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Gliomas are the most common primary brain cancer. While it has been known that calcium-related genes correlate with gliomagenesis, the relationship between calcium-related genes and glioma prognosis remains unclear. We assessed TCGA datasets of mRNA expressions with differentially expressed genes (DEGs) and enrichment analysis to specifically screen for genes that regulate or are affected by calcium levels. We then correlated the identified calcium-related genes with unsupervised/supervised learning to classify glioma patients into 2 risk groups. We also correlated our identified genes with immune signatures. As a result, we discovered 460 calcium genes and 35 calcium key genes that were associated with OS. There were 13 DEGs between Clusters 1 and 2 with different OS. At the same time, 10 calcium hub genes (CHGs) signature model were constructed using supervised learning, and the prognostic risk scores of the 3 cohorts of samples were calculated. The risk score was confirmed as an independent predictor of prognosis. Immune enrichment analysis revealed an immunosuppressive tumor microenvironment with upregulation of checkpoint markers in the high-risk group. Finally, a nomogram was generated with risk scores and other clinical prognostic independent indicators to quantify prognosis. Our findings suggest that calcium-related gene expression patterns could be applicable to predict prognosis and predict levels of immunosuppression. [ABSTRACT FROM AUTHOR]

Colon cancer is the most common type of malignant tumor. The cytotoxicity effect of lactic acid bacteria may be active by inhibiting cancer cell proliferation, producing anticancer compounds, and inducing apoptosis in cancer cells, but the mechanism is unclear. Our previous study revealed that Lactobacillus acidophilus KLDS1.0901 has good probiotic properties. In this study, We screened out the highest inhibition rate of L. acidophilus KLDS1.0901 and assessed the effects on the proliferation of HT-29, Caco-2, and IEC-6 cells. Then, the apoptosis mechanism of HT-29 cells was studied when treated with L. acidophilus KLDS1.0901. Results showed that L. acidophilus KLDS1.0901 inhibited the proliferation of HT-29 and Caco-2 cells in a dose-dependent manner and reached the maximum under the condition of multiplicity of infection (MOI) = 100 (rate of Lactobacillus to cells) at 48 h. With the increase in time and MOI, reactive oxygen species in HT-29 cells, the apoptosis rates of HT-29 cells were increased, and the amount of blue fluorescence of the cells was also increased after Hoechst 33258 staining. Furthermore, L. acidophilus KLDS1.0901 reduced the mitochondrial membrane potential of HT-29 cells. Notably, 1,133 differentially expressed genes were screened by transcriptomics research, including 531 up-regulated genes and 602 down-regulated genes. These genes were involved in the nuclear factor κB and PI3K-AKT signaling pathways related to the apoptosis of HT-29 cells. These findings suggested that L. acidophilus KLDS1.0901 has the potential to be used in the development of a new type of functional foods for adjuvant treatment of colon cancer. [ABSTRACT FROM AUTHOR]

Cow mastitis, which significantly lowers milk quality, is mainly caused by pathogenic bacteria such as E. coli. Previous studies have suggested that lactic acid bacteria can have antagonistic effects on pathogenic bacteria that cause mastitis. In the current study, we evaluated the in vitro and in vivo alleviative effects of L. plantarum KLDS 1.0344 in mastitis treatment. In vitro antibacterial experiments were performed using bovine mammary epithelial cell (bMEC), followed by in vivo studies involving mastitis mouse models. In vitro results indicate that lactic acid was the primary substance inhibiting the E. coli pathogen. Meanwhile, treatment with L. plantarum KLDS 1.0344 can reduce cytokines' mRNA expression levels in the inflammatory response of bMEC induced by LPS. In vivo , the use of this strain reduced the secretion of inflammatory factors IL-6, IL-1β, and TNF-α, and decreased the activity of myeloperoxidase (MPO), and inhibited the secretion of p-p65 and p-IκBα. These results indicate that L. plantarum KLDS 1.0344 pretreatment can reduce the expression of inflammatory factors by inhibiting the activation of NF-κB signaling pathway, thus exerting prevent the occurrence of inflammation in vivo. Our findings show that L. plantarum KLDS 1.0344 has excellent properties as an alternative to antibiotics and can be developed into lactic acid bacteria preparation to prevent mastitis disease. [ABSTRACT FROM AUTHOR]

Increasing evidence has indicated that oxidative stress is associated with the health of infants. Bifidobacterium , especially B. longum subsp. longum strains, are abundant in the gut microbiota of infants, which may have the potential to ameliorate oxidative damage. Thus, this study aimed to isolate and screen B. longum subsp. longum strains with probiotic characters and antioxidant properties as infants' dietary supplements. In this study, 24 B. longum subsp. longum strains were isolated from 15 healthy infants identified via 16S rRNA and heat shock protein 60 (hsp 60) sequences. B. longum subsp. longum B13, F2, K4, K5, K10, K13, and K15 strains were selected based on high values obtained from autoaggregation, hydrophobicity, and adhesion assays to HT-29 cells. Among these seven strains, B. longum subsp. longum F2, K5, K10, and K15 were selected according to the high tolerance of gastrointestinal tract conditions compared to Bifidobacterium animalis subsp. lactis BB-12. Among these four strains, B. longum subsp. longum K5 was susceptible to common antibiotics and showed the highest intestinal epithelial cell proliferation of CCD 841 CoN. Additionally, B. longum subsp. longum K5 showed a strong antioxidant capacity, and its supernatant exhibited better activity of reducing power, hydroxyl radical scavenging, and DPPH radical scavenging than that of the intact cells with cell-free extracts. The findings indicated that B. longum subsp. longum K5 could be used as a probiotic candidate in infant nutrition. [ABSTRACT FROM AUTHOR]

Alternative splicing (AS) event is a novel biomarker of tumor tumorigenesis and progression. However, the comprehensive analysis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is lacking. Differentially expressed analysis was used to identify the differentially expressed alternative splicing (DEAS) events between HCC or ICC tissues and their normal tissues. The correlation between DEAS events and functional analyses or immune features was evaluated. The cluster analysis based on DEAS can accurately reflect the differences in the immune microenvironment between HCC and ICC. Forty-five immune checkpoints and 23 immune features were considered statistically significant in HCC, while only seven immune checkpoints and one immune feature in ICC. Then, the prognostic value of DEAS events was studied, and two transcripts with different basic cell functions (proliferation, cell cycle, invasion, and migration) were produced by ADHFE1 through alternative splicing. Moreover, four nomograms were established in conjunction with relevant clinicopathological factors. Finally, we found two most significant splicing factors and further showed their protein crystal structure. The joint analysis of the AS events in HCC and ICC revealed novel insights into immune features and clinical prognosis, which might provide positive implications in HCC and ICC treatment. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that the Lactobacillus plantarum bacteria strain could be effective in ulcerative colitis (UC) management. However, its effects are strain-specific and the related mechanisms for its attenuating effects on UC remain unclear. This study aimed to elucidate the underlying mechanisms for the protective effect of L. plantarum on UC. Firstly, 15 L. plantarum strains were screened for potential probiotic characteristics with good tolerance to simulated human gastrointestinal transit and adhesion. Secondly, the inflammatory response of selected strains to the Caco-2 cells induced by lipopolysaccharide (LPS) was measured. Finally, an in vivo mouse model induced by dextran sulfate sodium (DSS) was used to assess the beneficial effects and likely action mechanisms the successfully screened in vitro strain, L. plantarum L15. In vitro results showed that L. plantarum L15 possessed the highest gastrointestinal transit tolerance, adhesion and reduction of pro-inflammatory abilities compared to the other screened strains. In vivo , high dose of L. plantarum L15 supplementation increased the body weight, colon length and anti-inflammatory cytokine production. Pro-inflammatory cytokine production, disease activity index (DAI) levels and myeloperoxidase (MPO) parameters decreased using this strain. In addition, L. plantarum L15 alleviated the histopathological changes in colon, modulated the gut microbiota, and decreased LPS secretion. The activities of this strain down-regulated the expression of TLR4 and MyD88 genes as well as genes associated with NF-κB signaling pathway. Our findings present L. plantarum L15 as a new probiotic, with promising application for UC management. [ABSTRACT FROM AUTHOR]

Human milk is compatible with infant intestinal microbiota and is vital for infant health. However, most infants do not receive sufficient exclusive breastfeeding, and the effects of including other types of animal milk on the gut microbiota of infants are unclear. Therefore, the objective of this study was to elucidate the impact of milk from various animal sources on infant fecal microbiota through in vitro fermentation. The types of milk assessed include cow milk, goat milk, camel milk, mare milk, human milk, and infant formula milk. Here we determined the gas pressure, pH, and microbiota after 24 h fermentation. Results showed that mare milk had the lowest gas pressure rating, with levels similar to human milk. More so, pH analysis demonstrated that other milk types were identical to human milk. Bacterial 16S rRNA gene sequence analysis revealed that all milk types increased the abundance of Bifidobacterium and Lactobacillus , which was proportional to the lactose content of milk. Moreover, mare milk also significantly increased the relative abundance of Akkermansia. Collectively, results from mare milk (gas pressure, pH, and microbiota) were comparable to that of human milk, and thus support the theoretical basis for exploring the development of a mare milk-based infant formula. Distinct effects of milks from various animal types on infant fecal microbiota through in vitro fermentations. [ABSTRACT FROM AUTHOR]

The microbiota is directly involved in the development and modulation of the intestinal immune system. In particular, members of the genus Bifidobacterium play a primary role in immune regulation. In the present study, Bifidobacterium bifidum H3-R2 was screened from 15 bifidobacterium strains by in vitro experiment, showing a positive tolerance to digestive tract conditions, adhesion ability to intestinal epithelial cells and a regulatory effect on immune cell activity. Immunostimulatory activity of B. bifidum H3-R2 was also elucidated in vivo in cytoxan (CTX)-treated mice. The results showed that the administration of B. bifidum H3-R2 ameliorated the CTX-induced bodyweight loss and imbalanced expression of inflammatory cytokines, enhanced the production of secretory immunoglobulin A (SIgA), and promoted splenic lymphocyte proliferation, natural killer (NK) cell activity and phagocytosis of macrophages in immunosuppressed mice. In addition, B. bifidum H3-R2 restored injured intestinal mucosal, and increased the villus length and crypt depth in CTX-treated mice. The results could be helpful for understanding the functions of B. bifidum H3-R2, supporting its potential as a novel probiotic for immunoregulation. [ABSTRACT FROM AUTHOR]

Human milk is closely correlated with infant gut microbiota and is important for infant development. However, most infants receive exclusively insufficient breast milk, and the discordance between effects of commercial formula and human milk exists. To elucidate the differences induced by various feeding methods, we determined microbiota and metabolites composition in fecal samples from 77 healthy infants in Northeast China and identified the differences in various feeding methods. Bacterial 16S rRNA gene sequence analysis demonstrated that the fecal samples of exclusively breastfed (BF) infants were abundant in Bifidobacterium and Lactobacillus ; the mixed-fed (MF) infants had the highest abundance of Veillonella and Klebsiella ; the exclusively formula-fed (FF) infants were enriched in Bacteroides and Blautia ; and the complementary food-fed (CF) infants were associated with higher relative abundance of Lachnoclostridium and Akkermansia. Liquid chromatography–mass spectrometry (LC-MS)-based metabolomics data revealed that the fecal samples of BF infants had the highest abundance of dl-citrulline, threonine, l-proline, l-glutamine, guanine, and l-arginine; the MF infants were abundant in d-maltose, stearidonic acid, capric acid, and myristic acid; the FF infants were enriched in itaconic acid, 4-pyridoxic acid, prostaglandin B2, thymine, dl-α-hydroxybutyric acid, and orotic acid; and the CF infants were associated with higher relative abundance of taurine, l-tyrosine, adenine, and uric acid. Furthermore, compared with the BF infants, the MF and FF infants were more abundant in fatty acid biosynthesis. Collectively, these findings will provide probable explanations for some of the risks and benefits related to infant feeding methods and will support a theoretical basis for the development of infant formula. [ABSTRACT FROM AUTHOR]

Multi-omics analyses, disease prediction, machine learning, complex diseases, data integration analysis Keywords: multi-omics analyses; disease prediction; machine learning; complex diseases; data integration analysis EN multi-omics analyses disease prediction machine learning complex diseases data integration analysis 1 3 3 08/23/21 20210818 NES 210818 Physiological data are the reflections of the physiological status of living systems (Terranova et al., [5]). [Extracted from the article]

Diabetes has become the second most severe disease to human health. Probiotics are important for maintaining gastrointestinal homeostasis and energy balance and have been demonstrated to play a positive role in the prevention and treatment of metabolic syndromes, such as obesity, inflammation, dyslipidemia, and hyperglycemia. The objective of this study was to screen potential antidiabetic strains in vitro and evaluate its effects in vivo. For the in vitro section, dipeptidyl peptidase IV (DPP-IV) inhibitory and antioxidant activities of 14 candidate Lactobacillus spp. strains were tested. Then hydrophobicity and acid and bile salt tolerance assays were determined. The most promising in vitro strain was further evaluated for its antidiabetic properties in vivo using type 2 diabetes mice induced by high-fat diet and intraperitoneal injection of streptozotocin (STZ). The reference strain for this study was Lactobacillus rhamnosus GG. Results showed that cell-free excretory supernatants and cell-free extracts of Lactobacillus acidophilus KLDS1.0901 had better DPP-IV inhibitory activity, antioxidative activities, and biological characteristics than other strains. At the end of the treatment, we found that L. acidophilus KLDS1.0901 administration decreased the levels of fasting blood glucose (FBG), glycosylated hemoglobin, insulin in serum and AUCglucose, and increased the level of glucagon-like peptide 1 in serum compared with diabetic mice (p < 0.05). Moreover, L. acidophilus KLDS1.0901 supplementation increased the activities of superoxide dismutase, glutathione peroxidase, the level of glutathione, and reduced the level of malondialdehyde in serum. These results indicated that L. acidophilus KLDS1.0901 could be used as a potential antidiabetic strain; its application as food supplement and drug ingredient is thus recommended. [ABSTRACT FROM AUTHOR]

Foodborne pathogens are a major source of morbidity and mortality worldwide. For this cause, exploring various effective ways of suppressing their spread is at the forefront of many research projects. The current study aims to investigate the in vitro organic acid production of S. thermophilus KLDS 3.1003 and L. bulgaricus KLDS 1.0207 strains, their in vivo suppression of and immuno-modulatory effects against E. coli ATCC 25922 and S. aureus ATCC 25923 pathogens. First, lactic and acetic acid production using three carbon sources – 1% glucose (control), 1% sucrose, and 1% fructo-oligosaccharides (FOS) – was determined by HPLC. For the in vivo section, a total of 40 BALB/c mice were purchased and divided into 10 treatment groups (control and nine treatments). Animals were given 1 week to acclimatize and then fed treatment diets for 14 days. Afterward, hematological (RBC, WBC, HB, PLT, Neutrophils, Eosinophils, Lymphocytes, and Monocytes) and histopathological analyses were carried out. All analyses were done in triplicate. Results show that lactic and acetic acid productions for both strains increased with supplementation and were highest after 1% FOS addition. Regardless of carbon source, L. bulgaricus KLDS 1.0207 produced higher (P < 0.05) amounts of lactic and acetic acids than S. thermophilus KLDS 3.1003. Also, generally better hematological parameters in probiotic groups than the control (P < 0.05) were observed. In some instances, mice in probiotic treatment groups had better immunity levels (lymphocytes, monocytes, neutrophils, eosinophils) than those in the control and pathogen groups. Histopathological studies showed that no anomalies were associated with S. thermophilus KLDS 3.1003 and L. bulgaricus KLDS 1.0207 administration. In conclusion, S. thermophilus KLDS 3.1003 and L. bulgaricus KLDS 1.0207 strains are not only probiotic candidates but can have therapeutic applications. [ABSTRACT FROM AUTHOR]

Modulating gut microbiota to promote host health is well recognized. Therefore, people consume dietary products containing traditional probiotics in wishing to improve their health, and they need more research-based advices on how to select products with suitable probiotic species. Probiotic designers are sometimes confused about how to design precision products for different consumers by taking advantages of different probiotic species' strengths. Additionally, large-scale analyses on traditional probiotic complementarity potentials and their roles in gut microbiome related to common diseases are not well understood. Here, we comprehensively analyzed 444 genomes of major traditional probiotic (sub) species (MTPS, n = 15) by combining one newly sequenced genome with all of the public NCBI-available MTPS-related genomes. The public human fecal metagenomic data (n = 1,815) of eight cohorts were used to evaluate the roles of MTPS, compared to other main gut bacteria, in disease association by examining the species enrichment direction in disease group or the control group. Our work provided a comprehensive genetic landscape and complementarity relations for MTPS and shed light on personalized probiotic supplements for consumers with different health status and the necessity that researchers and manufactures could explore novel probiotics as well as traditional ones. [ABSTRACT FROM AUTHOR]

Enterococcus durans KLDS6.0930 has previously been shown to have probiotic potential. However, being a potential clinical pathogen, it becomes necessary to evaluate its safety status for novel potential probiotic use. The purpose of this study is to systematically evaluate the safety of E. durans KLDS6.0930 based on its genomics, phenotypic characteristics and oral toxicity. The complete genome of E. durans KLDS6.0930 was sequenced and analyzed for safety-related genes. Antibiotic susceptibility and the production of harmful metabolites were tested. A 28-day repeated oral dose toxicity test was implemented in rats. In vitro, E. durans KLDS6.0930 was resistant to five antibiotics, with intrinsic resistances to four antibiotics and no identified genes for the last. E. durans KLDS6.0930 was not hemolytic and virulence factors were non-functional in its genome. E. durans KLDS6.0930 produced a small amount of tyramine and phenethylamine; genes encoding tyramine decarboxylase were identified. In addition, genotype and phenotype analyses showed that the strain did not have the ability to generate D-lactic acid, indole, or nitroreductase. In vivo, E. durans KLDS6.0930 did not induce adverse effects on the organs, hematological and serum biochemical parameters, or cecal bacterial populations in the oral toxicity test. These results indicate that E. durans KLDS6.0930 can be safely used as a potential probiotic for human consumption and animal feed. [ABSTRACT FROM AUTHOR]