High-Fat Diets with Differential Fatty Acids Induce Obesity and Perturb Gut Microbiota in Honey Bee.

HFD (high-fat diet) induces obesity and metabolic disorders, which is associated with the alteration in gut microbiota profiles. However, the underlying molecular mechanisms of the processes are poorly understood. In this study, we used the simple model organism honey bee to explore how different amounts and types of dietary fats affect the host metabolism and the gut microbiota. Excess dietary fat, especially palm oil, elicited higher weight gain, lower survival rates, hyperglycemic, and fat accumulation in honey bees. However, microbiota-free honey bees reared on high-fat diets did not significantly change their phenotypes. Different fatty acid compositions in palm and soybean oil altered the lipid profiles of the honey bee body. Remarkably, dietary fats regulated lipid metabolism and immune-related gene expression at the transcriptional level. Gene set enrichment analysis showed that biological processes, including transcription factors, insulin secretion, and Toll and Imd signaling pathways, were significantly different in the gut of bees on different dietary fats. Moreover, a high-fat diet increased the relative abundance of Gilliamella, while the level of Bartonella was significantly decreased in palm oil groups. This study establishes a novel honey bee model of studying the crosstalk between dietary fat, gut microbiota, and host metabolism.

Veno-Arterial Extracorporeal Membrane Oxygenation Support in Patients Undergoing Aortic Surgery.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an option for mechanical support for patients with postcardiotomy cardiogenic shock (PCS). However, the use of VA-ECMO in patients suffering from aortic disease with PCS has not been greatly reported. This is a retrospective review of adult patients undergoing aortic surgery who received VA-ECMO support to treat refractory PCS from August 2009 to May 2016. A total of 36 patients who underwent aortic surgery with VA-ECMO support for refractory PCS were included. Preoperative, perioperative, and postoperative variables were assessed and analyzed for possible correlation with in-hospital mortality. After a mean duration of 3.6 ± 2.9 days, 24 patients (67%) were weaned off VA-ECMO, and 18 patients (50%) were discharged from the hospital. The overall in-hospital mortality was 50%. The main cause of death was multiple organ dysfunction. The survivors had a lower level of preoperative creatine kinase-MB (CK-MB), a higher rate of antegrade cannulation, and a lower lactate level at 12 h, respectively. Relevant factors for in-hospital mortality were retrograde-flow cannulation (odds ratio [OR], 2.49), peak lactate levels greater than 20 mmol/L (OR, 5.0), and preoperative CK-MB greater than 100 IU/L (OR, 6.40). Antegrade cannulation may provide better perfusion and should be emphasized to improve outcomes. Additionally, levels of peak serum lactate and preoperative CK-MB may be relevant factors for in-hospital mortality in aortic patients with PCS.

Down-regulation of miR-30c promotes the invasion of non-small cell lung cancer by targeting MTA1.

BACKGROUND: The connection between microRNA expression and lung cancer development has been identified in recent literature. However, the mechanism of microRNA has been poorly elucidated in non-small-cell lung cancer (NSCLC). METHODS AND RESULTS: Comparing with adjacent tissues (n=75), miR-30c has a lower expression in lung cancer specimens (n=75). The knockdown of miR-30c enhanced the invasion of A549 cells; meanwhile, the overexpression of miR-30c could reverse the effect of the knockdown of miR-30c in vitro. A luciferase assay revealed that miR-30c was directly bound to the 3'-untranslated regions (3'-UTR) of MTA1. QRT-PCR and western blot shows MTA1 was up-regulated in mRNA and protein levels. The effect taken on the invasion of NSCLC by overexpression of MTA1 works the same as down-regulated miR-30c. CONCLUSION: miR-30c may play a pivotal role in controlling lung cancer invasion through regulating MTA1in NSCLC.

The fecal microbiota from children with autism impact gut metabolism and learning and memory abilities of honeybees.

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders, with an increasing incidence. Gastrointestinal symptoms are common comorbidities of ASD. The gut microbiota composition of children with autism is distinct from that of typical developmental (TD) children, suggesting that the gut microbiota probably influences on hosts via the microbiota-gut-brain axis. However, the relationship between intestinal dysbiosis and host brain function remains unclear. In this study, we creatively developed a honeybee model and investigated the potential effects of fecal microbiota on hosts. Fecal microbiota from children with autism and TD children were transplanted into microbiota-free honeybees (Apis mellifera), resulting in induced ASD-fecal microbiota transplantation (FMT) honeybees (A-BEE group) and TD-FMT honeybees (T-BEE group), respectively. We found that cognitive abilities of honeybees in the A-BEE group were significantly impaired in olfactory proboscis extension response conditioning. Metagenomics was used to evaluate fecal microbiota colonization, revealing several differential species responsible for altered tryptophan metabolism and taurine metabolism within the bee gut, including Bacteroides dorei, Bacteroides fragilis, Lactobacillus gasseri, and Lactobacillus paragasseri. Furthermore, fecal microbiota from children with autism downregulated brain genes involved in neural signaling and synaptic transmission within honeybees. Notably, differentially spliced genes observed within brains of honeybees from the A-BEE group largely overlapped with those identified in human diagnosed with autism via SFARI and SPARK gene sets. These differentially spliced genes were also enriched within pathways related to neural synaptic transmission. Our findings provide novel insights into the pivotal role of the human gut microbiota, which may contribute to neurological processes in honeybees. Additionally, we present a few research sources on gut-brain connections in ASD.

Engineered symbiotic bacteria interfering Nosema redox system inhibit microsporidia parasitism in honeybees.

Nosema ceranae is an intracellular parasite invading the midgut of honeybees, which causes serious nosemosis implicated in honeybee colony losses worldwide. The core gut microbiota is involved in protecting against parasitism, and the genetically engineering of the native gut symbionts provides a novel and efficient way to fight pathogens. Here, using laboratory-generated bees mono-associated with gut members, we find that Snodgrassella alvi inhibit microsporidia proliferation, potentially via the stimulation of host oxidant-mediated immune response. Accordingly, N. ceranae employs the thioredoxin and glutathione systems to defend against oxidative stress and maintain a balanced redox equilibrium, which is essential for the infection process. We knock down the gene expression using nanoparticle-mediated RNA interference, which targets the γ-glutamyl-cysteine synthetase and thioredoxin reductase genes of microsporidia. It significantly reduces the spore load, confirming the importance of the antioxidant mechanism for the intracellular invasion of the N. ceranae parasite. Finally, we genetically modify the symbiotic S. alvi to deliver dsRNA corresponding to the genes involved in the redox system of the microsporidia. The engineered S. alvi induces RNA interference and represses parasite gene expression, thereby inhibits the parasitism significantly. Specifically, N. ceranae is most suppressed by the recombinant strain corresponding to the glutathione synthetase or by a mixture of bacteria expressing variable dsRNA. Our findings extend our previous understanding of the protection of gut symbionts against N. ceranae and provide a symbiont-mediated RNAi system for inhibiting microsporidia infection in honeybees.

Inflammatory bowel disease-associated Escherichia coli strain LF82 in the damage of gut and cognition of honeybees.

Patients with inflammatory bowel disease (IBD) are often accompanied with some cognitive impairment, but the mechanism is unclear. By orally exposing honeybees (Apis mellifera) to IBD-associated Escherichia coli LF82 (LF82), and non-pathogenic Escherichia coli MG1655 (MG1655) as the normal strain, we investigated whether and how LF82 induces enteritis-like manifestations and cognitive behavioral modifications in honeybees using multiparametric analysis. LF82 significantly increased gut permeability, impaired learning and memory ability in olfactory proboscis extension response conditioning, and shortened the lifespan of honeybees. Compared to MG1655, LF82 reduced the levels of tryptophan metabolism pathway substances in the honeybee gut. LF82 also upregulated genes involved in immune and apoptosis-related pathways and downregulated genes involved in G protein-coupled receptors in the honeybee brain. In conclusion, LF82 can induce enteritis-like manifestations and cognition impairment through gut metabolites and brain transcriptome alteration in honeybees. Honeybees can serve as a novel potential model to study the microbiota-gut-brain interaction in IBD condition.

[Crosstalk among dietary lipids, gut microbiome, and host metabolic health].

As one of the three major nutrients, dietary lipids provide energy and nutrition for human. The quantity and quality of dietary lipids affect the composition of gut microbiota, which consequently may affect the host metabolic health. Development of disease animal models is an important approach to study the relationship between gut microbiota and human metabolic health. In this review, we discussed the types of dietary lipids, and summarized how dietary lipids affect the composition of gut microbiota and regulate the metabolic health of animal models. The clarification of potential underlying mechanisms will shed lights on future research in other live systems including human.

Extracorporeal Membrane Oxygenation as a Bridge for Heart Failure and Cardiogenic Shock.

Heart failure (HF) can be defined as cardiac structural or functional abnormality leading to a series of symptoms due to deficiency of oxygen delivery. In the clinical practice, acute heart failure (AHF) is usually performed as cardiogenic shock (CS), pulmonary edema, and single or double ventricle congestive heart failure. CS refers to depressed or insufficient cardiac output (CO) attributable to myocardial infarction, fulminant myocarditis, acute circulatory failure attributable to intractable arrhythmias or the exacerbation of chronic heart failure, postcardiotomy low CO syndrome, and so forth. Epidemiological studies have shown that CS has higher in-hospital mortality in patients with AHF. Besides, we call the induced, sustained circulatory failure even after administration of high doses of inotropes and vasopressors refractory cardiogenic shock. In handling these cases, mechanical circulatory support devices are usually needed. In this review, we discuss the current application status and clinical points in utilizing extracorporeal membrane oxygenation (ECMO).

Low expression of microRNA-30c promotes invasion by inducing epithelial mesenchymal transition in non-small cell lung cancer.

MicroRNA (miR)­30c has been identified as a tumor suppressor gene in numerous diseases. Aberrant miR­30c expression has been associated with the invasion of different types of cancer. However, the potential mechanisms underlying the association between miR­30c and invasion has been poorly elucidated in non­small­cell lung cancer (NSCLC). In the present study, quantitative polymerase chain reaction demonstrated that the expression of miR­30c was reduced in lung cancer specimens (n=85). Suppressing the expression of miR­30c promoted the invasion of A549 cells, while overexpressed miR­30c inhibited the invasion of A549 cells. Furthermore, aberrant miR­30c expression was able to control the expression levels of markers (E­cadherin, snail and vimentin) of epithelial mesenchymal transition (EMT). In conclusion, miR­30c regulated the invasion of NSCLC cells and low miR-30 levels induced EMT.

WT1 promotes cell proliferation in non-small cell lung cancer cell lines through up-regulating cyclin D1 and p-pRb in vitro and in vivo.

The Wilms' tumor suppressor gene (WT1) has been identified as an oncogene in many malignant diseases such as leukaemia, breast cancer, mesothelioma and lung cancer. However, the role of WT1 in non-small-cell lung cancer (NSCLC) carcinogenesis remains unclear. In this study, we compared WT1 mRNA levels in NSCLC tissues with paired corresponding adjacent tissues and identified significantly higher expression in NSCLC specimens. Cell proliferation of three NSCLC cell lines positively correlated with WT1 expression; moreover, these associations were identified in both cell lines and a xenograft mouse model. Furthermore, we demonstrated that up-regulation of Cyclin D1 and the phosphorylated retinoblastoma protein (p-pRb) was mechanistically related to WT1 accelerating cells to S-phase. In conclusion, our findings demonstrated that WT1 is an oncogene and promotes NSCLC cell proliferation by up-regulating Cyclin D1 and p-pRb expression.