ABSTRACT
In this research, the synbiotic effects of the probiotic Lactiplantibacillus plantarum YW11 and lactulose on intestinal morphology, colon function, and immune activity were evaluated in a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed that L. plantarum YW11 in combination with lactulose decreased the severity of colitis in mice and improved the structure of the damaged colon, as assessed using colon length and disease condition. Moreover, colonic levels of pro-inflammatory cytokines (IL-1ß, IL-6, IL-12, TNF-α, and IFN-γ) were significantly lower and anti-inflammatory factors (IL-10) were significantly higher following the synbiotic supplementation. The synbiotic also exerted antioxidant effects by up-regulating SOD and CAT levels and down-regulating MDA levels in colon tissue. It could also reduce the relative expression of iNOS mRNA and increase the relative expression of nNOS and eNOS mRNA. Western blot confirmed the increased expression of c-Kit, IκBα, and SCF and significantly reduced expression of the NF-κB protein. Therefore, the combination of L. plantarum YW11 and lactulose exerted therapeutic effects mainly through the NF-κB anti-inflammatory pathway, which represented a novel synbiotic approach in the prevention of colonic inflammation.
Subject(s)
Colitis, Ulcerative , Probiotics , Synbiotics , Animals , Mice , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/prevention & control , Lactulose/metabolism , Lactulose/pharmacology , Lactulose/therapeutic use , NF-kappa B/genetics , NF-kappa B/metabolism , Dextran Sulfate/toxicity , Dextran Sulfate/metabolism , Colon/metabolism , Anti-Inflammatory Agents/therapeutic use , Probiotics/therapeutic use , Disease Models, Animal , Mice, Inbred C57BLABSTRACT
Functional constipation is one of the most common gastrointestinal disorders. Oxidative stress can aggravate organ dysfunction. Enteric neurotransmitters have significant effects on the regulation of the enteric nervous system and intestinal muscle contraction. Oxidative stress and reduced gastrointestinal motility are considered to be one of the main causes of constipation. This study aimed to investigate whether LimosiLactobacillus pentosus CQZC02 alleviated loperamide hydrochloride (Lop)-induced constipation in mice under high-fat diet (HFD) conditions and to elucidate the underlying mechanism, focusing on enteric neurotransmitters. Four-week-old female BALB/c mice were randomly divided into five groups: normal group (Nor), constipation model group (H-Lop), L. pentosus CQZC02 low-dose group (H-Lop + ZC02L), L. pentosus CQZC02 high-dose group (H-Lop + ZC02H), and LimosiLactobacillus bulgaricus control group (H-Lop + LB). The fecal weight, water content, and total gastrointestinal transit time were measured to determine whether the mice were constipated. Small bowel and colon tissue damage was assessed by hematoxylin and eosin staining, while the degree of damage was determined by double-blind scoring. The levels of serum oxidative stress markers malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase and neurotransmitters motilin, gastrin, substance P, endothelin, somatostatin, and vasoactive intestinal peptide were measured. The gene expression levels of endothelial nitric oxide synthase, inducible nitric oxide synthase, neuronal nitric oxide synthase, nuclear factor kappa-B, and cyclooxygenase-2 in small intestine tissue were calculated. The constipation symptoms of mice in H-Lop group were manifested by a variety of physiological indicators. In addition, compared with the H-Lop group, H-Lop + ZC02H could effectively relieve the symptoms of constipation in mice. In symptom characterization, the mice in the H-Lop + ZC02H group lost weight and increased feces and water content. In functional experiments, gastrointestinal motility was enhanced; the inflammation score of intestinal tissue was decreased, and gene expression levels were modulated; serum oxidative factor levels were modulated, and oxidative stress levels were decreased.
Subject(s)
Diet, High-Fat , Mustard Plant , Mice , Female , Animals , Diet, High-Fat/adverse effects , Constipation/chemically induced , Constipation/drug therapy , Intestine, Small/metabolism , Neurotransmitter AgentsABSTRACT
The occurrence of intestinal diseases such as colon cancer is closely related to the intestinal flora. Lactobacillus fermentum is a gut probiotic that plays an important role in chronic intestinal inflammation and colon cancer. In the current study, we investigated the effect of Lactobacillus fermentum ZS40 on NF-κB signaling pathway of azomethane-dextran sulfate sodium (AOM-DSS) -induced colon cancer in mice. Animals were divided into control group (NC), AOM-DSS-induced model group (CRC), AOM-DSS plus high-dose Lactobacillus fermentum ZS40 (ZS40-H), AOM-DSS plus low-dose Lactobacillus fermentum ZS40 (ZS40-L), AOM-DSS plus Lactobacillus bulgaricus (BLA), and AOM-DSS plus sulfasalazine (SD)-treated group. Observation of animal physiological activity (body weight and defecation), biochemical measurements, histopathological examination of colon tissue, qPCR to evaluate the expression of inflammation-related genes, immunohistochemical analysis of CD34 and CD117, and Western blot analysis of NF-κB signaling pathway were performed. Compared with the CRC group, the ZS40-H, ZS40-L, BLA, and SD groups had decreased levels of colon cancer marker proteins CD34 and CD117, and the number of abnormal colonic lesions observed by colon histology decreased, while the ZS40-H group showed excellent results. In addition, all probiotic interventions showed weight loss effects. The expression of inflammatory stimulators TNF-α and IL-1ß in the probiotic treatment group decreased; the expression of key proteins IκBα and p65 in the NF-κB signaling pathway also decreased, resulting in a decrease in the expression of the target protein Cox-2. Therefore, administration of Lactobacillus fermentum ZS40 as a probiotic can alleviate intestinal inflammation and prevent colon cancer in mice.
ABSTRACT
This study aimed to examine the ameliorating effect of Lactobacillus plantarum (LP) KFY02 on low-fiber diet-induced constipation in mice. LP-KFY02 was isolated from the natural fermented yogurt in Korla of Xinjiang. The mice with low-fiber diet-induced constipation in experimental groups were administered 1 × 109 CFU/kg LP-KFY02 (KFY02H) and 1 × 108 CFU/kg LP-KFY02 (KFY02L). After LP-KFY02 treatment with constipation mice, the mice fecal water content, intestinal transit ability and defecation time of constipated mice were improved. The mice fecal flora diversity, abundance and structure of the intestinal flora were regulated to the balanced state. The mice serum levels of gut motility related neuroendocrine factors have been increased, the intestinal mucosal barrier function and gut motility related gene expression were regulated in mice colon tissues. At the same time, the mice colon tissue damage were improved. These parameters in the KFY02H group were close to the normal group. These results suggested that LP-KFY02 could be considered as a potential probiotic to help alleviate low-fiber diet-induced constipation. They also provided a theoretical basis for the study of probiotics to relieve constipation by regulating intestinal flora.
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Objective: The liver protection of blood coral polysaccharide (BCP) was investigated. Materials and Methods: We evaluated the effect of BCP on liver pathology, liver function, oxidation and inflammation-related indicators of D-Gal/LPS-induced acute liver failure (ALF) mice in vivo. Results: Liver index and liver pathology observation in mice showed that BCP could inhibit liver tissue swelling and hemorrhage, hepatocyte damage, and inflammatory infiltration in ALF. Serum liver function results showed that BCP effectively inhibits the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), total bilirubin (TBil), alkaline phosphatase (AKP), myeloperoxidase (MPO). High dose-blood coral polysaccharide (H-BCP) was better than silymarin. Serum antioxidant and immune results showed that BCP increased the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px), and inhibited the levels of malondialdehyde (MDA) and nitric oxide (NO). Also, BCP increased immunoglobulins G (IgG) and A (IgA) levels, thereby enhancing humoral immunity. Liver anti-inflammatory ELISA results showed that BCP reduced the levels of interleukin (IL)-6, IL-1ß, IL-17, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, and enhanced the level of anti-inflammatory factor IL-10. H-BCP was the most effective treatment. Real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) of liver tissues confirmed that BCP increases the relative expression levels of antioxidant and anti-inflammatory-related cuprozinc superoxide dismutase (Cu/Zn-SOD, SOD1), manganese superoxide dismutase (Mn-SOD, SOD2), CAT, GSH, GSH-Px, and IL-10. In contrast, it inhibits inflammation-related genes IL-6, IL-1ß, IL-17, TNF-α, IFN-γ, inducible nitric oxide synthase (iNOS, NOS2), and cyclooxygenase (COX)-2. In addition, BCP also inhibits the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and enhance B-cell inhibitor-α (IκB-α) gene relative expression in the liver, which may be related to NF-κB pathway inhibition. Conclusion: BCP prevents D-Gal/LPS-induced ALF in mice, and its effect is concentration dependent.
ABSTRACT
Inflammation is a characteristic of obesity. The rich compounds in lemon peel have anti-inflammatory effects. This study examined whether fermented lemon peel can have an anti-obesity effect on obese mice induced by a high-fat diet (HFD) by regulating inflammation. The lemon peel fermentation supernatant (LPFS) could inhibit the weight gain of mice and improve the lesions of the liver and epididymal adipose tissue. In addition, LPFS regulates blood lipids, liver function, and inflammation-related indicators in the serum of obese mice. LPFS plays a positive role in regulating the inflammation and obesity-related genes in liver tissue and adipose tissue of obese mice. High-performance liquid chromatography showed an increase in the contents of compounds with antioxidant or/and anti-inflammatory effects and compounds with anti-obesity effects. These results suggest that the LPFS could help reduce obesity in obese mice induced by an HFD by adjusting the balance of the inflammatory response. PRACTICAL APPLICATIONS: Obesity often increases the risk of chronic diseases, and mild inflammation is a feature of obesity. Therefore, timely suppression of inflammation in the body can help control the occurrence of obesity. This study clarified the anti-obesity effect of fermented lemon peel on a high-fat diet (HFD)-induced obese mice by regulating the body's inflammatory response and confirmed that fermentation improves the anti-inflammatory activity of lemon peel. This study provides important references for future investigation, prophylaxis, and treatment of inflammation and obesity-related diseases, as well as the advances in functional foods and fermented foods with anti-inflammatory and anti-obesity activities.
Subject(s)
Diet, High-Fat , Obesity , Animals , Diet, High-Fat/adverse effects , Inflammation/drug therapy , Liver , Mice , Mice, Obese , Obesity/drug therapy , Obesity/etiologyABSTRACT
In this study, a carrageenan-induced thrombus model was established in mice to observe the ability of Lactobacillus plantarum KFY05 (LP-KFY05) to inhibit thrombosis through an NF-κB-associated pathway. Biochemical analysis, microscopical observations, quantitative polymerase chain reactions (qPCR) and western blot analysis were used to examine relevant serum and tissue indexes, and the composition of intestinal microorganisms was determined by examining the abundance of microorganisms in feces. The results showed that LP-KFY05 could markedly reduce the degree of black tail in thrombotic mice; increase the activated partial thromboplastin time (APTT); and decrease the thrombin time (TT), fibrinogen (FIB) level, and prothrombin time (PT). LP-KFY05 could also reduce tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß) levels in sera and renal tissues of thrombotic mice. Hematoxylin and eosin staining showed that LP-KFY05 could alleviate renal tissue lesions and tail vein thrombosis. qPCR results showed that LP-KFY05 could down-regulate nuclear factor kappa-B (NF-κB) p65, IL-6, TNF-α, and interferon γ (IFN-γ) mRNA expression in renal tissues, as well as NF-κB p65, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin mRNA expression in tail vein vascular tissues of thrombotic mice. Western blot analysis showed that LP-KFY05 also down-regulated NF-κB protein expression in renal and tail vein vascular tissues of thrombotic mice. Lastly, LP-KFY05 increased the abundances of Bacteroidetes, Lactobacillus, and Bifidobacterium, as well as decreased the abundance of Firmicutes. These results show that LP-KFY05 can reduce inflammation and inhibit thrombosis in thrombotic mice, and the effects of high concentrations of LP-KFY05 were most pronounced, which were similar to the effects of dipyridamole.
ABSTRACT
In this article, the preventive and protective effect of a new Lactobacillus fermentum, (Lactobacillus fermentum TKSN02: LF-N2), which was isolated and identified from Xinjiang naturally fermented yogurt, on hydrochloric acid (HCl)/ethanol induced gastric injury in mice was studied. A total of 40 mice were divided into the following five groups: normal, model, LF-N2, LB (Lactobacillus bulgaricus), and Ranitidine groups. Except for the normal and model groups, mice in the other groups were treated with LF-N2, LB (Lactobacillus bulgaricus), and Ranitidine separately, and the injury of the gastric tissue was observed by taking photos and pathological sections. The levels of oxidation indicators, gastrointestinal hormone and the inflammatory cytokines in serum and gastric tissue in each group were measured. Further more, the gene expression levels of oxidative stress and inflammation related genes in the colon tissue were determined by the Real-Time PCR method. Pathological observation confirmed that LF-N2 could inhibit the gastric injury caused by HCl/ethanol. Observation of the appearance of the gastric indicated that LF-N2 could effectively reduce the area of gastric injury. Biochemical results showed that the serum gastrin (GAS) and gastric motilin (MTL) levels in the LF-N2 group were significantly lower and the serum somatostatin (SS) level was higher than in the model group and there was no significant difference between all treatment groups. The activities of total superoxide dismutase (T-SOD) and glutathione (GSH) were increased while the malondialdehyde (MDA) content was decreased in LF-N2 treatment group mice, which suggested that LF-N2 has a good antioxidant effect. Further RT-PCR experiments also showed that LF-N2 could promote the related mRNA expression of antioxidant enzymes (Cu/Zn-SOD, Mn-SOD, and CAT) and anti-inflammatory cytokines (IL-4, and IL-10), while it inhibited the gene expression of pro-inflammatory cytokine (IL-6) and apoptosis factor (Caspase-3). As observed, LF-N2 exerted a good preventive effect on HCl/ethanol induced gastric injury in mice, and the effect was close to that of LB, which indicated that LF-N2 has potential use as a probiotic due to its gastric injury treatment effects.
ABSTRACT
Lactobacillus plantarum ZS62 is a newly isolated strain from naturally fermented yogurt that might offer some beneficial effects in the setting of alcohol-induced subacute liver injury. The liver-protective effect of L. plantarum ZS62 was investigated by gavage feeding of mice with this Lactobacillus strain (1 × 109 CFU/kg BW) before alcohol administration daily for 7 days. We then compared hepatic morphology, liver function indexes, liver lipid levels, inflammation, oxidative stress levels, and mRNA expression of oxidative metabolism- and inflammation-related genes in mice that had been pretreated with Lactobacillus plantarum versus control mice that had not been pretreated. Our results showed that L. plantarum ZS62 attenuated alcohol-induced weight loss; prevented morphological changes in hepatocytes; reduced markers of liver damage including aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), hyaluronidase (HAase), precollagen III (PC III), and inflammatory cytokines; and enhanced the antioxidative status. L. plantarum ZS62 also significantly downregulated inflammation-related genes and upregulated lipid- and oxidative-metabolism genes. Thus, Lactobacillus plantarum pretreatment appears to confer hepatic protection by reducing inflammation and enhancing antioxidative capacity. The protective effect of L. plantarum ZS62 was even better than that of a commonly used commercial lactic acid bacteria (Lactobacillus delbrueckii subsp. Bulgaricus). The L. plantarum ZS62 might be a potentially beneficial prophylactic treatment for people who frequently drink alcoholic beverages.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Ethanol/toxicity , Inflammation/drug therapy , Lactobacillus plantarum/chemistry , Liver Diseases, Alcoholic/prevention & control , Probiotics/pharmacology , Animals , Central Nervous System Depressants/toxicity , Inflammation/etiology , Inflammation/metabolism , Inflammation/pathology , Liver Diseases, Alcoholic/etiology , Liver Diseases, Alcoholic/metabolism , Liver Diseases, Alcoholic/pathology , Male , Mice , Oxidative StressABSTRACT
Ulcerative colitis is an inflammatory disease of the intestine caused by many reasons, and it may even develop into colon cancer. Probiotics are normal bacteria that exist in the human body and have been proven to regulate the balance of intestinal flora and alleviate inflammation. The current study aimed to study the effect of Lactobacillus fermentum ZS40 (ZS40) on dextran sulfate sodium (DSS)-induced ulcerative colitis mice. The length and weight of the colon were measured, and the histopathological morphological changes of colon tissue were observed to evaluate the effects of ZS40 on colitis. Biochemical kits, ELISA kits, real-time quantitative PCR (RT-qPCR), and western blot were also used to detect the effects of ZS40 on serum and colon tissue related oxidative indicators and pro-inflammatory and anti-inflammatory cytokines. We found that ZS40 could reduce colonic inflammatory cell infiltration and goblet cell necrosis, increase total superoxide dismutase and catalase in mouse serum, and reduce myeloperoxidase and malondialdehyde levels. ZS40 could down-regulate the level of proinflammatory cytokines and up-regulate the level of anti-inflammatory cytokines. More importantly, ZS40 down-regulated the relative expression of nuclear factor-κB p65 (NF-κBp65), IL-6, and TNF-α mRNA and protein, up-regulated the relative expression of inhibitor kapa B alpha (IκB-α). By regulating the NF-κB and MAPK pathways to down-regulated the relative expression of p38 and JNK1/2 mRNA and p38, p-p38, JNK1/2, and p-JNK1/2 proteins. Our study suggested that ZS40 may serve as a potential therapeutical strategy for ulcerative colitis.
ABSTRACT
Xylooligosaccharide (XOS) is a source of prebiotics with multiple biological activities. The present study aimed to investigate the effects of XOS on mice fed a high-fat diet. Mice were fed either a normal diet or a high-fat diet supplemented without or with XOS (250 and 500 mg/kg), respectively, for 12 weeks. The results showed that the XOS inhibited mouse weight gain, decreased the epididymal adipose index, and improved the blood lipid levels, including triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels. Moreover, XOS reduced the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and alleviated the damage to the liver caused by the high-fat diet. XOS also reduced hyperlipidemia-associated inflammatory responses. Additionally, quantitative real-time polymerase chain reaction results showed that XOS intervention activated the AMP-activated protein kinase (AMPK) pathway to regulate the fat synthesis, decomposition, and ß oxidation; upregulated the mRNA expression levels of carnitine palmitoyl transferase 1 (CPT-1), peroxisome proliferator-activated receptors α (PPAR-α), and cholesterol 7-alpha hydroxylase (CYP7A1); and downregulated the mRNA expression levels of acetyl-CoA carboxylase (ACC), CCAAT/enhancer-binding protein alpha (C/EBPα), and lipoprotein lipase (LPL). On the other hand, XOS enhanced the mRNA expression levels of zonula occludens-1 (ZO-1), occludin, and claudin-1 in the small intestine; increased the strength of the intestinal barrier; and optimized the composition of the intestinal microbiota. Therefore, it was concluded that XOS regulated the intestinal barrier, changed the intestinal microecology, and played an important role in preventing hyperlipidemia through the unique anatomical advantages of the gut-liver axis.
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Chinese Sichuan pickle is a fermented food rich in microorganisms. Microorganisms have the potential to become an important new form of potent future therapeutic capable of treating human disease. Selecting vitamin C as a positive control, a lactic acid bacteria (Lactobacillus plantarum CQPC02, LP-CQPC02) isolated from Sichuan pickle was given to mice over 4 weeks to investigate the effect of CQPC02 on fatigue levels and biochemical oxidation phenomena in exercise-exhausted Institute of Cancer Research (ICR) mice. The fatigue model was established by forced swimming of mice, the levels of hepatic glycogen, skeletal muscle glycogen, lactic acid, blood urea nitrogen and free fatty acid were measured by physicochemical methods, serum serum creatine kinase (CK), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels were measured by kits, the histopathological changes in the livers of mice were observed by H&E slicing, and the mRNA changes in the livers and skeletal muscles were observed by quantitative polymerase chain reaction (qPCR). Both vitamin C and LP-CQPC02 increased swimming exhaustion time. The concentration of LP-CQPC02 and exhaustion time were positively correlated. LP-CQPC02 also increased liver glycogen, skeletal muscle glycogen and free fatty acid content in mice and reduced lactic acid and blood urea nitrogen content in a dose-dependent manner. As walnut albumin antioxidant peptide concentration increased, levels of mouse CK, AST, and AST gradually decreased. LP-CQPC02 increased SOD and CAT levels and decreased MDA levels in a dose-dependent fashion. LP-CQPC02 up-regulated expression of mRNA encoding copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese-superoxide dismutase (Mn-SOD), and CAT in swimming exhaustion mouse liver tissue. LP-CQPC02 also up-regulated alanine/serine/cysteine/threonine transporter 1 (ASCT1) expression while down-regulating syncytin-1, inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α) expression in swimming exhaustion mouse skeletal muscle. Overall, LP-CQPC02 had a clear anti-fatigue and anti-oxidation effect. This suggests that LP-CQPC02 can be developed as a microbiological therapeutic agent.
ABSTRACT
The protective effect of Lactobacillus plantarum HFY09 (LP-HFY09) on alcohol-induced gastric ulcers was investigated. Gastric morphology observation and pathological tissue sections showed that LP-HFY09 effectively relieved gastric tissue injury. The biochemical indicator detection showed that LP-HFY09 increased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione (GSH), prostaglandin E2 (PGE2), and somatostatin (SS) levels, and decreased malondialdehyde (MDA) levels. Moreover, LP-HFY09 inhibited the levels of inflammatory cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α), and elevated the level of anti-inflammatory cytokine IL-10. The quantitative polymerase chain reaction (q-PCR) examination revealed that LP-HFY09 enhanced the mRNA expression of nuclear factor E2-related factor 2 (Nrf2) and downstream genes, including copper/zinc superoxide dismutase (SOD1), heme oxygenase-1 (HO-1), gamma-glutamylcysteine synthetase (GSH1), manganese superoxide dismutase (SOD2), catalase (CAT), and GSH-Px. This study indicated that LP-HFY09 alleviated alcohol-induced gastric ulcers by increasing gastric mucosa defense factor, and inhibiting oxidative stress and the inflammatory response. PRACTICAL APPLICATIONS: LP-HFY09 has the potential to be investigated as a treatment for gastric injury induced by alcohol.
Subject(s)
Lactobacillus plantarum , Stomach Ulcer , Animals , Glutathione Peroxidase/metabolism , Lactobacillus plantarum/metabolism , Mice , Oxidation-Reduction , Oxidative Stress , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapyABSTRACT
Antarctic ice microalgae (Chlamydomonas sp.) are a polysaccharide-rich natural marine resource. In this study, we evaluated the impact of Antarctic ice microalgae polysaccharides (AIMP) on D-galactose-induced oxidation in mice. We conducted biological and biochemical tests on tissue and serum samples from mice treated with AIMP. We found that AIMP administration was associated with improved thymus, brain, heart, liver, spleen, and kidney index values. We also found that AIMP treatment inhibited the reduced aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, superoxide dismutase, glutathione peroxidase, and glutathione levels as well as the increased serum, splenic, and hepatic nitric oxide and malondialdehyde levels arising from oxidation in these animals. Pathological examination revealed that AIMP also inhibited D-galactose-induced oxidative damage to the spleen, liver, and skin of these animals. AIMP was additionally found to promote the upregulation of neuronal nitric oxide synthase, endothelial nitric oxide synthase, cuprozinc-superoxide dismutase, manganese superoxide dismutase, catalase, heme oxygenase-1, nuclear factor erythroid 2-related factor 2, γ-glutamylcysteine synthetase, and NAD(P)H dehydrogenase [quinone] 1 as well as the downregulation of inducible nitric oxide synthase in these animals. High-performance liquid chromatography analysis revealed AIMP to be composed of five monosaccharides (mannitol, ribose, anhydrous glucose, xylose, and fucose). Together, these results suggest that AIMP can effectively inhibit oxidative damage more readily than vitamin C in mice with D-galactose-induced oxidative damage, which underscores the value of developing AIMP derivatives for food purposes.
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MicroRNAs (miRNAs) play essential roles in regulating bone formation and homeostasis. Genomic variations within miRNA target sites may therefore be important sources of genetic differences in osteoporosis risk. The function of CCDC170 in bone biology is still unclear. To verify the function of CCDC170, we knocked down CCDC170 in cells and mice and searched for miRNA recognition sites within CCDC170 using the TargetScan, miRNASNP, and miRBase databases. In this study, our results demonstrated that CCDC170 plays an important role in the positive regulation of bone formation. MiR-153-3p, miR-374b-3p, miR-4274, miR-572 and miR-2964a-5p inhibited CCDC170 expression in an allele-specific manner by binding GWAS lead SNPs rs6932603, rs3757322 and rs3734806. These findings may improve our understanding of the association between CCDC170, miRNAs, GWAS lead SNPs, and osteoporosis pathogenesis and may provide a potential therapeutic target for osteoporosis therapy.
Subject(s)
Alleles , Carrier Proteins/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Osteoporosis/diagnosis , Osteoporosis/etiology , Polymorphism, Single Nucleotide , 3' Untranslated Regions , Animals , Biomarkers , Cell Line , Gene Expression Regulation , Gene Knockdown Techniques , Genetic Association Studies/methods , Genome-Wide Association Study , Humans , Mice , MicroRNAs/genetics , Osteogenesis/genetics , RNA Interference , X-Ray MicrotomographyABSTRACT
BACKGROUND: RNA binding proteins (RBPs) play an important role in a variety of cancers. However, their mechanisms in cancer progression are still limited especially in colorectal adenocarcinoma (COAD). Integrated analysis of RBPs will provide a better understanding of disease genesis and new insights into COAD treatment. METHODS: The gene expression data and corresponding clinical information for COAD were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression analysis was used to screen for RBPs associated with COAD recurrence, and multivariate Cox proportional hazards regression analyses were used to identify genes that were associated with COAD recurrence. A nomogram was constructed to predict the recurrence of COAD, and a receiver operating characteristic (ROC) curve analysis was performed to determine the accuracy of the prediction models. The Human Protein Atlas database was used in prediction models to confirm the expression of key genes in COAD patients. RESULTS: A total of 177 differentially expressed RBPs was obtained, comprising 123 upregulated and 54 downregulated. GO and KEGG enrichment analysis showed that the differentially expressed RBPs were mainly related to mRNA metabolism, RNA processing and translation regulation. Seven RBP genes (TDRD6, POP1, TDRD7, PPARGC1A, LIN28B, LRRFIP2 and PNLDC1) were identiï¬ed as prognosis-associated genes and were used to construct the prognostic model. CONCLUSIONS: We constructed a COAD prognostic model through bioinformatics analysis and the nomogram can effectively predict the 1-year, 2-year, and 3-year survival rate for COAD patients.
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OBJECTIVE: The epithelial-mesenchymal transition (EMT) pathway can mediate tumour migration, and the occurrence of EMT is closely related to the Wnt/ß-catenin signalling pathway. The purpose of this paper was to study the effect of Lactobacillus fermentum ZS09 (L. fermentum ZS09) on the EMT pathway in mouse with azoxymethane/dextran sulfate sodium salt (AOM/DSS) induced colon cancer and the potential underlying mechanism. MATERIALS AND METHODS: In this study, a mouse colon cancer model was established through intraperitoneal injection of 10 mg/kg azoxymethane (AOM) and three cycles of 2.5% dextran sulfate sodium salt (DSS) in the drinking water. H&E staining, enzyme-linked immunosorbent assay (ELISA), real-time fluorescent quantitative PCR (RT-qPCR) and Western blotting (WB) were used to study the antitumour mechanisms of L. fermentum ZS09 through the EMT pathway. RESULTS: The results of this study showed that compared with the model group, the high-dose L. fermentum ZS09 intervention group exhibited decreased serum levels of MMP-9, TNF-α, IL-6R, Ang-2 and VEGFR-2 and increased contents of DKK1 (P<0.05). The expression of Wnt/ß-catenin signalling pathway-related genes (Dv1, GSK-3ß, ß-catenin, c-myc, cyclinD1, Vim, and MMP-9) was significantly reduced, and the gene expression levels of APC, CDH1, and Axin were increased. The levels of related proteins (ß-catenin, N-cadherin, and VEGF) were downregulated, and the levels of p-ß-catenin and E-cadherin were upregulated. CONCLUSION: The results indicate that L. fermentum ZS09 could inhibit EMT and angiogenesis pathways by inhibiting the Wnt/ß-catenin signalling pathway, which could inhibit tumour metastasis.
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This study investigated kimchi-induced apoptosis in HT-29 human colon carcinoma cells. Three types of kimchi samples were prepared: standardized kimchi brined with general commercial Baechu cabbage by a standardized recipe (SK), Amtak Baechu kimchi brined with Amtak Baechu cabbage by a standardized recipe (AmK), and anticancer kimchi brined with organically cultivated Baechu cabbage by a functional recipe (AK). MTT assay, qRT-PCR, and Western blotting analysis were performed. The results indicate that AmK and AK, especially AK significantly upregulated mRNA expression of apoptosis-related genes Bim, Bax, Bak, caspase-8, -9, -3, and p53 but suppressed Bcl-xL and Bcl-2 expression. In addition, AK treatment significantly upregulated protein expression levels of caspase-3 but strikingly reduced the protein expression level of Bcl-2 (p < .05), followed by AmK treatment. Our data suggest that AK and AmK can markedly suppress the proliferation of HT-29 cells via activation of apoptosis. PRACTICAL APPLICATIONS: Colon cancer is the fourth cancer with the highest incidence in the world. Cell apoptosis is a type of programmed cell death and plays an important role in the cancer cells study. Kimchi is a traditional fermented food in Korea, with a relatively high daily consumption. Our present study used three kinds of kimchi which prepared with different main ingredients and recipes. The results suggest that organically cultivated Baechu cabbage and functional recipe in kimchi preparation play an important role in the anticancer efficacy of kimchi, which has been shown to promote induction of apoptosis in HT-29 cells.
Subject(s)
Carcinoma , Colonic Neoplasms , Fermented Foods , Apoptosis , Colonic Neoplasms/drug therapy , Fermentation , HT29 Cells , HumansABSTRACT
The purposes of this study were to explore the preventive and treatment effects of Hunan insect tea polyphenols (HITPs) on gastric injury in mice induced by HCl/ethanol and to investigate their molecular mechanisms of action. Both HITPs and ranitidine inhibited the formation and further deterioration of gastric mucosal lesions, reduced the secretion of gastric juice, and raised gastric juice pH compared to the control. The HITPs-H treated group had lower serum levels of motilin, substance P, and endothelin than the control group, but they had higher serum levels of vasoactive intestinal peptide and somatostatin. Mice treated with HITPs had lower serum levels of cytokines interleukin (IL)-6, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ than the control group. The activities of superoxide dismutase (SOD), nitric oxide, and glutathione peroxidase (GSH-Px) were higher in the gastric tissues of HITP-treated mice, but the malondialdehyde content was lower. Quantitative PCR analysis indicated that the mRNA expression of occludin, epidermal growth factor (EGF), EGF receptor (EGFR), vascular EGF (VEGF), inhibitor kappaB-α, cuprozinc-superoxide dismutase, manganese-superoxide dismutase, GSH-Px, neuronal nitric oxide synthase, and endothelial NOS increased significantly in the gastric tissues of HITP-treated mice. However, the activated B cell, inducible NOS, cyclooxygenase-2, TNF-α, IL-1 beta, and IL-6 mRNA expression levels in the HITPs group were lower than those in the control group. The protective effect of a high concentration (200 mg per kg bw) of HITPs on gastric injury induced by HCl/ethanol was stronger than that of a low concentration (100 mg per kg bw) of HITPs. High-performance liquid chromatography (HPLC) revealed that the HITPs contained cryptochlorogenic acid, (-)-epicatechin gallate, and isochlorogenic acid C. Taken together, our findings indicate that the HITPs played a role in the prevention of gastric damage. The antioxidant effect of the HITPs contributed to their potential value in the prevention and treatment of gastric injury. HITPs have broad prospects as biologically active substances for food development.
Subject(s)
Antioxidants/pharmacology , Beverages , Ethanol/toxicity , Hydrochloric Acid/toxicity , Insecta , Polyphenols/pharmacokinetics , Animals , Gastric Juice/chemistry , Mice , Polyphenols/chemistry , Purines , RNA, Messenger/genetics , RNA, Messenger/metabolism , Stomach/drug effects , Stomach/pathology , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapyABSTRACT
Liupao tea (LPT) is traditional dark Chinese tea. The effect of LPT extract on high-fat-diet-induced obese mice was investigated systematically. The results showed that LPT extract could reduce body weight and significantly alleviate liver damage and fat accumulation. LPT could also decrease the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (AKP), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) and increase the level of high-density lipoprotein cholesterol (HDL-C) in the liver. It also decreased the serum levels of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-1ß, and IL-6 and increased the serum levels of anti-inflammatory cytokines, including IL-10 and IL-4. Moreover, LPT improved the levels of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) and reduced the level of malondialdehyde (MDA) in the liver. Moreover, LPT could upregulate the mRNA and protein expressions of peroxisome proliferator-activated receptor alpha (PPAR-α), lipoprotein lipase (LPL), carnitine palmitoyltransferase 1(CPT1), and cholesterol 7 alpha-hydroxylase (CYP7A1) and downregulate those of PPAR-γ and CCAAT/enhancer-binding protein alpha (C/EBP-α) in the liver. It also increased the mRNA expression of copper/zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), CAT, gamma-glutamylcysteine synthetase 1 (GSH1), and GSH-Px. The components of LPT extract include catechin, rutin, taxifolin, and astragalin, which possibly have a wide range of biological activities. In conclusion, our work verified that LPT extract possessed an anti-obesity effect and alleviated obesity-related symptoms, including lipid metabolism disorder, chronic low-grade inflammation, and liver damage, by modulating lipid metabolism and oxidative stress.