Objective:To explore whether LBP3 exerts anti-tumor effects by promoting production of short-chain fatty acids(SCFAs)by intestinal microbiota and regulating function of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSC).Methods:A subcutaneous H22 liver cancer model was employed to assess anti-tumor activity of LBP3 and its regulatory effects on PMN-MDSC.Pseudo-sterile tumor-bearing mouse model was used to investigate role of intestinal microbiota in tumor suppression of LBP3.Fecal microbiota transplantation(FMT)was conducted to explore immune regulatory role of LBP3-modulated flora.Serum SCFAs levels in tumor-bearing mice were quantified using liquid chromatography-mass spectrometry,and effect of SCFAs butyrate on arginase 1(Arg-1)expression was evaluated in vitro.Results:Both low-dose(125 mg/kg)and high-dose(250 mg/kg)LBP3 signifi-cantly inhibited tumor growth in H22 tumor-bearing mice,also led to a marked reduction in proportion of PMN-MDSC in both spleen and tumor,a reduced proportion of Treg in lymphoid tissues,a decrease in Arg-1 level within tumor,infiltration of CD8+T cells into tumor was significantly enhanced.However,these effects of LBP3 were did not observed in pseudo-sterile mice,while the above changes could be reproduced after fecal supernatant transplantation in high-dose LBP3 treatment group,suggesting a crucial role for gut microbiota.Furthermore,co-expression of Ly6G and SCFA receptor GPR43 in tumor was also observed.LBP3 treatment resulted in increased levels of SCFAs,particularly butyrate,in both blood and tumor tissues.In vitro,butyrate was shown to inhibit Arg-1 expression in MSC-2 cells,further supporting hypothesis that SCFAs mediate immune-modulatory effects of LBP3.Conclusion:LBP3 exerts its anti-tumor effects by promoting SCFA production,which subsequently inhibits function of PMN-MDSC.This highlights LBP3's potential as an immunomodulatory agent in cancer therapy.

Objective:To explore whether LBP3 exerts anti-tumor effects by promoting production of short-chain fatty acids(SCFAs)by intestinal microbiota and regulating function of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSC).Methods:A subcutaneous H22 liver cancer model was employed to assess anti-tumor activity of LBP3 and its regulatory effects on PMN-MDSC.Pseudo-sterile tumor-bearing mouse model was used to investigate role of intestinal microbiota in tumor suppression of LBP3.Fecal microbiota transplantation(FMT)was conducted to explore immune regulatory role of LBP3-modulated flora.Serum SCFAs levels in tumor-bearing mice were quantified using liquid chromatography-mass spectrometry,and effect of SCFAs butyrate on arginase 1(Arg-1)expression was evaluated in vitro.Results:Both low-dose(125 mg/kg)and high-dose(250 mg/kg)LBP3 signifi-cantly inhibited tumor growth in H22 tumor-bearing mice,also led to a marked reduction in proportion of PMN-MDSC in both spleen and tumor,a reduced proportion of Treg in lymphoid tissues,a decrease in Arg-1 level within tumor,infiltration of CD8+T cells into tumor was significantly enhanced.However,these effects of LBP3 were did not observed in pseudo-sterile mice,while the above changes could be reproduced after fecal supernatant transplantation in high-dose LBP3 treatment group,suggesting a crucial role for gut microbiota.Furthermore,co-expression of Ly6G and SCFA receptor GPR43 in tumor was also observed.LBP3 treatment resulted in increased levels of SCFAs,particularly butyrate,in both blood and tumor tissues.In vitro,butyrate was shown to inhibit Arg-1 expression in MSC-2 cells,further supporting hypothesis that SCFAs mediate immune-modulatory effects of LBP3.Conclusion:LBP3 exerts its anti-tumor effects by promoting SCFA production,which subsequently inhibits function of PMN-MDSC.This highlights LBP3's potential as an immunomodulatory agent in cancer therapy.

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)pre-sents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2％dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2％ DSS-induced Rag1-/-mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage indepen-dently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned me-dium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

OBJECTIVETo analyze the distribution of matrix metalloproteinase-3 (MMP-3) genotype and its association with the blood pressure profiles in Guangzhou rural population.

METHODSThis study was conducted among 680 rural residents aged 40-70 years (including 314 men and 366 women) from 3 villages in an rural area of Guangzhou. The blood pressures of the subjects were measured and blood samples were collected for genotype analysis using polymerase chain reaction and direct sequencing of the MMP-3 gene promoter region to detect the 5 adenines (5A)/6 adenines (6A) polymorphisms.

RESULTSThe frequencies of MMP-3 genotypes 6A/6A, 5A/5A, and 5A/6A were 82.6%, 1.8% and 15.6% among these residents, respectively. The distribution of MMP-3 genotypes and allele frequencies showed no significant gender- or age-related variations. The men with different genotypes (6A/6A vs 5A/6A+5A/5A) did not show significant differences in blood pressure levels, whereas the women with 5A/6A+5A/5A genotypes had higher systolic and diastolic blood pressures than those with a 6A/6A genotype. The allele 5A was highly frequent in the hypertensive residents as compared with the normotensive residents.

CONCLUSIONSThe 6A homozygote is the predominant genotype of MMP-3 in Guangzhou rural population, which has a significantly lower proportion of 5A homozygote than the Western populations. The 5A allele is associated with a high risk of hypertension especially in women and may affect both systolic and diastolic blood pressures.

Adult ; Age Distribution ; Aged ; Alleles ; Blood Pressure ; China ; epidemiology ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension ; epidemiology ; genetics ; Male ; Matrix Metalloproteinase 3 ; genetics ; Middle Aged ; Risk Factors ; Rural Population ; Sex Distribution

The effects of Amrinone (AMR)on left ventricular function in 30 cases of congestive heart failure patients was assessed by M-mode and pulsed Doppler echocardiography. AMR improves the systolic and diastolic function of left ventricle during and after 10 min (AMR lmg ? kg-1, infusion ). The mean stroke volume increased 20% and 18% ; cardiac output increased 23% , 19% ; cardiac index increased 23% and 23% ; ejection fraction increased 32% , 30%; mVcf increased 50% and 48% ; filling velocity in early diastole increased 30% and 21 %; respectively. There were no significant differently between during and after AMR infusion, but there were signifcantly difference a-mong before, during and after AMR infusion. The heart rate changed slightly without statistic significance. The results suggest that AMR could improve the systolic and diastolic function of left ventricle in congestive heart failure patients.