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 Probioglu
TM
, 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× Probioglu
TM
group, STZ + 5× Probioglu
TM
group, and STZ + 10× Probioglu
TM
group, and physiological data were measured at weeks 0, 2, 4, 6, and 8. Our results indicate that supplementation with Probioglu
TM
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). Probioglu
TM
administration increased the β-cell mass in STZ-induced diabetic animal models, whereas it reduced the levels of proinflammatory cytokines TNF-α, IL-6, and IL-1β. 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 Probioglu
TM
attenuates STZ-induced type-2 diabetes by protecting β-cells, stabilizing glycemic levels, and reducing inflammation. Among all probiotic treating groups, the 10×Probioglu
TM
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.
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.
SUMMARY
Plants and bacteria have distinct pathways to synthesize the bioactive vitamin B1 thiamin diphosphate (TDP). In plants, thiamin monophosphate (TMP) synthesized in the TDP biosynthetic pathway ...is first converted to thiamin by a phosphatase, which is then pyrophosphorylated to TDP. In contrast, bacteria use a TMP kinase encoded by ThiL to phosphorylate TMP to TDP directly. The Arabidopsis THIAMIN REQUIRING2 (TH2)‐encoded phosphatase is involved in TDP biosynthesis. The chlorotic th2 mutants have high TMP and low thiamin and TDP. Ectopic expression of Escherichia coli ThiL and ThiL‐GFP rescued the th2‐3 mutant, suggesting that the bacterial TMP kinase could directly convert TMP into TDP in Arabidopsis. These results provide direct evidence that the chlorotic phenotype of th2‐3 is caused by TDP rather than thiamin deficiency. Transgenic Arabidopsis harboring engineered ThiL‐GFP targeting to the cytosol, chloroplast, mitochondrion, or nucleus accumulated higher TDP than the wild type (WT). Ectopic expression of E. coli ThiL driven by the UBIQUITIN (UBI) promoter or an endosperm‐specific GLUTELIN1 (GT1) promoter also enhanced TDP biosynthesis in rice. The pUBI:ThiL transgenic rice accumulated more TDP and total vitamin B1 in the leaves, and the pGT1:ThiL transgenic lines had higher TDP and total vitamin B1 in the seeds than the WT. Total vitamin B1 only increased by approximately 25–30% in the polished and unpolished seeds of the pGT1:ThiL transgenic rice compared to the WT. Nevertheless, these results suggest that genetic engineering of a bacterial vitamin B1 biosynthetic gene downstream of TMP can enhance vitamin B1 production in rice.
Significance Statement
Introducing a bacterial gene encoding thiamin monophosphate kinase into Arabidopsis and rice creates an additional route for thiamin diphosphate biosynthesis and increases vitamin B1 contents.
Gut microbiota is very important for energy metabolism and regulation, which in turn affect the health and physiological functions of the host, and provide energy required for exercise. ...Supplementation with probiotics may be one of the ways to change the gut microbiota. In recent years, many studies have shown that probiotic supplementation can effectively improve sports performance. In this study, we screened Lactobacillus plantarum (PL-02), a probiotic of human-origin, from the intestines of 2008 Olympic women's 48 kg weightlifting gold medalist and explored the role of PL-02 in improved exercise endurance performance, reduced fatigue biochemical parameters, and changes in body composition. Male Institute of Cancer Research (ICR) mice were assigned to 0, 2.05 × 10
, 4.10 × 10
and 1.03 × 10
CFU/kg/day groups and were fed by oral gavage once daily for 4 weeks. The results showed that 4 weeks of PL-02 supplementation could significantly increase muscle mass, muscle strength and endurance performance, and hepatic and muscular glycogen storage. Furthermore, PL-02 could significantly decrease lactate, blood urea nitrogen (BUN), ammonia, and creatine kinase (CK) levels after exercise (p < 0.05). We believe that PL-02 can be used as a supplement to improve exercise performance and for its anti-fatigue effect.
It has been widely reported that ketamine rescues chronic stress-induced depression-like behavior, but the underlying cellular mechanisms of the rapid antidepressant actions of ketamine remain ...largely unclear. Both male and female Sprague-Dawley rats were used and received modified learned helplessness paradigm to induce depression-like behavior. Depression-like behavior was assayed and manipulated using forced swim tests, sucrose preference tests and pharmacological microinjection. We conducted whole-cell patch-clamp electrophysiological recordings in the midbrain ventrolateral periaqueductal gray (vlPAG) neurons. Surface and cytosolic glutamate receptor 1 (GluR1) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor expression were analyzed using Western blotting. Phosphorylated GluR1 expression was quantified using Western blotting analysis. The results showed that a single systemic administration of a ketamine metabolite (2R,6R)-hydroxynorketamine (2R,6R-HNK) rapidly rescued chronic stress-induced depression-like behavior and persisted for up to 21 days. Consistently, the chronic stress-induced diminished glutamatergic transmission and surface GluR1 expression in the vlPAG were also reversed by a single systemic injection of (2R,6R)-HNK. Furthermore, bath application of (2R,6R)-HNK increased the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) in the vlPAG. Further evidence for the antidepressant action of (2R,6R)-HNK is provided by the finding that microinjection of (2R,6R)-HNK into the vlPAG exhibited a rapid-acting and long-lasting antidepressant effect. This antidepressant effect of (2R,6R)-HNK was prevented by the intra-vlPAG microinjection of AMPA receptor antagonist CNQX. Together, the current results provide evidence that (2R,6R)-HNK rescues chronic stress-induced depression-like behavior with rapid-acting and long-lasting antidepressant effects through enhancement of AMPA receptor-mediated transmission in the vlPAG.
•Both intraperitoneal and intra-vlPAG administration of (2R,6R)-HNK rescue chronic stress-induced depression-like behavior.•(2R,6R)-HNK rapidly rescues chronic stress-induced depression-like behavior.•Antidepressant effects of (2R,6R)-HNK persist for up to 21 days.•(2R,6R)-HNK increases glutamate release presynaptically and surface GluR1 expression postsynaptically in the vlPAG.•Blockage of AMPAR in the vlPAG antagonizes antidepressant effects of (2R,6R)-HNK.
MicroRNA-21 (miR-21) is one of the most frequently upregulated miRNAs in liver diseases such as nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). However, mechanistic ...pathways that connect NAFLD and HCC remain elusive. We developed a doxycycline (Dox)-inducible transgenic zebrafish model (LmiR21) which exhibited an upregulation of miR-21 in the liver, which in turn induced the full spectrum of NAFLD, including steatosis, inflammation, fibrosis, and HCC, in the LmiR21 fish. Diethylnitrosamine (DEN) treatment led to accelerated liver tumor formation and exacerbated their aggressiveness. Moreover, prolonged miR-21 expression for up to ten months induced nonalcoholic steatohepatitis (NASH)-related HCC (NAHCC). Immunoblotting and immunostaining confirmed the presence of miR-21 regulatory proteins (i.e., PTEN, SMAD7, p-AKT, p-SMAD3, and p-STAT3) in human nonviral HCC tissues and LmiR21 models. Thus, we demonstrated that miR-21 can induce NAHCC via at least three mechanisms: First, the occurrence of hepatic steatosis increases with the decrease of
,
, and activation of the PI3K/AKT pathway; second, miR-21 induces hepatic inflammation (or NASH) through an increase in inflammatory gene expression via STAT3 signaling pathways, and induces liver fibrosis through hepatic stellate cell (HSC) activation and collagen deposition via TGF-β/Smad3/Smad7 signaling pathways; finally, oncogenic activation of Smad3/Stat3 signaling pathways induces HCC. Our LmiR21 models showed similar molecular pathology to the human cancer samples in terms of initiation of lipid metabolism disorder, inflammation, fibrosis and activation of the PI3K/AKT, TGF-β/SMADs and STAT3 (PTS) oncogenic signaling pathways. Our findings indicate that miR-21 plays critical roles in the mechanistic perspectives of NAHCC development via the PTS signaling networks.
Background
The incidence of different soft tissue sarcoma (STS) histotypes among ethnic and geographic populations has not been comprehensively investigated.
Methods
Data from 2013 to 2016 were ...obtained from national cancer registry databases in France and Taiwan. Liposarcoma (LPS), leiomyosarcoma (LMS), angiosarcoma (AS), synovial sarcoma (SS), and malignant peripheral nerve sheath tumor (MPNST) were selected as index STSs to estimate the age‐standardized incidence rates (ASRs) and other clinical features between patients.
Results
In total, 9398 patients (7148 from France and 2250 from Taiwan) were included. The ASRs of AS (5.4 vs. 2.8) and MPNST (2.0 vs. 1.0) were significantly higher in Taiwan; France had significantly higher ASRs for LPS (12.0 vs. 10.0), LMS (9.7 vs. 7.6), and SS (1.7 vs. 1.2). Patients in Taiwan with LMS or LPS were younger than their French counterparts. With regard to the distribution according to primary anatomic site, French patients had higher odds for extremity and truncal LMS (odds ratio OR, 2.84; p < .001), AS (OR, 2.67; p < .001), MPNST (OR, 1.55; p = .027), and LPS (OR, 1.38; p < .001) and for breast AS (OR, 10.58; p < .001). Taiwanese patients had higher odds for liver AS (OR, 10.72; p < .001) and uterine LMS (OR, 3.21; p < .001). SS age and distribution according to primary anatomic site did not differ significantly between the French and Taiwanese populations.
Conclusions
Significant differences in the incidence and clinical characteristics of index STS suggested that geographic (environmental) and ethnicity factors likely play a vital role in the pathogenesis of STS.
In two nationwide, population‐based cancer registry databases outside of the United States, the epidemiology of soft tissue sarcoma was investigated between Europeans and Asians. The incidence of five index soft tissue sarcoma histology subtypes differed significantly, as did the distribution according to sex, primary anatomic site, and age, between the two populations, and the results increase awareness that ethnicity and geographic factors are important in the pathogenesis of sarcoma.
Personalized modeling has long been anticipated to approach precise noninvasive blood glucose measurements, but challenged by limited data for training personal model and its unavoidable outlier ...predictions. To overcome these long-standing problems, we largely enhanced the training efficiency with the limited personal data by an innovative Deduction Learning (DL), instead of the conventional Induction Learning (IL). The domain theory of our deductive method, DL, made use of accumulated comparison of paired inputs leading to corrections to preceded measured blood glucose to construct our deep neural network architecture. DL method involves the use of paired adjacent rounds of finger pulsation Photoplethysmography signal recordings as the input to a convolutional-neural-network (CNN) based deep learning model. Our study reveals that CNN filters of DL model generated extra and non-uniform feature patterns than that of IL models, which suggests DL is superior to IL in terms of learning efficiency under limited training data. Among 30 diabetic patients as our recruited volunteers, DL model achieved 80% of test prediction in zone A of Clarke Error Grid (CEG) for model training with 12 rounds of data, which was 20% improvement over IL method. Furthermore, we developed an automatic screening algorithm to delete low confidence outlier predictions. With only a dozen rounds of training data, DL with automatic screening achieved a correlation coefficient (Formula: see text) of 0.81, an accuracy score (Formula: see text) of 93.5, a root mean squared error of 13.93 mg/dl, a mean absolute error of 12.07 mg/dl, and 100% predictions in zone A of CEG. The nonparametric Wilcoxon paired test on Formula: see text for DL versus IL revealed near significant difference with p-value 0.06. These significant improvements indicate that a very simple and precise noninvasive measurement of blood glucose concentration is achievable.
Previously published photoplethysmography-(PPG) based non-invasive blood glucose (NIBG) measurements have not yet been validated over 500 subjects. As illustrated in this work, we increased the ...number subjects recruited to 2538 and found that the prediction accuracy (the ratio in zone A of Clarke’s error grid) reduced to undesirable 60.6%. We suspect the low prediction accuracy induced by larger sample size might arise from the physiological diversity of subjects, and one possibility is that the diversity might originate from medication. Therefore, we split the subjects into two cohorts for deep learning: with and without medication (1682 and 856 recruited subjects, respectively). In comparison, the cohort training for subjects without any medication had approximately 30% higher prediction accuracy over the cohort training for those with medication. Furthermore, by adding quarterly (every 3 months) measured glycohemoglobin (HbA1c), we were able to significantly boost the prediction accuracy by approximately 10%. For subjects without medication, the best performing model with quarterly measured HbA1c achieved 94.3% prediction accuracy, RMSE of 12.4 mg/dL, MAE of 8.9 mg/dL, and MAPE of 0.08, which demonstrates a very promising solution for NIBG prediction via deep learning. Regarding subjects with medication, a personalized model could be a viable means of further investigation.
The C-type lectin member 5A (CLEC5A) is a pattern recognition receptor for members of the Flavivirus family and has critical functions in response to dengue virus and Japanese encephalitis virus. ...Here we show that CLEC5A is involved in neutrophil extracellular trap formation and the production of reactive oxygen species and proinflammatory cytokines in response to Listeria monocytogenes. Inoculation of Clec5a
mice with L. monocytogenes causes rapid bacterial spreading, increased bacterial loads in the blood and liver, and severe liver necrosis. In these mice, IL-1β, IL-17A, and TNF expression is inhibited, CCL2 is induced, and large numbers of CD11b
Ly6C
CCR2
CX3CR1
inflammatory monocytes infiltrate the liver. By day 5 of infection, these mice also have fewer IL-17A
γδ T cells, severe liver necrosis and a higher chance of fatality. Thus, CLEC5A has a pivotal function in the activation of multiple aspects of innate immunity against bacterial invasion.The lectin receptor CLEC5A is a pattern recognition receptor that has been shown to detect dengue and Japanese encephalitis virus. Here the authors show that CLEC5A is needed for optimal ROS production, NET formation and other immune responses to Listeria monocytogenes in mice.
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