Design, synthesis, and biological antitumor evaluation of tetrahydroisoquinoline derivatives.

Cancer, as a public health issue, is the leading cause of death worldwide. Tetrahydroisoquinoline derivatives have effective biological activities and can be used as potential therapeutic agents for antitumor drugs. In this work, we designed and synthesized a series of novel tetrahydroisoquinoline compounds and evaluated their antitumor activity in vitro on several representative human cancer cell lines. The results showed that the vast majority of compounds showed good inhibitory activities against the cancer cell lines of HCT116, MDA-MB-231, HepG2, and A375.

Humoral immune response following the inactivated quadrivalent influenza vaccination among HIV-infected and HIV-uninfected adults.

BACKGROUND: A limited amount of information is available about the immunogenicity of the quadrivalent inactivated influenza vaccine among human immunodeficiency virus (HIV)-infected individuals, especially in low and middle-income countries (LMICs). METHODS: HIV-infected adults and HIV-uninfected adults received a dose of quadrivalent inactivated influenza vaccine including strains of H1N1, H3N2, BV and BY. Enzyme-linked immunosorbent assay (ELISA) and hemagglutination-inhibition assay (HAI) were used to determine IgA, IgG antibody concentration and geometric mean titers (GMT) at day 0 and day 28, respectively. Associated factors contributing to seroconversion or GMT changes were analyzed using simple logistic regression model. RESULTS: A total of 131 HIV-infected and 55 HIV-uninfected subjects were included in the study. In both HIV-infected and uninfected arms, IgG and IgA against influenza A and B all increased significantly at day 28 after receiving QIV (P < 0.001). GMTs of post-vaccination at day 28 showed that HIV-infected persons with CD4 + T cell counts ≤ 350 cells/mm3 were statistically less immunogenic to all strains of QIV than HIV-uninfected ones (P < 0.05). HIV-infected participants with CD4 + T cell counts ≤ 350 cells/mm3 were less likely to achieve seroconversion to QIV (H1N1, BY and BV) than HIV-uninfected individuals at day 28 after vaccination (P < 0.05). Compared with HIV-infected patients with baseline CD4 + T cell counts ≤ 350 cells/mm3, individuals with baseline CD4 + T cell counts > 350 cell/mm3 seemed more likely to generate antibody responses to H1N1 (OR:2.65, 95 %CI: 1.07-6.56) and BY (OR: 3.43, 95 %CI: 1.37-8.63), and showed a higher probability of seroconversion to BY (OR: 3.59, 95 %CI: 1.03-12.48). Compared with nadir CD4 + T cell count ≤ 350 cell/mm3, individuals with nadir CD4 + T cell count > 350 cell/mm3 showed a higher probability of seroconversion to H1N1(OR: 3.15, 95 %CI: 1.14-8.73). CONCLUSION: Influenza vaccination of HIV-infected adults might be effective despite variable antibody responses. HIV-positive populations with CD4 + T cell counts ≤ 350 are less likely to achieve seroconversion. Further vaccination strategies could be developed for those with low CD4 T cell counts.

Case report: incidental parathyroid adenoma in a Chinese diabetic patient with hypercalcemia and normal parathyroid hormone levels.

RATIONALE: Parathyroid hormone PTH) levels are the main parameters to differentiate primary hyperparathyroidism (PHPT) from non-PTH-dependent hypercalcemia. We report a case of hypercalcemia with normal PTH levels due to a parathyroid adenoma. PATIENT CONCERNS: A 52-year-old female patient presented with 2-year history of documented sustained high-normal serum calcium and hypercalcemia (2.51-3.03 mmol/L) with normal serum intact PTH levels (21.95-40.15 pg/ mL). DIAGNOSES: A parathyroid tumor was localized by ultrasonography and 99mTc-sestamibi dual-phase fusion imaging with single-photon emission computed tomography/computed tomography. INTERVENTIONS: Parathyroidectomy was performed to excise the tumor completely. OUTCOMES: A 1.2-cm-sized parathyroid adenoma was removed surgically. The serum calcium was declined to normal level immediately after resection, as well as in 4- month follow-ups. The immunohistological diagnosis proved to be a PTH positive parathyroid adenoma. LESSONS: In case of hypercalcemia, serum intact PTH and parathyroid imaging should be monitored to evaluate the presence of parathyroid adenoma with care because PHPT could present with inappropriate normal PTH.

CPVL/CHN2 genetic variant is associated with diabetic retinopathy in Chinese type 2 diabetic patients.

OBJECTIVE: Diabetic nephropathy and retinopathy are two important microvascular diabetes complications with a high concordance rate in diabetic patients. A recent genome-wide association study in type 1 diabetic patients of European descent identified four loci to be associated with diabetic nephropathy. The aim of this study was to test the effects of single nucleotide polymorphisms (SNPs) from these four loci on diabetic nephropathy and retinopathy in Chinese type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In stage 1, we recruited 1,276 type 2 diabetic patients, including 378 patients with diabetic nephropathy but no retinopathy, 374 patients with diabetic retinopathy but no nephropathy, 244 patients with both diabetic retinopathy and nephropathy, and 280 control subjects with diabetes for >10 years and no diabetic retinopathy or nephropathy. Fifty-five SNPs from four loci (CPVL/CHN2, FRMD3, CARS, and IRS2) were genotyped. The SNPs that showed associations to diabetic retinopathy or nephropathy were genotyped in stage 2 samples for replication. RESULTS: SNPs from CPVL/CHN2 and FRMD3 were associated with diabetic retinopathy with rs39059 and rs10868025 as the top SNPs (odds ratio [OR] 1.292, 95% CI 1.097-1.523, P = 0.0022, for rs39059; 1.201, 1.014-1.422, P = 0.0343, for rs10868025) in stage 1 samples. In stage 2 analysis, only rs39059 showed similar effect to diabetic retinopathy (OR 1.269, 0.989-1.628, P = 0.0689), and meta-analysis showed a significant association between rs39059 and diabetic retinopathy, with an OR of 1.285 (1.120-1.474, P = 0.0003). CPVL/CHN2 rs39059 was also associated with levels of diabetic retinopathy (P = 0.0007 for trend). However, no association was detected between these SNPs and diabetic nephropathy. CONCLUSIONS: In this study, we found CPVL/CHN2 rs39059 was associated with diabetic retinopathy in the Chinese type 2 diabetic patients.

Macrophage infiltration into adipose tissue may promote angiogenesis for adipose tissue remodeling in obesity.

The biological role of macrophage infiltration into adipose tissue in obesity remains to be fully understood. We hypothesize that macrophages may act to stimulate angiogenesis in the adipose tissue. This possibility was examined by determining macrophage expression of angiogenic factor PDGF (platelet-derived growth factor) and regulation of tube formation of endothelial cells by PDGF. The data suggest that endothelial cell density was reduced in the adipose tissue of ob/ob mice. Expression of endothelial marker CD31 was decreased in protein and mRNA. The reduction was associated with an increase in macrophage infiltration. In the obese mice, PDGF concentration was elevated in the plasma, and its mRNA expression was increased in adipose tissue. Macrophages were found to be a major source of PDGF in adipose tissue, as deletion of macrophages led to a significant reduction in PDGF mRNA. In cell culture, PDGF expression was induced by hypoxia, and tube formation of endothelial cells was induced by PDGF. The PDGF activity was dependent on S6K, as inhibition of S6K in endothelial cells led to inhibition of the PDGF activity. We conclude that, in response to the reduced vascular density, macrophages may express PDGF in adipose tissue to facilitate capillary formation in obesity. Although the PDGF level is elevated in adipose tissue, its activity in angiogenesis is dependent on the availability of sufficient endothelial cells. The study suggests a new function of macrophages in the adipose tissue in obesity.