Multifunctional effects of Lactobacillus sakei HEM 224 on the gastrointestinal tract and airway inflammation.

Mucosal tissues serve as the first defense line and their commensal microbiota play a role in sustaining of host health. This study aimed to isolate and evaluate a putative probiotic strain on various mucosal regions. Lactobacillus sakei HEM 224 was isolated from traditional Korean kimchi and identified. In the safety assessment L. sakei HEM 224 showed negative results for hemolysis, biogenic amine production and transferable antibiotic resistance. The probiotic potential of strain HEM 224 in diverse mucosal areas was shown in two different models, viz. a murine model with colitis induced by dextran sulfate sodium (DSS) and an allergic airway inflammation model induced by ovalbumin (OVA). In the colitis model, oral administration of L. sakei HEM 224 improved colitis physiology with immunomodulation, enhancing barrier components and gut microbiota alteration. In the allergic airway inflammation model, the intranasal administration of the strain decreased type 2 inflammation and enhanced epithelial barrier integrity from the airways. These results demonstrate that L. sakei HEM 224 can ameliorate inflammatory conditions in both the gastrointestinal and respiratory tracts through the reinforcement of the epithelial barrier and immunomodulation.

Bacillus Strains Isolated from Korean Fermented Food Products with Antimicrobial Activity Against Staphylococci, an Alternative for Control of Antibiotic-Resistant Pathogens.

Multidrug resistance in foodborne and clinical pathogens is a worldwide health problem. The urgent need for new alternatives to the existing antibiotics is emerging. Bacteriocin-like inhibitory substances can be considered part of the new generation of antimicrobials, which can be potentially applied in the food industry and health care practices. This study aimed to select Bacillus strains with antimicrobial activity against Staphylococcus spp. with future application in the formulation of pharmaceutical antimicrobial preparations. Putative antimicrobial agent-producing strains, previously isolated and preidentified as Bacillus spp. were profiled by repetitive element sequence-based polymerase chain reaction (rep-PCR) and 16s rRNA sequencing identified the strains as Bacillus tequilensis ST1962CD with 99.47% identity confidence and as Bacillus subtilis subsp. stercoris ST2056CD with 98.45% identity confidence. Both the selected Bacillus strains were evaluated via biomolecular and physiological approaches related to their safety and virulence, beneficial properties, enzyme production profile, and presence of corresponding genes for the production of antimicrobials and virulence. Both strains were confirmed to harbor srfa and sbo genes and be free of hemolysin binding component (B) and two lytic components (L1 and L2) [BL] and nonhemolytic enterotoxin-associated genes. Produced antimicrobial agents by strains ST1962CD and ST2056CD were partially purified through the combination of ammonium sulfate precipitation and hydrophobic-based chromatography on SepPakC18 and evaluated regarding their cytotoxicity. The dynamics of bacterial growth, pH change, accumulation of produced antimicrobials, and the mode of action were evaluated. Obtained results were pointing to the potential application of safe B. tequilensis ST1962CD and B. subtilis subsp. stercoris ST2056CD strains as functional beneficial microbial cultures that are putative producers of surfactin and/or subtilosin, as potent antimicrobials, for the treatment of some staphylococcal-associated infections. Expressed antimicrobials were shown to be not cytotoxic, and appropriate biotechnological approaches need to be developed for cost-effective production, isolation, and purification of expressed antimicrobials by studied strains.

CycloZ Improves Hyperglycemia and Lipid Metabolism by Modulating Lysine Acetylation in KK-Ay Mice.

BACKGRUOUND: CycloZ, a combination of cyclo-His-Pro and zinc, has anti-diabetic activity. However, its exact mode of action remains to be elucidated. METHODS: KK-Ay mice, a type 2 diabetes mellitus (T2DM) model, were administered CycloZ either as a preventive intervention, or as a therapy. Glycemic control was evaluated using the oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels. Liver and visceral adipose tissues (VATs) were used for histological evaluation, gene expression analysis, and protein expression analysis. RESULTS: CycloZ administration improved glycemic control in KK-Ay mice in both prophylactic and therapeutic studies. Lysine acetylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, liver kinase B1, and nuclear factor-κB p65 was decreased in the liver and VATs in CycloZ-treated mice. In addition, CycloZ treatment improved mitochondrial function, lipid oxidation, and inflammation in the liver and VATs of mice. CycloZ treatment also increased the level of ß-nicotinamide adenine dinucleotide (NAD+), which affected the activity of deacetylases, such as sirtuin 1 (Sirt1). CONCLUSION: Our findings suggest that the beneficial effects of CycloZ on diabetes and obesity occur through increased NAD+ synthesis, which modulates Sirt1 deacetylase activity in the liver and VATs. Given that the mode of action of an NAD+ booster or Sirt1 deacetylase activator is different from that of traditional T2DM drugs, CycloZ would be considered a novel therapeutic option for the treatment of T2DM.

Disturbance of lipid metabolism in germ-free mice transplanted with gut microbiota of DSS-induced colitis mice.

Hepatobiliary abnormality and metabolic disorders are frequently observed complications in patients with inflammatory bowel diseases (IBD). Given that microbiota dysbiosis is a common pathophysiological feature of both IBD and metabolic diseases, we examined how the IBD-induced dysbiosis affects the host metabolism and contributes to the development of associated metabolic diseases using germ-free (GF) mice transplanted with fecal microbiota of DSS-induced colitis mice. There was no significant change in inflammation or barrier integrity in the gut of GF mice that received microbiota from colitis mice compared to their counterparts that were transplanted with microbiota from non-colitis healthy mice. Interestingly, it was observed that the GF recipients of colitis-induced altered microbiota showed a significant decrease in the weight of adipose tissues including mesenteric, epididymal, subcutaneous, and brown fat without any change in body weight, which was accompanied by abnormalities in adipose tissue functions such as fat storage and adiponectin production. Transplantation of colitis-induced altered microbiota also disrupted hepatic lipid metabolism in the GF recipient mice, which was observed by increases in synthesis and accumulation of cholesterol and bile acids in hepatocytes and a decrease in plasma HDL-cholesterol. Additional observations including elevated plasma levels of insulin, decreased hepatic production of FGF21, and decreased levels of fecal short chain fatty acids (SCFAs) and hepatic expression of SCFA receptors led to a conclusion that the transplantation of the colitis-associated dysbiotic microbiota was causally associated with impairments of insulin action and FGF21-adiponectin axis, possibly due to the low SCFA-producing capacity of the colonized microbiota, leading to metabolic abnormalities including adipose tissue dysfunction and dysregulated hepatic lipid metabolism. Our findings suggest potential mechanisms that explain how colitis-associated gut dysbiosis may contribute to the development of metabolic dysfunctions, which could be applied to clinical practice to improve the efficacy of treatment of IBD patients with comorbid metabolic disorders or vice versa.

Lactiplantibacillusplantarum APsulloc331261 (GTB1™) promotes butyrate production to suppress mucin hypersecretion in a murine allergic airway inflammation model.

Introduction: Allergic airway diseases are one of the serious health problems in worldwide and allergic airway inflammation is a prerequisite led to the exacerbated situation such as mucus hypersecretion, epithelial barrier damage and microbiota dysbiosis. Because of side effects and low efficiencies of current therapeutics, the need for novel alternatives has been urged. Probiotics in which have diverse and beneficial modulatory effects have been applied to the airway inflammation model and the underlying mechanism needs to be investigated. Methods: We aimed to evaluate whether our target strain, Lactiplantibacillus plantarum APsulloc331261 (GTB1TM) isolated from green tea, can ameliorate allergic airway inflammation in mice and to figure out the mechanism. We induced allergic airway inflammation to mice by ovalbumin (OVA) and administered GTB1 orally and the immune and epithelial barrier markers were assessed. The gut metabolite and microbiota were also analysed, and the in vitro cell-line experiment was introduced to confirm the hypothesis of the study. Results: GTB1 ameliorated type 2 inflammation and suppressed mucin hypersecretion with the inhibition of MUC5AC in inflamed mice. Moreover, GTB1 increased the butyrate production and the relative abundance of butyrate producer, Clostridium cluster IV. We assumed that butyrate may have a potential role and investigated the effect of butyrate in mucin regulation via human airway epithelial cell line, A549. Butyrate significantly reduced the gene expression of MUC5AC in A549 cells suggesting its regulatory role in mucus production. Conclusion: Therefore, our study demonstrates that the oral administration of GTB1 can ameliorate allergic airway inflammation and mucin hypersecretion by butyrate production.

Characterization and safety evaluation of two beneficial, enterocin-producing Enterococcus faecium strains isolated from kimchi, a Korean fermented cabbage.

Enterococcus faecium ST20Kc and ST41Kc were isolated from kimchi, a traditional Korean fermented cabbage. Bacteriocins produced by both strains exhibited strong activity against Listeria monocytogenes and various Enterococcus spp., including 30 vancomycin-resistant enterococcal strains, but not against other lactic acid bacteria (LAB) on the evaluated test panel. The antimicrobials produced by the strains were found to be proteinaceous and stable even after exposure to varying pH, temperature, and chemicals used in the industry and laboratory processes. Antimicrobial activity of both strains was evaluated as bactericidal against exponentially growing cultures of L. monocytogenes ATCC® 15313™ and Enterococcus faecalis 200A. Based on tricine-SDS-PAGE, the molecular weights of the bacteriocins produced by the strains were between 4 and 6 kDa. Additionally, both strains were susceptible to antibiotics, including vancomycin, kanamycin, gentamycin, ampicillin, streptomycin, tylosin, chloramphenicol, clindamycin, and tetracycline. Adhesion genes, map, mub, and EF-Tu, were also detected in the genomes of both strains. With gastrointestinal stress induction, both strains showed high individual survival rates, and capability to reduce viable counts of L. monocytogenes ATCC® 15313™ and Enterococcus faecalis 200A in mixed cultures. Based on the metabolomics analysis, both strains were found to produce additional antimicrobial compounds, particularly, lactic acid, phenyllactic acid, and phenethylamine, which can be potentially involved in the antimicrobial interaction with pathogenic microorganisms.

A Study on the Performance of a Silicon Photodiode Sensor for a Particle Dosimeter and Spectrometer.

A lunar vehicle radiation dosimeter (LVRAD) has been proposed for studying the radiation environment on the lunar surface and evaluating its impact on human health. The LVRAD payload comprises four systems: a particle dosimeter and spectrometer (PDS), a tissue-equivalent dosimeter, a fast neutron spectrometer, and an epithermal neutron spectrometer. A silicon photodiode sensor with compact readout electronics was proposed for the PDS. The PDS system aims to measure protons with 10-100 MeV of energy and assess dose in the lunar space environment. The manufactured silicon photodiode sensor has an effective area of 20 mm × 20 mm and thickness of 650 µm; the electronics consist of an amplifier, analog pulse processor, and a 12-bit analog-to-digital converter for signal readout. We studied the responses of silicon sensors which were manufactured with self-made electronics to gamma rays with a wide range of energies and proton beams.

Development of a core outcome set for interventions to prevent stillbirth.

AIMS: To develop a core outcome set for trials investigating interventions to prevent stillbirth. MATERIALS & METHODS: Outcomes identified from a systematic literature review and semi-structured interviews with parents in Australia and the UK were entered into a two-round online Delphi survey and focus group/consensus meetings. RESULTS: A core outcome set containing 11 outcomes in two categories. Five outcomes were related to the mother; fetal loss, onset of and mode of delivery, maternal mortality or near miss, psychological and social impact on the women, women's knowledge. Six outcomes were related to the baby; timing of stillbirth, neonatal mortality, gestational age at delivery, birthweight, congenital anomaly, NICU/SCBU or other higher-level neonatal care length of stay. CONCLUSIONS: Implementation and dissemination of this core outcome set in future trials will contribute towards coordinated outcome reporting and advancing usefulness of research to guide clinical practice.

A core outcome set for genitourinary symptoms associated with menopause: the COMMA (Core Outcomes in Menopause) global initiative.

OBJECTIVE: Genitourinary symptoms, such as vaginal dryness and pain with sex, are commonly experienced by postmenopausal women. Comparing treatments for these genitourinary symptoms are restricted by the use of different outcome measures in clinical trials and the omission of outcomes, which may be relevant to women. The aim of this project was to develop a Core Outcome Set (COS) to be reported in clinical trials of treatments for genitourinary symptoms associated with menopause. METHODS: We performed a systematic review of randomized controlled trials of treatments for genitourinary symptoms associated with menopause and extracted their outcomes. This list was refined and entered into a two-round modified Delphi survey, which was open to clinicians, researchers, and postmenopausal women from November 2019 to March 2020. Outcomes were scored on a nine-point scale from "not important" to "critically important." The final COS was determined following two international consensus meetings. RESULTS: A total of 26 unique outcomes were included in the Delphi process, which was completed by 227 participants of whom 58% were postmenopausal women, 34% clinicians, and 8% researchers. Predefined thresholds were applied to the Delphi scores to categorize outcomes by importance, which informed the e consensus meetings, attended by 43 participants from 21 countries. The final COS includes eight outcomes: (1) pain with sex, (2) vulvovaginal dryness, (3) vulvovaginal discomfort or irritation, (4) discomfort or pain when urinating, (5) change in most bothersome symptom, (6) distress, bother or interference of genitourinary symptoms, (7) satisfaction with treatment, (8) side effects of treatment. CONCLUSION: These eight core outcomes reflect the joint priorities of postmenopausal women, clinicians, and researchers internationally. Standardized collection and reporting of these outcomes in clinical trials will facilitate the comparison of different treatments for genitourinary symptoms, advance clinical practice, and ultimately improve outcomes for symptomatic women.

Video Summary:http://links.lww.com/MENO/A765 .

Assessment of the safety and anti-inflammatory effects of three Bacillus strains in the respiratory tract.

Chronic respiratory diseases are part of accumulating health problems partly due to worldwide increase in air pollution. By their antimicrobial and immunomodulatory properties, some probiotics constitute promising alternatives for the prevention and treatment of chronic respiratory diseases. We have isolated Bacillus strains from Korean fermented foods and selected three potentially probiotic strains (two Bacillus subtilis and one Bacillus amyloliquefaciens) based on safety, antimicrobial efficacy, activity against airborne pathogens and their immunomodulatory properties in vivo. Safety evaluation included in silico analysis for confirming absence of virulence genes. Safety for the respiratory tract was confirmed by an in vivo pathogenicity test using a murine model. Antimicrobial activity was displayed against several airborne pathogens. Potential antimicrobial metabolites such as 2,3-butanediol and propylene glycol were identified as possible antagonistic agents. Immunomodulatory properties in vitro were confirmed by upregulation of IL-10 expression in a macrophage cell line. Intranasal instillation and inhalation in an ovalbumin (OVA)-induced lung inflammation murine model reduced T helper type 2 (Th2) cytokines at transcriptional and protein levels in the lungs. The safety and potentially beneficial role of these Bacillus strains could be demonstrated for the respiratory tract of a murine model.

A core outcome set for vasomotor symptoms associated with menopause: the COMMA (Core Outcomes in Menopause) global initiative.

OBJECTIVE: Vasomotor symptoms (VMS) (hot flashes and night sweats) affect most women over the menopause transition. Comparing the safety and effectiveness of treatments for vasomotor symptoms is limited by the use of inconsistent outcome measures, and uncertainty as to which outcomes are most important to symptomatic women. To address this, we have developed a Core Outcome Set (COS) for use in clinical trials of treatments for VMS. METHODS: We systematically reviewed the primary outcomes measured in randomized controlled trials of treatments for VMS. These were refined and entered into a two-round modified Delphi survey completed by clinicians, researchers, and postmenopausal women between November 2019 and March 2020. Outcomes were scored on a nine-point scale from "not important" to "critically important." Two international consensus meetings were held to finalize the COS. RESULTS: Based on the systematic review, 13 separate outcomes were included in the Delphi process. This was completed by 227 participants of whom 58% were postmenopausal women, 34% clinicians, and 8% researchers. Predefined thresholds were applied to categorize importance scores obtained during Round 2 of the Delphi survey. These informed discussions at the consensus meetings which were attended by 56 participants from 28 countries. The final COS includes six outcomes: 1) frequency of VMS, 2) severity of VMS, 3) distress, bother or interference caused by VMS, 4) impact on sleep, 5) satisfaction with treatment, and 6) side-effects of treatment. CONCLUSION: Implementation of this COS will: better enable research studies to accurately reflect the joint priorities of postmenopausal women, clinicians and researchers, standardize outcome reporting, and facilitate combining and comparing results from different studies, and ultimately improve outcomes for women with bothersome VMS.

Video Summary:http://links.lww.com/MENO/A763 .

Analysis of Post-Transplant Lymphoproliferative Disorder (PTLD) Outcomes with Epstein-Barr Virus (EBV) Assessments-A Single Tertiary Referral Center Experience and Review of Literature.

Post-transplant lymphoproliferative disorders (PTLDs) are lymphoid or plasmacytic proliferations ranging from polyclonal reactive proliferations to overt lymphomas that develop as consequence of immunosuppression in recipients of solid organ transplantation (SOT) or allogeneic bone marrow/hematopoietic stem cell transplantation. Immunosuppression and Epstein-Barr virus (EBV) infection are known risk factors for PTLD. Patients with documented histopathologic diagnosis of primary PTLD at our institution between January 2000 and October 2019 were studied. Sixty-six patients with PTLD following SOT were followed for a median of 9.0 years. The overall median time from transplant to PTLD diagnosis was 5.5 years, with infant transplants showing the longest time to diagnosis at 12.0 years, compared to pediatric and adolescent transplants at 4.0 years and adult transplants at 4.5 years. The median overall survival (OS) was 19.0 years. In the monomorphic diffuse large B-cell (M-DLBCL-PTLD) subtype, median OS was 10.7 years, while median OS for polymorphic subtype was not yet reached. There was no significant difference in OS in patients with M-DLBCL-PTLD stratified by quantitative EBV viral load over and under 100,000 copies/mL at time of diagnosis, although there was a trend towards worse prognosis in those with higher copies.

DSS-induced colitis is associated with adipose tissue dysfunction and disrupted hepatic lipid metabolism leading to hepatosteatosis and dyslipidemia in mice.

Considering high prevalence of non-alcoholic fatty liver diseases (NAFLD) in patients with inflammatory bowel disease (IBD), this study aimed to elucidate molecular mechanisms for how intestinal inflammatory conditions are causally linked to hepatic steatosis and dyslipidemia. Both younger and older mice treated with acute or chronic dextran sodium sulfate (DSS) developed colitis, which was evidenced by weight loss, colon length shortening, and elevated disease activity index and inflammation score. They also showed decreased expression of intestinal barrier function-related proteins and elevated plasma lipopolysaccharide level, indicating DSS-induced barrier dysfunction and thereby increased permeability. Interestingly, they displayed phenotypes of hepatic fat accumulation and abnormal blood lipid profiles. This DSS-induced colitis-associated lipid metabolic dysfunction was due to overall disruption of metabolic processes including fatty acid oxidation, lipogenesis, lipolysis, reverse cholesterol transport, bile acid synthesis, and white adipose tissue browning and brown adipose tissue thermogenesis, most of which are mediated by key regulators of energy homeostasis such as FGF21, adiponectin, and irisin, via SIRT1/PGC-1α- and LXRα-dependent pathways. Our study suggests a potential molecular mechanism underlying the comorbidity of NAFLD and IBD, which could provide a key to understanding how the two diseases are pathogenically linked and discovering critical therapeutic targets for their treatment.

Developing a core outcome set in interventions to prevent stillbirth: A systematic review on variations of outcome reporting.

OBJECTIVE: To determine which outcomes have been previously reported in previous stillbirth prevention studies. RESEARCH DESIGN: Systematic review of reviews: We searched the Cochrane Database of Systematic Reviews, EMBASE and Pubmed for systematic reviews and meta- analyses investigating interventions to prevent stillbirth and its major risk factors. DATA COLLECTION AND ANALYSIS: Two reviewers identified and extracted outcomes independently. Outcomes were categorised under relevant domains for analysis. Frequency of each outcome was also determined. MAIN RESULTS: From 51 eligible reviews, 16 reviews addressed stillbirth prevention specifically while 35 reviews evaluated the efficacies of prevention or management of the eight major risk factors of stillbirth. Two hundred and thirty-seven outcomes were extracted, including 150 maternal outcomes and 87 offspring outcomes. Stillbirth (35/51), perinatal mortality (34/51) and neonatal mortality (33/51) were the most commonly reported outcomes followed by birthweight (29/51), caesarean section (28/51) and preeclampsia/eclampsia (23/51). Self-reported mother/family focused outcomes on their experiences and views were reported in 10/51 reviews. CONCLUSION: In studies evaluating prevention of stillbirth there is a large variety in outcomes, with discrepancies in nomenclature and measurements. Woman/family-centred outcomes are often missing from studies. There is a need for a core outcome sets agreed by all stakeholders containing the recommended minimum data to be reported in future studies investigating prevention of stillbirth.

A dietary anthocyanin cyanidin-3-O-glucoside binds to PPARs to regulate glucose metabolism and insulin sensitivity in mice.

We demonstrate the mechanism by which C3G, a major dietary anthocyanin, regulates energy metabolism and insulin sensitivity. Oral administration of C3G reduced hepatic and plasma triglyceride levels, adiposity, and improved glucose tolerance in mice fed high-fat diet. Hepatic metabolomic analysis revealed that C3G shifted metabolite profiles towards fatty acid oxidation and ketogenesis. C3G increased glucose uptake in HepG2 cells and C2C12 myotubes and induced the rate of hepatic fatty acid oxidation. C3G directly interacted with and activated PPARs, with the highest affinity for PPARα. The ability of C3G to reduce plasma and hepatic triglycerides, glucose tolerance, and adiposity and to induce oxygen consumption and energy expenditure was abrogated in PPARα-deficient mice, suggesting that PPARα is the major target for C3G. These findings demonstrate that the dietary anthocyanin C3G activates PPARs, a master regulators of energy metabolism. C3G is an agonistic ligand of PPARs and stimulates fuel preference to fat.

Protocol for development of a core outcome set for menopausal symptoms (COMMA).

OBJECTIVE: Menopause is the natural cessation of menstruation and may be accompanied by troublesome symptoms including hot flushes and night sweats (vasomotor symptoms) and genitourinary symptoms. Randomized trials evaluating the safety and effectiveness of interventions for these symptoms have reported a wide range of outcomes and used inconsistent measures. This variation precludes comparing and combining data from different trials. To overcome this limitation, we will develop a Core Outcome Set for Menopausal Symptoms. METHODS: We will systematically review the literature to identify the outcomes reported in the interventional trials for vasomotor and genitourinary symptoms. This list will be entered into a two-round modified Delphi survey to be completed by clinicians, researchers, and consumers (women who have experienced menopause). Participants will score outcomes on a nine-point scale from "not important" to "critically important." Representatives from each stakeholder group will then meet to discuss the results and finalize the Core Outcome Set. Ethics approval was not required as this was considered service evaluation and development. The study is registered with the Core Outcome Measures in Effectiveness Trials Initiative (http://www.comet-initiative.org/studies/details/917). RESULTS: An agreed upon set of minimum outcomes and outcome measures will facilitate combining and comparing findings from future trials of treatments for menopausal symptoms. CONCLUSIONS: This Core Outcome Set will better enable women and clinicians to select effective treatments, improve the quality of trial reporting, reduce research wastage, and improve care for women with troublesome menopausal symptoms. VIDEO SUMMARY:: http://links.lww.com/MENO/A633.

http://links.lww.com/MENO/A633.

B-Cell-Activating Factor Depletion Ameliorates Aging-Dependent Insulin Resistance via Enhancement of Thermogenesis in Adipose Tissues.

Impaired glucose tolerance is a common feature associated with human aging, which is caused by defects in insulin secretion, insulin action or both. Recent studies have suggested that B-cell-activating factor (BAFF), a cytokine that modulates proliferation and differentiation of B cells, and its receptors are expressed in mature adipocytes and preadipocytes, proposing BAFF as a potential regulator of energy metabolism. In this study, we show that systemic BAFF depletion improves aging-dependent insulin resistance. In aged (10-month-old) BAFF-/- mice, glucose tolerance and insulin sensitivity were significantly improved despite higher adiposity as a result of expansion of adipose tissues compared to wild-type controls. BAFF-/- mice displayed an improved response to acute cold challenge, commensurate with the up-regulated expression of thermogenic genes in both brown and subcutaneous adipose tissues. These changes were found to be mediated by both increased M2-like (alternative) macrophage activation and enhanced leptin and FGF21 production, which may account for the improving effect of BAFF depletion on insulin resistance. In addition, leptin-deficient mice (ob/ob) showed augmented BAFF signaling concomitant with impaired thermogenic activity, identifying BAFF as a suppressive factor to thermogenesis. Our findings suggest that suppression of BAFF could be a therapeutic approach to attenuate aging-dependent insulin resistance.

Aedes albopictus Autophagy-Related Gene 8 (AaAtg8) Is Required to Confer Anti-Bacterial Gut Immunity.

Autophagy is an important process by which pathogens and damaged or unused organelles are eliminated. The role of autophagy in development and the immune response to pathogens is well established. Autophagy-related protein 8 (Atg8) is involved in the formation of the autophagosome and, with the help of the serine protease Atg4, mediates the delivery of both vesicles and the autophagosome to the vacuole. Here, we cloned the Aedes albopictus autophagy-related protein 8 (AaAtg8) gene and characterized its role in the innate immunity of the mosquito against microbial infections. AaAtg8 is comprised of an open reading frame (ORF) region of 357 bp encoding a polypeptide of 118 amino acid residues. A domain analysis of AaAtg8 revealed an Atg8 ubiquitin-like domain, Atg7/Atg4 interaction sites, and peptide binding sites. The AaAtg8 mRNA expression was high in the Malpighian tubules and heads of both sugar-fed and blood-fed adult female mosquitoes. The expression level of AaAtg8 mRNA increased in the midgut and abdominal carcass following being challenged with Listeria monocytogenes. To investigate the role of AaAtg8 in the innate immune responses of Ae. albopictus, AaAtg8 gene-silenced adult mosquitoes were challenged by injection or by being fed microorganisms in blood. High mortality rates were observed in mosquitoes in which AaAtg8 was silenced after challenges of microorganisms to the host by blood feeding. This suggests that Atg8-autophagy plays a critical role in the gut immunity in Ae. albopictus.

TmAtg6 Plays an Important Role in Anti-Microbial Defense Against Listeria monocytogenes in the Mealworm, Tenebrio molitor.

Autophagy-related gene-6 (Beclin-1 in mammals) plays a pivotal role in autophagy and is involved in autophagosome formation and autolysosome maturation. In this study, we identified and characterized the autophagy-related gene-6 from Tenebrio molitor (TmAtg6) and analyzed its functional role in the survival of the insect against infection. The expression of TmAtg6 was studied using qRT-PCR for the assessment of the transcript levels at various developmental stages in the different tissues. The results showed that TmAtg6 was highly expressed at the 6-day-old pupal stage. Tissue-specific expression studies revealed that TmAtg6 was highly expressed in the hemocytes of late larvae. The induction patterns of TmAtg6 in different tissues of T. molitor larvae were analyzed by injecting Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, or Candida albicans. The intracellular Gram-positive bacteria, L. monocytogenes, solely induced the expression of TmAtg6 in hemocytes at 9 h-post-injection, whilst in the fat body and gut, bimodal expression times were observed. RNAi-mediated knockdown of the TmAtg6 transcripts, followed by a challenge with microbes, showed a significant reduction in larval survival rate against L. monocytogenes. Taken together, our results suggest that TmAtg6 plays an essential role in anti-microbial defense against intracellular bacteria.

Comprehensive amelioration of high-fat diet-induced metabolic dysfunctions through activation of the PGC-1α pathway by probiotics treatment in mice.

Although the beneficial effects of probiotics in the prevention or treatment of metabolic disorders have been extensively researched, the precise mechanisms by which probiotics improve metabolic homeostasis are still not clear. Given that probiotics usually exert a comprehensive effect on multiple metabolic disorders, defining a concurrent mechanism underlying the multiple effects is critical to understand the function of probiotics. In this study, we identified the SIRT1-dependent or independent PGC-1α pathways in multiple organs that mediate the protective effects of a strain of Lactobacillus plantarum against high-fat diet-induced adiposity, glucose intolerance, and dyslipidemia. L. plantarum treatment significantly enhanced the expression of SIRT1, PPARα, and PGC-1α in the liver and adipose tissues under HFD-fed condition. L. plantarum treated mice also exhibited significantly increased expressions of genes involved in bile acid synthesis and reverse cholesterol transport in the liver, browning and thermogenesis of adipose tissue, and fatty acid oxidation in the liver and adipose tissue. Additionally, L. plantarum treatment significantly upregulated the expressions of adiponectin in adipose tissue, irisin in skeletal muscle and subcutaneous adipose tissue (SAT), and FGF21 in SAT. These beneficial changes were associated with a significantly improved HFD-induced alteration of gut microbiota. Our findings suggest that the PGC-1α-mediated pathway could be regarded as a potential target in the development of probiotics-based therapies for the prevention and treatment of metabolic disorders.