The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

This study explores the effects of enhancing the definitive hematopoiesis(DH)signals during the differentiation of human embryonic stem cells(hESCs)into hematopoietic stem/progenitor cells on the generation efficiency and effector function of natural killer(NK)cells generated from hESCs(also known as hESC-NK cells).The hESC(H1)were transformed into embryoid bodies(Ebs)by centrifugation,and during the induction of K562,were used to analyze the efficiency of hematopoietic differentiation,the efficiency of NK cell generation from hESC,the in vitro effector functions,and the expression of effector function related surface receptors.Compared to the control group,the DH group had a significant increase in the number of arterial hematopoietic endothelial cells(CD34+DLL4+)and a significant decrease in primitive hematopoietic related cells(CD34-CD43+)on day 8 of hematopoietic differentiation(P<0.05).On day 28 of NK cell differentiation,the DH group demonstrated a significant increase in the number of NK cells(CD45+CD56+),while a slight increase in the expression of effector function-related molecules such as IFN-γ,Granzyme B,Perforin and CD107a without statistical significance.Furthermore,the activation receptors CD16a and CD69 were significantly increased,NKP46 was significantly decreased,the inhibitory receptor NKG2A was significantly increased,while CD96 was significantly decreased on hESC-NK cells of DH groups(P<0.05).Conclusively,enhancing the signals for definitive hematopoiesis during hESC differentiation into hematopoietic stem/progenitor cells significantly improves the yield of NK cells and the expression of CD16a without affecting their in vitro effector functions.Our study provides a new approach to improving the efficiency of hESC-NK cell or iPSC-NK cell generation.

BACKGROUND:More and more evidence suggests that macrophages and inflammation reactions are involved in the formation and development of nephrolithiasis. Previous studies have found that calculi crystals can stimulate macrophages to release high mobility group protein B1.
OBJECTIVE:To investigate the synergistic effect of high mobility group protein B1 in calcium phosphate induced release of interleukin-1β, interleukin-6, tumor necrosis factorαand monocyte chemotactic factor 1 from human macrophages.
METHODS:(1) The induced U937 cells were respectively stimulated with RPMI (blank), 100 mg/L calcium phosphate, 100μg/L high mobility group protein B1 and 100 mg/L calcium phosphate+100μg/L high mobility group protein B1 for 1, 2 and 4 hours to col ect cellsupernatant. (2) The induced U937 cells were respectively stimulated with 100 mg/L calcium phosphate, 100 mg/L calcium phosphate+10μg/L high mobility group protein B1, 100 mg/L calcium phosphate+50μg/L high mobility group protein B1, 100 mg/L calcium phosphate+100μg/L high mobility group protein B1 for 4 hours to col ect cellsupernatant. Levels of interleukin-1β, interleukin-6, tumor necrosis factorαand monocyte chemotactic factor 1 were determined by ELISA.
RESULTS AND CONCLUSION:The levels of interleukin-1β, interleukin-6, tumor necrosis factorαand monocyte chemotactic factor 1 in the cellculture supernatant of 100 mg/L calcium phosphate group and 100μg/L high mobility group protein B1 group were both higher than those in the blank group in a time-dependent manner (P<0.05). The levels of interleukin-1β, interleukin-6, tumor necrosis factorαand monocyte chemotactic factor 1 in the cellculture supernatant of different concentrations of high mobility group protein B1 groups were al higher than those in the 100 mg/L calcium phosphate group in a concentration-dependent manner (P<0.05). The results suggest that both calcium phosphate and high mobility group protein B1 can induce the release of interleukin-1β, interleukin-6, tumor necrosis factorαand monocyte chemotactic factor 1 from human macrophages and the high mobility group protein B1 has the synergistic effect with calcium phosphate to induce interleukin-1β, interleukin-6, tumor necrosis factorαand monocyte chemotactic factor 1 from human macrophages.

Objective To analyze the influence of Helicobacter pylori (H.pylori) and smoking on serum pepsinogen (PG) levels in gastric adenocarcinoma (GAC).Methods Serum PGⅠand PGⅡ levels were measured by using radioimmunoassay method;H.pylori infection was determined by Hp-IgG antibodies in stored serum samples by using enzyme-linked immunosorbent assay and 14C urea breath test.Results In H.pylori negative cases,the serum PGⅠmean level in current smoking GACs was significantly increased compared with those non-smoking or ever-smoking GACs (the former:t=2.709,P