Alterations of the gut microbiome and metabolic profile in CVB3-induced mice acute viral myocarditis.

BACKGROUND: Acute viral myocarditis (AVMC) is an inflammatory disease of the myocardium. Evidence indicates that dysbiosis of gut microbiome and related metabolites intimately associated with cardiovascular diseases through the gut-heart axis. METHODS: We built mouse models of AVMC, then applied 16 S rDNA gene sequencing and UPLC-MS/MS metabolomics to explore variations of gut microbiome and disturbances of cardiac metabolic profiles. RESULTS: Compared with Control group, analysis of gut microbiota showed lower diversity in AVMC, decreased relative abundance of genera mainly belonging to the phyla Bacteroidetes, and increased of phyla Proteobacteria. Metabolomics analysis showed disturbances of cardiac metabolomics, including 62 increased and 84 decreased metabolites, and mainly assigned to lipid, amino acid, carbohydrate and nucleotide metabolism. The steroid hormone biosynthesis, cortisol synthesis and secretion pathway were particularly enriched in AVMC. Among them, such as estrone 3-sulfate, desoxycortone positively correlated with disturbed gut microbiome. CONCLUSION: In summary, both the structure of the gut microbiome community and the cardiac metabolome were significantly changed in AVMC. Our findings suggest that gut microbiome may participate in the development of AVMC, the mechanism may be related to its role in dysregulated metabolites such as steroid hormone biosynthesis.

Copper-catalyzed radical-mediated intermolecular cyanomonofluoroalkylation of alkenes and alkynes.

A novel copper-catalyzed three-component reaction of monofluoroalkylation agents, alkenes and TMSCN is described. In addition, alkynes could also be compatible with the reaction system to obtain three-component products for the first time with moderate yield and excellent E/Z stereoselectivity. This reaction provides a facile method for the synthesis of cyanomonofluoroalkyl compounds, which may serve as potentially useful organic intermediates for further transformations. Preliminary mechanistic investigation indicated that monofluoroalkyl free radicals were involved in the cyanomonofluoroalkylation process.

Periodontitis-induced oral microbiome alterations provide clues on how periodontitis exacerbates colitis.

AIM: To evaluate whether and how microbiota-derived metabolites associated with periodontitis aggravate colitis in mice. MATERIALS AND METHODS: A mouse model of periodontitis and colitis was constructed. Unbiased transcriptomic analyses of the colon were performed to explore important pathways through which periodontitis exacerbated colitis. Oral and gut bacteria were analysed using 16S rRNA sequencing. Gas chromatography-mass spectrometry was used to observe the alterations of oral and gut metabolites. Isolated intestinal lamina propria lymphocytes were analysed by flow cytometry. Inflammasome pathway was detected using qRT-PCR, Western blotting or ELISA. RESULTS: Periodontitis activated the colonic inflammasome pathway and altered the gut microbial composition and metabolite profiles in mice with colitis. Notably, periodontitis induced increase of the faecal metabolite isoleucine (Ile) which was synthesized by microbiota and plants. Moreover, periodontitis upregulated the Ile levels in saliva, but not in serum, indicating that Ile might be an oral pathobiont-synthesizing metabolite that transited from the oral cavity to the gut. Ile triggered the inflammasome pathway, upregulated the number of inflammatory IL-1ßhigh MHCIIhigh Ly6Chigh monocytes in colonic lamina propria, and exacerbated colitis. Further studies found that the Ile metabolite acetyl-coenzyme A positively regulated NLRP3 inflammasome by KAT5-mediated acetylation of NLRP3. CONCLUSIONS: Our study revealed that alteration in periodontitis-induced microbial metabolites deteriorated colitis in a mouse model and that this was associated with Ile production.

Development of a multicriteria decision-making model for evaluating hybrid offspring in the sweetpotato (Ipomoea batatas L.) breeding process.

Sweetpotato variety breeding is always a long process. Screening of hybrid offspring is dominated by empirical judgment in this process. Data analysis and decision fatigue have been troubling breeders. In recent years, the low-efficiency screening mode has been unable to meet the requirements of sweetpotato germplasm innovation. Therefore, it is necessary to construct a high-efficiency method that can screen germplasms for different usages, for mining elite genotypes, and to create dedicated sweetpotato varieties. In this article, the multicriteria decision-making (MCDM) model was constructed based on six agronomic traits, including fresh root yield, vine length, vine diameter, branch number, root number and the spatial distribution of storage roots, and five quality traits, including dry matter content, marketable root yield, uniformity of roots, starch content and the edible quality score. Among these, the edible quality score was calculated by using fuzzy comprehensive evaluation to integrate the sensory scores of color, odor, sweetness, stickiness and fibrous taste. The MCDM model was compared with the traditional screening method via an evaluation in 25 sweetpotato materials. The interference of subjective factors on the evaluation results was significantly reduced. The MCDM model is more overall, more accurate and faster than the traditional screening method in the selection of elite sweetpotato materials. It could be programmed to serve the breeders in combination with the traditional screening method.

Animal models in intrauterine adhesion research.

Intrauterine adhesion (IUA) is a gynaecological disease caused by uterine cavity surgeries and infections that leads to partial or total occlusion of the uterine cavity. However, the underlying mechanism(s) and progression of the disease have not yet been identified. IUA has a high recurrence rate and poor prognosis, and effective drugs to prevent adhesion are lacking. Therefore, establishing an effective animal model of IUA is of great significance for revealing the pathogenesis of IUA and the mechanism(s) governing drug effects. Rats, mice, rabbits, and other animals are currently used to establish intrauterine adhesion models. The IUA induction methods include chemical, thermal, or mechanical damage and mechanical damage combined with an infective method. We analysed the advantages and disadvantages of various models and their clinical simulations in order to provide a precise animal model for exploring the pathogenesis, treatment strategies, and prevention of IUA.

Contrasting effects of carbon source recalcitrance on soil phosphorus availability and communities of phosphorus solubilizing microorganisms.

Carbon (C) additions to soil interact through chemical and microbiological processes to cause changes in soil phosphorus (P) availability. However, the response of soil P transformations and relevant microbial communities to C additions having different degrees of recalcitrance remains uncertain. We studied the effects of glucose, hemicellulose and lignin addition on soil P availability, P transformation processes and relevant microbial activity and communities in a P-deficient flooded soil. Lignin significantly increased soil available P concentrations, which was attributed to chemical release of inorganic P and increased alkaline phosphatase activity. Glucose and hemicellulose additions stimulated microbial metabolism of C thereby enhancing microbial demand for P, with increased soil P availability especially in the early incubation period. Glucose or hemicellulose addition changed soil microbial diversity and community composition, leading to enhanced growth and interactions of P solubilizing microorganisms such as Desulfitobacterium, Bacillus and Desulfosporosinus. Our results infer the importance of pH alteration and competitive sorption between PO4 and functional groups of recalcitrant C (e.g., lignin) with Fe/Al (hydr) oxides in regulating soil P availability. Further, the microbial response to labile C additions led to increased P availability in the P-deficient soil. This study provides important mechanistic information to guide microbially-regulated soil P management in agricultural ecosystems.

Elevated temperature shifts soil N cycling from microbial immobilization to enhanced mineralization, nitrification and denitrification across global terrestrial ecosystems.

We assessed the response of soil microbial nitrogen (N) cycling and associated functional genes to elevated temperature at the global scale. A meta-analysis of 1,270 observations from 134 publications indicated that elevated temperature decreased soil microbial biomass N and increased N mineralization rates, both in the presence and absence of plants. These findings infer that elevated temperature drives microbially mediated N cycling processes from dominance by anabolic to catabolic reaction processes. Elevated temperature increased soil nitrification and denitrification rates, leading to an increase in N2 O emissions of up to 227%, whether plants were present or not. Rates of N mineralization, denitrification and N2 O emission demonstrated significant positive relationships with rates of CO2 emissions under elevated temperatures, suggesting that microbial N cycling processes were associated with enhanced microbial carbon (C) metabolism due to soil warming. The response in the abundance of relevant genes to elevated temperature was not always consistent with changes in N cycling processes. While elevated temperature increased the abundances of the nirS gene with plants and nosZ genes without plants, there was no effect on the abundances of the ammonia-oxidizing archaea amoA gene, ammonia-oxidizing bacteria amoA and nirK genes. This study provides the first global-scale assessment demonstrating that elevated temperature shifts N cycling from microbial immobilization to enhanced mineralization, nitrification and denitrification in terrestrial ecosystems. These findings infer that elevated temperatures have a profound impact on global N cycling processes with implications of a positive feedback to global climate and emphasize the close linkage between soil microbial C and N cycling.

A typical C-type lectin, perlucin-like protein, is involved in the innate immune defense of whiteleg shrimp Litopenaeus vannamei.

C-type lectins are a large group of the pattern-recognition proteins, and have been reported to be involved in invertebrate innate immunity, such as cell adhesion, bacterial clearance, phagocytosis, prophenoloxidase activation and encapsulation. Here, a perlucin-like protein (PLP), a typical C-type lectin, was identified from the cDNA library of the shrimp, Litopenaeus vannamei. LvPLP contains a 540 bp open reading frame, encoding a protein of 179 amino acids that includes a single carbohydrate-recognition domain. Phylogenetic analysis showed that LvPLP was clustered into a single group together with other perlucins from molluscs. Quantitative real-time PCR revealed that LvPLP was expressed mainly in the hemocytes, hemolymph, heart and gills. The transcription of LvPLP was significantly induced at 9 h by both Gram- bacteria Vibrio parahaemolyticus and Vibrio anguillarum. Meanwhile, recombinant LvPLP (rLvPLP) bound directly to lipopolysaccharide and peptidoglycan with different affinity. rLvPLP showed a strong ability to bind to Gram+ (Staphylococcus aureus and Bacillus subtilis) and Gram- bacteria (V. parahaemolyticus and V. anguillarum), and could induce agglutination of V. parahaemolyticus and V. anguillarum, but not S. aureus and B. subtilis in the presence Ca2+. Further study showed that when LvPLP was knocked down by RNAi, three phagocytosis-related genes (peroxinectin, mas-like protein and dynamin) and four antimicrobial peptide (AMP) genes (crustin, ALF1, ALF2 and ALF3) were significantly decreased. Altogether, these results demonstrated that LvPLP played a vital role in L. vannamei immune response towards bacterial challenge by binding and agglutinating bacteria and influencing phagocytosis and AMP expression.

Mettl3 Regulates Osteogenic Differentiation and Alternative Splicing of Vegfa in Bone Marrow Mesenchymal Stem Cells.

Bone mesenchymal stem cells (BMSCs) can be a useful cell resource for developing biological treatment strategies for bone repair and regeneration, and their therapeutic applications hinge on an understanding of their physiological characteristics. N6-methyl-adenosine (m6A) is the most prevalent internal chemical modification of mRNAs and has recently been reported to play important roles in cell lineage differentiation and development. However, little is known about the role of m6A modification in the cell differentiation of BMSCs. To address this issue, we investigated the expression of N6-adenosine methyltransferases (Mettl3 and Mettl14) and demethylases (Fto and Alkbh5) and found that Mettl3 was upregulated in BMSCs undergoing osteogenic induction. Furthermore, we knocked down Mettl3 and demonstrated that Mettl3 knockdown decreased the expression of bone formation-related genes, such as Runx2 and Osterix. The alkaline phosphatase (ALP) activity and the formation of mineralized nodules also decreased after Mettl3 knockdown. RNA sequencing analysis revealed that a vast number of genes affected by Mettl3 knockdown were associated with osteogenic differentiation and bone mineralization. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed that the phosphatidylinositol 3-kinase/AKT (PI3K-Akt) signaling pathway appeared to be one of the most enriched pathways, and Western blotting results showed that Akt phosphorylation was significantly reduced after Mettl3 knockdown. Mettl3 has been reported to play an important role in regulating alternative splicing of mRNA in previous research. In this study, we found that Mettl3 knockdown not only reduced the expression of Vegfa but also decreased the level of its splice variants, vegfa-164 and vegfa-188, in Mettl3-deficient BMSCs. These findings might contribute to novel progress in understanding the role of epitranscriptomic regulation in the osteogenic differentiation of BMSCs and provide a promising perspective for new therapeutic strategies for bone regeneration.

TET1 Knockdown Inhibits Porphyromonas gingivalis LPS/IFN-γ-Induced M1 Macrophage Polarization through the NF-κB Pathway in THP-1 Cells.

Tet-eleven translocation 1 (TET1) is a dioxygenase that plays an important role in decreasing the abundance of DNA methylation and changing the expression levels of specific genes related to inflammation. Porphyromonas gingivalis (Pg.) lipopolysaccharide (LPS) can induce periodontal diseases that present with severe bone loss and collagen fiber destruction accompanied by a high number of M1 macrophages. M1-polarized macrophages are pivotal immune cells that promote the progression of the periodontal inflammatory response, but the function of TET1 during M1 macrophage activation is still unknown. Our results showed that the mRNA and protein expression levels of TET1 decreased in THP-1 cells during M1 macrophage differentiation. TET1 knockdown resulted in a significant decrease in the production of proinflammatory markers such as IL-6, TNF-α, CCL2, and HLA-DR in Pg. LPS/IFN-γ- and Escherichia coli (E. coli) LPS/IFN-γ-induced M1 macrophages. Mechanistically, TET1 knockdown downregulated the activity of the NF-κB signaling pathway. After treatment with the NF-κB inhibitor BAY 11-7082, M1 marker expression showed no significant difference between the TET1 knockdown group and the control group. Taken together, these results suggest that TET1 depletion inhibited Pg. LPS/IFN-γ-induced M1 macrophage polarization through the NF-κB pathway in THP-1 cells.

Expression of CD80 and CD86 on B cells during coxsackievirus B3-induced acute myocarditis.

INTRODUCTION: The pathogenesis of viral myocarditis (VMC) is unclear, but many studies have shown that VMC is associated with an excessive immune response. CD80 and CD86 are important costimulatory molecules that play a critical role in autoimmunity. However, whether CD80+/CD86+ B cells participate in the pathogenesis of acute VMC is unknown. MATERIAL AND METHODS: Male C57BL/6 mice were infected by intraperitoneal injection with coxsackievirus B3 (CVB3) to establish a VMC model. Control mice were administered phosphate-buffered saline intraperitoneally. At one week and two weeks post injection, histopathological changes in heart tissue were assessed with haematoxylin and eosin staining. The frequency of splenic CD80+/CD86+ B cells was measured with flow cytometry. RESULTS: The frequency of CD80+ B cells was significantly increased in VMC, while the frequency of CD86+ B cells was significantly decreased. Furthermore, the frequency of CD80+ B cells related to the severity of VMC. CONCLUSIONS: These data show that CD80+/CD86+B cells are involved in the pathogenesis of VMC, with CD80+B cells being more important than CD86+B cells.

Delayed endovascular aortic repair is associated with reduced in-hospital mortality in patients with blunt thoracic aortic injury.

OBJECTIVE: The traditional approach to stable blunt thoracic aortic injury (BTAI) endorsed by the Society for Vascular Surgery is early (<24 hours) thoracic endovascular aortic repair (TEVAR). Recently, some studies have shown improved mortality in stable BTAI patients repaired in a delayed manner (≥24 hours). However, the indications for use of delayed TEVAR for BTAI are not well characterized, and its overall impact on the patient's survival remains poorly understood. We sought to determine whether delayed TEVAR is associated with a decrease in mortality compared with early TEVAR in this population. METHODS: We conducted a retrospective cohort study of adult patients with BTAI (International Classification of Diseases, Ninth Revision diagnosis code 901.0) who underwent TEVAR (International Classification of Diseases, Ninth Revision procedure code 39.73) from 2009 to 2013 using the National Sample Program data set. Missing physiologic data were imputed using chained multiple imputation. Patients were parsed into groups based on the timing of TEVAR (early, <24 hours, vs delayed, ≥24 hours). The χ2, Mann-Whitney, and Fisher exact tests were used to compare baseline characteristics and outcomes of interest between groups. Multivariable logistic regression for mortality was performed that included all variables significant at P ≤ .2 in univariate analyses. RESULTS: A total of 2045 adult patients with BTAI were identified, of whom 534 (26%) underwent TEVAR. Patients with missing data on TEVAR timing were excluded (n = 27), leaving a total of 507 patients for analysis (75% male; 69% white; median age, 40 years [interquartile range, 27-56 years]; median Injury Severity Score [ISS], 34 [interquartile range, 26-41]). Of these, 378 patients underwent early TEVAR and 129 underwent delayed TEVAR. The two groups were similar with regard to age, sex, race, ISS, and presenting physiology. Mortality was 11.9% in the early TEVAR group vs 5.4% in the delayed group, with the early group displaying a higher odds of death (odds ratio, 2.36; 95% confidence interval, 1.03-5.36; P = .042). After adjustment for age, ISS, and admission physiology, the association between early TEVAR and mortality was preserved (adjusted odds ratio, 2.39; 95% confidence interval, 1.01-5.67; P = .047). CONCLUSIONS: Consistent with current Society for Vascular Surgery recommendations, more BTAI patients underwent early TEVAR than delayed TEVAR during the study period. However, delayed TEVAR was associated with significantly reduced mortality in this population. Together, these findings support a need for critical appraisal and clarification of existing practice guidelines in management of BTAI. Future studies should seek to understand this survival disparity and to determine optimal selection of patients for early vs delayed TEVAR.

National Variation in Opioid Prescribing and Risk of Prolonged Use for Opioid-Naive Patients Treated in the Emergency Department for Ankle Sprains.

STUDY OBJECTIVE: To inform opioid stewardship efforts, we describe the variation in emergency department (ED) opioid prescribing for a common minor injury, ankle sprain, and determine the association between initial opioid prescription intensity and transition to prolonged opioid use. METHODS: We analyzed 2011 to 2015 US private insurance claims (Optum Clinformatics DataMart) for ED-treated ankle sprains among opioid-naive patients older than 18 years. We determined the patient- and state-level variation in the opioid prescription rate and characteristics, and the risk-adjusted association between total morphine milligram equivalents (MMEs) of the prescription and transition to prolonged use (filling 4 or more opioid prescriptions 30 to 180 days after the index visit). RESULTS: A total of 30,832 patients met inclusion criteria. Of these patients, 25.1% received an opioid prescription with a median total MME of 100 (interquartile range 75 to 113), tablet quantity of 15 (interquartile range 12 to 20), and days supplied of 3 (interquartile range 2 to 4). State-level prescribing rates ranged from 2.8% in North Dakota to 40.0% in Arkansas. Among patients who received a total MME of greater than 225 (equivalent to >30 tabs of oxycodone 5 mg), the adjusted rate of prolonged opioid use was 4.9% (95% CI 1.8% to 8.1%) compared with 1.1% (95% CI 0.7% to 1.5%) among those who received at total MME of 75 and 0.5% (95% CI 0.4% to 0.6%) among those who did not fill an opioid prescription. CONCLUSION: Opioid prescribing for ED patients treated for ankle sprains is common and highly variable. Although infrequent in this population, prescriptions greater than 225 MME were associated with higher rates of prolonged opioid use. This is concerning because these prescriptions could still fall within 5- or 7-day supply limit policies aimed at promoting safer opioid prescribing.

Cognitive Skills Training for Homeless Transition-Age Youth: Feasibility and Pilot Efficacy of a Community Based Randomized Controlled Trial.

Cognitive impairments are common in homeless youth and negatively impact academic and vocational outcomes. We examined the feasibility and efficacy of cognitive interventions provided to 18- to 22-year-old homeless youth living in urban supportive housing. Ninety-one homeless youth were randomized to receive either targeted cognitive training (cognitive remediation) or general cognitive activation (computer skills training). Cognitive and psychological outcomes were assessed at baseline, after 13 and 26 sessions, and 1 month postintervention. A high dropout rate highlighted the feasibility challenges of treating this population. Intent-to-treat analysis found significant improvements across groups in specific and global measures of cognition and psychological distress, with no significant group differences. Transition-age homeless youth show improvements in cognitive and psychological functioning when engaged in interventions that address their cognitive development. This speaks to the malleability of cognitive skills in this cohort and lays the groundwork for future research to address their cognitive health.

Application of CRISPR/Cas9 system in breeding of new antiviral plant germplasm.

With the development and improvement of CRISPR/Cas9 system in genomic editing technology, the system has been applied to the prevention and control of animal viral infectious diseases, which has made considerable achievements. It has also been applied to the study of highly efficient gene targeting editing in plant virus genomes. The CRISPR/Cas9-mediated targeted gene modification has not only achieved the genome editing of plant DNA virus, but also showed the genome editing potential of plant RNA virus. In addition, the CRISPR/Cas9 system functions at the gene transcriptional and post-transcriptional level, indicating that the system could regulate the replication of plant viruses through different ways. Compared with other plant viral disease control strategies, this system is more accurate in genome editing, more stable in gene expression regulation, and has broader spectrum of resistance to virus disease. In this review, we summarized the advantages, main problems and development tendency of CRISPR/cas9 system in breeding of new antiviral plant germplasms.

Paclitaxel combined with trastuzumab chemotherapy-related posterior reversible encephalopathy syndrome: A case report and literature review.

Posterior reversible encephalopathy syndrome (PRES) in breast carcinoma is a rare disease in clinical practice that is often misdiagnosed and ignored. This study reported a case of a patient admitted to our hospital and discussed the clinical, imaging, and pathogenesis properties of the disease. We retrospectively analyzed the clinical data of this patient and reviewed the relevant literature. Imaging was used to diagnose PRES based on clinical findings, and clinical symptoms improved after discontinuation of the relevant drugs.

CD4+TEM cells drive the progression from acute myocarditis to dilated cardiomyopathy in CVB3-induced BALB/c mice.

Acute viral myocarditis can progress to chronic myocarditis leading to dilated cardiomyopathy (DCM). Persistent CD4+ T-cell-mediated autoimmunity triggered by infection plays a critical role in this progression. Increasing evidence demonstrates that effector memory CD4+T (CD4+TEM) cells, a subset of memory CD4+ T cells, are crucial pathogenic mediators of many autoimmune diseases. However, the role of CD4+TEM cells during the progression from acute viral myocarditis to DCM remains unknown. In this study, we observed an increase in CD4+TEM cells both in the periphery and the heart, and memory CD4+ T cells were the predominant sources of IL-17A and IFN-γ among inflamed heart-infiltrating CD4+ T cells during the progression from acute myocarditis to chronic myocarditis and DCM in CVB3-induced BALB/c mice. Moreover, splenic CD4+TEM cells sorted from DCM mice induced by CVB3 were found to respond to cardiac self-antigens ex vivo. Additionally, adoptive transfer experiments substantiated their pathogenic impact, inducing sustained myocardial inflammation, tissue fibrosis, cardiac injury, and impairment of cardiac systolic function in vivo. Our findings illustrate that long-lived CD4+TEM cells are important contributors to the progression from acute viral myocarditis into DCM.

A facile ratiometric near-infrared fluorescent probe using conjugated 1,8-naphthalimide and dicyanoisophorone with a vinylene linker for detection and bioimaging of hypochlorite.

A new ratiometric near-infrared fluorescent probe 3 for detecting ClO- using conjugated 1,8-naphthalimide and dicyanoisophorone with a vinylene linker was reported. Probe 3 exhibited a ratiometric signal (I705/I535), large Stokes shift (205 nm), high selectivity and sensitivity, low detection limit (0.738 µM), rapid response (within 3 s) and good biocompatibility. The sensing mechanism involved the oxidation of the olefin double bond by ClO- to release the initial N-butyl-4-hydroxyl-3-formyl-1,8-naphthalimide 1, followed by inhibition of an ICT process from the electron-donor 4-hydroxyl-1,8-naphthalimide to dicyanoisophorone. At the same time, the probe 3-loaded test strips were applied in sensing of ClO- with moderate "naked-eye" color changes. Additionally, probe 3 has been successfully used for ratiometric bioimaging of ClO- in HeLa cells with low cytotoxicity.

Trehalose induces B cell autophagy to alleviate myocardial injury via the AMPK/ULK1 signalling pathway in acute viral myocarditis induced by Coxsackie virus B3.

Viral myocarditis (VMC) is the main cause of sudden acute heart failure and cardiac death in adolescents; however, treatment for VMC is limited. Trehalose is a natural non-reductive disaccharide that protects against cardiovascular diseases by inducing autophagy. The protective effect of trehalose on VMC and the specific mechanism remains unclear. In this study, we established a VMC mouse model, treated with trehalose in vivo, and cultured B cells from VMC mice with trehalose in vitro to elucidate the effect of trehalose on B cells in acute VMC. Trehalose alleviated myocardial injury in VMC mice and increased the number of autophagosomes, LC3II/LC3I ratio, and expression level of LAMP2, whereas it decreased the expression of p62 in VMC-B cells. Bafilomycin A1 suppressed VMC-B cell autophagy induced by trehalose. At the mechanistic level, trehalose treatment significantly upregulated the phosphorylation of AMPK and ULK1 in VMC-B cells. Dorsomorphin and SBI-0206965 abolished the increased phosphorylation level and altered the expression levels of autophagy-related proteins. In conclusion, trehalose alleviates myocardial inflammatory damage of VMC by inducing B cell autophagy, mediated by the AMPK/ULK1 signalling pathway. Thus, trehalose may be a potentially useful molecule for alleviating myocardial injury in VMC.

Expression of IL-23/Th17 pathway in a murine model of Coxsackie virus B3-induced viral myocarditis.

BACKGROUND: The IL-23/Th17 pathway is implicated in the pathogenesis of a number of chronic inflammatory and autoimmune diseases. Whether it regulates the viral myocarditis (VMC) is unknown. RESULTS: To examine the pathogenesis role of IL-23/Th17 axis in VMC, we used male BALB/c mice to induced VMC by Coxsackie virus B3 (CVB3) peritoneal injection. IL-23, IL-17, and signal transducer and activator of transcription 3 (STAT3) mRNA in the myocardium of VMC mice were assessed by semi-quantitative RT-PCR. IL-23 and IL-17 protein from blood serum were evaluated by ELISA. Phosphorylated-STAT3 (p-STAT3) protein expression in the myocardium was evaluated by immunohistochemical staining. Flow cytometric analysis was used to evaluate the frequencies of Th17 subsets. Isolated CD4+ T cells from VMC mice were cultured with recombinant IL-23(rIL-23) in vitro. In addition, a STAT3-specific inhibitor (S3I-201) was used to test whether regulation of STAT3 could be partly responsible for Th17 diminution. Results showed that expression of IL-23, IL-17, STAT3 mRNA and protein increased in VMC mice. When purified CD4+ T cells derived from VMC mice were cultured in vitro with rIL-23, the frequency of Th17 cells was dramatically increased, accompanied by significantly enhanced production of IL-17 in the supernatants of cultured CD4+ T cells. S3I-201 significantly restrained Th17 cell proliferation. CONCLUSIONS: The IL-23/Th17 pathway axis is strongly expressed in murine VMC, identifying a novel pathway of potential significance in viral myocarditis.