(5R)-5-hydroxytriptolide ameliorates diabetic kidney damage by inhibiting macrophage infiltration and its cross-talk with renal resident cells.

OBJECTIVE: Diabetic nephropathy (DN) is the main cause of end-stage renal disease, and there are no targeted treatment options at present. The efficacy of the new immunosuppressive drug (5R)-5-hydroxytriptolide (LLDT8) in improving kidney inflammation has been demonstrated in multiple studies. The present study was intended to investigate the preventive and therapeutic effects of LLDT8 on DN and to reveal its potential pharmacological mechanisms. METHODS: The effects of LLDT8 on liver and kidney functions, and urine microprotein of Streptozotocin (STZ) induced DN mice were detected. The protective effect of LLDT8 on the kidney tissue was observed by pathological staining and transmission electron microscopy. Cell culture experiments were performed to detect the effects of LLDT8 on the expression of chemokines and epithelial-mesenchymal transition (EMT) in high glucose-induced TCMK1 cells using real-time polymerase chain reaction (RT-PCR) and western blot (WB) techniques and to detect the influence of LLDT8 on the secretion of pro-inflammatory and pro-fibrotic factors in high glucose-induced RAW264.7 cells. RESULTS: In animal experiments, treatment with high-dose LLDT8 (0.25 mg/kg/2d) reduced 24 h urinary albumin excretion, improved structural kidney damage, and delayed fibrosis progression in DN mice. Immunofluorescence results showed that LLDT8 intervention reduced macrophage infiltration in kidney tissues of DN mice. PCR and WB results of kidney tissues showed reduced expressions of chemokines CCL2 and M-CSF1 in the LLDT8 intervention group compared to the DN group. In cellular assays, LLDT8 treatment reduced chemokine secretion in high glucose-induced TCMK1 cells, but had no effect on EMT of TCMK1 cells. LLDT8 treatment reduced the secretion of pro-inflammatory and pro-fibrotic factors in high glucose-induced RAW264.7 cells. CONCLUSIONS: The present study suggests that LLDT8 could effectively inhibit the secretion of pro-inflammatory and pro-fibrotic factors by macrophages, which could alleviate high glucose-induced renal tissue injury and slow down the process of tissue fibrosis and DN.

Study on the correlation between the prevalence of thyroid nodule and blood glucose, lipid metabolism and iodine nutrient level / 中国综合临床

Objective:To analyze the correlation between simple thyroid nodule and blood lipid and glucose metabolism and iodine nutrition level.Methods:A cross-sectional study was conducted by collecting data of the population undergoing epidemiological investigation in Jinshan District, Shanghai from July to December 2015, to calculate the prevalence of thyroid nodules and analyze relevant functional indicators.Results:Simple thyroid nodules were detected in 603 subjects, with a prevalence of 22.6% (603/2 669). There were 358 female patients with simple thyroid nodules, with a prevalence rate of 26.9%, and 245 male patients with simple thyroid nodules, with a prevalence rate of 18.3%. The prevalence of simple thyroid nodule in female was higher than that in male, and the difference was statistically significant (χ 2=27.686, P<0.001). In addition, the prevalence of simple thyroid nodules increased with age (13.1% (92/704) and 20.2% (104/514) and 25.1% (145/578) and 24.4% (107/439) and 36.3% (98/270) and 34.8% (57/164), χ 2=83.872,P<0.001). In the ≤30 years group (8.0% (30/704) vs. 18.8% (62/331), χ 2=35.716, P<0.001), >30 to ≤40 years old group (14.1% (37/263) vs. 26.7% (67/251), χ 2=12.683, P<0.001), >60 to ≤70 years old group (26.2% (33/126) vs. 45.1% (65/144), χ 2=10.435, P<0.001), and the 70-year-old group (24.4% (21/86) vs. 46.2% (36/78), χ 2=8.521, P<0.001). The prevalence of simple thyroid nodules in males was lower than that in females. In the simple positive thyroid nodule group, Fasting blood glucose (5.12 (4.80, 5.69) and 5.02 (4.72, 5.48)), total cholesterol (1.24 (0.85, 1.86) and 1.13 (0.77, 1.76)), triglyceride (4.77 (4.09, 5.48) and 4.49 (3.92, 5.16)), low density lipoprotein((2.79 (2.26, 3.36) and 2.63 (2.19, 3.16)), and high density lipoprotein cholesterol (1.41 (1.18, 1.66) and 1.35 (1.13, 1.61)) were higher than those in the negative group ( U values were 554 818, 578 468, 535 622, 556 067 and 567 960, respectively, all P<0.01). The BMI index grade distribution of thyroid nodule positive group was higher than that of negative group, and the difference was statistically significant (3.7% (77/2 066), 50.1% (1 034/2 066), 32.4% (669/2 066), 13.8% (286/2 066), 3.2% (19/603), 43.6% (263/603), 38.1% (230/603), 15.1% (91/603), χ2=9.5201, P=0.023). The prevalence of simple thyroid nodules was significantly lower in the iodized salt group than in the non-iodized salt group (20.7% (436/2 102) vs. 29.5% (167/567), χ 2=19.376, P<0.001). The urinary iodine level in the positive thyroid nodule group was significantly lower than that in the negative group (148.4(100.2, 213.7) vs. 169.5(115.4, 241.75), U=545 129.5, P<0.001). After Logistic regression screening, age ( OR=1.57, 95% CI: 1.292-1.908, P<0.001), gender ( OR=1.278, 95% CI: 1.193-1.368, P<0.001), BMI grade ( OR=1.166, 95% CI: 1.022-1.330, P=0.022), total cholesterol ( OR=1.105, 95% CI: 1.005-1.214, P=0.040), iodized salt ( OR=0.689, 95% CI: 0.556-0.854, P=0.001) were independent influencing factors of thyroid nodule. Conclusion:The prevalence of simple thyroid nodules in Shanghai is relatively low. Age, sex, BMI level, total cholesterol and iodized salt are independent factors causing thyroid nodules. In addition, blood glucose level may also be related to the prevalence of thyroid nodules.

CXCL-13 Regulates Resistance to 5-Fluorouracil in Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#5-Fluorouracil (5-Fu) is used as a conventional chemotherapy drug in chemotherapy forpatients with advanced colorectal cancer, but many patients still suffer from treatment failuredue to 5-Fu resistance. Emerging observations revealed the important role of chemokine(C-X-C motif) ligand 13 (CXCL-13) in tumor microenvironment and its relationship with prognosisin patients with colorectal cancer. This study is designed to reveal the important roleof CXCL-13 in causing colorectal cancer resistance to 5-Fu. @*Materials and Methods@#CXCL-13 levels of patient's serum or cell culture supernatants were measured separatelyby enzyme-linked immunosorbent assay. In cell assays, cell viability is detected by Cell CountingKit-8. Therefore, the recombinant human CXCL-13 was used to simulate its high expressionin cells while its antibody and siRNA were used to reduce CXCL-13 expression in cells. @*Results@#In this study, we demonstrated that CXCL-13 is associated with 5-Fu resistance by culturemedium exchange experiments and cytokine arrays of colorectal cancer resistant and nonresistantcells. Clinical studies showed that CXCL-13 is highly expressed in the serum of5-Fu–resistant patients. High levels of serum CXCL-13 also predict a worse clinical outcome.The addition of recombinant CXCL-13 cytokine resulted in 5-Fu resistance, while its antibodyovercame 5-Fu resistance, and knockdown of CXCL-13 expression by siRNA also reduced5-Fu resistance, which can be saved by added recombination CXCL-13. @*Conclusion@#These results not only identify a CXCL-13 mediated 5-Fu resistance mechanism but alsoprovide a novel target for 5-Fu–resistant colorectal cancer in prevention and treatmentstrategies.