Lozenges with probiotic strains enhance oral immune response and health.

OBJECTIVE: Probiotics participate in regulating oral microbiota and reducing the prevalence of oral diseases; however, clinical research on probiotics is insufficient. Therefore, in this study, we performed in vitro screening of potential oral protective probiotic strains and then evaluated the clinical efficacy of the selected strains on maintaining oral health. MATERIALS AND METHODS: Fifty healthy individuals were recruited and randomly assigned into the placebo group and probiotics group, which included three strains of probiotics, Lactobacillus salivarius subs. salicinius AP-32, Lactobacillus paracasei ET-66, and Lactobacillus plantarum LPL28. Each group was blindly administered placebo or probiotics for four weeks. RESULTS: Next-generation sequencing results showed that the oral microbiota of Lactobacillus salivarius in the oral cavity were significantly increased in subjects supplemented with mixed probiotic lozenges. The anti-bacterial activities of viable probiotics were observed within two weeks. Both IgA levels and Lactobacillus and Bifidobacterium abundances in the oral cavity were significantly increased in the experimental groups, along with a reduced formation of plaque. Most participants reported that their oral health conditions and intestinal symptoms had improved. CONCLUSIONS: Overall, our clinical study suggests that oral probiotic lozenges may enhance oral immunity, modulate oral microbiota, and improve oral health.

Plasma Glial Cell-Derived Neurotrophic Factor and Insulin-like Growth Factor-1 Levels Were Not Correlated with the Severity of Age-Related Hearing Impairment in Humans.

The relationship between plasma glial cell-derived neurotrophic factor (GDNF) or insulin-like growth factor-1 (IGF-1) levels and age-related hearing impairment (ARHI) has not been reported in humans. By cross-sectional design, 268 subjects older than 33, with normal cognitive function and normal or symmetric sensorineural hearing loss, were selected randomly. Multivariate linear regression analysis was performed to test the impact of the plasma GDNF or IGF-1 level on the pure tone threshold of low frequencies (PTA-low) and high frequencies (PTA-high), respectively. Results showed that plasma GDNF and IGF-1 levels decreased with age without statistical significance. Multivariate linear regression analysis showed that GDNF or IGF-1 levels were not significantly correlated with PTA-low or PTA-high after adjusting age, gender, body mass index, systemic diseases, habits, and noise exposure. In conclusion, plasma GDNF or IGF-1 levels were not associated with the severity of ARHI in humans. However, these findings did not support the roles of GDNF or IGF-1 genotypes on hearing.

Potential of probiotic strains to modulate the inflammatory responses of epithelial and immune cells in vitro.

Lactobacilli are important human commensal microbiota that are considered to be probiotic as they have been shown to reduce pathogenic infections and chronic inflammation. This study compared 4 strains of lactobacilli for their probiotic potential. These 4 strains showed varying capacities for adhesion and cytokine induction (interleukin [IL]-8 and IL-10) in different human epithelial cells, such as primary cultures of buccal cavity cells, and established cell lines derived from epithelia of the pharynx, intestine and cervix. After exposure to lactobacilli, secretion of cytokines (IL- 10, IL-12p70, interferon-?, and tumor necrosis factor-?) was induced at varying levels in different cultures of human immune cells, including dendritic cells, monocyte-depleted peripheral blood mononuclear cells, CD14+ cells, CD4+CD25- T cells, and regulatory T-cells. Growth inhibition of pathogenic strains was detectable in the presence of lactobacilli in vitro. Moreover, among the 4 strains tested, Lactobacillus salivarius sp. salicinius AP-32 was found to have the highest probiotic potential. This study highlights the complex host-pathogen-microbiota interactions and indicates that a combination of strains may have to be used to provide all the desirable probiotic benefits.

Eradication of Helicobacter pylori infection by the probiotic strains Lactobacillus johnsonii MH-68 and L. salivarius ssp. salicinius AP-32.

BACKGROUND: The current therapy for Helicobacter pylori infection includes antimicrobial agents and proton pump inhibitors. We have examined the ability of Lactobacillus spp. to inhibit H. pylori infection. MATERIALS AND METHODS: Probiotic strains isolated from samples of adult feces, infant feces, breast milk, and vaginal swab collected from healthy volunteers in Taiwan and commercially available strains were screened for antagonism toward H. pylori. Inhibition liquid culture assay was used to screen potential anti-H. pylori activity. Then, we performed agar plate inhibition assay, and assays to determine the capacity of probiotics for adhesion, and inhibition and killing of H. pylori, and measured the levels of IL-8 and IL-10. Using animal models, we studied regulation of gastric acid and histopathological changes accompanying anti-H. pylori activity. RESULTS: We found that six of the tested strains suppressed urease activity of H. pylori: Lactobacillus acidophilus TYCA08, L. acidophilus TYCA15, L. johnsonii MH-68, and L. salivarius subsp. salicinius AP-32 were more effective than the others. In vivo, L. johnsonii MH-68 and L. salivarius subsp. salicinius AP-32 alone or in combination, reduced the H. pylori load in the gastric mucosa, and also reduced inflammatory chemokine expression and lymphocyte infiltration. CONCLUSIONS: Lactobacillus johnsonii MH-68 and L. salivarius subsp. salicinius AP-32 effectively suppress H. pylori viability, and when used as probiotics, they may help decrease the occurrence of gastritis, and even reduce the risk of H. pylori infection.

Comparison of the test characteristics of procalcitonin to C-reactive protein and leukocytosis for the detection of serious bacterial infections in children presenting with fever without source: a systematic review and meta-analysis.

STUDY OBJECTIVE: We determine the usefulness of the procalcitonin for early identification of young children at risk for severe bacterial infection among those presenting with fever without source. METHODS: The design was a systematic review and meta-analysis of diagnostic studies. Data sources were searches of MEDLINE and EMBASE in April 2011. Included were diagnostic studies that evaluated the diagnostic value of procalcitonin alone or compared with other laboratory markers, such as C-reactive protein or leukocyte count, to detect severe bacterial infection in children with fever without source who were aged between 7 days and 36 months. RESULTS: Eight studies were included (1,883 patients) for procalcitonin analysis, 6 (1,265 patients) for C-reactive protein analysis, and 7 (1,649 patients) for leukocyte analysis. The markers differed in their ability to predict serious bacterial infection: procalcitonin (odds ratio [OR] 10.6; 95% confidence interval [CI] 6.9 to 16.0), C-reactive protein (OR 9.83; 95% CI 7.05 to 13.7), and leukocytosis (OR 4.26; 95% CI 3.22 to 5.63). The random-effect model was used for procalcitonin analysis because heterogeneity across studies existed. Overall sensitivity was 0.83 (95% CI 0.70 to 0.91) for procalcitonin, 0.74 (95% CI 0.65 to 0.82) for C-reactive protein, and 0.58 (95% CI 0.49 to 0.67) for leukocyte count. Overall specificity was 0.69 (95% CI 0.59 to 0.85) for procalcitonin, 0.76 (95% CI 0.70 to 0.81) for C-reactive protein, and 0.73 (95% CI 0.67 to 0.77) for leukocyte count. CONCLUSION: Procalcitonin performs better than leukocyte count and C-reactive protein for detecting serious bacterial infection among children with fever without source. Considering the poor pooled positive likelihood ratio and acceptable pooled negative likelihood ratio, procalcitonin is better for ruling out serious bacterial infection than for ruling it in. Existing studies do not define how best to combine procalcitonin with other clinical information.

The effect of healthcare policy signals on patients' perceived value, trust and intention to use services offered by a healthcare provider.

OBJECTIVE: Capitation is a healthcare reimbursement scheme in which a healthcare provider equitable access to funding for services and greater flexibility and budgeting. The objectives of the study are to investigate the effect of capitation signaling on patients' perceived value and trust and on their use intention. METHODS: This study was a scenario-based survey to examine interaction design, including capitation policy information and value-added health services information, which act as a combination of to test the hypotheses using signaling theory. Subject may receive the information about health services, information about a capitation policy, both of these two signals, or neither of them. RESULTS: The results of this study show that signal capitation policy and value-added health service information positively affects patients' perceived value, but not patients' trust. When a patient receives a signal either capitation policy information or value-added health service information, their perceived value, trust, and use intention are significantly higher than those who receive neither signal. CONCLUSION: We suggest that high-quality healthcare institutions should consider distinguishing themselves from other low-quality providers by signaling information and allocate resources on value-added health services to enhance patients' awareness of healthy behavior and benefit from implementing a capitation payment scheme. This research contributes to healthcare stakeholders, especially policymakers and service providers, in terms of how best to engage with patients.

Association between various breathing indexes during sleep and the Epworth Sleepiness Scale score in adults.

Some breathing indexes during sleep, including the apnea-hypopnea index, oxygen desaturation index, and oxygen saturation during sleep, can be recorded by overnight polysomnography. We aimed to investigate the association of various breathing indexes during sleep with the Epworth Sleepiness Scale (ESS) score in adults. We retrospectively collected the clinical and overnight polysomnography data of 2829 adults aged 20 years or older from November 2011 to June 2017. The association of various breathing indexes during sleep and ESS score was analyzed using univariate and multivariate logistic regression analysis for all adults (20-91 years), and in each sex and of body mass index (<26 kg/m2 vs ≥26 kg/m2). The mean ESS score was 6.2 (standard deviation = 4.3; range = 0-24) for all adults. After adjustment for age, sex, many common diseases, and health-related habits, apnea-hypopnea index, oxygen desaturation index, percentage of oxygen saturation below 90% during sleep, and percentage of oxygen saturation below 85% during sleep were significantly positively associated with ESS score in all adults, whereas mean oxygen saturation during sleep, minimal oxygen saturation during sleep, and awake oxygen saturation during sleep were significantly negatively associated with ESS score in all adults. In subgroup analysis, we found that the association between breathing indexes during sleep and ESS score was similar in both sex, but was significant in subjects of body mass index ≥ 26 kg/m2. All breathing indexes during sleep had significant positive or negative correlation with ESS score in all adults, especially in obese subjects.

Impact of cognitive behavior therapy on osteoarthritis-associated pain, insomnia, depression, fatigue, and physical function in patients with knee/hip osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.

Background: This meta-analysis aimed at evaluating the efficacy of cognitive behavior therapy (CBT) against osteoarthritis-associated symptoms in patients with knee/hip osteoarthritis. Methods: Medline, PubMed, Cochrane Library, and EMBASE databases were searched from inception to July 2022 to identify randomized controlled trials (RCTs) comparing the efficacy of CBT with other treatment approaches in adults with confirmed knee/hip osteoarthritis. The pain intensity (primary outcome) and the secondary outcomes including insomnia severity, sleep efficiency, physical function as well as the severity of depression and fatigue were assessed at two time points (i.e., immediately after treatment and during the follow-up period). The effect size is expressed as standardized mean difference (SMD) with SMDs of < 0.2, 0.2-0.5, and 0.5-0.8, and > 0.8 representing negligible, small, medium, and large effect sizes, respectively. Results: Fifteen RCTs were included for analysis. Immediately after CBT intervention, meta-analysis showed similar treatment effect in pain severity [SMD = -0.46, 95% confidence interval (CI): -0.95 to 0.04, 11 studies, 1557 participants] and other symptoms including depression (SMD = -0.26, 95% CI: -0.58 to 0.06, five studies, 735 participants), fatigue (SMD = -2.44, 95% CI:-6.53 to 1.65, two RCTs, 511 participants), and physical function (SMD = -0.11, 95% CI:-0.25 to 0.02, five RCTs, 720 participants) between CBT and control groups, while there was an improvement in insomnia severity (SMD = -0.65, 95% CI: -1.06 to -0.24, four RCTs, 639 participants, medium treatment effect) and sleep efficiency (SMD = 0.32, 95% CI: 0.04 to 0.59, three RCTs, 352 patients, small treatment effect). During follow-up, CBT improved pain severity (SMD = -0.52, 95% CI: -1.03 to -0.01, eight studies, 1447 participants, medium treatment effect), insomnia (SMD = -0.43, 95% CI: -0.85 to -0.01, three RCTs, 571 participants, small treatment effect), and depression (SMD = -0.39, 95% CI: -0.59 to -0.18, four RCTs, 791 participants, small treatment effect). Nevertheless, sleep efficiency, fatigue, and physical function were not improved in the follow-up period. Conclusion: Our results may suggest the durability of CBT-associated treatment benefits, supporting its role as a potential promising alternative or complementary intervention for patients with knee/hip osteoarthritis, especially against pain and insomnia. Future large-scale investigations are warranted to verify our findings. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022331165].

Impact of the food grade heat-killed probiotic and postbiotic oral lozenges in oral hygiene.

The oral cavity plays a crucial role in food digestion and immune protection. Thus, maintaining oral health is necessary. Postbiotic and heat-killed probiotic cells have shown increased antibacterial potential with stable viability compared with live strains. However, clinical evidence regarding their effect on oral health is insufficient. Therefore, in this study, we tested postbiotic lozenges of Lactobacillus salivarius subsp. salicinius AP-32, L. paracasei ET-66, and L. plantarum LPL28 and heat-killed probiotic lozenges of L. salivarius subsp. salicinius AP-32 and L. paracasei ET-66 for their effect on oral health. In total, 75 healthy individuals were blindly and randomly divided into placebo, postbiotic lozenge, and heat-killed probiotic lozenge groups and were administered the respective lozenge type for 4 weeks. Postbiotic and heat-killed probiotic lozenge groups demonstrated antibacterial activities with a considerable increase in L. salivarius in their oral cavity. Furthermore, their salivary immunoglobulin A, Lactobacillus, and Bifidobacterium increased. Subjective questionnaires completed by the participants indicated that participants in both the experimental groups developed better oral health and intestinal conditions than those in the placebo group. Overall, our study revealed that a food additive in the form of an oral postbiotic or heat-killed probiotic lozenge may effectively enhance oral immunity, inhibit the growth of oral pathogens, and increase the numbers of beneficial oral microbiota.

Understanding consumer behavior in the multimedia context: incorporating gamification in VR-enhanced web system for tourism e-commerce.

This study aims to investigate how gamification and virtual reality (VR)-enhanced web services can be integrated to influence consumer behavior in the context of tourism e-commerce. A gamified VR-enhanced tourism web system (VRTWS) was designed and developed for this investigation, while a research framework with 12 hypotheses was proposed and empirically tested by adopting PLS-SEM approach to analyze 208 valid data collected from survey. The results reveal that both Enjoyment and Activation in Gamification significantly and positively affected Media Richness. Additionally, Media Richness significantly and positively affected both Usefulness and Ease of Use in using VR technology with gamification. Also, a user's Perceived Value is not only positively affected by Usefulness and Ease of Use but also Interactivity and Immersion in a gamified VRTWS. Immersion was found to be positively affected by Presence. Through the positive effect on Satisfaction, user's Perceived Value had positive effect on the Intention toward adoption. The proposed gamified VRTWS and the study results with implications are expected to be referenced by the researchers and practitioners for managing incorporation of gamification into designing, developing, and managing their VR-enhanced service in tourism e-commerce.

Lactobacillus spp. reduces ethanol-induced liver oxidative stress and inflammation in a mouse model of alcoholic steatohepatitis.

Alcoholic steatohepatitis (ASH) is a complex multifactorial disease that can lead to liver fibrosis and cirrhosis if not treated promptly. Alcohol-induced oxidative stress and inflammation are the main factors that cause steatohepatitis and liver injury; however, probiotic bacteria in the gastrointestinal tract have been revealed to regulate immune responses and reduce oxidative stress, suggesting that functional probiotics could help to prevent ASH and liver injury. Despite numerous reports on the interactions between ASH and probiotics, the mechanisms underlying probiotic-mediated liver protection remain unknown. Therefore, the aim of the present study was to screen probiotics with high antioxidant capacity and investigate the ability of different probiotic combinations to reduce alcoholic liver disease (ALD) in a mouse model. It was identified that Lactobacillus plantarum (TSP05), Lactobacillus fermentum (TSF331) and Lactobacillus reuteri (TSR332) neutralized free radicals and displayed high antioxidant activity in vitro. In addition, these three functional probiotic strains protected mice from alcohol-induced liver injury in vivo. Mice treated with the probiotics demonstrated significantly lower alanine aminotransferase, aspartate aminotransferase and triglyceride levels, which were associated with the downregulation of the proinflammatory cytokines TNF-α and IL-6. Furthermore, probiotic treatment upregulated glutathione and glutathione peroxidase activity, which are bioindicators of oxidative stress in the liver. Collectively, the present results indicated that Lactobacillus strains TSP05, TSF331 and TSR332 reduced oxidative stress and inflammatory responses, thus preventing ASH development and liver injury.

Randialic acid B and tomentosolic acid block formyl peptide receptor 1 in human neutrophils and attenuate psoriasis-like inflammation in vivo.

Psoriasis is a long-lasting inflammatory skin disease lacking proper cure. Dysregulated activation of neutrophils is a major pathogenic factor in psoriasis. Formyl peptide receptor 1 (FPR1) triggers neutrophil activation in response to bacteria- or mitochondria-derived N-formyl peptides, but its significance in neutrophilic psoriasis remains unknown. In this study, we discovered two derivatives of ursolic acid, 3ß-hydroxyurs-12,18-dien-28-oic acid (randialic acid B, RAB) and 3ß-hydroxyurs-12,19-dien-28-oic acid (tomentosolic acid, TA), as FPR1 inhibitors in human neutrophils with ability to suppress psoriatic symptoms in mice. Both RAB and TA, triterpenoids of traditional medicinal plant Ilex kaushue, selectively inhibited reactive oxygen species production, elastase release, and CD11b expression in human neutrophils activated by FPR1, but not non-FPR1 agonists. Importantly, RAB and TA inhibited the binding of N-formyl peptide to FPR1 in human neutrophils, neutrophil-like THP-1 cells, and hFPR1-transfected HEK293 cells, indicating FPR1 antagonism. Moreover, in assays induced by various concentrations of FPR1 agonist, both RAB and TA acted competitively for its binding to the FPR1 receptor. The FPR1-downstream signaling such as Ca2+ mobilisation and activation of Akt and MAPKs was also competitively inhibited. In addition, imiquimod-induced psoriasis-like symptoms, including epidermal hyperplasia, desquamation with scaling, neutrophil skin infiltration, and transepidermal water loss were significantly reduced by both RAB and TA. The results illustrate a possible role of human neutrophils FPR1 receptor in psoriasis-like inflammation. Accordingly, triterpenoids RAB and TA represent novel FPR1 antagonists and exhibit therapeutic potential for treating neutrophilic inflammatory skin diseases.

Probiotic Supplementation Facilitates Recovery of 6-OHDA-Induced Motor Deficit via Improving Mitochondrial Function and Energy Metabolism.

Parkinson's disease (PD) is a neurodegenerative disease associated with progressive impairment of motor and non-motor functions in aging people. Overwhelming evidence indicate that mitochondrial dysfunction is a central factor in PD pathophysiology, which impairs energy metabolism. While, several other studies have shown probiotic supplementations to improve host energy metabolism, alleviate the disease progression, prevent gut microbiota dysbiosis and alter commensal bacterial metabolites. But, whether probiotic and/or prebiotic supplementation can affect energy metabolism and cause the impediment of PD progression remains poorly characterized. Therefore, we investigated 8-weeks supplementation effects of probiotic [Lactobacillus salivarius subsp. salicinius AP-32 (AP-32)], residual medium (RM) obtained from the AP-32 culture medium, and combination of AP-32 and RM (A-RM) on unilateral 6-hydroxydopamine (6-OHDA)-induced PD rats. We found that AP-32, RM and A-RM supplementation induced neuroprotective effects on dopaminergic neurons along with improved motor functions in PD rats. These effects were accompanied by significant increases in mitochondrial activities in the brain and muscle, antioxidative enzymes level in serum, and altered SCFAs profile in fecal samples. Importantly, the AP-32 supplement restored muscle mass along with improved motor function in PD rats, and produced the best results among the supplements. Our results demonstrate that probiotic AP-32 and A-RM supplementations can recover energy metabolism via increasing SCFAs producing and mitochondria function. This restoring of mitochondrial function in the brain and muscles with improved energy metabolism might additionally be potentiated by ROS suppression by the elevated generation of antioxidants, and which finally leads to facilitated recovery of 6-OHDA-induced motor deficit. Taken together, this work demonstrates that probiotic AP-32 supplementation could be a potential candidate for alternate treatment strategy to avert PD progression.

Effect of a Probiotic Combination in an Experimental Mouse Model and Clinical Patients With Chronic Kidney Disease: A Pilot Study.

The aim of the present study was to evaluate whether probiotic administration could slow declining renal function. C57BL/6 mice (6-8 weeks of age, male) were fed a diet supplemented with adenine to induce chronic kidney disease (CKD). The experimental groups were additionally supplemented with 109 colony-forming units (CFU)/day (high-dose) and 107 CFU/day (low-dose) probiotics containing Lactobacillus acidophilus (TYCA06), Bifidobacterium longum subspecies infantis (BLI-02), and B. bifidum (VDD088). Renal function and histology were examined. Patients with stage 3-5 CKD and not on dialysis were recruited from July 2017 to January 2019. Two capsules of probiotics containing 2.5 × 109 CFU with the same composition were administered twice daily for 6 months. The decline in the estimated glomerular filtration rate (eGFR) was measured before and after the intervention. In addition, changes in the serum endotoxin and cytokine levels, gastrointestinal symptom scores, and the stool microbiota were measured. Probiotics could attenuate renal fibrosis and improve renal function in CKD mice. Thirty-eight patients completed the 6-month study. The mean baseline eGFR was 30.16 ± 16.52 ml/min/1.73 m2. The rate of decline in the eGFR was significantly slower, from -0.54 (-0.18, -0.91) to 0.00 (0.48, -0.36) ml/min/1.73 m2/month (P = 0.001) after 6 months of treatment. The serum levels of TNF-α, IL-6, IL-18, and endotoxin were significantly decreased after probiotic administration. Borborygmus and flatulence scores, as well as stool formation improved significantly. The abundance of B. bifidum and B. breve in the stool microbiota increased significantly. In conclusion, a combination of probiotics might attenuate renal function deterioration in CKD mice and human patients.

Multi-strain probiotic supplement attenuates streptozotocin-induced type-2 diabetes by reducing inflammation and ß-cell death in rats.

Probiotics are health beneficial bacterial populations colonizing the human gut and skin. Probiotics are believed to be involved in immune system regulation, gut microbiota stabilization, prevention of infectious diseases, and adjustments of host metabolic activities. Probiotics such as Lactobacillus and Bifidobacterium affect glycemic levels, blood lipids, and protein metabolism. However, the interactions between probiotics and metabolic diseases as well as the underlying mechanisms remain unclear. We used streptozotocin (STZ)-induced diabetic animal models to study the effect of ProbiogluTM, a multi-strain probiotic supplement including Lactobaccilus salivarius subsp. salicinius AP-32, L. johnsonii MH-68, L. reuteri GL-104, and Bifidobacterium animalis subsp. lactis CP-9, on the regulation of physiochemical parameters related to type-2 diabetes. Experimental rats were randomly assigned into five groups, control group, streptozotocin (STZ)-treated rats (STZ group), STZ + 1× ProbiogluTM group, STZ + 5× ProbiogluTM group, and STZ + 10× ProbiogluTM group, and physiological data were measured at weeks 0, 2, 4, 6, and 8. Our results indicate that supplementation with ProbiogluTM significantly improved glucose tolerance, glycemic levels, insulin levels, and insulin resistance (HOMA-IR). Furthermore, we observed reduction in urea and blood lipid levels, including low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC). ProbiogluTM administration increased the ß-cell mass in STZ-induced diabetic animal models, whereas it reduced the levels of proinflammatory cytokines TNF-α, IL-6, and IL-1ß. In addition, the enhancement of oxidative stress biomarkers and superoxide dismutase (SOD) activities was associated with a decrease in malondialdehyde (MDA) levels. We conclude that ProbiogluTM attenuates STZ-induced type-2 diabetes by protecting ß-cells, stabilizing glycemic levels, and reducing inflammation. Among all probiotic treating groups, the 10×ProbiogluTM treatment revealed the best results. However, these experimental results still need to be validated by different animal models of type-2 diabetes and human clinical trials in the future.

Effects of Cinnamaldehyde on the Viability and Expression of Chemokine Receptor Genes in Temozolomide-treated Glioma Cells.

BACKGROUND/AIM: The effects of cinnamaldehyde on glioma are still unclear. We aimed to investigate the effects of cinnamaldehyde on the viability and expression of chemokine receptors CXCR4 and CXCR7 in temozolomide (TMZ)-treated glioma cells. MATERIALS AND METHODS: Cell viability and CXCR4 and CXCR7 expression were measured by western blotting at 72 h after treatment with various concentrations of cinnamaldehyde and TMZ. RESULTS: Cell viability was significantly lower after treatment with 300 µM TMZ, 50 µM cinnamaldehyde, 75 µM cinnamaldehyde, or combined treatment with 300 µM TMZ plus 50 µM or 75 µM cinnamaldehyde than after no treatment (i.e., without TMZ or cinnamaldehyde); and significantly lower after combined treatment with 300 µM TMZ plus 75 µM cinnamaldehyde but not 50 µM cinnamaldehyde, than treatment with 300 µM TMZ alone. Western blotting showed that either single treatments or combined treatments had lower CXCR4 expression (compared to the no-treatment control). Compared to 300 µM TMZ alone, both combined treatment of 300 µM TMZ plus 50 µM cinnamaldehyde or 75 µM cinnamaldehyde had significantly lowered CXCR4 expression. However, CXCR7 expression was not significantly different in all groups. CONCLUSION: Cinnamaldehyde, acting with TMZ, reduces glioma cell viability possibly via decreasing CXCR4 expression.

Lactobacillus salivarius AP-32 and Lactobacillus reuteri GL-104 decrease glycemic levels and attenuate diabetes-mediated liver and kidney injury in db/db mice.

OBJECTIVES: Patients with type 2 diabetes mellitus (T2DM) exhibit strong insulin resistance or abnormal insulin production. Probiotics, which are beneficial live micro-organisms residing naturally in the intestinal tract, play indispensable roles in the regulation of host metabolism. However, the detailed mechanisms remain unclear. Here, we evaluate the mechanisms by which probiotic strains mediate glycemic regulation in the host. The findings should enable the development of a safe and natural treatment for patients with T2DM. RESEARCH DESIGNS AND METHODS: Sugar consumption by more than 20 strains of Lactobacillus species was first evaluated. The probiotic strains that exhibited high efficiency of sugar consumption were further coincubated with Caco-2 cells to evaluate the regulation of sugar absorption in gut epithelial cells. Finally, potential probiotic strains were selected and introduced into a T2DM animal model to study their therapeutic efficacy. RESULTS: Among the tested strains, Lactobacillus salivarius AP-32 and L. reuteri GL-104 had higher monosaccharide consumption rates and regulated the expression of monosaccharide transporters. Glucose transporter type-5 and Na+-coupled glucose transporter mRNAs were downregulated in Caco-2 cells after AP-32 and GL-104 treatment, resulting in the modulation of intestinal hexose uptake. Animal studies revealed that diabetic mice treated with AP-32, GL-104, or both showed significantly decreased fasting blood glucose levels, improved glucose tolerance and blood lipid profiles, and attenuated diabetes-mediated liver and kidney injury. CONCLUSION: Our data elucidate a novel role for probiotics in glycemic regulation in the host. L. salivarius AP-32 and L. reuteri GL-104 directly reduce monosaccharide transporter expression in gut cells and have potential as therapeutic probiotics for patients with T2DM.

In Vivo Ergogenic Properties of the Bifidobacterium longum OLP-01 Isolated from a Weightlifting Gold Medalist.

In recent years, probiotics of human origin have shown superior results and performance compared to probiotics from plant or dairy sources, in both in vitro and animal studies. Towards this end, the current study was conducted to explore the ergogenic properties of Bifidobacterium longum subsp. longum OLP-01 isolated from the intestinal microbiome of the gold medalist from the 2008 Beijing Olympics women's 48 kg weightlifting competition. Male Institute of Cancer Research (ICR) mice were divided into four groups (n = 10 per group) and orally administered OLP-01 for 4 weeks at 0 (vehicle), 2.05 × 109 (OLP-01-1X), 4.10 × 109 (OLP-01-2X), and 1.03 × 1010 (OLP-01-5X) CFU/kg/day. Physical performance tests including grip strength and endurance time were measured, with OLP-01 supplementation dose-dependently elevating grip strength and endurance. The anti-fatigue activity levels of serum lactate, ammonia, glucose, blood urea nitrogen (BUN), and creatine kinase (CK) were measured after an acute exercise challenge, and OLP-01 was found to significantly decrease lactate, ammonia, and CK levels. OLP-01 treatment was also found to significantly increase the resting levels of both hepatic and muscular glycogen, an indicator of energy storage. Supplementation by OLP-01 showed no subchronic toxic effects while supporting many health-promoting, performance-improving, and fatigue-ameliorating functions.

Risk of betel quid chewing on the development of liver cirrhosis: a community-based case-control study.

PURPOSE: The role of betel quid on the development of liver cirrhosis is unclear; we thus designed a community-based case-control study to evaluate the association between betel quid chewing and liver cirrhosis. METHODS: A total of 42 cases of liver cirrhosis and 165 matched controls were included for analysis. Questionnaires were administered to obtain histories of betel quid chewing, alcohol consumption, smoking, and family history of liver disease. Hepatitis B surface antigen and anti-hepatitis C antibody were also determined by immunoassay. RESULTS: Individuals with more betel quid chewing (more than 55 quid-years vs. less than 55 quid-years and never-chewers, matched odds ratio [OR(m)] = 2.2; 95% confidence interval [CI]: 1.0-5.0) had higher risks for liver cirrhosis. The combined effects on liver cirrhosis by betel quid chewing and the number of other risk factors, including hepatitis B virus (HBV) infection, smoking, and alcohol drinking, were also observed. When individuals with less betel quid chewing (less than 55 quid-years and never-chewers) and with no other risk factors used as a reference, betel quid chewers expressing greater betel quid chewing (more than 55 quid-years) and more risk factors of HBV infection, cigarette smoking, and habitual alcohol drinking expressed a greater risk of liver cirrhosis (OR(m) = 70.8; 95% CI: 4.0-1260.1). CONCLUSIONS: Our results suggest that betel quid chewing may play an important role in the development of hepatic cirrhosis. Larger study and cohort studies would be necessary to provide further evidence regarding this finding.

Heat-killed cells of lactobacilli skew the immune response toward T helper 1 polarization in mouse splenocytes and dendritic cell-treated T cells.

It is believed that probiotics play an important role for the health of the host, including modulation of immune responses. Most studies have focused on the immunomodulatory effects of viable cells of lactic acid bacteria; however, we investigated those of heat-killed cells of lactic acid bacteria in this study. We first observed the effects on immune functions via stimulating splenocytes with three heat-killed Lactobacillus strains. Furthermore, we also investigated the effect of mouse dendritic cells (DCs) treated with these heat-killed Lactobacillus strains on T cell responses. The results showed that these Lactobacillus strains were able to stimulate cell proliferation and interleukin (IL)-10, IL-12 p70, and interferon (IFN)-gamma production but not transforming growth factor (TGF)-beta in splenocytes. In addition, these heat-killed Lactobacillus strains also stimulated high-level secretion of IL-12 p70 in DCs and switched T cells to T helper (Th) 1 immune responses, as evidenced by the elevated secretion of IFN-gamma but not IL-5, IL-13, and TGF-beta. These results showed that lactobacilli play a potentially important role in modulating immune responses and allergic reactions.