Association between VDR gene FokI polymorphism and renal function in patients with IgA nephropathy.

BACKGROUND: Studies have shown that the occurrence and development of IgA nephropathy (IgAN) are genetically susceptible, but the relationship between vitamin D receptor (VDR) gene polymorphisms and renal function in IgAN patients is unclear. METHODS: We investigated the relationship between VDR FokI (rs2228570) single nucleotide polymorphism (SNP) and renal function and related clinicopathologic parameters in IgAN patients. Clinical and pathological data of 282 IgAN patients treated at the First Affiliated Hospital of Guangxi Medical University were collected, and FokI genotypes were determined by PCR and direct sequencing. Patients were divided into the renal dysfunction group and normal renal function (control) group by estimated glomerular filtration rate (eGFR) and serum creatinine level. RESULTS: Frequencies of TT genotype and T allele in the renal dysfunction group were higher than those of the control group. Blood urea nitrogen, serum phosphorus (P), proportions of mesangial cell proliferation, interstitial fibrosis/tubular atrophy and crescents in T allele carriers were higher than those in non-T allele carriers, while eGFR and 25-Hydroxyvitamin D3 were lower in T allele carriers than non-T allele carriers. Multiple linear regression analysis showed that eGFR was affected by FokI genotypes in IgAN patients. Logistics regression analysis showed that middle and elderly age, elevated P, intact parathyroid hormone and TT genotype were independent risk factors for renal dysfunction in IgAN patients; the odds ratio of carrying the TT genotype was as high as 84.77 (P < 0.05 for all). CONCLUSIONS: IgA nephropathy patients carrying the VDR FokI TT genotype have an increased risk of renal dysfunction. VDR FokI SNP is closely related to renal function, calcium-phosphate metabolism, and related pathological damage in IgAN patients.

Matrine suppresses lipopolysaccharide-induced fibrosis in human peritoneal mesothelial cells by inhibiting the epithelial-mesenchymal transition.

BACKGROUND: Peritoneal fibrosis is the primary reason that patients with end-stage renal disease (ESRD) have to cease peritoneal dialysis. Peritonitis caused by Gram-negative bacteria such as Escherichia coli (E. coli) were on the rise. We had previously shown that matrine inhibited the formation of biofilm by E. coli. However, the role of matrine on the epithelial-mesenchymal transition (EMT) in peritoneal mesothelial cells under chronic inflammatory conditions is still unknown. METHODS: We cultured human peritoneal mesothelial cells (HPMCs) with lipopolysaccharide (LPS) to induce an environment that mimicked peritonitis and investigated whether matrine could inhibit LPS-induced EMT in these cells. In addition, we investigated the change in expression levels of the miR-29b and miR-129-5p. RESULTS: We found that 10 µg/ml of LPS induced EMT in HPMCs. Matrine inhibited LPS-induced EMT in HPMCs in a dose-dependent manner. We observed that treatment with matrine increased the expression of E-cadherin (F = 50.993, P < 0.01), and decreased the expression of alpha-smooth muscle actin (F = 32.913, P < 0.01). Furthermore, we found that LPS reduced the expression levels of miR-29b and miR-129-5P in HPMCs, while matrine promoted the expression levels of miR-29b and miR-129-5P. CONCLUSIONS: Matrine could inhibit LPS-induced EMT in HPMCs and reverse LPS inhibited expressions of miR-29 b and miR-129-5P in HPMCs, ultimately reduce peritoneal fibrosis. These findings provide a potential theoretical basis for using matrine in the prevention and treatment of peritoneal fibrosis.

Kallikrein gene-modified EPCs induce angiogenesis in rats with ischemic hindlimb and correlate with integrin αvß3 expression.

BACKGROUND: Human tissue kallikrein (hTK) plays an essential role in the physiological and pathological mechanisms of blood vessels. This study aimed to determine whether angiogenesis induced by endothelial progenitor cells (EPCs) transduced with the adenovirus-mediated hTK gene could improve blood flow in rat hindlimb ischemia in vivo and to establish a promising mechanism in vitro. METHODS: EPCs transduced with adenovirus encoding hTK-162 (i.e., Ad/hTK-transduced EPCs or Ad/GFP-transduced EPCs) were administered to Wister rats with hindlimb ischemia through therapeutic neovascularization. Muscular capillary density (MCD), blood flow (BF), and the number of myofibers were measured at days 7, 14, and 21 after treatment. Expressions of integrin αvß3 and endothelial nitric oxide synthase (eNOS) were detected on the surface of EPCs. RESULTS: MCD, BF, and the number of myofibers in rats with Ad/hTK-transduced EPCs remarkably increased at day 21 after treatment compared with rats with Ad/GFP-transduced EPCs or the control group (P<0.01). Expressions of integrin αvß3 and eNOS protein on the surface of EPCs also increased in rats with Ad/hTK-transduced EPCs. The levels of integrin αvß3 expression were reduced by PI3K and eNOS blockade, and the inhibitor of integrin αvß3 abrogated the migration and adhesion of hTK-transduced EPCs (P<0.05). CONCLUSION: hTK gene delivery in vivo improves the natural angiogenic response to ischemia. The ability of hTK gene-transduced EPCs can be enhanced in vitro, in which integrin αvß3 plays a role in the process.

Smoking and air pollution exposure and lung cancer mortality in Zhaoyuan County.

BACKGROUND: Simultaneous exposure to high levels of air pollution and high tobacco consumption at the same place is rare. The aim of the present study was to evaluate the impact of the two factors on the risk of developing lung cancer. METHODS: Data on the number of deaths due to lung cancer and on population from 1970 to 2009 were obtained from Zhaoyuan County. Data on the smoking populations were obtained at random sampling survey during the time in Zhaoyuan. Data on the components of atmospheric surveillance were obtained from the local environmental protection offices. Logarithmic linear regression and general log-linear Poisson age-period-cohort (APC) models were used to estimate age, period, cohort, gender, smoking, and air pollution effects on the risk of lung cancer mortality. RESULTS: The standardized mortality rates of lung cancer drastically increased from 8.43 in per 100 000 individuals in the 1970-1974 to 25.67 in per 100 000 individuals in the 2005-2009 death survey. The annual change of lung cancer mortality was 3.20%. In the log linear regression model, the age, proportion of smokers, gender, period, and air pollution are significantly associated with lung cancer mortality. The APC analysis shows that the relative risks (RRs) of gender, smoking, and air pollution are 2.29 (95% confidence interval (CI): 2.16-2.43), 3.05 (95% CI = 2.76-3.36), and 1.42 (95% CI = 1.19-1.69), respectively. Compared with the period 1970-1974, high RRs were found during 1995-2009. Compared with the birth cohort 1950-1954, the RRs increased in the birth cohorts of 1910 to the 1940. Compared the aged 35-59 and 60-84 in the 1980-1984 death survey (not exposed to air pollution) with that in the 2005-2009 death survey (exposed to air pollution), The two age groups exposed to air pollution, 25 years later, had an increased mortality rates for lung cancer by 2.27 and 3.55 times for males and by 1.47 and 3.35 times for females. CONCLUSION: The mortality rates of lung cancer drastically increased in the past 35 years. The trend of lung cancer mortality may be in a great extent possibly due to the effects of combined smoking and air pollution exposure.

Nutrition deficiency increases the risk of stomach cancer mortality.

BACKGROUND: The purpose of the study is to determine whether exposure to malnutrition during early life is associated with increased risk of stomach cancer in later life. METHODS: The design protocol included analyzing the trend of gastric cancer mortality and nutrition and evaluating the association between nutrient deficiency in early life and the risk of gastric cancer by hierarchical age-period-birth cohort (APC) analysis using general log-linear Poisson models and to compare the difference between birth cohorts who were exposed to the 1959-1961 Chinese famine and those who were not exposed to the famine. Data on stomach cancer mortality from 1970 to 2009 and the dietary patterns from 1955 to 1985 which included the 1959-1961 Chinese famine period in the Zhaoyuan County population were obtained. The nutrition information was collected 15 years prior to the mortality data as based on the latest reference of disease incubation. RESULTS: APC analysis revealed that severe nutrition deficiency during early life may increase the risk of stomach cancer. Compared with the 1960-1964 birth cohort, the risk for stomach cancer in all birth cohorts from 1900 to 1959 significantly increased; compared with the 1970-1974 cohort, the risk for stomach cancer in the 1975-1979 cohort significantly increased, whereas the others had a steadily decreased risk; compared with 85-89 age group in the 2005-2009 death survey, the ORs decreased with younger age and reached significant levels for the 50-54 age group after adjusting the confounding factors. The 1930 to 1964 group (exposed to famine) had a higher mortality rate than the 1965 to 1999 group (not exposed to famine). For males, the relative risk (RR) was 2.39 and the 95% confidence interval (CI) was 1.51 to 3.77. For females, RR was 1.64 and 95% CI was 1.02 to 2.62. CONCLUSION: The results of the present study suggested that prolonged malnutrition during early life may increase the risk of stomach cancer mortality in later life.