Inhibition of miR-1298-5p attenuates sepsis lung injury by targeting SOCS6.

Sepsis is one of the leading causes of morbidity and mortality and a major cause of acute lung injury (ALI). carried by exosomes play a role in a variety of diseases. However,there are not many studies of exosomal miRNAs in sepsis and sepsis lung injury.miR-1298-5p and suppressor of cytokine signaling 6 (SOCS6) were silenced or overexpressed in human bronchial epithelial cells (BEAS-2B). PKH-67 Dye was used to trace exosome endocytosis. Cell permeability was evaluated by measuring trans-epithelial electrical resistance (TEER) and FITC dextran flux. ELISA kits were used for cytokine detection. Quantitative RT-PCR and western blots were used to evaluate gene expression. miR-1298-5p was elevated in exosomes from patients with sepsis lung injury (Sepsis_exo). Treatment of BEAS-2B cells using Sepsis_exo significantly inhibited cell proliferation, and induced cell permeability and inflammatory response. miR-1298-5p directly targeted SOCS6. Overexpressing SOCS6 reversed miR-1298-5p-induced cell permeability and inflammatory response. Inhibition of STAT3 blocked SOCS6-silencing caused significant increase of cell permeability and inflammation. Exosomes isolated from patients of sepsis lung injury increased cell permeability and inflammatory response in BEAS-2B cells through exosomal miR-1298-5p which targeted SOCS6 via STAT3 pathway. The findings highlight the importance of miR-1298-5p/SOCS6/STAT3 axis in sepsis lung injury and provide new insights into therapeutic strategies for sepsis lung injury.

Mining of the Novel Virulent ATP-Binding Cassette Importers in Mycobacterium abscessus by Comparative Genomic Strategy.

Background: The virulent ATP-binding cassette (ABC) importers from Mycobacterium abscessus, the most common native multidrug resistant and emerging opportunistic pathogen in rapidly growing NTM, were explored by comparative genomic study, in view of the fact that the ABC importers of Mycobacterium tuberculosis, responsible for uptaking metals, anions, amino acids, peptides, sugars, and other crucial substances from the host, had been proved to be closely related with the bacillus's virulence, survival in the host macrophages, antibiotic resistance, modulation of host immune system, and so on, although detailed mechanism was unclear. Methods: For virulent ABC importers from M. abscessus predicted by orthology and phylogeny analysis of nucleotide-binding domains (NBDs) of Mycobacterium smegmatis, M. abscessus, and M. tuberculosis, the antibiotic susceptibility of overexpression transformant and knockout mutant was assayed after confirmation by in vitro experiment. Results: Three-domain importers were dominant ones in M. abscessus (60.0%), four-domain ones dominant in M. tuberculosis (87.5%), whereas both types were same in M. smegmatis (41.9%). In the phylogenetic tree, the importers of M. abscessus (53.3%) and M. tuberculosis (62.5%) were mainly distributed in clay A, whereas the clay E was exclusively composed of M. smegmatis NBDs, which hinted possible reprogramming of the transporter system during the pathogen evolution. In clay A, MAB_2178 and others were predicted virulence-associated because of high sequence similarity to M. tuberculosis virulence importers. Conclusions: The importance and complexity of antibiotics resistance mechanisms of MAB_2176-2177-2178 were pointed out by its overexpression enhancing bacterial resistance to ciprofloxacin, clarithromycin, cefoxitin, and sensitivity to amikacin, and knockout having opposite phenotypes.

Chemical conversion of human lung fibroblasts into neuronal cells.

It has been previously reported that human embryonic fibroblasts and mouse embryonic fibroblasts can be converted into neuronal cells using chemical agents, along with forced expression specific transcriptional factors. However, the materials required for reprogramming in these approaches presents major technical difficulties and safety concerns. The current study investigated whether a cocktail of small molecules can convert human lung fibroblast cells into neurons. The small molecules valproic acid, CHIR99021, DMH1, Repsox, forskolin, Y­27632 and SP600125 (VCHRFYS) were used to induce MRC­5 cells into neuronal cells in vitro. Neuronal markers were analyzed by immunofluorescence staining. The gene profiles were analyzed by reverse transcription­quantitative polymerase chain reaction. MRC­5 is a human lung fibroblast cell line derived from normal lung tissue of a 14­week­old male fetus. The results of the current study demonstrated that MRC­5 fibroblasts can be directly converted into neuronal cells using a cocktail of seven small molecules (VCHRFYS), with a yield of ~90% Tuj1­positive cells after 7 days of induction. Following a further maturation period, these chemically-induced neurons possessed neuronal morphology and expressed multiple neuron­specific genes. In conclusion, a cocktail of small molecules that can convert fibroblasts MRC­5 cells into functional neurons without the exogenous genetic factors was identified, which has the potential to be useful in neurological disease therapy.

The strategies for treating primary hepatocellular carcinoma with portal vein tumor thrombus.

PURPOSE: To further improve the effectiveness and prognosis of primary hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), the current status of treatment for HCC with PVTT was reviewed. METHODS: A Medline search was undertaken to identify articles using the keywords "HCC", "PVTT" and "therapy". Additional papers were identified by a manual search of the references from the key articles. RESULTS: PVTT, as a common complication of HCC, was divided into type I ∼ IV. The therapeutic approach is mainly composed of five types: surgical resection, regional interventional therapy, radiotherapy, combination therapy, targeted therapy. All of these therapeutic approaches were separately evaluated in detail. CONCLUSIONS: For those resectable tumors, the better choice for treatment of HCC with PVTT should be hepatectomy and removal of PVTT. For those unresectable tumors, TACE (especially the super-selective TACE) has been the preferred palliative treatment, the other regional interventional therapy and/or radiotherapy could improve the therapeutic effects. The multidisciplinary treatments may further improve the quality of life and prolong the survival period for the HCC patients associated with PVTT.