Relationship of the lung microbiome with PD-L1 expression and immunotherapy response in lung cancer

IL-35 subunit EBI3 is up-regulated in pulmonary fibrosis tissues. In this study, we investigated the pathological role of EBI3 in pulmonary fibrosis and dissected the underlying molecular mechanism. Bleomycin-induced pulmonary fibrosis mouse model was established, and samples were performed gene expression analyses through RNAseq, qRT-PCR and Western blot. Wild type and EBI3 knockout mice were exposed to bleomycin to investigate the pathological role of IL-35, via lung function and gene expression analyses. Primary lung epithelial cells were used to dissect the regulatory mechanism of EBI3 on STAT1/STAT4 and STAT3. IL-35 was elevated in both human and mouse with pulmonary fibrosis. EBI3 knockdown aggravated the symptoms of pulmonary fibrosis in mice. EBI3 deficiency enhanced the expressions of fibrotic and extracellular matrix-associated genes. Mechanistically, IL-35 activated STAT1 and STAT4, which in turn suppressed DNA enrichment of STAT3 and inhibited the fibrosis process. IL-35 might be one of the potential therapeutic targets for bleomycin-induced pulmonary fibrosis.     

Bacillus daqingensis sp. nov. isolated from near poultry farm soil

A novel bacterial strain, designated PFS-5^T, was isolated from the soil environment with feces of a live poultry farm located in Cheonan, Republic of Korea. Strain PFS-5^T was Gram-staining-positive, motile, strictly aerobic bacterium, rod-shaped, and endospore-forming. The strain contained meso-diaminopimelic acid in their peptidoglycan and MK-7 menaquinone. The major fatty acids were anteiso-C_15:0 (44.2%), C_16:0 (22.2%), and iso-C_15:0 (16.7%). The DNA G+C content was 40.1 mol%. Comparative 16S rRNA gene sequence analysis identified strain PFS-5^T in the genus Bacillus, exhibiting the highest level of sequence similarity with type strain of B. herbersteinensis D-1,5a^T (96.9%), B. humi LMG 22167^T (96.7%), B. alkalitelluris BA288^T (96.1%), B. litoralis SW-211^T (96.0%), and B. luteolus YIM93174^T (95.5%). The major polar lipids of PFS-5^T were diphosphatidylglycerol and phosphatidylglycerol. On the basis of result from poly-phasic data, strain PFS-5^T represents a novel species, for which the name Bacillus cheonanensis sp. nov. is proposed (Type strai PFS-5^T = KACC 17469^T = JCM19333^T).     

Phagocytosis, a potential mechanism for myeloid-derived suppressor cell regulation of CD8+ T cell function mediated through programmed cell death-1 and programmed cell death-1 ligand interaction

CD8(+) T cells become exhausted, inducing cell surface protein programmed cell death-1 (PD-1) as chronic virus diseases or tumors progress, but underlying mechanisms of this are unclear. We previously showed that M-CSF is important for developing tolerogenic dendritic cells (DCs) from human CD14(+) monocytes. In this article, we identify M-CSF-derived DCs (M-DCs) after stimulation with IL-10 as myeloid-derived suppressor cells with additional tolerogenic activities to CD8(+) T cells. IL-10 increased PD-1 ligand expression on M-DC, and IL-10-stimulated M-DCs (M-DC/IL-10) induced expression of PD-1 on, and apoptosis of, CD8(+) T cells and phagocytosed CD8(+) T cells. Enhanced phagocytic activity of M-DC/IL-10 required IFN-γ, which further increased PD-1 ligand and PD-2 ligand expression on M-DC/IL-10. IFN-γ-stimulated M-DC/IL-10 cells were phenotypically macrophage-like cells with little or no expression of CD86, a costimulatory molecule, but with high expression levels of CD14, CD200R, and CD80. No phagocytic activity was detected with GM-CSF-derived DCs. We propose that phagocytosis by IFN-γ-stimulated M-DC/IL-10 cells, which may be DCs or, alternatively, a unique subset of macrophages, may be a mechanism by which IFN-γ-producing CD8(+) T cells are tolerized after type 1 immune responses to chronic virus or tumor, and that IFN-γ links effector CD8(+) T cells to their phagocytic clearance.     

A plethora of painful molecules

Pain is a fundamental experience with a complex and multi-layered neurobiological basis. In recent years a powerful battery of techniques has been brought to bear to unravel the mechanisms by which painful stimuli are transduced and processed. There have been several recent discoveries regarding the molecular transduction mechanisms in nociceptors and novel molecular and cellular mechanisms underlying the spinal processing of painful stimuli. The mechanisms by which sensory neurons initiate hyperalgesia and touch evoked pain (allodynia) have been addressed particularly successfully in recent studies. The rich variety of key molecular players that have emerged in physiological and pathophysiological pain states reflects the sophistication and uniqueness of this vitally important sense.     

Soy peptide-induced stem cell proliferation: involvement of ERK and TGF-β1

This study was conducted to investigate the proliferative effect of vegetable soy peptides on adult stem cells (ASCs) in the absence of serum and their possible mechanisms of action. The proliferation of human adipose tissue-derived mesenchymal stem cells (ADSCs) and cord blood-derived mesenchymal stem cells (CB-MSCs) treated with soy peptides was found to increase significantly upon 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Click-iT 5-ethynyl-2'-deoxyuridine flow cytometry assay. In addition, soy peptides led to stepwise phosphorylation of the p44/42 MAPK (ERK), mammalian target of rapamycin (mTOR), p70 S6 kinase, S6 ribosomal protein (S6RP) and eukaryotic initiation factor 4E (eIF4E) in ADSCs. Furthermore, quantitative analysis of the cytokines revealed that the production of transforming growth factor-beta1 (TGF-β1), vascular endothelial growth factor and interleukin-6 increased significantly in response to treatment with soy peptides in both ADSCs and CB-MSCs. Similarly, soy peptide-induced phosphorylation of the ERK/mTOR/S6RP/eIF4E pathway was blocked in response to pretreatment with PD98059, a specific ERK inhibitor. Moreover, inhibition of TGF-β1 through PD98059 pretreatment and a consecutive decrease in ADSC proliferation revealed that TGF-β1 induces the phosphorylation of mTOR/S6RP/eIF4E. Collectively, the results of this study indicate that ERK-dependent production of TGF-β1 plays a crucial role in the soy peptide-induced proliferation of ADSCs under serum-free conditions.     

Highly pathogenic H5N1 influenza virus causes coagulopathy in chickens

Severe hemorrhage at multiple organs is frequently observed in chickens infected with highly pathogenic avian influenza (HPAI) A viruses. In this study we examined whether HPAI virus infection leads to coagulation disorder in chickens. Pathological examinations showed that the fibrin thrombi were formed in arterioles at the lung, associated with the viral antigens in endothelial cells of chickens infected intravenously with HPAI virus. Hematological analyses of peripheral blood collected from the chickens revealed that coagulopathy was initiated at early stage of infection when viral antigens were detected only in the endothelial cells and monocytes/macrophages. Furthermore, gene expression of the tissue factor, the main initiator of blood coagulation, was upregulated in the spleen, lung, and brain of HPAI virus-infected chickens. These results suggest that dysfunction of endothelial cells and monocytes/macrophages upon HPAI virus infection may induce hemostasis abnormalities represented by the excessive blood coagulation and consumptive coagulopathy in chickens.     

Development and characterization of new microsatellite markers for ginseng (<Emphasis Type="Italic">Panax ginseng</Emphasis> C. A. Meyer)

Panax ginseng C.A. Meyer, commonly known as Korean or Asian ginseng, is a perennial herb native to Korea and China. Its roots are highly prized for several medicinal properties. The present study describes development and characterization of twenty-two polymorphic microsatellite markers for this species. A total of 99 alleles were detected with an average of 4.5 alleles per locus across 20 accessions. Values for observed (H _O ) and expected (H _E ) heterozygosities ranged from 0.05 to 1.00 and from 0.18 to 0.73, respectively. Eleven loci deviated from Hardy–Weinberg equilibrium (P < 0.001). Significant (P < 0.05) heterozygote deficiency was observed at 13 loci. Exact test for linkage disequilibrium showed significant values (P < 0.05) between 12 pairs of loci. These microsatellite markers provide powerful tools for understanding population and conservation genetics of this species and also for genetic differentiation and authentication of different Panax species being used in commercial ginseng products.     

Efficacy of β-mannanase supplementation to corn–soya bean meal-based diets on growth performance,nutrient digestibility,blood urea nitrogen,faecal coliform and lactic acid bacteria and faecal noxious gas emission in growing pigs

A study was conducted to determine the efficacy of β-mannanase supplementation to a diet based on corn and soya bean meal (SBM) on growth performance, nutrient digestibility, blood urea nitrogen (BUN), faecal coliforms and lactic acid bacteria, and noxious gas emission in growing pigs. A total of 140 pigs [(Landrace × Yorkshire) × Duroc; average body weight 25 ± 3 kg] were randomly allotted to a 2 × 2 factorial arrangement with dietary treatments consisting of hulled or dehulled SBM without or with supplementation of 400 U β-mannanase/kg. During the 6 weeks of experimental feeding, β-mannanase supplementation had no effect on body weight gain, feed intake and gain:feed (G:F) ratio. Compared with dehulled SBM, feeding hulled SBM caused an increased feed intake of pigs in the entire trial (p = 0.05). The G:F ratio was improved in pigs receiving dehulled SBM (p < 0.05). Dietary treatments did not influence the total tract digestibility of dry matter, nitrogen and gross energy. Enzyme supplementation reduced (p < 0.05) the population of faecal coliforms and tended to reduce the NH₃ concentration after 24 h of fermentation in a closed box containing faecal slurry. Feeding hulled SBM tended to reduce NH₃ emission on days 3 and 5 of fermentation. In conclusion, mannanase supplementation had no influence on growth performance and nutrient digestibility but showed a positive effect on reducing coliform population and tended to reduce NH₃ emission. Dehulled SBM increased G:F ratio and hulled SBM tended to reduce NH₃ emission.