disease with dermatomyositis were confirmed. We reviewed the relevant literature and found that co-existence of Fabry disease and autoimmune diseases was very rare, but it is not rare for patients with Fabry disease to have some autoimmune antibody positive, suggesting that Fabry disease and autoimmune diseases may be related in pathogenesis.

Case Report: Left bundle branch pacing in an amyloid light-chain cardiac amyloidosis patient with atrioventricular block.

Introduction: Amyloid light-chain cardiac amyloidosis is a progressive infiltrative disease characterized by the deposition of amyloid fibrils in the cardiac tissue, which can cause serious atrioventricular block requiring pacemaker implantation. Left bundle branch pacing has emerged as an alternative method for delivering physiological pacing to achieve electrical synchrony of the left ventricle. However, left bundle branch pacing in patients with amyloid light-chain cardiac amyloidosis has not been studied in detail. Therefore, in this study, we present a case of left bundle branch pacing in a patient with amyloid light-chain cardiac amyloidosis. Case summary: A 66-year-old male patient with amyloid light-chain cardiac amyloidosis presented with syncope for 1 month. Holter monitoring revealed intermittent third-degree atrioventricular block. Left bundle branch pacing was performed successfully. During the 1-year follow-up, it was observed that the left bundle branch capture threshold remained stable without any pacemaker-related complications or left ventricle systolic dysfunction, and there was no recurrence of syncope. Conclusion: Left bundle branch pacing appears to be a safe and feasible option for patients with amyloid light-chain cardiac amyloidosis experiencing atrioventricular block.

Molecular characterization of gut microbiome in weaning pigs supplemented with multi-strain probiotics using metagenomic, culturomic, and metabolomic approaches.

BACKGROUND: Probiotics have been reported to exhibit positive effects on host health, including improved intestinal barrier function, preventing pathogenic infection, and promoting nutrient digestion efficiency. These internal changes are reflected to the fecal microbiota composition and, bacterial metabolites production. In accordance, the application of probiotics has been broadened to industrial animals, including swine, which makes people to pursue better knowledge of the correlation between changes in the fecal microbiota and metabolites. Therefore, this study evaluated the effect of multi-strain probiotics (MSP) supplementation to piglets utilizing multiomics analytical approaches including metagenomics, culturomics, and metabolomics. RESULTS: Six-week-old piglets were supplemented with MSP composed of Lactobacillus isolated from the feces of healthy piglets. To examine the effect of MSP supplement, piglets of the same age were selected and divided into two groups; one with MSP supplement (MSP group) and the other one without MSP supplement (Control group). MSP feeding altered the composition of the fecal microbiota, as demonstrated by metagenomics analysis. The abundance of commensal Lactobacillus was increased by 2.39%, while Clostridium was decreased, which revealed the similar pattern to the culturomic approach. Next, we investigated the microbial metabolite profiles, specifically SCFAs using HPLC-MS/MS and others using GC-MS, respectively. MSP supplement elevated the abundance of amino acids, including valine, isoleucine and proline as well as the concentration of acetic acid. According to the correlation analyses, these alterations were found out to be crucial in energy synthesizing metabolism, such as branched-chain amino acid (BCAA) metabolism and coenzyme A biosynthesis. Furthermore, we isolated commensal Lactobacillus strains enriched by MSP supplement, and analyzed the metabolites and evaluated the functional improvement, related to tight junction from intestinal porcine enterocyte cell line (IPEC-J2). CONCLUSIONS: In conclusion, MSP administration to piglets altered their fecal microbiota, by enriching commensal Lactobacillus strains. This change contributed amino acid, acetic acid, and BCAA concentrations to be increased, and energy metabolism pathway was also increased at in vivo and in vitro. These changes produced by MSP supplement suggests the correlation between the various physiological energy metabolism functions induced by health-promoting Lactobacillus and the growth performance of piglets.

Culturomic-, metagenomic-, and transcriptomic-based characterization of commensal lactic acid bacteria isolated from domestic dogs using Caenorhabditis elegans as a model for aging.

In tandem with the fast expansion of the pet-economy industry, the present aging research has been noticing the function of probiotics in extending the healthy lifetime of domestic animals. In this study, we aimed to understand the bacterial compositions of canine feces and isolating lactic acid bacteria (LAB) as commensal LAB as novel potential probiotics for the use of antiaging using Caenorhabditis elegans surrogate animal model. Under an anaerobic, culturomic, and metagenomic analysis, a total of 305 commensal LAB were isolated from diverse domestic dogs, and four strains, Lactobacillus amylolyticus, L. salivarius, Enterococcus hirae, and E. faecium, made prominence as commensal LAB by enhancing C. elegans life span and restored neuronal degeneration induced by aging by upregulating skn-1, ser-7, and odr-3, 7, 10. Importantly, whole transcriptome results and integrative network analysis revealed extensive mRNA encoding protein domains and functional pathways of naturally aging C. elegans were examined and we built the gene informatics basis. Taken together, our findings proposed that a specific gene network corresponding to the pathways differentially expressed during the aging and selected commensal LAB as potential probiotic strains could be provided beneficial effects in the aging of domestic animals by modulating the dynamics of gut microbiota.

In tandem with the fast expansion of the pet-economy industry, the present aging research has been noticing the function of probiotics in extending the healthy lifetime of domestic animals. In this study, collaborating with understanding the characteristics of gut microbiome from canine feces by multiomics approaches including culturomics, metagenomics, and transcriptomics, we isolate and identify commensal lactic acid bacteria (LAB) as novel potential probiotics for the use of antiaging using Caenorhabditis elegans surrogate animal model and multiomics analysis. The selected commensal LAB could be provided beneficial effects in the aging of domestic animals by modulating the dynamics of gut microbiome and applied in the future companion animal market by clarifying their purpose and function.

Homeostatic regulation of the aryl hydrocarbon receptor-cytochrome P450 1a axis by Scutellaria baicalensis-Coptis chinensis herb pair and its main constituents.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis (SB) and Coptis chinensis (CC) are widely used traditional Chinese medicine (TCM) for "heat-clearing and damp-drying" and "purging fire and detoxifying". SB-CC are commonly used as a herbal pair for synergistic treatment of various diseases such as bacteria-related infections, metabolic syndromes, and some inflammatory disorders. This herbal pair is commonly used in many famous TCM formula, like Huang-Lian-Jie-Du, Gegen-Qinlian, Banxia Xiexin decoction. Aryl hydrocarbon receptor (AHR) plays an essential role in the disposition of both xenobiotics and endogenous substances through the induction of cytochrome P450 1A (CYP1A) enzymes. Regulation of the AHR-CYP1A axis is increasingly implicated in drug-drug and drug-herb interactions. Research on SB-CC for regulatory effect on the AHR-CYP1A axis is only limited to few compounds. AIM OF THE STUDY: This study aimed to systematically investigate the regulatory effect of SB-CC and its main constitutes on the AHR-CYP1A axis in vitro and in vivo. MATERIALS AND METHODS: The livers of mice treated with SB-CC extract were subjected to RNA-sequencing (RNA-seq). The key target genes related to drug metabolism were screened, and the differential expression genes (DEGs) were validated by qRT-PCR, Western blot, and enzyme activity assay. Luciferase reporter gene, qRT-PCR, and Western blot assays were used to determine whether SB-CC and their main constituents could activate AHR and regulate CYP1A expression in HepG2 cells. The effect of SB-CC on the pharmacokinetics of phenacetin, a CYP1A substrate, were further observed in mice to test the net effect of SB-CC on CYP1A functions. The potential CYP1A inhibitors in SB-CC were screened and their inhibitory mechanisms were also studied using human liver microsomes. RESULTS: AHR and drug metabolism system, especially CYP1A1 and CYP1A2, were strongly affected in the liver of SB-CC-treated mice. These results were further validated by the findings that SB-CC increased CYP1A's mRNA, protein expression and activity in mouse liver. In HepG2 cells, SB, CC, baicalin, baicalein, chrysin, oroxylin A, berberine, coptisine and epiberberine increased CYP1A1 mRNA expression in an AHR-dependent way. Interestingly, SB-CC treatment for 14 days only slightly increased the systemic exposure of paracetamol in mice. In the CYP1A inhibition assay, SB, CC, baicalin, baicalein, wogonoside, wogonin, chrysin, oroxylin A, scutellarein, columbamine, coptisine, palmatine, epiberberine, and berberrubine inhibited CYP1A activity in different degree. CONCLUSIONS: These results suggested that SB-CC exerted dual regulatory effect on the AHR-CYP1A axis by increasing CYP1A expression but simultaneously inhibiting CYP1A activity, which may contribute to a tight modulation of AHR signaling for homeostatic control.

Sesquiterpene lactones-rich fraction from Aucklandia lappa Decne. alleviates dextran sulfate sodium induced ulcerative colitis through co-regulating MAPK and Nrf2/Hmox-1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Aucklandia lappa Decne. (ALDE) is the general name for Asteraceae plants Yunmuxiang, which has traditionally been proven to have the efficacy in relieving depression by regulating qi, alleviating cold by warming, attenuating pain in stomach and relieving diarrhea in intestines. Therefore, ALDE is always recommended as an herbal remedy for gastrointestinal dysfunction. AIM OF THE STUDY: The purpose of this study was to explore the therapeutic potential and mechanism of action of the sesquiterpene lactone-rich fraction (SLRF) of ALDE extracts in vivo and in vitro. MATERIALS AND METHODS: An aqueous extract (AE) and SLRF of ALDE were prepared and the contents of the main components were quantified by high performance liquid chromatography (HPLC). The therapeutic effects of the extracts were evaluated in C57BL/6 mice with dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). Body weight, disease activity index (DAI), and colon length were recorded, and histopathological changes in the colon were characterized using hematoxylin and eosin (H&E) staining. The in vitro anti-inflammatory activity and possible mechanisms of the two main sesquiterpene lactones in ALDE (costunolide and dehydrocostus lactone) were studied by quantitative proteomic analysis. Finally, based on bioinformatic analysis, we used polymerase chain reaction (PCR), immunofluorescence, and western blot experiments to verify the anti-inflammatory mechanism of the extracts in C57BL/6 mice. RESULTS: The SLRF of ALDE significantly improved the pathological symptoms and inflammatory pathology of UC, whereas the AE had a weak protective effect. In RAW264.7 cells stimulated with lipopolysaccharide (LPS), costunolide and dehydrocostus lactone significantly reduced the mRNA levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, suggesting that these two sesquiterpene lactones had strong anti-inflammatory activity. Quantitative proteomics results indicated that the anti-inflammatory mechanism of these lactones was associated with the NF-κB/MAPK and Nrf2-Hmox-1 pathways. These results were further validated in SLRF-treated mice. CONCLUSION: This study confirmed that the SLRF of ALDE exerted protective activity against UC by regulating the Nrf2-Hmox-1, NF-κB, and MAPK pathways.

Characterization of the chemical constituents and in vivo metabolic profile of Scutellaria barbata D. Don by ultra high performance liquid chromatography with high-resolution mass spectrometry.

Scutellaria barbata D. Don (S. barbata) is one of the most frequently used anticancer herb medicine in China. Mechanistic understanding of the biological activities of S. barbata is hindered by limited knowledge regarding its components and metabolic profile. In this study, ultra-high-performance liquid chromatography coupled with high resolution mass spectrometry (quadrupole time-of-flight mass spectrometry) was used to identify the chemical constituents in S. barbata and their metabolic profiles in rats. By applying cleavage rules and comparison with reference substances, 89 components were identified in S. barbata, which included 45 flavonoids, 28 diterpenoids, 10 phenolics, and 6 others. A total of 110 compounds, including 32 prototype compounds and 78 metabolites, were identified or tentatively characterized in vivo. Methylation, sulfonation, and glucuronidation were the main metabolic pathways, which could be attributed to the fact that several of the compounds in S. barbata have phenolic hydroxyl groups. This is the first systematic study on the chemical constituents and in vivo metabolic profile of S. barbata. The analytical method features a quick and comprehensive dissection of the chemical composition and metabolic profile of S. barbata and provides a basis for exploring its various biological activities.