The association between serum vitamin D levels and renal tubular dysfunction in a general population exposed to cadmium in China

<div><p>Cadmium exposure can cause renal tubular dysfunction. Recent studies show that vitamin D can play multiple roles in the body. However, the association between serum vitamin D levels and renal tubular dysfunction in a general population exposed to cadmium has not been clarified. We performed study to assess the effects of cadmium on serum 25(OH) D levels and the association between serum 25(OH) D levels and renal tubular dysfunction in a population environmentally exposed to cadmium. A total of 133 subjects living in control area and two cadmium polluted areas were included in the present study. Cadmium in urine (UCd) and blood (BCd), urinary β2Microglobulin (UBMG), urinary retinol binding protein (URBP) and serum 25 (OH) D were determined. Logistic regression was used to estimate the association between 25 (OH) D and prevalence of renal tubular dysfunction. No significant differences were observed in serum 25(OH) D levels among the four quartile of UCd and BCd after adjusting with cofounders. After adjusted with the confounders, the odds ratio (OR) of subjects with 25(OH) D ≥ 40 ng/ml were 0.20 (95%CI: 0.1–0.8) if UBMG was chosen as indicators of renal dysfunction and 0.28 (95%CI: 0.1–1.1) if URBP was chosen as indicators of renal dysfunction, compared with those with 25(OH) D < 30 ng/ml, respectively. Similar results were observed in those subjects living in cadmium polluted areas or with high level of UCd or BCd. Our data indicated that cadmium exposure did not affect serum 25(OH) D level and high 25 (OH) D levels were associated with a decreased risk of renal tubular dysfunction induced by cadmium.</p></div

DataSheet_1_Wenzi Jiedu Recipe ameliorates colorectal cancer by remodeling the gut microbiota and tumor microenvironment.docx

IntroductionWenzi Jiedu Recipe (WJR), traditional Chinese medicine (TCM) formula, has been proven to be clinically useful in the treatment of colorectal cancer (CRC). However, its underlying mechanisms are still elusive, which limits its wider application. Thus, we aimed to evaluate the effect of WJR on CRC and elucidate mechanisms underlying its action.MethodsNetwork pharmacology was employed to clarify the “herb-active ingredient-target” network of WJR. The 16S rDNA sequencing method was used to analyze the changes of gut microbes mediated by WJR in tumor-bearing mice with CRC. The proportions of CD4+ T cell and CD8+ T cell were measured by flow cytometry. Levels of the cytokines interleukin (IL)-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were assessed by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA).ResultsWJR showed significant anti-CRC effects both in vitro and in vivo. Network pharmacology revealed that WJR exerts anti-CRC therapeutic effect on multiple targets and signaling pathways. Gut microbiota analysis revealed that WJR therapy significantly enriched for Oscillibacter and Bacteroides_acidifacien. In particular, we found that WJR significantly increased the proportion of CD8+ T cells and the expression of immune-associated cytokines IL-10, IFN-γ, and TNF-α.ConclusionThe regulation of gut microbiota by WJR may be the breakthrough point to clarify its mechanism of action in the treatment of CRC, and it has a good prospect of clinical application.</p

Odds ratios (ORs) and 95% confidence intervals (CIs) of renal dysfunction and serum 25 (OH) D in total population.

<p>Odds ratios (ORs) and 95% confidence intervals (CIs) of renal dysfunction and serum 25 (OH) D in total population.</p

Hepatic expression of <i>Dnmts</i> and <i>Tets</i> in WT mice.

<p>The mRNA expression of (A) <i>Dnmt1</i>, (B) <i>Dnmt3a</i>, (C) <i>Dnmt3b</i>, (D) <i>Tet2</i> and (E) <i>Tet3</i> in WT livers. One-way ANOVA showed significant variations of the expression of <i>Dnmt3a</i>, <i>Dnmt3b</i>, <i>Tet2</i> and <i>Tet3</i> over time in liver (<i>p</i> < 0.05) and no significant variations in <i>Dnmt1</i> (<i>p</i> > 0.05). Data represent means ± S.E.M. (n = 3–4). *<i>p</i> < 0.05, **<i>p</i> < 0.01 for LSD post hoc test compared with ZT13. (F) The hepatic <i>Dnmt3a</i> mRNA levels in mice under LD and DD. Data represent means ± S.E.M. (n = 4). (G) Western blotting analysis for DNMT3A protein levels. The signal intensities of DNMT3A were normalized to the intensities of β-actin. Data represent means ± S.E.M. from three independent experiments. *<i>p</i> < 0.05 compared with ZT1, ^#<i>p</i> < 0.05 compared with CT1. ZT: zeitgeber time, CT: circadian time.</p

Primer sequences for real-time RT-PCR analysis.

<p>Primer sequences for real-time RT-PCR analysis.</p

The serum 25(OH) D at different UCd and BCd levels.

<p>UCd and BCd were categorized based on their quartile distribution (<25th percentile, 25-50th percentile, 50-75th percentile and ≥75th percentile). UCd: cadmium in urine; BCd: cadmium in blood.</p

Odds ratios (ORs) and 95% confidence intervals (CIs) of renal dysfunction and serum 25 (OH) D in population with BCd ≥ 2.0 μg/L.

<p>Odds ratios (ORs) and 95% confidence intervals (CIs) of renal dysfunction and serum 25 (OH) D in population with BCd ≥ 2.0 μg/L.</p

Daily changes of SAH concentration and SAM/SAH ratio in WT liver.

<p>One-way ANOVA showed that both (A) SAH and (B) SAM/SAH ratio displayed a clear diurnal variation (<i>p</i> < 0.01). Data represent means ± S.E.M. (n = 4). *<i>p</i> < 0.05, **<i>p</i> < 0.01 for LSD post hoc test compared with ZT17.</p

Characteristics of subjects.

<p>Characteristics of subjects.</p

Odds ratios (ORs) and 95% confidence intervals (CIs) of renal dysfunction and serum 25 (OH) D in population living in polluted areas.

<p>Odds ratios (ORs) and 95% confidence intervals (CIs) of renal dysfunction and serum 25 (OH) D in population living in polluted areas.</p