1.The effect of folic acid on the development of stomach and other gastrointestinal cancers.
Shunshi ZHU ; Joel MASON ; Yao SHI ; Yunbiao HU ; Rongrong LI ; Min WAHG ; Yihe ZHOU ; Guanqiu JIN ; Yuye XIE ; Guiquan WU ; Dehuang XIA ; Zhenhua QIAN ; Hailian SOHG ; Lidong ZHANG ; Robert RUSSELL ; Shudong XIAO
Chinese Medical Journal 2003;116(1):15-19
OBJECTIVETo evaluate the roles of folic acid and beta-carotene in the chemoprevention of gastric and other gastrointestinal (GI) cancers.
METHODSIn a randomized, double-blind, placebo-controlled trial, a total of 216 patients with atrophic gastritis were randomly assigned to one of the four groups: (1) folate (FA, 20 mg per day plus vitamin B(12) 1 mg, intramuscularly, per month for one year, then 20 mg two times a week plus 1 mg per three months for the next year); (2) natural beta-carotene (N-betaC, 30 mg per day for first year, then 30 mg two times a week for the next); (3) synthetic beta-carotene (S-betaC, administered as in N-betaC); and (4) placebo. Follow-ups continued from 1994 to 2001.
RESULTSA total of 7 new cases of gastrointestinal cancers were diagnosed with 3 stomach, 1 colon and 1 esophageal cancers occurring in the placebo group; 1 stomach cancer in both of the N-betaC and S-betaC groups, and no cancer occurring in FA group. In terms of GI cancers, there was a significant reduction in the FA group, compared with the placebo group (P = 0.04). A similar trend was observed in both N-betaC and S-betaC groups (P = 0.07 - 0.08). Taken together, the three intervention groups displayed a highly significant decrease in occurrence (P = 0.004, vs placebo), and a lower risk for GI cancers (OR = 0.12; 95% confidence interval, 0.03 - 0.51). For development of gastric cancer, any one of the three active-treated groups did not reach statistically significant reduction. The FA group showed obvious improvement of the gastric mucosal lesions with more patients displaying lesions reversed or stable atrophy and inflammation (P = 0.04), reversed intestinal metaplasia (P = 0.06) at the end of follow-up, and reversed displasia (P = 0.017) at 12 months. Two cases of false jaundice were found in beta-carotene groups with no influence on administration, and no side-effects were reported in FA group.
CONCLUSIONSThis trial revealed the interventional effect of folic acid on the development of GI cancers, a similar effect of beta-carotene was also detected. Also, folic acid may be of use to treat atrophic gastritis by preventing or reversing the precancerous lesions.
Adult ; Aged ; Anticarcinogenic Agents ; therapeutic use ; Double-Blind Method ; Female ; Folic Acid ; adverse effects ; therapeutic use ; Gastric Mucosa ; pathology ; Gastrointestinal Neoplasms ; prevention & control ; Humans ; Male ; Middle Aged ; Patient Compliance ; Stomach Neoplasms ; prevention & control ; beta Carotene ; therapeutic use
2.OxLDL/β2GPⅠ/β2GPⅠ-Ab complex in regulating the phenotypic transformation of A7r5 and the expression of lipid transporters
Peng ZHANG ; Hong ZHOU ; Chao HE ; Yudan CHEN ; Ting WANG ; Guiting ZHANG ; Yuye YAO ; Qianqian WU ; Ren WANG
Chinese Journal of Clinical Laboratory Science 2019;37(3):195-201
Objective:
To investigate the effects of oxidized low-density lipoprotein/β2 glycoproteinⅠ/β2 glycoproteinⅠantibody (oxLDL/β2GPⅠ/β2GPⅠ-Ab) complex on the phenotypic transformation and lipid transpoters on the surface of rat thoracic aorta smooth muscle cell line (A7r5), and their correlation with toll-like receptor 4 (TLR4) signaling pathway.
Methods:
A7r5 cells were stimulated by oxLDL, oxLDL/β2GPⅠ complex, oxLDL/β2GPⅠ-Ab complex, β2GPⅠ/β2GPⅠ-Ab complex and oxLDL/β2GPⅠ/β2GPⅠ-Ab complex respectively, and then total RNA and protein were collected. The expressions of α-smooth muscle actin (α-SMA), macrophage surface marker CD68, galectin-3 (LGALS3), scavenger receptor class B member 3 (CD36) and ATP-binding cassette transporter A1/G1 (ABCA1/ABCG1) were detected by real-time quantitative PCR (RT-qPCR), western blot and immunofluorescence (IF) respectively. The roles of TLR4 and its downstream signaling molecules in the phenotypic transformation and expression changes of lipid transporters of A7r5 cells induced by oxLDL/β2GPⅠ/β2GPⅠ-Ab complex were investigated by the pretreatment of TLR4 blocker TAK-242 (5 μmol/L) or c-Jun N-terminal kinases 1/2 (JNK 1/2) blocker SP600125 (90 nmol/L).
Results:
The oxLDL/β2GPⅠ/β2GPⅠ-Ab complex significantly increased the levels of CD68 and LGALS3, and decreased the level of α-SMA, while TAK-242 could reverse this phenomenon. The oxLDL/β2GPⅠ/β2GPⅠ-Ab complex could promote the expression of CD36 and inhibit the expression of ABCA1/ABCG1, while TAK-242 and SP600125 could reverse this process.
Conclusion
The oxLDL/β2GPⅠ/β2GPⅠ-Ab complex promotes the phenotypic transformation of A7r5 cells to macrophage-like cells, regulates the expression of lipid transport-related molecules and enhances the ability of lipids transport into cells. TLR4 and JNK1/2 are closely related to this process.
3.β2GP/anti-β2GP complex inhibits oxLDL-mediated lipid accumulation and FAK activation in THP-1 macrophages
Chao He ; Hong ZHOU ; Guiting ZHANG ; Yudan CHEN ; Peng ZHANG ; Ren WANG ; Qianqian WU ; Yuye YAO ; Ming KUANG
Chinese Journal of Clinical Laboratory Science 2019;37(6):401-406
Objective:
To investigate the effects of β2 glycoprotein Ⅰ/anti-β2 glycoprotein Ⅰ complex (β2/aβ2) on oxidized low density lipoprotein (oxLDL)-mediated lipid accumulation and focal adhesion kinase (FAK) activation in THP-1 macrophage, as well as the role of Toll-like receptor 4 (TLR4) during the process.
Methods:
THP-1 cells were differentiated into THP-1 macrophage by PMA (100 ng/mL). THP-1 macrophages were treated with RPMI 1640 medium, oxLDL, oxLDL+β2/aβ2 or oxLDL+lipopolysaccharide (LPS). The mRNA expressions of lipid transportation molecules, ACAT1, ABCA1 and ABCG1 were detected by RT-qPCR. Intracellular total cholesterol (TC) and free cholesterol (FC) in THP-1 macrophages were evaluated by Trinder assay, then the content and proportion of intracellular cholesteryl ester (CE) were calculated. The expression and phosphorylation of FAK were detected by immune fluorescence, RT-qPCR and western blot. To evaluate the role of TLR4, THP-1 macrophages were pre-treated with or without TLR4 inhibitor TAK-242 (1 μg/mL).
Results:
β2/aβ2 treatment significantly inhibited oxLDL-mediated lipid accumulation and FAK expression and phosphorylation in THP-1 macrophages, which could be reversed by TLR4 blockage.
Conclusion
β2/aβ2 inhibits the oxLDL-mediated lipid accumulation and FAK activation of THP-1 macrophage, which is related to the function of TLR4.