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AMPK-related protein kinase 5 (ARK5) promotes the deterioration of hepatocellular carcinoma (HCC). From the perspective of lncRNA-miRNA-mRNA, this study explored in-depth the intervention mechanism of ARK5. The binding relationship between miR-424-5p and two genes (LINC00922 and ARK5) were analyzed by Bioinformatics and dual-luciferase experiments. After clinical sample collection, the expressions of miR-424-5p, LINC00922 and ARK5 in HCC tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between LINC00922, miR-424-5p, and ARK5 in HCC tissues was analyzed by Pearson correlation. The influences of miR-424-5p, LINC00922 and ARK5 on the basic functions (viability, migration and invasion) of cancer cells were detected by cell counting kit-8, wound healing, and Transwell experiments, and their regulatory effects on related genes, as well as their relationship, were tested by qRT-PCR and Western blot. MiR-424-5p was low expressed, whereas LINC00922 and ARK5 were high expressed in HCC tissues. MiR-424-5p was negatively associated with LINC00922 and ARK5 that was positively associated with LINC00922. Interestingly, LINC00922 partially shared an identical binding site of miR-424-5p with ARK5. LINC00922 its overexpression partially offset the inhibitory effect of miR-424-5p on cancer cell functions. ARK5 silencing repressed the malignant phenotype of cancer cells and inhibited the expressions of epithelial-to-mesenchymal transition (EMT)-related molecules (Vimentin, Snail and N-Cadherin). However, these effects were partially neutralized by miR-424-5p inhibitors. LINC00922 increases the cell viability, migration, invasion and EMT process of HCC cells by regulating the miR-424-5p/ARK5 axis, and thus may serve as a potential target for targeted therapy.

Haemophilus parasuis is a commensal Gram-negative bacterial pathogen in the upper respiratory tract of pigs, which causes Glässer's disease. More than 15 serotypes of H. parasuis have been identified with apparent differences in virulence. In this research, we surveyed the prevalence and distribution of serotypes and known virulence genes of the H. parasuis isolates collected from sick and healthy pigs in Quang Binh and Thua Thien Hue provinces in Central Vietnam. By using bacterial isolation and polymerase chain reaction (PCR), 56 out of 814 (6.9%) samples were positive for H. parasuis. The most prevalent serotypes were serotype 5 (15/56, 26.8%), followed by serotype 2 (13/56, 23.2%) and serotype 4 (10/56, 17.9%). The vta1 was the most frequently detected virulence gene which was present in 62.5% of the strains, followed by vta3 (42.9%), vta2 (39.3%), HPM-1371 (35.7%), capD (30.4%), HPM-1372 (12.5%), lsgB and HPM-1373 (both shared 8.9%). Strong correlations between some serotypes and known virulence genes were observed, in which virulence genes HPM-1371, HPM-1372, vta3, vta2 and capD were mainly clustered in serotypes 5/12, and vta2 clustered in serotype 2. This study presents the first baseline information on the epidemiological characteristics of H. parasuis isolates from Central Vietnam.

Peripheral nerve injury is a serious health problem and repairing long nerve deficits remains a clinical challenge nowadays. Nerve guidance conduit (NGC) serves as the most promising alternative therapy strategy to autografts but its repairing efficiency needs improvement. In this study, we investigated whether modulating the immune microenvironment by Interleukin-17F (IL-17F) could promote NGC mediated peripheral nerve repair. Chitosan conduits were used to bridge sciatic nerve defect in IL-17F knockout mice and wild-type mice with autografts as controls. Our data revealed that IL-17F knockout mice had improved functional recovery and axonal regeneration of sciatic nerve bridged by chitosan conduits comparing to the wild-type mice. Notably, IL-17F knockout mice had enhanced anti-inflammatory macrophages in the NGC repairing microenvironment. In vitro data revealed that IL-17F knockout peritoneal and bone marrow derived macrophages had increased anti-inflammatory markers after treatment with the extracts from chitosan conduits, while higher pro-inflammatory markers were detected in the Raw264.7 macrophage cell line, wild-type peritoneal and bone marrow derived macrophages after the same treatment. The biased anti-inflammatory phenotype of macrophages by IL-17F knockout probably contributed to the improved chitosan conduit guided sciatic nerve regeneration. Additionally, IL-17F could enhance pro-inflammatory factors production in Raw264.7 cells and wild-type peritoneal macrophages. Altogether, IL-17F may partially mediate chitosan conduit induced pro-inflammatory polarization of macrophages during nerve repair. These results not only revealed a role of IL-17F in macrophage function, but also provided a unique and promising target, IL-17F, to modulate the microenvironment and enhance the peripheral nerve regeneration. Supplementary Information The online version contains supplementary material available at 10.1186/s40478-021-01227-1.

Our previous studies showed that high fructose diet (HFrD)-driven gut dysbiosis caused fecal short-chain fatty acids (SCFAs) reduction and intestinal epithelial barrier (IEB) damage in mice, which might play an important role in hippocampal neuroinflammatory injury. Mulberroside A is reported to have neuroprotective effects in animal experiments, while the underlying mechanisms are not yet fully elucidated. Here, we investigated whether and how mulberroside A prevented HFrD-induced neuroinflammatory injury. HFrD-fed mice were treated orally with mulberroside A (20 and 40 mg/kg) for 8 weeks. Mulberroside A was found to inhibit hippocampal neuroinflammation and neurogenesis reduction in HFrD-fed mice. It reshaped gut dysbiosis, increased fecal and serum SCFAs contents, reactivated signaling of the colonic NLR family, pyrin domain containing 6 (NLRP6) inflammasome, and up-regulated Muc2 expression to prevent IEB damage, as well as subsequently, reduced serum endotoxin levels in this animal model. Additionally, mulberroside A inhibited oxidative stress in colon of HFrD-fed mice and hydrogen peroxide (H2 O2 )-stimulated Caco-2 cells. Blood-brain barrier (BBB) structure defects were also observed in HFrD-driven hippocampal neuroinflammatory injury of mice. Interestingly, mulberroside A maintained astrocyte morphology and up-regulated tight junction proteins to repair BBB structure defects in hippocampus dentate gyrus (DG). Our results demonstrated that mulberroside A was capable of preventing HFrD-induced damage of IEB and BBB in mice, which might contribute to the suppression of hippocampal neuroinflammatory injury.

Dendritic cells (DCs) are important in tumor immunology. Identifying DC subset markers in the peripheral blood, which are informative for gastric cancer stages, is not only useful for prognosis but may also provide mechanistic insights into processes facilitating therapy. The present study investigated plasmacytoid dendritic cells (pDCs) and myeloid CD1c+ dendritic cells (mDC1s) in the peripheral blood of patients with gastric cancer and healthy controls using flow cytometry. Using peripheral DC staining and subset analysis, patients with gastric cancer were identified to have substantially higher numbers of peripheral pDCs and mDC1s. In addition, there was a trend of elevated circulating pDCs with advanced stages and lymph node metastasis in gastric cancer, whereas no differences in circulating mDC1s were observed among the various groups. The results suggested that circulating pDCs are a positive prognostic indicator in patients with gastric cancer of different stages and highlighted the critical role of pDCs immunity in the development of gastric cancer.