Protective effect of Lactiplantibacillus pentosus CQZC01 in Kunming mice of subacute alcoholic liver injury.

To decrease the climbing rate of alcoholic liver disease, the protective effect in subacute alcoholic liver injury of newly isolated Lactiplantibacillus pentosus CQZC01 has been investigated. Lactiplantibacillus pentosus CQZC01 (1 × 109 CFU/kgbw) administered orally could keep weight of mice at 30.54 ± 1.15 g; alleviate alcoholic damage on hepatic morphology; decrease the activities of hyaluronidase (147 ± 19 U/L), procollagen III (4.82 ± 0.54 ng/mL), alanine transaminase (10.66 ± 2.32 U/L), and aspartate aminotransferase (15.18 ± 1.98 U/L); enhance the activities of alcohol dehydrogenase (65.15 ± 3.2 U/mgprot), aldehyde dehydrogenase (16.50 ± 0.96 U/mgprot), superoxide dismutase (623 ± 39 U/mgprot), and glutathione (19.54 ± 2.46 µmol/gprot); and decrease liver total cholesterol (3.59 ± 0.50 mmol/gprot) and triglyceride (0.88 ± 0.24 mmol/gprot) (p < 0.05). Moreover, L. pentosus CQZC01 elevated the level of interleukin-10 (IL-10; 807 ± 44 pg/mL) but significantly decreased the levels of IL-1ß (29.75 ± 5.27pg/mL), IL-6 (58 ± 8 pg/mL), and tumor necrosis factor-α (TNF-α, 564 ± 13 pg/mL). Liver malondialdehyde was also significantly decreased by treatment with L. pentosus CQZC01 from 3.61 ± 0.14  to 2.03 ± 0.49 nmol/mgprot. The relative expression of C-Jun N-terminal kinase, extracellular regulated protein kinases, and cyclooxygenase-1 was downregulated, and the SOD1, SOD2, peroxisome proliferator-activated receptor-α, glutathione peroxidase, catalase, nuclear factor erythroid-2-related factor 2, heme oxygenase-1 and nicotinamide adenine dinucleotide phosphate were upregulated by L. pentosus CQZC01. The overall protective effect of L. pentosus CQZC01 was comparable to commercial Lactobacillus delbrueckii subsp. Bulgaricus. Lactobacillus pentosus CQZC01 might be a suitable hepatoprotective measure for people who frequently ingest alcoholic drinks. PRACTICAL APPLICATION: L. pentosus CQZC01 can alleviate subacute alcoholic liver injury by raising the antioxidant status and upregulating the antioxidant-related genes.

LimosiLactobacillus pentosus Isolated from Mustard Relieves Drug-induced Constipation in Mice Fed a High-fat Diet by Modulating Enteric Neurotransmitter Function.

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.

Effect of Lactobacillus fermentum ZS40 on the NF-κB signaling pathway in an azomethane-dextran sulfate sodium-induced colon cancer mouse model.

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.

Preventive Effect of Limosilactobacillus fermentum SCHY34 on Lead Acetate-Induced Neurological Damage in SD Rats.

Lead poisoning caused by lead pollution seriously affects people's health. Lactic acid bacteria has been shown to be useful for biological scavenging of lead. In this experiment, Sprague-Dawley (SD) rats were treated with 200 mg/L of lead acetate solution daily to induce chronic lead poisoning, and oral Limosilactobacillus fermentum (L. fermentum) SCHY34 to study its mitigation effects and mechanisms on rat neurotoxicity. The L. fermentum SCHY34 showed competent results on in vitro survival rate and the lead ion adsorption rate. Animal experiments showed that L. fermentum SCHY34 maintained the morphology of rat liver, kidney, and hippocampi, reduced the accumulation of lead in the blood, liver, kidney, and brain tissue. Further, L. fermentum SCHY34 alleviated the lead-induced decline in spatial memory and response capacity of SD rats, and also regulated the secretion of neurotransmitters and related enzyme activities in the brain tissue of rats, such as glutamate (Glu), monoamine oxidase (MAO), acetylcholinesterase (AchE), cyclic adenosine monophosphate (cAMP), and adenylate cyclase (AC). In addition, the expression of genes related to cognitive capacity, antioxidation, and anti-apoptotic in rat brain tissues were increased L. fermentum SCHY34 treatment, such as brain-derived neurotrophic factor (BDNF), c-fos, c-jun, superoxide dismutase (SOD)1/2, Nuclear factor erythroid 2-related factor 2 (Nrf2), and B-cell lymphoma 2 (Bcl-2), and so on. L. fermentum SCHY34 showed a great biological scavenging and potential effect on alleviating the toxicity of lead ions.

Preventive effect of Lactobacillus plantarum HFY15 on carbon tetrachloride (CCl4 )-induced acute liver injury in mice.

Carbon tetrachloride (CCl4 ) is the main chemical causing liver damage. In this experiment, the effect of Lactobacillus plantarum HFY15 treatment on CCl4 -induced acute liver injury was investigated using mice. Fifty adult mice were randomized into five study groups, each group with 10 ml kg-1 saline, 50 mg kg-1 silymarin, and 109 CFU kg-1 L. plantarum HFY15 and LDSB per day, and all the mice expect the normal group were injected 0.8% CCl4 (10 ml kg-1 ) on the 14th day. Following the 16 h induction of the liver injury, various biochemical markers were assessed for blood and liver tissue. After L. plantarum HFY15 treatment, the content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), malondialdehyde (MDA), and reactive oxygen species (ROS) in serum decreased by 67.7%, 65.0%, 41.9%, 59.5%, and 51.5%, respectively, and the level of antioxidant enzymes (total superoxide dismutation [T-SOD], catalase [CAT], glutathione [GSH]) increased by more than twofold. Pro-inflammatory cytokine interleukin-6 (IL-6), interferon-γ (INF-γ), and tumor necrosis factor-α (TNF-α) decreased by more than 45% in serum and live. What is more, L. plantarum HFY15 increased the expression of antiapoptosis genes Bcl-2 by eightfold, inhibiting the expression of proapoptotic genes Caspase-3 and Bax by about threefold. Lactobacillus plantarum HFY15 has obvious protective effects on CCl4 -induced liver injury by inhibiting oxidation, reducing the release of inflammatory factors, and exerting suppressive effect on apoptotic process in the CCl4 -induced liver injury. Lactobacillus plantarum HFY15 can be developed as edible lactic acid bacteria for preventing liver toxicity. PRACTICAL APPLICATION: L. plantarum HFY15 can alleviate liver injury caused by carbon tetrachloride toxicity through antioxidant, anti-inflammatory and anti-apoptotic pathways.

Inhibitory Effect of Lotus Leaf-Enriched Flavonoid Extract on the Growth of HT-29 Colon Cancer Cells through the Expression of PI3K-Related Molecules.

Objectives: Lotus leaf is rich in flavonoids, and this study is aimed at examining the inhibitory effect of lotus leaf-enriched flavonoid extract (LLEFE) on HT-29 colon cancer cells through phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) expression regulation. Methods: Lotus leaves were extracted by ethanol and purified using FL-3 macroporous resin to create the LLEFE. HT-29 colon cancer cells were tested using various methods: their proliferation was observed by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, their survival status was observed by fluorescence staining, their oxidative stress level was observed by biochemical kits, and their mRNA expression was determined by quantitative polymerase chain reaction (qPCR) assay. Additionally, the composition of the flavonoids in lotus leaf was determined by HPLC. Results: The results showed that the proliferation of NCM460 normal human colon cells was not affected by 0-500 µg/mL LLEFE but the proliferation of HT-29 human colon cancer cells decreased. LLEFE increased the LDH level in an HT-29 colon cancer cell culture medium; also increased the superoxide dismutase (SOD), catalase (CAT) activities, and glutathione (GSH) level in HT-29 cells; and decreased the malondialdehyde (MDA) level. Further experimental results showed that LLEFE upregulated the expression of SOD1, CAT, and GSH mRNA and downregulated the expression of PI3K, Akt, and mammalian target of rapamycin (mTOR) in HT-29 cells. The high-performance liquid chromatography (HPLC) results showed that kaempferin, hyperoside, astragaloside, phloridzin, and quercetin were the main chemical constituents of lotus leaf. Conclusion: Lotus leaves contain functional flavonoids that inhibit the proliferation of HT-29 colon cancer cells and regulate the expression of PI3K/Akt through five important chemicals.

Anti-obesity effect of fermented lemon peel on high-fat diet-induced obese mice by modulating the inflammatory response.

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.

Prophylactic Effect of Lactobacillus fermentum TKSN02 on Gastric Injury Induced by Hydrochloric Acid/Ethanol in Mice Through Its Antioxidant Capacity.

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.

Lactobacillus fermentum ZS40 Ameliorates Inflammation in Mice With Ulcerative Colitis Induced by Dextran Sulfate Sodium.

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.

ß-Nicotinamide Mononucleotide (NMN) Administrated by Intraperitoneal Injection Mediates Protection Against UVB-Induced Skin Damage in Mice.

OBJECTIVE: Ultraviolet light is an important environmental factor that induces skin oxidation, inflammation, and other diseases. Nicotinamide mononucleotide (NMN) has the effect of anti-oxidation and improving various physiological processes. This study explores the protective effect of NMN monomers given via intraperitoneal injection on UVB-induced photodamage. METHODS: We used a murine model of UVB-induced photodamage to evaluate the effect of an NMN monomer on photoaging skin by assessing skin and liver tissue sections, serum and skin oxidative stress levels, inflammatory markers, mRNA expression, and protein expression of skin- and liver-related genes. RESULTS: The results showed that NMN treatment blocked UVB-induced photodamage in mice, maintaining normal structure and amount of collagen fibers, normal thickness of epidermis and dermis, reducing the production of mast cells, and maintaining complete organized skin structure. NMN intraperitoneal injection also maintained the normal morphology of the mouse liver after UVB exposure. Meanwhile, NMN intraperitoneal injection was found to increase antioxidant ability and regulate the proinflammatory response of the skin and liver to UVB irradiation by enhancing the activity of antioxidant enzymes, release of anti-inflammatory cytokines, reduction of hydrogen peroxide production (H2O2), and decreased inflammatory cytokines. Furthermore, RT-qPCR results indicated that NMN reduced oxidative stress of skin and liver by promoting the activation of the AMP-activated protein kinase (AMPK) signaling pathway and further increasing the expression of downstream antioxidant genes of AMPK. RT-qPCR results also revealed that NMN treatment could downregulate the mRNA expression of interleukin (IL)-6, interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α, and upregulate NF-kappa-B inhibitor-α (IκB-α) and interleukin (IL)-10 by inhibiting the activation of nuclear factor-κBp65 (NFκB-p65). Finally, NMN upregulated AMPK, IκB-α, SOD1, and CAT in the skin and downregulated NF-κBp65 protein expression, which is in line with the RT-qPCR results. CONCLUSION: Based on the above results, NMN monomer treatment with intraperitoneal injection also block the photodamage caused by UVB irradiation in mice by regulating the oxidative stress response and inflammatory response.

Antioxidant Effect of Lactobacillus fermentum CQPC04-Fermented Soy Milk on D-Galactose-Induced Oxidative Aging Mice.

The aim of this study is to evaluate the changes in soy isoflavones and peptides in soy milk after lactic acid bacterial fermentation, and explore the positive effects of fermented soy milk on an oxidative aging mouse model induced with D-galactose. We found that free soybean isoflavones and peptides increased after soy milk was fermented by Lactobacillus fermentum CQPC04. The in vivo results indicated that L. fermentum CQPC04-fermented soy milk enhanced the organ index of the liver and spleen, and improved the pathological morphology of the liver, spleen, and skin. L. fermentum CQPC04-fermented soy milk increased the enzymatic activity of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), and catalase (CAT), increased glutathione (GSH), but decreased the levels of nitric oxide (NO) and malondialdehyde (MDA) in serum, liver, and brain tissues of oxidative aging mice. The above mentioned fermented soy milk also increased the levels of collagen I (Col I), hyaluronic acid (HA), and collagen III (Col III), and decreased the levels of advanced glycation End products (AGEs) and hydrogen peroxide (H2O2). The RT-qPCR results showed that L. fermentum CQPC04-fermented soy milk upregulated the mRNA expression of nuclear factor erythroid 2?related factor (Nrf2), heme oxygenase-1 (HMOX1), quinone oxido-reductase 1 (Nqo1), neuronal nitric oxide synthase (NOS1), endothelial nitric oxide synthase (NOS3), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-superoxide dismutase (Mn-SOD), and CAT, but downregulated the expression of inducible nitric oxide synthase (NOS2) and glutamate cysteine ligase modifier subunit (Gclm) in liver and spleen tissues. Lastly, the fermented soy milk also increased the gene expression of Cu/Zn-SOD, Mn-SOD, CAT, GSH-Px, matrix metalloproteinases 1 (TIMP1), and matrix metalloproteinases 2 (TIMP2), and decreased the expression of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in skin tissue. In conclusion, L. fermentum CQPC04-fermented soy milk was able to satisfactorily delay oxidative aging effects, and its mechanism may be related to the increase in free soy isoflavones and peptides.

Hepatoprotective Effect of Lactobacillus plantarum HFY09 on Ethanol-Induced Liver Injury in Mice.

Lactobacillus plantarum is a bacterial strain that is used as a probiotic with health-promoting effects. Our study investigated the hepatoprotective effect of Lactobacillus plantarum HFY09 (LP-HFY09) in mice with ethanol-induced liver injury. The protection afforded by LP-HFY09 was evaluated by observing the morphology of hepatic tissue and measuring liver lipid indexes and function indexes, levels of anti-oxidative enzymes, and anti-inebriation enzymes, as well as oxidative metabolism-related gene expression. Gavage administration of LP-HFY09 [1 × 109 CFU/kg body weight (bw)] limited the loss of bw, alcohol damage to the liver, and maintained the normal hepatic tissue morphology. Lactobacillus plantarum HFY09 intervention in ethanol-induced mice led to decreases in serum triglyceride (TG), total cholesterol (TC), aspartic transaminase, alanine transaminase, hyaluronidase (HAase), and precollagen III (PC III), and increases in liver alcohol dehydrogenase (ADH), and acetaldehyde dehydrogenase (ALDH). Lactobacillus plantarum HFY09 assisted with alleviating inflammation by elevating the level of interleukin 10 (IL-10) and decreasing the levels of pro-inflammatory factors [IL-6, IL-1ß, and tumor necrosis factor-α (TNF)-α]. Lactobacillus plantarum HFY09 significantly elevated hepatic levels of superoxide dismutase (SOD) and glutathione (GSH), and decreased liver malondialdehyde (MDA) from 3.45 to 1.64 nmol/mg protein. Lactobacillus plantarum HFY09 exhibited an overall strong regulatory effect on liver protection when compared to that of commercial Lactobacillus delbrueckii subsp. bulgaricus. The hepatoprotective effect of LP-HFY09 was reflected by the upregulated expression of peroxisome proliferator activated-receptors α, SOD1, SOD2, glutathione peroxidase (GSH-Px), nicotinamide adenine dinucleotide phosphate (NADPH), and catalase (CAT), and the downregulated expression of cyclooxygenase-1 (COX1), c-Jun N-terminal kinase (JNK), and extracellular regulated protein kinases (ERK). Administration of LP-HFY09 at a concentration of 1.0 × 109 CFU/kg bw could be a potential intervention, for people who frequently consume alcohol.

Effects of Cold-Pressing and Hydrodistillation on the Active Non-volatile Components in Lemon Essential Oil and the Effects of the Resulting Oils on Aging-Related Oxidative Stress in Mice.

The aim of this study was to analyze the non-volatile composition and antioxidant differences of lemon essential oils (LEOs) obtained by cold-pressing vs. hydrodistillation. Pathological observations showed that LEO effectively inhibited liver injury caused by oxidative stress, and CPLEO was more effective than HDLEO. CPLEO increased serum T-AOC, SOD, GSH, and GSH-Px levels while decreasing NO, COX-2, IL-6, IL-1ß, IFN-γ, and TNF-α levels in mice with oxidative damage. The effects of CPLEO were stronger than those of HDLEO and similar to those of vitamin C. CPLEO upregulated mRNA and protein expressions of Cu/Zn-SOD, Mn-SOD, CAT, HO-1, Nrf2, and NQO1 while downregulating nNOS, iNOS, IL-1ß, COX-2, TNF-α, and NF-κB mRNA expression and nNOS, eNOS, iNOS, and COX-2 protein expression in mice with oxidative damage. The results demonstrate that LEO has good antioxidant effects and that CPLEO has a better antioxidant effect than HDLEO as it retains more active non-volatile substances.

The Effect of Lactobacillus plantarum CQPC02 on Fatigue and Biochemical Oxidation Levels in a Mouse Model of Physical Exhaustion.

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.

Lactobacillus fermentum CQPC08 protects rats from lead-induced oxidative damage by regulating the Keap1/Nrf2/ARE pathway.

In this experiment, Lactobacillus fermentum CQPC08 (LF-CQPC08) isolated from traditionally fermented pickles was used to study its mitigation effect on lead acetate-induced oxidative stress and lead ion adsorption capacity in rats. In vitro experiments showed that the survival rate in artificial gastric juice and the growth efficiency in artificial bile salt of LF-CQPC08 was 93.6% ± 2.2% and 77.2% ± 0.8%, and the surface hydrophobicity rate was 45.5% ± 0.3%. The scavenging rates of hydroxyl radical, superoxide anion, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) were 47.8% ± 0.9%, 63.9% ± 1.2%, and 83.6% ± 1.5%, respectively, and the reduction power was 107.3 ± 2.8 µmol L-1. LF-CQPC08 could not only adsorb 76.9% ± 1.0% lead ions in aqueous solution but also reduce the lead content in serum, liver, kidneys, and brain tissue of Sprague-Dawley (SD) rats, as well as maintain the cell structure and tissue state of the liver and kidneys. In addition, by examining the indicators of inflammation and oxidation in the serum, liver, and kidneys of SD rats, we found that LF-CQPC08 can reduce the proinflammatory factors interleukin (IL)-1 beta (1ß), IL-6, tumor necrosis factor alpha, and interferon gamma in the body, increase the level of anti-inflammatory factor IL-10, enhance the activity of antioxidant enzymes such as superoxide dismutase and catalase and glutathione levels in serum and organ tissues, and reduce the production of reactive oxygen species and accumulation of lipid peroxide malondialdehyde. LF-CQPC08 can also activate the Keap1/Nrf2/ARE signaling pathway to promote high-level expression of the downstream antioxidants heme oxygenase 1 (HO-1), NAD(P)H : quinone oxidoreductase 1 (NQO1), and γ-glutamylcysteine synthetase (γ-GCS). As food-grade lactic acid bacteria, LF-CQPC08 has great potential and research value in removing heavy metals from food and alleviating the toxicity of heavy metals in the future.

Inhibitory Effect of Lactococcus lactis subsp. lactis HFY14 on Diphenoxylate-Induced Constipation in Mice by Regulating the VIP-cAMP-PKA-AQP3 Signaling Pathway.

AIM: The naturally fermented yak yogurt of pastoralists in the Tibetan Plateau, China, because of its unique geographical environment and the unique lifestyle of Tibetan pastoralists, is very different from other kinds of sour milk, and the microorganisms it contains are special. Lactococcus lactis subsp. lactis HFY14 (LLSL-HFY14) is a new lactic acid bacterium isolated from naturally fermented yak yogurt. The purpose of this study was to study the inhibitory effect of the bacterium on constipation. METHODS: Constipation was induced in ICR mice with diphenoxylate, and the constipated mice were treated with LLSL-HFY14. The weight and feces of the mice were visually detected. Colonic tissues were observed on hematoxylin and eosin-stained sections. Serum indices were detected with kits. mRNA expression in the colon was determined by quantitative polymerase chain reaction assay. RESULTS: Constipation caused weight loss, the number of defecation granules, defecation weight, fecal water content decreased, and the first black stool excretion time increased. LLSL-HFY14 alleviated these symptoms, and the effects were similar to those of lactulose (drug). The pathological examination revealed that constipation caused pathological changes in the colon, and LLSL-HFY14 effectively alleviated the disease. LLSL-HFY14 increased serum levels of motilin, gastrin, endothelin, substance P, acetylcholinesterase, and vasoactive intestinal peptide (VIP) and decreased serum levels of somatostatin in constipated mice. In addition, LLSL-HFY14 upregulated VIP, cAMP, protein kinase A, and aquaporin 3 expression in colonic tissues of constipated mice in a dose-dependent manner. CONCLUSION: LLSL-HFY14 inhibited constipation, similar to lactulose, and has the potential to become a biological agent.

Lactobacillus plantarum ZS62 Alleviates Alcohol-Induced Gastric Injury in Mice via an Anti-Oxidative Mechanism.

AIM: Gastric mucosal injury is a typical characteristic of gastric diseases. The prevalence of gastric mucosal injury caused by alcohol has been on the rise, which has been considered a serious problem. The purpose of this study is to explore the protective effect on gastric injury of Lactobacillus plantarum ZS62 (LP-ZS62) isolated from naturally fermented yak yoghurt. METHODS: We established a gastric injury model through alcohol and evaluated the protective effect of LP-ZS62 on gastric injury in mice. The injury to the gastric mucosa, histopathological sections, related biochemical indicators, and related genes were examined to evaluate the protective effect of LP-ZS62. RESULTS: LP-ZS62 effectively alleviated alcohol-induced gastric injury according to visual observations of gastric tissue and pathological tissue sections. The experimental results revealed that LP-ZS62 decreased malondialdehyde (MDA) level, and elevated superoxide dismutase (SOD) and glutathione (GSH) levels in gastric tissues. Additionally, LP-ZS62 increased glutathione peroxidase (GSH-Px), prostaglandin E2 (PGE2), and somatostatin (SS) levels. LP-ZS62 also decreased inflammatory cytokines interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α) and IL-6 levels, and increased the anti-inflammatory cytokine IL-10 level. The quantitative polymerase chain reaction results showed that LP-ZS62 upregulated mRNA expression of nuclear factor E2-related factor 2 (Nrf2), copper/zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), catalase (CAT), gamma-glutamylcysteine synthetase (GSH1), and glutathione peroxidase (GSH-Px). CONCLUSION: This study confirmed that LP-ZS62 alleviated alcohol-induced gastric injury by regulating antioxidant capacity. Therefore, LP-ZS62 could be developed as a probiotic product to treat alcoholic gastric injury.

Protective effect of Lactobacillus plantarum YS3 on dextran sulfate sodium-induced colitis in C57BL/6J mice.

The protective effect of Lactobacillus plantarum YS3 (LP-YS3) on ulcerative colitis (UC) was assessed using a mouse model of dextran sodium sulfate (DSS)-induced colitis. Different concentrations of LP-YS4 were administered to the experimental mice by daily gavage. Several inflammatory and biochemical indices, such as interleukin-2 (IL-2), interleukin-10 (IL-10), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO), were examined in mouse serum and colon tissue. The mRNA and protein expression levels of c-Kit, CXC chemokine receptor type 2 (CXCR2), interleukin-8 (IL-8), and stem cell factor (SCF) in mouse colon tissue were assessed using Western blot and quantitative polymerase chain reaction (qPCR) assays. The findings indicated that LP-YS3 remarkably decreased the disease activity index (DAI) of UC mice (p < .05), inhibited colon length shortening induced by UC, and elevated the value of colon weight/length ratio. LP-YS3 could also markedly reduce (p < .05) the activities of MDA, MPO, and NO; while an increase in the GSH content in the colonic tissue of UC mice. Moreover, LP-YS3 remarkably increased (p < .05) the serum level of IL-2 in UC mice, while reduced those of IL-10, IL-6, IL-1ß, TNF-α cytokines. qPCR data revealed that LP-YS3 could markedly upregulate the expression levels of c-Kit and SCF, while downregulate those of CXCR2 and IL-8 in the colonic tissue of UC mice (p < .05). LP-YS3 exerted an outstanding protective effect on DSS-induced colitis in C57BL/6J mice, especially at higher concentrations. PRACTICAL APPLICATIONS: Lactobacillus plantarum YS3 is a newly isolated and identified lactic acid bacteria. This study confirmed that L. plantarum YS3 can inhibit colitis and has good probiotic potential, which needs further development and utilization.

Construction of a prognostic risk model of colorectal adenocarcinoma through integrated analysis of RNA-binding proteins.

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 identified 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.

Inhibitory effect of Jangkanghwan (Korean traditional food) on experimental ulcerative colitis in mice.

Jangkanghwan (JKH) can delay weight loss in mice, promote weight gain during recovery, and reduce colonic shortening and colon weight. In addition, the murine disease activity index was controlled after treatment using JKH. It can reduce the content of pro-inflammatory factors in serum and expression in tissues, such as interleukin (IL)-6, IL-1ß, tumor necrosis factor-α, interferon-γ, cyclooxygenase-2, and nuclear factor kappa-B; in contrast, the content and expression of IL-10 and the inhibitor of nuclear factor kappa-B kinase-α in the serum and tissues were increased. The mRNA expression of the colitis characteristic biomarker monocyte chemoattractant protein-1 and macrophage inflammatory protein-3α were reduced in colon tissues. Using next-generation sequencing technology, the Bacteroidetes phylum in the JKH group decreased, while the Firmicutes phylum increased, and the number of beneficial bacteria-Bifidobacteriaceae, Lactobacillaceae, and Akkermansiaceae-increased. PRACTICAL APPLICATIONS: JKH is a mixture of colonic healthy foods composed of Atractylodes macrocephala koidzumi, radish leaves, Viscum album var. coloratum, dried Zingiber officinale Roscoe, etc. According to UPLC-Q-TOF MS analysis, JKH consists mainly of 17 active substances, such as pheophorbide A, nabumetone alcohol, dehydrocostus lactone, plantamajoside, kaempferol 3, 7-dirhamnoside, quercetin 3-D-glucuronide, and viscumneoside III. We investigated the preventive effects of JKH on dextran sulfate sodium (DSS)-induced ulcerative colitis in a murine model and found that JKH can reduce the damage in mice caused by DSS treatment.