Mitigation of Dextran-Sodium-Sulfate-Induced Colitis in Mice through Oral Administration of Microbiome-Derived Inosine and Its Underlying Mechanisms.

BACKGROUND: Colonic and serum inosine are significantly reduced in patients with inflammatory bowel disease (IBD). METHODS: This study aimed to explore whether microbiome-derived inosine alleviates colitis and its underlying mechanisms. RESULTS: An inosine intervention effectively improved the clinical signs in colitis mice, suppressed inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1ß) by regulating the nuclear factor-kappa B (NF-κB) pathway, and elevated the activities of anti-oxidative enzymes (including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)) by regulating the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway. Additionally, the inosine intervention significantly elevated the expression of tight junction proteins (ZO-1, occudin, and claudin-1) in mice with colitis. High-throughput sequencing revealed that the inosine intervention also prevented gut microbiota disorder by increasing the abundance of beneficial bacteria (Lachnospiraceae NK4A136 group, Romboutsia, Marvinbryantia, Clostridium sensu stricto 1, and Bifidobacterium) and reducing the abundance of harmful bacteria (Pseudomonas, Acinetobacter, and Tyzzerella) in mice with colitis. CONCLUSIONS: Inosine played a significant role in mitigating colitis-related intestinal barrier injury and could potentially be used for therapy in clinical practice.

The Protective Effect of Broccoli Seed Extract against Lipopolysaccharide-Induced Acute Liver Injury via Gut Microbiota Modulation and Sulforaphane Production in Mice.

Broccoli seed extract (BSE) is rich in glucoraphanin (GRP), which may be transformed by intestinal microbes into sulforaphane (SFN), a compound with strong anti-inflammatory and antioxidant activities. Liver injury usually presents with inflammation and oxidative damage. Thus, dietary BSE supplementation may be an effective approach for alleviating liver injury. In this study, a mouse lipopolysaccharide (LPS)-induced acute liver injury model was used to evaluate the preventive effect of BSE and explore the relevant mechanisms. Compared with the LPS model group, the mice in the BSE group showed significantly lower activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) and higher levels of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity. Meanwhile, BSE significantly reduced the levels of pro-inflammatory cytokines (including IL-6 and TNF-α) in the liver and increased the level of anti-inflammatory factor (IL-10), indicating that BSE had a good preventive effect on acute liver injury. Additionally, after BSE intervention, the diversity of intestinal microbiota in the mice was higher than that in the LPS model group. The relative abundance of Akkermansia and Lactobacillus increased, while the relative abundance of Xylanophilum decreased. A correlation analysis revealed that the activities of SOD, GSH-Px, CAT and levels of IL-10 were positively correlated with the relative abundance of Lactobacillus. Furthermore, sulforaphane (SFN) and (Sulforaphane-N-Acetyl-Cysteine) SFN-NAC were detected in the urine of the mice after BSE intervention. Both q-PCR and an immunohistochemical analysis showed that BSE significantly regulated the expression level of the NF-κB (IκB-α, NF-κB) and Nrf2 (Nrf2, p-Nrf2 and HO-1) signaling pathways in the liver. In conclusion, BSE was shown to reduce LPS-induced acute liver injury through the conversion of glucoraphanin into sulforaphane and the regulation of the gut microbiota composition. These results suggest that BSE could be a promising ingredient in functional foods.

Protective Effects of Naringenin and Apigenin in Ameliorating Skin Damage via Mediating the Nrf2 and NF-κB Pathways in Mice.

Naringenin and apigenin are common flavonoids derived from edible plants with the potential to alleviate inflammation and improve skin antioxidation. This study aimed to evaluate the effects of naringenin and apigenin on oleic acid-induced skin damage in mice and compare their underlying mechanisms of action. Triglycerides and non-esterified fatty acids were significantly decreased by naringenin and apigenin, while apigenin intervention resulted in a better recovery of skin lesions. Naringenin and apigenin improved the antioxidative abilities of the skin by increasing catalase and total antioxidant capacity levels and decreasing malondialdehyde and lipid peroxide levels. The release of skin proinflammatory cytokines, such as interleukin (IL)-6, IL-1ß, and tumor necrosis factor α, was inhibited after naringenin and apigenin pretreatments, but naringenin only promoted the excretion of IL-10. Additionally, naringenin and apigenin regulated antioxidant defense and inflammatory response by activating nuclear factor erythroid-2 related factor 2-dependent mechanisms and suppressing the expression of nuclear factor-kappa B. In summary, naringenin and apigenin are prospective ingredients that contribute to the amelioration of skin damage by activating anti-inflammatory and antioxidative responses.

Lactobacillus reuteri CCFM1175 and Lactobacillus paracasei CCFM1176 Could Prevent Capsaicin-Induced Ileal and Colonic Injuries.

Capsaicin (CAP) is usually reported to have many biological activities. However, a large intake of CAP may cause heartburn, gastrointestinal pain, and diarrhea. In this study, mice were gavaged with nine lactic acid bacteria (LAB) strains for two weeks, in which the mice were treated with CAP at the second week and lasted for one week. We tried to identify potential probiotics that could prevent CAP-induced intestinal injury and investigate the mechanisms. The modulation of transient receptor potential vanilloid 1 (TRPV1), levels of short-chain fatty acids (SCFAs), and the composition of gut microbiota were analyzed. The results showed that Lactobacillus reuteri CCFM1175 and Lactobacillus paracasei CCFM1176 effectively attenuated CAP-induced injuries to the ileum and colon, including relieving the damage to colonic crypt structures, increasing the number of goblet cells, decreasing levels of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), increasing levels of anti-inflammatory factors (IL-10), and reducing levels of substance P (SP) and calcitonin gene-related peptide (CGRP) in serum and colon tissue. Further analysis showed that L. reuteri CCFM1175 increased the relative abundance of Ruminococcaceae UCG_014 and Akkermansia. L. paracasei CCFM1176 downregulated the expression of TRPV1 in the ileal and colonic tissues and promoted the relative abundance of Ruminococcaceae UCG_014 and Lachnospiraceae UCG_006. These results indicate that L. reuteri CCFM1175 and L. paracasei CCFM1176 could prevent CAP-induced intestinal injury and be used as probiotics to improve the gastrointestinal health.

Prognostic effect of preoperative Controlling Nutritional Status score in patients with locally advanced rectal cancer: A two-center, retrospective study.

OBJECTIVES: This study aimed to identify the prognosis relevant to the Controlling Nutritional Status (CONUT) score in locally advanced rectal cancer patients who were treated with neoadjuvant chemoradiotherapy before radical surgery. METHODS: From a retrospective database of 568 patients undergoing radical surgery for rectal cancer at two Chinese institutions between 2012 and 2022, data for 300 patients with locally advanced rectal cancer were identified. The optimal cutoff value for the CONUT score in predicting overall survival (OS) was determined using X-tile software. The associations of the CONUT score with the recurrent metastasis and clinicopathologic parameters were analyzed. The CONUT score's ability to predict OS was also compared with other prognostic markers. Univariate and multivariate Cox regression analysis for OS was performed. Subgroup analysis was conducted to evaluate further the CONUT score's predicting value. RESULTS: The optimal CONUT score cutoff value was determined as 5 according to X-tile. Patients were divided into CONUT-high (CONUT score ≥ 5) and CONUT-low (CONUT score < 5) groups. CONUT score is significantly correlated with hemoglobin, globulin, and platelets. Time-dependent receiver operating characteristic of the CONUT score predicting OS outperformed all common prognostic markers. Multivariate Cox regression analysis identified CONUT score as an independent prognostic factor for OS (hazard ratio = 5.701; 95% CI, 2.336-13.914; P < 0.001). In the subgroups of age, sex, carcinoembryonic antigen, ypTNM, and tumor response status, significant statistical differences can be observed between CONUT-high and -low. CONCLUSIONS: The present study finds that the preoperative CONUT score may be a useful prognostic indicator in clinical scenarios.

Intestinal microbiomics and hepatic metabolomics insights into the potential mechanisms of probiotic Bifidobacterium pseudolongum CCFM1253 preventing acute liver injury in mice.

BACKGROUND: Bifidobacterium pseudolongum is widely exists in mammal gut and its abundance is associated with human and animal health. The present study aimed to investigate the potential mechanisms of B. pseudolongum CCFM1253 on protecting against lipopolysaccharide (LPS)-induced acute liver injury (ALI) by metagenomic analysis and liver metabolomic profiles. RESULTS: Bifidobacterium pseudolongum CCFM1253 preintervention remarkably attenuated the influence of LPS on serum alanine transaminase and aspartate amino transferase activities. B. pseudolongum CCFM1253 preintervention remarkably attenuated the inflammation responses (tumor necrosis factor-α, interleukin-1ß, and interleukin-6) and elevated antioxidative enzymes activities [total antioxidant capacity, superoxide dismutase, catalase, and glutathione peroxidase] in ALI mice by intervening in the Nf-kß and Nrf2 pathways, respectively. Bifidobacterium pseudolongum CCFM1253 treatment elevated the proportion of Alistipes and Bifidobacterium, and decreased the proportion of uncultured Bacteroidales bacterium, Muribaculum, Parasutterella and Ruminococcaceae UCG-010 in ALI mice, which were strongly correlated with the inhibition of inflammation responses and oxidative stress. Untargeted liver metabolomics exhibited that the hepatoprotective efficacy of B. pseudolongum CCFM1253 might be achieved by altering liver metabolites-related riboflavin metabolism, phenylalanine metabolism, alanine, citrate cycle (tricarboxylic acid cycle), and so on. Furthermore, riboflavin exposure could control the contents of malondialdehyde, superoxide dismutase, and catalase in hydrogen peroxide-treated HepG2 cells. CONCLUSION: Bifidobacterium pseudolongum CCFM1253 can effectively alleviate inflammatory response and oxidative stress, and regulate the intestinal microbiota composition and liver metabolism, and elevate the liver riboflavin content in LPS-treated mice. Therefore, B. pseudolongum CCFM1253 could serves as a potential probiotic to ameliorate the host health. © 2023 Society of Chemical Industry.

Effects of individualized dietary counseling on nutritional status and quality of life in post-discharge patients after surgery for gastric cancer: A randomized clinical trial.

Background: Currently, the supporting evidence for dietary counseling is insufficient. The aim of this study is to evaluate the impact of individualized dietary counseling on nutritional outcomes and quality of life (QOL) in patients undergoing surgery for gastric cancer. Methods: This study was a prospective, single-center, randomized controlled trial. The patients after surgery for gastric cancer were randomly assigned (1:1) to the intervention group and the control group. In the intervention group, patients receive individualized dietary counseling based on individual calorie needs and symptom assessment at 24 h before discharge, 14, 21, 30, and 60 days postoperatively. Patients in the control group received routine dietary counseling. The primary endpoint was body mass index (BMI) loss at 30, 60, and 90 days after surgery; the secondary endpoints were calorie and protein intake at 30 and 60 days after surgery, blood parameters, the 90-day readmission rate, and QOL at 90 days after surgery. Results: One hundred thirty patients were enrolled; 67 patients were assigned to the intervention group and 63 patients to the control group. Compared with the control group, patients in the intervention group were significantly less BMI loss at 30 days (-0.84 ± 0.65 vs. -1.29 ± 0.83), 60 days (-1.29 ± 0.92 vs. -1.77 ± 1.13), and 90 days (-1.37 ± 1.05 vs. -1.92 ± 1.66) after surgery (all P< 0.05). Subgroups analysis by surgery type showed that the intervention could significantly reduce BMI loss in patients undergoing total and proximal gastrectomy at 30 days (-0.75 ± 0.47 vs. -1.55 ± 1.10), 60 days (-1.59 ± 1.02 vs. -2.55 ± 1.16), and 90 days (-1.44 ± 1.19 vs. -3.26 ± 1.46) after surgery (all P< 0.05). At 60 days after surgery, calorie goals were reached in 35 patients (77.8%) in the intervention group and 14 patients (40.0%) in the control group (P = 0.001), and protein goals were reached in 40 patients (88.9%) in the intervention group and 17 patients (48.6%) in the control group (P< 0.001). Regarding the QOL at 90 days after surgery, the patients in the intervention group had a significantly lower level of fatigue, shortness of breath and stomach pain, better physical function, and cognitive function (P< 0.05). Conclusions: Post-discharge individualized dietary counseling is an effective intervention to reduce post-gastrectomy patient weight loss and to elevate calorie intake, protein intake, and QOL.

Potential Probiotic Properties of Blautia producta Against Lipopolysaccharide-Induced Acute Liver Injury.

Blautia is a genus of anaerobic microbe extensively present in the intestine and feces of mammals. This study aims to investigate the influence of Blautia producta to prevent lipopolysaccharide (LPS)-induced acute liver injury (ALI) and elaborate on its hepatoprotective mechanisms. B. producta D4 and DSM2950 pretreatment decreased the activities of serum aspartate transferase (AST), and alanine transaminase (ALT) in mice with LPS treatment significantly decreased the levels of inflammatory tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) and increased the activities of antioxidative superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Compared with the model group, B. producta D4 and B. producta DSM2950 pretreatment slightly increased the levels of cecal propionic acid, isobutyric acid, butyric acid, valeric acid, and isovaleric acid (p > 0.05). Metagenomic analysis showed that B. producta D4 and DSM2950 pretreatment remarkably increased the relative abundance of [Eubacterium] xylanophilum group, Lachnospira, Ruminiclostridium, Ruminiclostridium 9, Coprococcus 2, Odoribacter, Roseburia, Alistipes, and Desulfovibrio in ALI mice, and their abundance is negatively related to the levels of inflammatory TNF-α, IL-1ß, and IL-6 as revealed by Spearman's correlation analysis. Moreover, transcription and immunohistochemistry analysis revealed that B. producta D4 and B. producta DSM2950 intervention remarkably suppressed the transcription and expression levels of hepatic Tlr4, MyD88, and caspase-3 (p < 0.05). These data indicated that B. producta may be a good candidate for probiotics in the prevention of ALI.

Absorption, metabolism, bioactivity, and biotransformation of epigallocatechin gallate.

Epigallocatechin gallate (EGCG), a typical flavone-3-ol polyphenol containing eight free hydroxyl groups, is associated with a variety of bioactivities, such as antioxidant, anti-inflammatory, anti-cancer, and antibacterial activities. However, the poor bioavailability of EGCG restricts its use. In this review, we discuss the processes involved in the absorption and metabolism of EGCG, with a focus on its metabolic interactions with the gut microbiota. Next, we summarize the bioactivities of some key metabolites, describe the biotransformation of EGCG by different microorganisms, and discuss its catabolism by specific bacteria. A deeper understanding of the absorption, metabolism, and biotransformation of EGCG may enable its disease-preventive and therapeutic properties to be better utilized. This review provides a theoretical basis for further development and utilization of EGCG and its metabolites for improving the gut microbiota and physiological health.

Bifidobacterium longum CCFM1206 Promotes the Biotransformation of Glucoraphanin to Sulforaphane That Contributes to Amelioration of Dextran-Sulfate-Sodium-Induced Colitis in Mice.

Glucoraphanin, rich in broccoli seed extract (BSE), is generally inert but can be biotransformed into active sulforaphane by gut bacteria. This study aimed to screen probiotics with glucoraphanin-metabolizing ability and explore the effect of a combination of strain and BSE on colitis induced by dextran sulfate sodium (DSS) in mice. Bifidobacterium longum CCFM1206 was isolated from healthy adult feces. Ultra-high-performance liquid chromatography Q Exactive mass spectrometry analysis revealed the presence of sulforaphane, sulforaphane-l-cysteine, and erucin in the BSE supernatant fermented by B. longum CCFM1206 in vitro. Combined and individual interventions of BSE and B. longum CCFM1206 were applied to explore the effects on DSS-induced colitis. The results suggested that the combination of B. longum CCFM1206 and BSE could ameliorate colitis symptoms, relieve colonic inflammatory reactions and oxidative stress, and protect the intestinal barrier in DSS-induced mice. In comparison to the BSE intervention alone, the combined intervention of B. longum CCFM1206 and BSE promoted the generation of sulforaphane and sulforaphane-N-acetylcysteine in mice colon from 220.88 ± 19.81 to 333.99 ± 36.46 nmol/g and from 232.04 ± 26.48 to 297.50 ± 40.08 nmol/g dry weight feces, respectively. According to quantitative reverse transcription polymerase chain reaction and immunohistochemical analysis, B. longum CCFM1206 and BSE effectively activated the transcription and expression of genes related to the Nrf2 signaling pathway. These results were intended to elucidate that probiotics could elevate the bioactivity of dietary phytochemicals in vivo, and the combination had potential for therapeutic treatment of colitis.

Ellagic acid and intestinal microflora metabolite urolithin A: A review on its sources, metabolic distribution, health benefits, and biotransformation.

Foods rich in ellagic tannins are first hydrolyzed into ellagic acid in the stomach and small intestine, and then converted into urolithins with high bioavailability by the intestinal flora. Urolithin has beneficially biological effects, it can induce adipocyte browning, improve cholesterol metabolism, inhibit graft tumor growth, relieve inflammation, and downregulate neuronal amyloid protein formation via the ß3-AR/PKA/p38MAPK, ERK/AMPKα/SREBP1, PI3K/AKT/mTOR signaling pathways, and TLR4, AHR receptors. But differences have been reported in urolithin production capacity among different individuals. Thus, it is of great significance to explore the biological functions of urolithin, screen the strains responsible for biotransformation of urolithin, and explore the corresponding functional genes. Tannin acyl hydrolase can hydrolyze tannins into ellagic acid, and the genera Gordonibacter and Ellagibacter can metabolize ellagic acid into urolithins. Therefore, application of "single bacterium", "single bacterium + enzyme", and "microflora" can achieve biotransformation of urolithin A. In this review, the source and metabolic pathway of ellagic tannins, and the mechanisms of the biological function of a metabolite, urolithin A, are discussed. The current strategies of biotransformation to obtain urolithin A are expounded to provide ideas for further studies on the relationship between urolithin and human health.

Broccoli seed extract rich in polysaccharides and glucoraphanin ameliorates DSS-induced colitis via intestinal barrier protection and gut microbiota modulation in mice.

BACKGROUND: Broccoli has received widespread attention because of its anti-inflammatory and antioxidant effects. The present study aimed to explore the composition of broccoli seed extract (BSE) and its effect on colitis induced by dextran sulfate sodium (DSS). RESULTS: BSE mainly comprises glucoraphanin and polysaccharides composed of arabinose, galactose, glucose and mannose. Animal experiments suggested that BSE intervention effectively reversed body weight loss, suppressed the levels of proinflammatory interleukin-6, tumor necrosis factor-α and interleukin-1ß, and elevated the levels of anti-inflammatory interleukin-10 and the activities of superoxide dismutase and glutathione in DSS-induced colitis mice. According to histopathologic and immunohistochemical analysis of colon tissue, BSE intervention may repair the intestinal barrier by upregulating mRNA levels and the expression of tight junction proteins (claudin-1, occludin and zonula occludens-1). Gas chromatography-mass spectrometry (MS) analysis demonstrated that cecal short-chain fatty acids in mice with BSE administration were significantly increased compared with the model group. Sulforaphane and sulforaphane-N-acetylcysteine were only detected in BSE group mice by ultra-performance liquid chromatography-MS analysis. In addition, BSE intervention evidently increased the abundance of Alistipeds, Coriobacteriaceae UCG-002 and Bifidobacterium and decreased the abundance of Escheichia-Shinella, Lachnospiraceae others, Parabacteroides, Ruminococcaceae others and Turicibacter, which possibly promoted carbohydrate metabolism and short-chain fatty acid production. CONCLUSION: The present study aimed to elucidate the effect of BSE on colitis and found that BSE, as a novel food ingredient, has great potential for the improvement of colitis. © 2022 Society of Chemical Industry.

The preoperative geriatric nutritional risk index predicts long-term prognosis in elderly locally advanced rectal cancer patients: a two-center retrospective cohort study.

BACKGROUND: The objective is to explore the value of preoperative geriatric nutritional risk index (GNRI) in evaluating long-term prognosis in elderly locally advanced rectal cancer (LARC) patients who accepted neoadjuvant chemoradiotherapy (NCRT) and to compare GNRI with established nutritional markers, including prognostic nutritional index (PNI) and controlling nutritional status (CONUT) score. METHODS: Preoperative GNRI was retrospectively assessed in 172 LARC patients aged ≥ 60 years who underwent radical resection after NCRT at two centers. Optimal cutoff value of GNRI was determined by X-tile program. The association of GNRI with clinicopathological parameters and nutritional markers was analyzed. The survival ability of markers was evaluated using time-dependent receiver-operating characteristic (ROC) curve analysis. Finally, survival analysis was performed using Kaplan-Meier and Cox regression analysis. RESULTS: GNRI was highly correlated with nutritional markers. An optimal cutoff value for the GNRI was 96. In the time-dependent ROC curve, GNRI demonstrated a stable predictive ability for both disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed that GNRI was the only nutritional marker that independently predicted DFS (HR 2.457, 95% CI 1.066-5.665, P = 0.035) and OS (HR 9.002, 95% CI 3.100-26.146, P < 0.001). As an additional benefit, GNRI was able to stratify survival in subgroups of ypTNM and tumor response. CONCLUSION: Preoperative GNRI is a promising predictor of long-term survival for elderly LARC patients undergoing NCRT, superior to the established nutritional markers.

Cyanidin Alleviated CCl4-Induced Acute Liver Injury by Regulating the Nrf2 and NF-κB Signaling Pathways.

Acute liver injury has multiple causes and can result in liver failure. In this study, we evaluated the hepatoprotective ability of cyanidin (Cy) and investigated its associated mechanisms. Cy administration significantly and dose-dependently ameliorated acute liver injury induced by carbon tetrachloride (CCl4). High-dose Cy showed effects comparable to those achieved by the positive control (silymarin). Severe oxidative stress and inflammatory responses in the liver tissue induced by CCl4 were significantly mitigated by Cy supplementation. The total antioxidant capacity and the activity of superoxide dismutase, catalase, and glutathione peroxidase were increased and the content of malondialdehyde, lipid peroxide, tumor necrosis factor α, interleukin-1ß, and interleukin-6 were decreased. Additionally, the Nrf2 and NF-κB signaling pathways, which regulate antioxidative and inflammatory responses, were analyzed using quantitative real-time polymerase chain reaction and western blot assay. Cy treatment not only increased Nrf2 transcription and expression but also decreased NF-κB signaling. Moreover, molecular docking simulation indicated that Cy had high affinity for Keap1 and NF-κB/p65, which may promote nuclear translocation of Nrf2 and inhibit that of NF-κB. In summary, Cy treatment exerted antioxidative and anti-inflammatory effects and ameliorated liver injury by increasing Nrf2 and inhibiting the NF-κB pathway, demonstrating the potential of Cy as a therapeutic agent in liver injury.

Effect of Dual Trigger In Vitro Fertilization and Intracytoplasmic Sperm Injection During the Gonadotropin-releasing Hormone-Antagonist Cycle on Final Oocyte Maturation and Cumulative Live Birth Rate in Women with Diminished Ovarian Reserve.

OBJECTIVE: It is well known that a dual trigger treatment can improve clinical outcomes of in vitro fertilization (IVF) in high or normal ovarian responders. However, it is not clear whether dual triggering also benefits patients with diminished ovarian reserve (DOR). The aim of this study was to investigate whether a dual trigger treatment of gonadotropin-releasing hormone (GnRH) agonist combined with human chorionic gonadotropin (hCG) for final follicular maturation improves the cumulative live birth rate (CLBR) during the GnRH-antagonist cycle in patients with DOR. METHODS: This retrospective study included patients with DOR who received a GnRH-antagonist protocol during IVF and intracytoplasmic sperm injection (IVF-ICSI) cycles at Peking University People's Hospital from January 1, 2017 through December 31, 2017. Oocyte maturation was triggered by GnRH combined with hCG (n=110) or hCG alone (n=71). Embryos were transferred on the third day after oocyte retrieval or during a subsequent freeze-thaw cycle. Patients were followed up for 3 years. RESULTS: The dual trigger treatment did not affect CLBR, which is an overall determinant of the success rate of assisted reproductive technology (ART). Women in the dual trigger group had significantly higher rates of fertilization than those in the hCG group (90.1% vs. 83.9%, P=0.040). CONCLUSION: Dual trigger with GnRH agonist and hCG did not improve CLBR in patients with DOR, but did slightly improve fertilization rate, oocyte count, and embryo quality.

Lactobacillus paracasei CCFM1223 Protects against Lipopolysaccharide-Induced Acute Liver Injury in Mice by Regulating the "Gut-Liver" Axis.

BACKGROUND: Lactobacillus paracasei CCFM1223, a probiotic previously isolated from the healthy people's intestine, exerts the beneficial influence of preventing the development of inflammation. METHODS: The aim of this research was to explore the beneficial effects of L. paracasei CCFM1223 to prevent lipopolysaccharide (LPS)-induced acute liver injury (ALI) and elaborate on its hepatoprotective mechanisms. RESULTS: L. paracasei CCFM1223 pretreatment remarkably decreased the activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in mice with LPS treatment and remarkably recovered LPS-induced the changes in inflammatory cytokines (tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß), interleukin (IL)-1ß, IL-6, IL-17, IL-10, and LPS) and antioxidative enzymes activities (total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT)). Metagenomic analysis showed that L. paracasei CCFM1223 pretreatment remarkably increased the relative abundance of Catabacter compared with the LPS group but remarkably reduced the relative abundance of [Eubacterium] xylanophilumgroup, ASF356, LachnospiraceaeNK4A136group, and Lachnoclostridium, which is closely associated with the inflammation cytokines and antioxidative enzymes. Furthermore, L. paracasei CCFM1223 pretreatment remarkably increased the colonic, serum, and hepatic IL-22 levels in ALI mice. In addition, L. paracasei CCFM1223 pretreatment remarkably down-regulated the hepatic Tlr4 and Nf-kß transcriptions and significantly up-regulated the hepatic Tlr9, Tak1, Iκ-Bα, and Nrf2 transcriptions in ALI mice. CONCLUSIONS: L. paracasei CCFM1223 has a hepatoprotective function in ameliorating LPS-induced ALI by regulating the "gut-liver" axis.

Inosine Pretreatment Attenuates LPS-Induced Lung Injury through Regulating the TLR4/MyD88/NF-κB Signaling Pathway In Vivo.

Inosine is a type of purine nucleoside, which is considered to a physiological energy source, and exerts a widely range of anti-inflammatory efficacy. The TLR4/MyD88/NF-κB signaling pathway is essential for preventing host oxidative stresses and inflammation, and represents a promising target for host-directed strategies to improve some forms of disease-related inflammation. In the present study, the results showed that inosine pre-intervention significantly suppressed the pulmonary elevation of pro-inflammatory cytokines (including tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß)), malondialdehyde (MDA), nitric oxide (NO), and reactive oxygen species (ROS) levels, and restored the pulmonary catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and myeloperoxidase (MPO) activities (p < 0.05) in lipopolysaccharide (LPS)-treated mice. Simultaneously, inosine pre-intervention shifted the composition of the intestinal microbiota by decreasing the ratio of Firmicutes/Bacteroidetes, elevating the relative abundance of Tenericutes and Deferribacteres. Moreover, inosine pretreatment affected the TLR4/MyD88/NF-κB signaling pathway in the pulmonary inflammatory response, and then regulated the expression of pulmonary iNOS, COX2, Nrf2, HO-1, TNF-α, IL-1ß, and IL-6 levels. These findings suggest that oral administration of inosine pretreatment attenuates LPS-induced pulmonary inflammatory response by regulating the TLR4/MyD88/NF-κB signaling pathway, and ameliorates intestinal microbiota disorder.

Protective Effects of a Novel Probiotic Bifidobacterium pseudolongum on the Intestinal Barrier of Colitis Mice via Modulating the Pparγ/STAT3 Pathway and Intestinal Microbiota.

Colitis has become a major health concern worldwide. The objective of the present study was to determine the probiotic influence of different strains of B. pseudolongum (Bp7 and Bp8) on alleviating colitis and to explore its possible potential mechanisms. Our results displayed that Bp7 and Bp8 intervention effectively reduced dextran sodium sulfate (DSS)-caused body weight loss and the release of several pro-inflammatory factors (interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α)) and increased the activities of antioxidant enzymes (T-AOC, SOD, and GSH) and the concentrations of tight junction proteins (occludin, claudin-1, and ZO-1). Moreover, Bp7 and Bp8 intervention drastically down-regulated the expression of colonic MyD88, NF-κB, iNOS and COX2 and drastically elevated the expression of colonic STAT3, Nrf2, and PPARγ. Gas chromatography-mass spectrometry results revealed that the cecal levels of isobutyric, butyric, and isovaleric acids were drastically increased in colitis mice intervened with Bp7 and Bp8. Moreover, 16S rRNA sequencing revealed that Bp7 and Bp8 intervention modulated the intestinal microbiota structure, particularly by enhancing the proportion of Eubacterium coprostanoligenes group, Marvinbryantia, Enterorhabdus, Faecalibaculum, Coriobacteriaceae UCG 002, Alistipes, and Bifidobacterium, which are relevant to the levels of cecal isobutyric acid, butyric acid, isovaleric acid, and inflammatory cytokines. Collectively, these findings suggest that Bp7 and Bp8 intervention alleviates the intestinal barrier function, possibly by blocking the secretion of proinflammatory cytokines, maintaining the intestinal physical barrier integrity, activating the PPARγ/STAT3 pathway, and modulating intestinal microbiota composition. Our study also suggested that B. pseudolongum is a promising probiotic for colitis treatment.

Inhibitory effect of Lactobacillus gasseri CCFM1201 on Gardnerella vaginalis in mice with bacterial vaginosis.

Gardnerella vaginalis is the core pathogen of bacterial vaginosis (BV), the most common vaginal infection in women. G. vaginalis exerts pathogenicity through various factors, such as biofilm formation and the local host immune response stimulation. Therefore, this study aimed to evaluate the inhibitory effect of Lactobacillus gasseri CCFM1201 on G. vaginalis using experimental BV models. We evaluated L. gasseri in vitro to inhibit pathogen biofilm formation and adhesion capacity in HeLa cells using crystal violet staining. Further in vivo studies were conducted to assess the inhibitory effects of L. gasseri CCFM1201 on BV induced by G. vaginalis. L. gasseri exhibited strain-specific adhesion and inhibition of pathogen biofilm formation in vitro. L. gasseri CCFM1201 significantly reduced G. vaginalis in mice (p < 0.05), inhibited sialidase activity, modulated tumor necrosis factor-α and interleukin-1ß expression, and reduced myeloperoxidase activity (p < 0.05). Histopathological examination indicated that L. gasseri CCFM1201 improved inflammatory cell infiltration of vaginal tissue and restored its structure. Vaginal epithelial cell exfoliation, the main clinical feature of BV, was significantly improved by L. gasseri CCFM1201 intervention (p < 0.05). Thus, L. gasseri CCFM1201 is a potential candidate for treating G. vaginalis-induced vaginal diseases.

Effects of Zn-Enriched Bifidobacterium longum on the Growth and Reproduction of Rats.

Zn is an essential trace element required for maintaining normal growth and development. Zn deficiency can cause growth retardation and reproductive system dysplasia, while Zn supplementation for treating Zn deficiency requires the use of high-quality Zn preparations. In this study, Bifidobacterium longum CCFM1195 was screened for its high Zn enrichment capacity, and the effects of different Zn supplementation regimens and doses on the growth and development of rats after Zn supplementation were investigated by supplementing Zn-deficient rat pups with different doses of various Zn supplements (ZnO, CCFM1195 + ZnO, and Zn-enriched CCFM1195). It was shown that the bioavailability of Zn was positively correlated with indicators of recovery after Zn supplementation, with Zn-enriched CCFM1195 having the best effect, followed by CCFM1195 + ZnO, while ZnO had the worst effect. Significant differences were also observed between the gut microbiota of control, model, and Zn-supplemented rats. Overall, administration of Zn-enriched CCFM1195 was more effective than the other approaches in restoring physical indicators of Zn deficiency after Zn supplementation, and this advantage was more significant at low-dose Zn supplementation.