Immunomodulation of adipose-derived mesenchymal stem cells on peripheral blood mononuclear cells in colorectal cancer patients with COVID-19

BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors(TFs)and cytokine release in peripheral blood mononuclear cells(PBMCs).AIM To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer(CRC)patients with severe COVID-19(CRC^(+)patients).METHODS PBMCs from CRC^(+)patients(PBMCs-C+)and age-matched CRC patients(PBMCs-C)were stimulated and cultured in the presence/absence of ADSCs.The mRNA levels of T-box TF TBX21(T-bet),GATA binding protein 3(GATA-3),RAR-related orphan receptor C(RORC),and forkhead box P3(FoxP3)in the PBMCs were determined by reverse transcriptase-polymerase chain reaction.Culture supernatants were evaluated for levels of interferon gamma(IFN-γ),interleukin 4(IL-4),IL-17A,and transforming growth factor beta 1(TGF-β1)using an enzyme-linked immunosorbent assay.RESULTS Compared with PBMCs-C,PBMCs-C+exhibited higher mRNA levels of T-bet and RORC,and increased levels of IFN-γ and IL-17A.Additionally,a significant decrease in FoxP3 mRNA and TGF-β1,as well as an increase in Tbet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios were observed in PBMCs-C+.Furthermore,ADSCs significantly induced a functional regulatory T cell(Treg)subset,as evidenced by an increase in FoxP3 mRNA and TGF-β1 release levels.This was accompanied by a significant decrease in the mRNA levels of T-bet and RORC,release of IFN-γ and IL-17A,and T-bet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios,compared with the PBMCs-C+alone.CONCLUSION The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+,favoring Treg responses.Thus,ADSC-based cell therapy could be a beneficial approach for patients with severe COVID-19 who fail to respond to conventional therapies.

Correlation between blood lipids and serum uric acid in the elderly patients with coronary heart disease

Objective:To explore the relationship between blood lipids and serum uric acid(UA)in the elderly patients with coronary heart disease(CHD).Method:Quartered patients according to their uric acid level.Systematic review and compare lipid level among this four groups.Polynary logistic stepwise regression analysis were employed to analyze independent risk factor of coronary heart disease.Results:Serum level of triglycerides(TAG)and very low density lipoprotein cholesterol(VLDL-C)increase significantly(F=7.42,p<0.01;F=5.42,p<0.01 respectively)while high density lipoprotein cholesterol(HDL-C)and Apolipoprotein A1(Apo A1)decrease(F=5.03,p<0.01;F=7.03,p<0.01)upon elevated serum uric acid level among coronary heart disease patients.Gender(OR=0.16,95%CI 0.078~0.315,p=0.001),Ccr(OR=0.95,CI=0.935~0.969,p=0.001),associated hypertension(OR=2.23,CI=1.156~4.285,p=0.017)or DM(OR=2.44,CI=1.154~5.168,p=0.02),TC(OR=1.56,CI=1.119~2.186,p=0.009),HDL-C(OR=0.02,CI=0.004~0.076,p=0.001),UA(OR=1.09,1.086~1.094,p=0.001)are all independent risk factors for coronary heart disease.Conclusion:TAG,VLDL-C were positively related to UA while HDL-C and Apo A1were negatively linked to UA among CHD patients.Gender,Ccr,Hypertension,DM,TC,HDL-C and UA are independent risk factors for CHD while BMI,TAG,LDL-C were not.