Analysis of gut microecological characteristics and differences between children with biliary atresia and non-biliary atresia in infantile cholestasis.

Introduction: In infants with cholestasis, variations in the enterohepatic circulation of bile acids and the gut microbiota (GM) characteristics differ between those with biliary atresia (BA) and non-BA, prompting a differential analysis of their respective GM profiles. Methods: Using 16S rDNA gene sequencing to analyse the variance in GM composition among three groups: infants with BA (BA group, n=26), non-BA cholestasis (IC group, n=37), and healthy infants (control group, n=50). Additionally, correlation analysis was conducted between GM and liver function-related indicators. Results: Principal component analysis using Bray-Curtis distance measurement revealed a significant distinction between microbial samples in the IC group compared to the two other groups. IC-accumulated co-abundance groups exhibited positive correlations with aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, and total bile acid serum levels. These correlations were notably reinforced upon the exclusion of microbial samples from children with BA. Conclusion: The varying "enterohepatic circulation" status of bile acids in children with BA and non-BA cholestasis contributes to distinct GM structures and functions. This divergence underscores the potential for targeted GM interventions tailored to the specific aetiologies of cholestasis.

Exploring the Association between Anxiety, Depression, and Gut Microbiota during Pregnancy: Findings from a Pregnancy Cohort Study in Shijiazhuang, Hebei Province, China.

Negative emotions and gut microbiota during pregnancy both bear significant public health implications. However, the relationship between them has not been fully elucidated. This study, utilizing data from a pregnancy cohort, employed metagenomic sequencing to elucidate the relationship between anxiety, depression, and gut microbiota's diversity, composition, species, and functional pathways. Data from 87 subjects, spanning 225 time points across early, mid, and late pregnancy, were analyzed. The results revealed that anxiety and depression significantly corresponded to lower alpha diversity (including the Shannon entropy and the Simpson index). Anxiety and depression scores, along with categorical distinctions of anxiety/non-anxiety and depression/non-depression, were found to account for 0.723%, 0.731%, 0.651%, and 0.810% of the variance in gut-microbiota composition (p = 0.001), respectively. Increased anxiety was significantly positively associated with the abundance of Oscillibacter sp. KLE 1745, Oscillibacter sp. PEA192, Oscillibacter sp. KLE 1728, Oscillospiraceae bacterium VE202 24, and Treponema socranskii. A similar association was significantly noted for Oscillibacter sp. KLE 1745 with elevated depression scores. While EC.3.5.3.1: arginase appeared to be higher in the anxious group than in the non-anxious group, vitamin B12-related enzymes appeared to be lower in the depression group than in the non-depression group. The changes were found to be not statistically significant after post-multiple comparison adjustment.

Curcumin Alleviates High-fat Diet-induced Nonalcoholic Steatohepatitis via Improving Hepatic Endothelial Function with Microbial Biotransformation in Rats.

Hepatic endothelial function is central to the development of nonalcoholic steatohepatitis (NASH). Curcumin (Cur) is reportedly hepatoprotective, however, it remains unknown whether Cur improves hepatic endothelial function in NASH. Additionally, the poor bioavailability of Cur renders it difficult to elucidate its hepatoprotective effect, hence, its biotransformation should be considered. Herein, we investigated the effects and mechanisms of Cur and its bioconversion on hepatic endothelial function against high-fat diet-induced NASH in rats. The results revealed that Cur improved hepatic lipid accumulation, inflammation, and endothelial dysfunction by inhibiting NF-κB and PI3K/Akt/HIF-1α pathways, however, these effects were weakened via antibiotic addition, which was closely related to reduced tetrahydrocurcumin (THC) produce in the liver and intestinal content. Moreover, THC exerted a better effect than Cur on restoring liver sinusoidal endothelial cells function to attenuate steatosis and injury in L02 cells. Thus, these findings indicate that the effect of Cur on NASH is closely related to hepatic endothelial function improvement with intestinal microbial biotransformation.

Dynamic changes in gut microbiota during pregnancy among Chinese women and influencing factors: A prospective cohort study.

Gut microbiota (GM) dynamics during pregnancy vary among different populations and are affected by many factors, such as living environments and diet. This study aims to observe and evaluate the changes in the structure and function of the GM from the first to the third trimester of pregnancy in Chinese women, and to explore the main factors affecting the changes in intestinal microecology. Fifty-five Chinese pregnant women were recruited for this study and their fecal samples were collected during the first (P1), second (P2), and third trimesters (P3) of pregnancy. We exploited metagenomic sequencing to compare the composition and function of the GM in different pregnancy periods. Bioinformatic analysis revealed that there were differences in the composition of the GM among P1, P2, and P3, as indicated by the increase in α-diversity and ß-diversity of the GM and the differences in the relative abundances of distinct bacterial phyla. Gestational diabetes mellitus (GDM) was the main factor (P < 0.05) that affected the changes in GM at various stages of pregnancy. There were also disparities in the structure of the GM between the GDM group and non-GDM group in the P1, P2, and P3. The GDM group exhibited increased abundances in Ruminococcus_gnavus, Akkermansia_muciniphila, Alistipes_shahii, Blautia_obeum, and Roseburia_intestinalis; while, the abundances of Bacteroides coprocola, Bacteroides plebeius, Erysipelatoclostridium ramosum, and Prevotella copri were increased in the non-GDM group. Three of the four species enriched in the non-GDM group manifestied significantly negative correlations with the insulin-signaling pathway and lipopolysaccharide biosynthesis (r ≤ -0.3, adjusted P < 0.05). In the GDM group, Bacteroides vulgatus and Ruminococcus gnavus were significantly and positively correlated with insulin signaling pathway and lipopolysaccharide biosynthesis (r ≤ -0.3, adjusted P < 0.05) among the species enriched from early pregnancy. Virtually all of the species enriched in P2 and P3 were positively correlated with steroid hormone biosynthesis. These results suggest a potential role for the GM in the development of GDM, enabling the potential prevention of GDM by targeting the GM.

Effects of Smartphone-Based Remote Interventions on Dietary Intake, Physical Activity, Weight Control, and Related Health Benefits Among the Older Population With Overweight and Obesity in China: Randomized Controlled Trial.

BACKGROUND: Traditional health management requires many human and material resources and cannot meet the growing needs. Remote medical technology provides an opportunity for health management; however, the research on it is insufficient. OBJECTIVE: The objective of this study was to assess the effects of remote interventions on weight management. METHODS: In this randomized controlled study, 750 participants were randomly assigned to a remote dietary and physical activity intervention group (group DPI), remote physical activity intervention group (group PI), or control group (group C). At baseline (time 1), day 45 (time 2), and day 90 (time 3), data were collected, including data on dietary intake, physical activity, indexes related to weight control, and health benefits. RESULTS: A total of 85.6% (642/750) of participants completed the follow-up. Compared with group C, group DPI showed a significant decrease in energy intake (-581 vs -82 kcal; P<.05), protein intake (-17 vs -3 g; P<.05), fat intake (-8 vs 3 g; P<.05), and carbohydrate intake (-106.5 vs -4.7 g; P<.05) at time 3. Compared with time 1, groups DPI and PI showed a significant decrease in cereal and potato intake (P<.05). Compared with time 1, the physical activity levels related to transportation (group PI: 693 vs 597 metabolic equivalent [MET]-min/week, group C: 693 vs 594 MET-min/week; P<.05) and housework and gardening (group PI: 11 vs 0 MET-min/week, group C: 11 vs 4 MET-min/week; P<.05) in groups PI and C were improved at time 3. Compared with groups PI and C, group DPI showed a significant decrease in weight (-1.56 vs -0.86 kg and -1.56 vs -0.66 kg, respectively; P<.05) and BMI (-0.61 vs -0.33 kg/m2 and -0.61 vs -0.27 kg/m2, respectively; P<.05) at time 2. Compared with groups PI and C, group DPI showed a significant decrease in body weight (-4.11 vs -1.01 kg and -4.11 vs -0.83 kg, respectively; P<.05) and BMI (-1.61 vs -0.40 kg/m2 and -1.61 vs -0.33 kg/m2, respectively; P<.05) at time 3. Compared with group C, group DPI showed a significant decrease in triglyceride (-0.06 vs 0.32 mmol/L; P<.05) at time 2. Compared with groups PI and C, group DPI showed a significant decrease in systolic blood pressure (-8.15 vs -3.04 mmHg and -8.15 vs -3.80 mmHg, respectively; P<.05), triglyceride (-0.48 vs 0.11 mmol/L and -0.48 vs 0.18 mmol/L, respectively; P<.05), and fasting blood glucose (-0.77 vs 0.43 mmol/L and -0.77 vs 0.14 mmol/L, respectively; P<.05). There were significant differences in high-density lipoprotein cholesterol (-0.00 vs -0.07 mmol/L; P<.05) and hemoglobin A1c (-0.19% vs -0.07%; P<.05) between groups DPI and C. CONCLUSIONS: Remote dietary and physical activity interventions can improve dietary intake among participants with overweight and obesity, are beneficial for weight control, and have potential health benefits. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900023355; https://www.chictr.org.cn/showproj.html?proj=38976.

Huangqin Decoction ameliorates ulcerative colitis by regulating fatty acid metabolism to mediate macrophage polarization via activating FFAR4-AMPK-PPARα pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Decoction (HQD), a traditional Chinese medicine (TCM) formula chronicled in Shang Han Lun, is safe and effective for treatment of ulcerative colitis (UC). AIM OF THE STUDY: To investigate the effect of HQD against dextran sulfate sodium (DSS)-induced UC mice by regulating gut microbiota and metabolites, and further explore the mechanism of fatty acid metabolism on macrophage polarization. MATERIALS AND METHODS: Based on 3% dextran sulfate sodium (DSS)-induced UC mice model, clinical symptoms observation (body weight, DAI, and colon length) and histological inspection were used to evaluate the efficacy of HQD and fecal microbiota transplantation (FMT) from HQD-treated mice. The gut microbiota and metabolites were detected by 16S rRNA sequencing and metabolomics analysis. The parameters of fatty acid metabolism, macrophage polarization, and FFAR1/FFAR4-AMPK-PPARα pathway were analyzed by immunofluorescence analysis, western blotting, and real-time PCR. Then, the effects of FFAR1 and FFAR4 on macrophage polarization were examined by agonists based on LPS-induced RAW264.7 cell model. RESULTS: The results showed that FMT, like HQD, ameliorated UC by improving weight loss, restoring colon length, and reducing DAI scores and histopathological scores. Besides, HQD and FMT both enhanced the richness of gut microbiota, and modulated intestinal bacteria and metabolites to achieve a new balance. Untargeted metabolomics analysis revealed that fatty acids, especially long-chain fatty acids (LCFAs), dominated in HQD against DSS-induced UC by regulating the gut microenvironment. Further, FMT and HQD recovered the expression of fatty acid metabolism-related enzymes, and simultaneously activated FFAR1/FFAR4-AMPK-PPARα pathway but suppressed NF-κB pathway. Combined with cell experiment, HQD and FMT promoted macrophage polarization from M1 toward M2, which were well associated with anti-inflammatory cytokines and combined with the activated FFAR4. CONCLUSIONS: The mechanism of HQD against UC was related to regulating fatty acid metabolism to mediate M2 macrophage polarization by activating the FFAR4-AMPK-PPARα pathway.

Huangqin decoction ameliorates DSS-induced ulcerative colitis: Role of gut microbiota and amino acid metabolism, mTOR pathway and intestinal epithelial barrier.

BACKGROUND: The clinical treatment of ulcerative colitis (UC) is limited. A traditional Chinese medicinal formula, Huangqin decoction (HQD), is chronicled in Shang Han Lun and is widely used to ameliorate gastrointestinal disorders, such as UC; however, its mechanism is yet to be clarified. PURPOSE: The present study aimed to investigate the effect of HQD on 7-day colitis induced by 3% dextran sulfate sodium (DSS) in mice and further explore the inhibitory effect of metabolites on DSS-damaged FHC cells. METHODS: The therapeutic efficacy of HQD was evaluated in a well-established DSS-induced colitis mice model. The clinical symptoms were analyzed, and biological samples were collected for microscopic examination, metabolomics, metagenomics, and the evaluation of the epithelial barrier function. The mechanism of metabolites regulated by HQD was evaluated in the DSS-induced FHC cell damage model. The samples were collected to detect the physiological functions of the cells. RESULTS: HQD suppressed the inflammation of DSS-induced colitis in vivo, attenuated DSS-induced clinical manifestations, reversed colon length reduction, and reduced histological injury. After HQD treatment, the DSS-induced gut dysbiosis was modulated, and the gut microbiota achieved a new equilibrium state. In addition, HQD activated the mTOR signaling pathway by upregulating amino acid metabolism. Significant phosphorylation of S6 and 4E-BP1 ameliorated intestinal epithelial barrier dysfunction. Moreover, HQD-regulated metabolites protected the epithelial barrier integrity by inhibiting DSS-induced apoptosis of FHC cells and regulating the proteins affecting apoptosis and cell-cell junction. CONCLUSIONS: These findings indicated that the mechanism of HQD was related to regulating the gut microbiota and amino acid metabolism, activating the mTOR signaling pathway, and protecting the intestinal mucosal barrier integrity.

Bruceae Fructus Oil Inhibits Triple-Negative Breast Cancer by Restraining Autophagy: Dependence on the Gut Microbiota-Mediated Amino Acid Regulation.

Triple-negative breast cancer (TNBC) has been acknowledged as an aggressive disease with worst prognosis, which requires endeavor to develop novel therapeutic agents. Bruceae fructus oil (BO), a vegetable oil derived from the fruit of Brucea javanica (L.) Merr., is an approved marketable drug for the treatment of cancer in China for several decades. Despite that the anti-breast cancer activity of several quassinoids derived from B. javanica has been found, it was the first time that the potential of BO against TNBC was revealed. Although BO had no cytotoxicity on TNBC cell lines in vitro, the oral administration of BO exhibited a gut microbiota-dependent tumor suppression without toxicity on the non-targeted organs in vivo. By metagenomics and untargeted metabolomics, it was found that BO not only altered the composition and amino acid metabolism function of gut microbiota but also regulated the host's amino acid profile, which was in accordance with the metabolism alternation in gut microbiota. Moreover, the activity of mTOR in tumor was promoted by BO treatment as indicated by the phosphorylation of 4E-binding protein 1 (4E-BP1) and ribosomal protein S6, and hyper-autophagy was consequently restrained. By contrast, the failure of tumor suppression by BO under pseudo germ-free (PGF) condition came with indistinctive changes in autophagy and mTOR activity, implying the critical role of the gut microbiota in BO's anticancer activity. The present study highlighted a promising application of BO against breast cancer with novel efficacy and safety.

Effect of Mobile-Based Lifestyle Intervention on Weight Loss among the Overweight and Obese Elderly Population in China: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Overweight or obesity, as an independent risk factor for chronic diseases, has been on the rise globally. Adopting a healthy lifestyle is positive to weight control. Mobile-based lifestyle interventions have shown potential benefits in weight loss, but most studies were carried out among non-elderly population, so it is necessary to perform well-designed randomized controlled trials among the elderly with overweight or obesity. The purpose of this study is to assess the effect of mobile-based lifestyle intervention on weight loss among the overweight and obese elderly population in China. METHODS: This is a prospective, open-labeled, three-month, multicenter, randomized controlled trial involving 750 participants from five cities who were randomly assigned to dietary and physical activity interventions group (DPG; mobile phone with the App and bracelet), physical activity interventions group (PG; mobile phone with the App and bracelet) and control group (CG; no interventions and kept their lifestyle as before). The outcomes evaluated were changes in weight, body mass index (BMI), waist circumference (WC), and hip circumference (HC). RESULTS: In total, 642 (85.6%) participants completed the study, 237 (94.8%), 203 (81.2%), and 202 (80.8%) for DPG, PG, and CG respectively. Comparing with PG and CG, the DPG showed a significant decrease in all outcomes after three months, including body weight (-4.1 kg vs. -1.0 kg; -4.1 kg vs. -0.8 kg; p < 0.05), BMI (-1.6 kg/m2 vs. -0.4 kg/m2; -1.6 kg/m2 vs. -0.3 kg/m2; p < 0.05), WC (-2.8 cm vs. -0.1 cm; -2.8 cm vs. -0.5 cm; p < 0.05), and HC (-3.8 cm vs. -1.3 cm; -3.8 cm vs. -1.3 cm; p < 0.05). Similar effects were seen across sex and BMI subgroups. CONCLUSIONS: Mobile-based lifestyle intervention obtained beneficial effect in weight loss among the elderly with overweight or obesity. Nevertheless, further studies are needed to confirm the effectiveness and its sustainability.

Effect of Mobile-Based Lifestyle Intervention on Body Weight, Glucose and Lipid Metabolism among the Overweight and Obese Elderly Population in China: A Randomized Controlled Trial Protocol.

Background: Promotion of a healthy lifestyle is considered a good strategy for dealing with chronic diseases. Mobile-based lifestyle interventions have shown beneficial effects in the control and treatment of chronic diseases such as diabetes, obesity and metabolic syndrome. Current clinical trials for mobile-based lifestyle intervention were mainly conducted among non-elderly populations, thus well-designed trials performed among the elderly who are more susceptible to chronic diseases are needed. The study aims to assess the effect of the mobile-based lifestyle intervention on the improvement of body weight, glucose and lipid metabolism among overweight and obese elderly adults in China. Materials and Methods: Participants aged 60-80 years who are overweight or obese will be randomly assigned to receive mobile-based nutrition and exercise intervention, mobile-based exercise intervention and no intervention for 3 months. Before the intervention, participants will receive the training of the mobile application and sports bracelet. The primary outcome will be the between-group (three groups) difference in body mass index at the end of intervention. The secondary outcomes will include body composition, parameters of glucose and lipid metabolism, blood pressure, dietary data and physical activity data. All these outcomes will be assessed at baseline, day 45 and day 90. Ethics and dissemination: The trial has been approved by the Ethics Committee of Peking University Health Science Center (IRB00001052-18039).

Polysaccharides of Sporoderm-Broken Spore of Ganoderma lucidum Modulate Adaptive Immune Function via Gut Microbiota Regulation.

Ganoderma lucidum (Leyss.Fr.) Karst is one of the well-known medicinal macrofungi all over the world, and mounting researches have focused on the polysaccharides derived from the spores of G. lucidum. In the present study, BALB/c mice (n = 8-10) were administered with crude polysaccharides of G. lucidum spores (CPGS) and the refined polysaccharides of G. lucidum spores (RPGS) for 30 days to investigate their effect on the adaptive immune system. Results showed that CPGS and RPGS displayed diverse effects on the lymphocyte activity in the spleen. The splenocyte proliferation activity upon mitogen was suppressed by CPGS and RPGS, while the NK cell's tumor-killing ability was promoted by CPGS. Both CPGS and RPGS could increase the proportion of naïve T cells in thymus, but only RPGS significantly uplifted the percentage of T cells, as well as the T cell subsets, in peripheral blood, and promoted the activation by upregulating the expression of costimulatory factor CD28. Moreover, 16S sequencing results showed that the effects of CPGS and RPGS were closely related to the regulation of gut microbiota. ß-diversity of the microbiome was evidently changed by CPGS and RPGS. The phytoestrogen/polysaccharide-metabolizing bacteria (Adlercreutzia, Parabacteroides, and Prevotella), and an unclassified Desulfovibrionaceae, were remarkably enriched by CPGS or RPGS, and functions involving carbohydrate metabolism, membrane transport, and lipid metabolism were regulated. Moreover, the enrichments of Adlercreutzia, Prevotella, and Desulfovibrionaceae were positively related to the immune regulation by CPGS and RPGS, while that of Parabacteroides displayed a negative correlation. These findings suggested a promising effect of the polysaccharide from sporoderm-broken spore of G. lucidum in immune regulation to promote health control.

Effects of Huangqin Decoction on ulcerative colitis by targeting estrogen receptor alpha and ameliorating endothelial dysfunction based on system pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Decoction (HQD), a traditional Chinese medicinal (TCM) formula chronicled in Shang Han Lun, has been used to treat gastrointestinal diseases for nearly 1800 years. OBJECTIVE: To investigate the effects and underlying mechanisms of HQD on ulcerative colitis (UC). METHODS: The bioactive compounds in HQD were obtained from the traditional Chinese medicine systems pharmacology database. Then, the HQD and UC-related targets were analyzed by establishing HQD-Compounds-Targets (H-C-T) and protein-protein interaction (PPI) networks. Enrichment analysis was used for further study. The candidate targets for the effects of HQD on UC were validated using a dextran sulfate sodium-induced UC mouse experiment. RESULTS: The results showed that 51 key targets were gained by matching 284 HQD-related targets and 837 UC-related targets. Combined with H-C-T and PPI network analyses, the key targets were divided into endothelial growth, inflammation and signal transcription-related targets. Further experimental validation showed that HQD targeted estrogen receptor alpha (ESR1) and endothelial growth factor receptors to relieve endothelial dysfunction, thereby improving intestinal barrier function. The expression of inflammatory cytokines and signal transducers was suppressed by HQD treatment and inflammation was inhibited. CONCLUSIONS: HQD may acts on UC via the regulation of targets and pathways related to improving the intestinal mucosal barrier and ameliorating endothelial dysfunction. Additionally, ERS1 may be a new target to explore the mechanisms of UC.

Breastfeeding restored the gut microbiota in caesarean section infants and lowered the infection risk in early life.

BACKGROUND: The initialization of the neonatal gut microbiota (GM) is affected by diverse factors and is associated with infant development and health outcomes. METHODS: In this study, we collected 207 faecal samples from 41 infants at 6 time points (1, 3, and 7 days and 1, 3, and 6 months after birth). The infants were assigned to four groups according to delivery mode (caesarean section (CS) or vaginal delivery (VD)) and feeding pattern (breastfeeding or formula milk). RESULTS: The meconium bacterial diversity was slightly higher in CS than in VD. Three GM patterns were identified, including Escherichia/Shigella-Streptococcus-dominated, Bifidobacterium-Escherichia/Shigella-dominated and Bifidobacterium-dominated patterns, and they gradually changed over time. In CS infants, Bifidobacterium was less abundant, and the delay in GM establishment could be partially restored by breastfeeding. The frequency of respiratory tract infection and diarrhoea consequently decreased. CONCLUSION: This study fills some gaps in the understanding of the restoration of the GM in CS towards that in VD.

Association between Neighborhood Food Environment and Body Mass Index among Older Adults in Beijing, China: A Cross-Sectional Study.

OBJECTIVE: To investigate the association between the neighborhood food environment and body mass index (BMI) among Chinese older adults. METHODS: A multi-stage stratified random sampling method was used to recruit participants from 12 communities in Beijing, China, in 2019. Participants (n = 1764, 1034 women) in this study were older adults aged 65 to 80. We collected the participants' basic information, measured their height and weight, and calculated their BMI. Neighborhood food environments were measured by the density of and proximity to different food outlets using the Baidu Map Application Programming Interface. Adjusted multiple linear regression was performed to estimate the association between the food environment and BMI. RESULTS: Participants had a mean age of 69.7 ± 4.32 years old and an average BMI of 26.3 ± 3.50 kg/m2. Among the three types of stores, convenience stores had the easiest access, followed by greengrocers and supermarkets. Sit-down restaurants had the best access among different restaurants, followed by Chinese fast-food restaurants, and western fast-food restaurants had the worst access. Easier access to greengrocers (ß = 0.281, p < 0.001) and sit-down restaurants (ß = 0.304, p < 0.001) was associated with higher BMI in the 250 m buffer zone. More supermarkets were associated with higher BMI in the 500 m buffer zone (ß = 0.593, p < 0.001). Access to convenience stores was positively associated with BMI in the 800 m buffer zone (ß = 0.057, p < 0.001). Better access to Chinese fast-food restaurants was associated with higher BMI (ß = 0.071, p = 0.001), and better access to western fast- food restaurants was associated with lower BMI (ß = -0.400, p < 0.001) in the 1000 m buffer zone. There was a negative association between the nearest distance to greengrocers and BMI (ß = -0.004, p < 0.001). CONCLUSION: Although we found some significant associations between the neighborhood food environment and obesity, the current results are not strong enough to draw specific conclusions. Policymakers will need to rely on more evidence to derive concrete policy recommendations.

Corrigendum: Alterations of Gut Microbiota in Cholestatic Infants and Their Correlation With Hepatic Function.

[This corrects the article DOI: 10.3389/fmicb.2018.02682.].

Polysaccharide from spore of Ganoderma lucidum ameliorates paclitaxel-induced intestinal barrier injury: Apoptosis inhibition by reversing microtubule polymerization.

Side effects of chemotherapy are burning questions for physicians and patients involved in cancers. Ganoderma lucidum is a widely consumed traditional Chinese medicine and edible mushroom with multiple functional properties. The present study aims to investigate the potential of polysaccharides from spore of G. lucidum (SGP) on small intestinal barrier function recovery against paclitaxel (PTX) challenge in a breast cancer mice model and IEC-6 cell line. The 4T1 tumor-bearing mice were treated with PTX together with four-week daily oral administration of SGP. Results indicated that combination of PTX and SGP reversed body weight lost and remolded the histology of small intestine, accompanied with promoted proliferation but suppressed apoptosis in intestinal cells. Intestinal barrier function was enhanced by the combination as indicated by reduced endotoxemia and the up-regulation of tight junction proteins, including Zonula occludens-1 (ZO-1), E-cadherin, ß-catenin and Occludin. The protection of SGP was further confirmed in IEC-6 cells affected by PTX in vitro. The combination treatment prevented PTX-induced apoptosis in IEC-6 by inhibiting microtubule polymerization, and the aforementioned tight junction proteins were also upregulated. These findings suggest a promising protective effect of SGP against small intestinal barrier injury caused by PTX, highlighting its clinical implication against the chemotherapy side effects.

Ethanol extract of Pycnoporus sanguineus relieves the dextran sulfate sodium-induced experimental colitis by suppressing helper T cell-mediated inflammation via apoptosis induction.

Inflammatory bowel disease (IBD) is a chronic relapsing inflammation involving the gut system, and disequilibrium of T helper (Th) cell paradigm has been recognized as critical pathogenesis. Pycnoporus sanguineus (L.) Murrill is a species of the white-rot basidiomycetes listed as food- and cosmetic-grade microorganisms. In this study, anti-inflammatory activity of the ethanol extract from P. sanguineus (PSE) was investigated in dextran sulfate sodium (DSS)-induced experimental colitis model. PSE recovered the DSS-caused weight loss, reversed the colon shortening, and ameliorated the histopathological lesion in colon, resulting in lower disease activity index (DAI). Levels of serumal lipopolysaccharide (LPS), colonic myeloperoxidase (MPO) in the colitis-suffering mice were declined by PSE treatment. PSE also improved the mucosal integrity by enhancing the expression of tight junction and adherens junction proteins in the colon, including ZO-1, occludin, claudin-1, and E-cadherin. Besides, PSE reduced helper T cells (Th) in the colon, together with an evident decrease of several Th cell-related cytokines. Moreover, it was found that in vitro, PSE suppressed T cells and the Th subset upon Concanavalin A (ConA)-stimulation by inducing apoptosis. In summary, PSE displayed a remission on the colitis-related inflammation, which would possibly rely on the epithelial barrier restoration by suppressing Th cells via apoptosis induction, highlighting a promising potential in the treatment for IBD.

Ethanol Extract of Brucea javanica Seed Inhibit Triple-Negative Breast Cancer by Restraining Autophagy via PI3K/Akt/mTOR Pathway.

Triple-negative breast cancer (TNBC) is an aggressive disease with worst prognosis than other subtypes of breast cancer. Owing to the lack of hormone receptors and HER2 expression on TNBC cells, patients do not have targeted therapy options available with other breast cancer subtypes. Extensive efforts have been made to identify novel therapeutics against TNBC. Interestingly, recent studies had shown that plant-derived natural products could modulate the autophagy and induce the breast cancer cells death. Seed of Brucea javanica has been used as an important traditional Chinese medicine against cancers. In the present study, the anti-breast cancer potential of ethanol crude extracts from B. javanica seed (BJE) was explored. Data demonstrated that BJE could inhibit the TNBC cell line MDA-MB-231 proliferation and induced apoptosis. In the cells exposed to BJE, protein expressions of UNC-51-like kinase-1 (ULK1) and Beclin-1 and the ratio of light chain 3 II/I (LC3 II/I) were reduced, while the expression of p62 was increased, indicating an inhibition on autophagy. Moreover, BJE promoted the phosphorylation of mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and Akt in MDA-MB-231. BJE also suppressed the MDA-MB-231 tumor growth in vivo. Coincide with the results in vitro, autophagy in the tumor tissue was weakened as indicated by decreased ratio of LC 3 II/I and Beclin-1 accompanied by enhanced phosphorylation of mTOR, which confirmed that autophagy restraint via the PI3K/Akt/mTOR signaling pathway contributes to the suppression by BJE. Notably, no noticeable toxicity in non-targeted organs was found, including small intestine, liver, and kidney. Taken together, this study revealed anti-breast cancer activity of BJE based on autophagy restraint, highlighting its clinical importance as a novel natural agent against TNBC.

Polysaccharide from Pycnoporus sanguineus ameliorates dextran sulfate sodium-induced colitis via helper T cells repertoire modulation and autophagy suppression.

Inflammatory bowel disease (IBD) is a chronic autoimmune disease associated with various risk factors. Pycnoporus sanguineus (L.) Murrill is a saprotrophic fungus used worldwide for its industrial and medical purposes. Here, polysaccharide from P. sanguineus (PPS) was explored for its antiinflammatory potential in a murine colitis model of IBD induced by dextran sulfate sodium (DSS). PPS ameliorated the colitis as manifested by the lowered disease activity index (DAI), prolonged colon, and reduced serum lipopolysaccharide (LPS). PPS recovered the histological lesion by upregulating the expressions of Zonula occludens-1 (ZO-1), E-cadherin, and proliferating cell nuclear antigen (PCNA). PPS inhibited the helper T cells (Th)-mediated immune response by decreasing the proportions of Th cells (including Th2 cells, Th17 cells, and regulatory T cells), which was accompanied with reductions on myeloperoxidase (MPO) activity and releases of several interleukins and chemokines within the colon. Moreover, PPS exhibited an evident inhibition on autophagy, in which the ratio of light chain 3 (LC3) II/I was declined, while the expression of p62 and Beclin-1 was increased. The present study highlighted important clinical implications for the treatment application of PPS against IBD, which relies on the regulation of Th cells repertoire and autophagy suppression to restore epithelium barrier.