Lijuan Xu

Impact of Vitamin D on Chronic Kidney Diseases in Non-Dialysis Patients: A Meta-Analysis of Randomized Controlled Trials

Background and Objectives Recent studies have supported a role for both newer and more established vitamin D compounds in improving proteinuria, although systematic evaluation is lacking. Furthermore, concerns remain regarding the influence of vitamin D on the progression of renal function. We analyzed the efficacy and safety of vitamin D in non-dialysis patients and compared the use of newer versus established vitamin D compounds by performing a meta-analysis of randomized controlled trials. Design A literature search of PubMed (1975 to September, 2012), EMBASE.com (1966 to September, 2012) and Ovid EBM Reviews (through September, 2012) was conducted. Results Eighteen studies were eligible for final inclusion; of these, six explored the effects of vitamin D on proteinuria, twelve studied the effects of supplementation on renal function, and fifteen discussed the incidence of hypercalcemia. Compared to the placebo or no interference, both the newer and established vitamin D sterols reduced proteinuria to a similar extent (RR, 2.00; 95% CI, 1.42 to 2.81). No decrease in the glomerular filter rate was observed (SMD, −0.10; 95%CI, −0.24 to 0.03), and the risk for dialysis initiation was 1.48 (95% CI, 0.54 to 4.03) with vitamin D treatment. Additionally, there was an increased risk of hypercalcemia for patients treated with either newer or established vitamin D compounds as compared with the controls (RR, 4.78; 95% CI, 2.20 to 10.37). The head-to-head studies showed no differences in the effects of either newer or established compounds on proteinuria or the risk of hypercalcemia. No serious adverse events were associated with the administration of vitamin D. Conclusions Vitamin D therapy appears to decrease proteinuria and have no negative influence on renal function in non-dialysis patients. But the occurrence of hypercalcemia should be evaluated when vitamin D is provided. No superiority for newer versus established vitamin D analogue is found.

Down-regulation of SOSTDC1 promotes thyroid cancer cell proliferation via regulating cyclin A2 and cyclin E2

Sclerostin domain containing protein 1 (SOSTDC1) is down-regulated and acts as a tumor suppressor in some kinds of cancers. However, the expression pattern and biological significance of SOSTDC1 in thyroid cancer are largely unknown. We demonstrated that SOSTDC1 was significantly down-regulated in thyroid cancer. Ectopic over-expression of SOSTDC1 inhibited proliferation and induced G1/S arrest in thyroid cancer cells. Moreover, SOSTDC1 over-expression suppressed the growth of tumor xenografts in nude mice. We also found that elevated SOSTDC1 led to inhibition of cyclin A2 and cyclin E2. Together, our results demonstrate that SOSTDC1 is down-regulated in thyroid cancer and might be a potential therapeutic target in the treatment of thyroid cancer.

Adverse effect of metformin therapy on serum vitamin B12 and folate: Short-term treatment causes disadvantages?

Diabetes is a global public health challenge that imposes heavy burdens on communities and individuals. Metformin, the first-line medication for diabetes, has the superiority of reducing risk of macrovascular diseases, all-cause mortality and even possibly cancers. Recent observational studies, however, have demonstrated that long-term metformin therapy increases the probability of vitamin B12 and folate deficiency, and might contribute to the progression of diabetic peripheral neuropathy. Despite metformin is widely used and extensively studied, randomized controlled trials performed to explore the effects of metformin on vitamin B12 and folate are limited. Besides, whether short-term treatment causes vitamin deficiency is a pending issue. We postulate that even a few-month treatment with metformin results in the decrease of vitamin B12 and folate. However, supplementation of vitamin B12 rather than the combination of vitamin B12 and folate might be profitable based on the mechanism of metformin on vitamins in patients with type 2 diabetes. This viewpoint differs from those of majority that a combined supplementation of vitamin B12 and folate is inclined to be advised.

Effects of short-term therapy with different insulin secretagogues on glucose metabolism, lipid parameters and oxidative stress in newly diagnosed Type 2 Diabetes Mellitus

AIM To compare effects of three different insulin secretagogues on early-phase insulin secretion, metabolism of glucose and lipids, and lipid peroxidation in newly diagnosed Type 2 Diabetes Mellitus (T2DM). METHODS Totally 60 newly diagnosed T2DM outpatients were randomized to three groups with 1-month monotherapy of repaglinide (Rg), glimepiride (Gm) or gliclazide MR (Gli), respectively. Some indexes of early-phase insulin secretion, glucose, lipids, and lipid peroxidation were inspected. RESULTS Fasting plasma glucose (FPG), glycosylated hemoglobin (HbA(1c)) and fructosamine (FA) were improved in all groups similarly (p>0.05). Rg group was with the highest early-phase insulin secretion index (DeltaI30/DeltaG30) (p=0.026), lower mean amplitude of glycaemic excursion (MAGE) (p<0.05), lowest mean peak value of post-lunch glucose (p=0.043), and lowest postprandial triglyceride (TG) (p=0.039). Postprandial free fatty acid (FFA) was lower after Rg and Gli treatment (p<0.05). Serum 8-iso prostaglandin F(2alpha) (8-iso PGF(2alpha)) was improved in all groups, but the improvement showed statistically significant only in Rg group (p=0.04). CONCLUSION Rg, Gm and Gli can all decrease blood glucose effectively in newly diagnosed T2DM patients, while Rg performs outstandingly in the aspects of improving early-phase insulin secretion, glucose excursion, postprandial lipids and 8-iso PGF(2alpha).

Fulminant type 1 diabetes mellitus with rhabdomyolysis: have we overlooked the situation?

Fulminant type 1 diabetes mellitus (FT1DM) is characterized as remarkably abrupt onset and severe metabolic disorder. Prominent derangement of serum electrolytes was frequently observed, which could be associated with rhabdomyolysis. But the issue was not touched upon in most of the articles concerning FT1DM. Herein, we reported 2 cases. Since the clinical features of rhabdomyolysis vary, and creatine kinase levels are not routinely tested in young patients, the situation of rhabdomyolysis associated with FT1DM may be overlooked.

Trop2 enhances invasion of thyroid cancer by inducing MMP2 through ERK and JNK pathways

BackgroundMounting evidence has showed that Tumor-associated calcium signal transducer 2 (Trop2) is upregulated in various kinds of human cancers and plays important roles in tumorigenesis. However, the expression status and functional significance of Trop2 in thyroid cancer are largely unknown.MethodsWe first determined the expression of Trop2 by using RNAseqV2 data sets for thyroid cancer deposited on The Cancer Genome Atlas (TCGA) website. The expression of Trop2 was then confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry assays. Cell invasion and migration were assessed by conducting Transwell and wound healing assays. Furthermore, we explored the underlying mechanisms by using real-time RT-PCR, Western blot, zymography, and luciferase reporter assays.ResultsIn this study, we demonstrated that the expression of Trop2 was significantly elevated in thyroid cancer and that its expression level was correlated with the tumor-node-metastasis (TNM) staging and N classification. Dysregulation of Trop2 altered the invasive capability of thyroid cancer cells. Further mechanistic study revealed that MMP2 expression was upregulated by Trop2. Moreover, we found that the effects of Trop2 were dependent on ERK and JNK pathways. The results from clinical specimens showed that Trop2 expression correlated with MMP2 expression in primary thyroid cancer.ConclusionThe current study suggests that elevated expression of Trop2 may represent an important molecular hallmark that is biologically and clinically relevant to the progression of thyroid cancer.

Vitamin D and its receptor regulate lipopolysaccharide-induced transforming growth factor-β, angiotensinogen expression and podocytes apoptosis through the nuclear factor-κB pathway.

To investigate the effects of vitamin D and its receptor on cytokines expression and podocytes apoptosis.

Lower mean blood glucose during short‐term intensive insulin therapy is associated with long‐term glycemic remission in patients with newly diagnosed type 2 diabetes: Evidence‐based recommendations for standardization

Optimal glycemic targets during short‐term intensive insulin therapy in patients with newly diagnosed type 2 diabetes are not standardized. The present study was carried out to determine the optimal glycemic targets during therapy by analyzing the impacts of glucose levels on therapeutic outcomes.

Glimepiride treatment in a patient with type A insulin resistance syndrome due to a novel heterozygous missense mutation in the insulin receptor gene

Glimepiride is a sulfonylurea known to have unique insulin mimetic and sensitizing effects. We aimed to study the efficacy of glimepiride in a patient with type A insulin resistance syndrome.

Exendin-4 modifies adipogenesis of human adipose-derived stromal cells isolated from omentum through multiple mechanisms

Background:Abdominal obesity is considered a major factor in the development of metabolic disorders. Glucagon-like peptide-1 (GLP-1) has been reported to have positive effects on improving body metabolism and to reducing insulin resistance. However, it remains less clear whether GLP-1 plays a role in the adipogenesis process of visceral fat.Methods:Here, we analyzed the in vitro actions and probable mechanisms of Exendin-4, a GLP-1 receptor agonist, on human adipose-derived stromal cells (hADSCs) isolated from omentum.Results:Our results demonstrated that Exendin-4 improved cell viability via promoting proliferation and inhibiting apoptosis in hADSCs isolated from omentum. Mechanistically, the activation of MAPK/ ERK1/2, Akt/GSK-3β, and PKA/CREB pathways and downstream consequences induced are involved in the proliferative and anti-apoptotic roles of Exendin-4. More intriguingly, Exendin-4 could promote the differentiation of omental hADSCs. Underlying mechanisms of the differentiation of hADSCs are associated with the upregulation of the expression of pro-adipogenic genes and downregulation of the expression of anti-adipogenic genes.Conclusion:Our data demonstrate that Exendin-4 modifies adipogenesis of hADSCs isolated from omentum through multiple mechanisms, these effects could contribute to the protective actions of GLP-1 receptor agonist body metabolism and insulin sensitivity.