Anemia is a risk factor for rapid eGFR decline in type 2 diabetes.

Objective: To investigate the association between anemia and progression of diabetic kidney disease (DKD) in type 2 diabetes. Methods: This was a retrospective study. A total of 2570 in-patients with type 2 diabetes hospitalized in Jinan branch of Huashan hospital from January 2013 to October 2017 were included, among whom 526 patients were hospitalized ≥ 2 times with a median follow-up period of 2.75 years. Annual rate of eGFR decline was calculated in patients with multiple admissions. A rate of eGFR decline exceeding -5 ml/min per 1.73 m2 per year was defined as rapid eGFR decline. The prevalence of DKD and clinical characteristics were compared between anemia and non-anemia patients. Correlation analysis was conducted between anemia and clinical parameters. Comparison of clinical features were carried out between rapid eGFR decline and slow eGFR decline groups. The risk factors for rapid DKD progression were analyzed using logistic regression analysis. Results: The prevalence of anemia was 28.2% among the 2570 diabetic patients, while in patients with DKD, the incidence of anemia was 37.8%. Patients with anemia had greater prevalence of DKD, higher levels of urinary albumin-to-creatinine ratio (UACR), serum creatinine, BUN, urine α1-MG, urine ß2-MG, urine NAG/Cr, hsCRP, Cystatin C, homocysteine and lower eGFR, as compared to the patients without anemia. Anemia was correlated with age, UACR, eGFR, urinary NAG/Cr, hsCRP and diabetic retinopathy (DR). Logistic regression analysis of 526 patients with type 2 diabetes during the follow-up period showed that anemia was an independent risk factor for rapid eGFR decline. Conclusion: Anemia is associated with worse renal function and is an independent risk factor for rapid eGFR decline in type 2 diabetes.

Preparation and Antioxidant Activities of High Fischer's Ratio Oligopeptides from Goat Whey.

This study aimed to obtain high Fischer's ratio oligopeptides from goat whey (HFO) and investigate antioxidant property of it. Hydrolysis of goat whey was done with the approach of sequential digestion of pepsin and flavourzyme. With the adsorption of aromatic amino acids by activated carbon, HFO with a Fischer's ratio of 27.070 and a molecular weight of 200-1,000 Da were obtained, and the branched-chain amino acids accounted for 22.87%. Then the antioxidant activity of HFO was evaluated. At the concentrations of 2.0 mg/mL and 0.50 mg/mL, HFO scavenged 77.27% and 99.63% of 1,1-diphenyl-2-picrylhydrazyl and 3-ethylbenzthiazoline-6-sulphonate free radicals respectively. The scavenging rate of HFO against hydroxyl radicals reached 92.31% at the concentration of 0.25 mg/mL. Animal experiments demonstrated that HFO could moderate the changes of malondialdehyde, superoxide dismutase and glutathione peroxidase caused by CCl4-induced oxidative stress in vivo. This study indicated that HFO from goat whey was capable of oxidation resistance both in vivo and in vitro, which provided a scientific basis for the high-value processing and application of goat milk whey.

Effects of Long-Acting Somatostatin Analogues on Lipid Metabolism in Patients with Newly Diagnosed Acromegaly: A Retrospective Study of 120 Cases.

The short-term effects of long-acting somatostatin analogues (SSAs) on lipid profiles in patients with acromegaly are not well studied. We retrospectively analyzed the effects of SSAs on lipid profiles and associated cardiovascular risk factors in a cohort of 120 newly diagnosed acromegaly patients. In this study, 69 females and 51 males were included. These patients were treated with either octreotide LAR (OCT) or lanreotide SR (LAN) for 3 months. After SSAs treatment, both GH and IGF-1 significantly decreased (p<0.001). Triglyceride (TG), total to high-density lipoprotein cholesterol (HDL-C) ratio, and lipoprotein (a) [Lp(a)] levels were significantly decreased, while HDL-C levels were increased (p<0.05). The reduction of mean serum GH (GHm) was positively associated with the decrease of TG (r=0.305, p=0.001) and Lp(a) (r=0.257, p=0.005), as well as the increase of HDL-C (r=-0.355, p<0.001). The changes of lipid profiles were observed only in OCT group, but not in LAN group. In addition, systolic blood pressure (SBP) had significantly declined after SSAs treatment, with an average reduction of 4.4 mmHg (126.7±1.28 vs. 122.3±1.44 mmHg, p=0.003), while no change was observed regarding diastolic blood pressure (DBP) (p>0.05). Fasting insulin, fasting C-peptide, and HOMA-IR were significantly decreased after SSAs treatment. In conclusion, our current study revealed that short-term SSAs treatment improves lipid profiles and other cardiovascular risk factors in patients with acromegaly.

Treatment of acromegaly by rosiglitazone via upregulating 15-PGDH in both pituitary adenoma and liver.

Rosiglitazone, a synthetic peroxisome proliferator-activated receptor γ (PPARγ) ligand, has been reported to reduce growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in 10 patients with acromegaly. However, the mechanisms remain unknown. Here, we reveal that PPARγ directly enhances 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression, whose expression is decreased and negatively correlates with tumor size in acromegaly. Rosiglitazone decreases GH production and promotes apoptosis and autophagy in GH3 and primary somatotroph adenoma cells and suppresses hepatic GH receptor (GHR) expression and IGF-1 secretion in HepG2 cells. Activating the PGE2/cAMP/PKA pathway directly increases GHR expression. Rosiglitazone suppresses tumor growth and decreases GH and IGF-1 levels in mice inoculated subcutaneously with GH3 cells. The above effects are all dependent on 15-PGDH expression. Rosiglitazone as monotherapy effectively decreases GH and IGF-1 levels in all nineteen patients with active acromegaly. Evidence suggests that rosiglitazone may be an alternative pharmacological approach for acromegaly by targeting both pituitary adenomas and liver.

Erectile Dysfunction Is Associated With Excessive Growth Hormone Levels in Male Patients With Acromegaly.

Objective: To determine the risk factors for erectile dysfunction (ED) in male patients with acromegaly and to prospectively investigate the short-term changes of erectile function after surgery or medical treatment. Methods: Sixty-three male patients were subjected to nocturnal penile tumescence and rigidity (NPTR) test for the evaluation of erectile function. The measurement of serum nitric oxide (NO) was also performed. Twenty-seven patients were re-evaluated by NPTR after surgery or long-term somatostatin analogues (SSA) treatment. Results: Twenty-two patients (34.9%) had ED. Patients with ED showed higher random GH (17.89 [10.97-44.19] µg/L vs 11.63 [4.31-28.80] µg/L, p = 0.020) and GH nadir (GHn) (10.80 [6.69-38.30] µg/L vs 8.76 [3.62-18.19] µg/L, p = 0.044) during oral glucose tolerance test (OGTT). The NO levels of ED patients were lower than non-ED patients (9.15 [5.58-22.48] µmol/L vs 16.50 [12.33-31.78] µmol/L, p = 0.012). After treatment, patients who present improvement in erectile function showed lower post-GHn (0.07 [0.03-0.12] ng/ml vs 1.32 [0.09-3.60] ng/ml, p = 0.048) and post-IGF-1 index (1.03 ± 0.38 vs 1.66 ± 0.95, p = 0.049). The multivariate analysis indicated post-GHn was still associated with the improvement of erectile function after correction of other covariates (OR: 0.059, 95% CI: 0.003-1.043, p = 0.053). Conclusions: Excessive GH is related to ED in male patients with acromegaly. GH normalization after treatment is beneficial for short-term erectile function recovery.

[Comparison of Enrichment and Transport of Cadmium in the Fruit of High and Low Enrichment Pepper Varieties and Its Distribution in Subcells].

Peppers are a high Cd-enriched vegetable. On the basis of a preliminary screening experiment of 91 pepper varieties and soil culture experiments during the entire growth period of 26 varieties, a high Cd variety (X15), medium Cd variety (X39), and two low varieties (X45 and X55) were selected to study the effect of different cadmium levels (0, 5, and 10 mg·kg-1 Cd) on enrichment, transport, and accumulation as well as its subcellular distribution and chemical form. Based on the results, 5 mg·kg-1 and 10 mg·kg-1 of Cd inhibited shoot dry weights of four pepper varieties but increased the root dry weights of X15, X45, and X55 varieties. Sodium chloride-bound cadmium and acetate-bound cadmium are the main forms of cadmium in the pepper fruits. Subcellular cadmium concentrations in the roots, leaves, and fruits of pepper plants were ranked in order cytoplasm > cell wall > organelle, and in the stems the order was cell wall > cytoplasm > organelle. Cd compartmentalization plays an important role in pepper resistance to cadmium stress. Under dosages of 5 mg·kg-1 Cd and 10 mg·kg-1 Cd, Cd concentrations in stems and leaves were ranked in order X39 > X15 > X55 > X45, with fruit Cd concentrations ranked in order X15 > X39 > X55 > X45. The Cd concentration was lowest in the roots of X15 whereas this variety has the highest concentrations in its fruit. The Cd concentrations in the roots, stems, and leaves of X39 were the highest among the four varieties whereas the concentration in the fruit was lower than in the X15 variety. The concentration of Cd in pepper fruits depends on the Cd transport capacity redistribution ability to the shoots.

Probing protein dissociation from gold nanoparticles and the influence of temperature from the protein corona formation mechanism.

Gold nanoparticles (AuNPs) provide a novel approach for protein enrichment and analysis due to their protein adsorption properties, forming a so called protein corona. This corona can significantly influence the protein's structure and characteristics, hindering their identification in situ. Dissociation is an important solution to analyze and identify the composition of protein coronas. However, a comprehensive picture of adsorbed protein dissociation is lacking. In this study, the protein dissociation from the protein corona and influencing factors were investigated on the basis of the formation mechanism and time evolution. Temperature and cysteine are the key factors influencing protein dissociation by altering the protein's binding ability. The results showed that half Au-S formation time is an important time point for thio-protein dissociation by the method of high speed centrifugation. When incubated for longer than that time, the thio-protein located in the hard corona could only be separated by ß-mercaptoethanol replacement under analytical ultracentrifugation. However, Fourier-transform infrared spectroscopy (FTIR) revealed significant changes that occurred in ßlg's secondary structure after ultracentrifugation. The Au-S bond formation time offers the potential to define the protein enrichment time of AuNPs.

Changes of serum lipopolysaccharide, inflammatory factors, and cecal microbiota in obese rats with type 2 diabetes induced by Roux-en-Y gastric bypass.

OBJECTIVES: Previous studies have shown that Roux-en-Y gastric bypass (RYGB) leads to rapid regression of obesity and type 2 diabetes (T2D). However, the underlying mechanism remains unclear. This study aimed to investigate the effect of RYGB on serum lipopolysaccharide (LPS), interleukin (IL)-1, IL-6, tumor necrosis factor alpha (TNF-α), and cecal microbiota in obese rats with T2D. METHODS: Obese Sprague-Dawley rats with T2D were randomly divided into RYGB diabetes operation (DO; n = 8), diabetes sham operation (DS; n = 8), and diabetic control (DC; n = 8) groups. Healthy Sprague-Dawley rats were grouped as normal control (NC; n = 8). Fasting plasma glucose and body weight were measured. The levels of peripheral serum LPS, IL-1, IL-6, and TNF-α were measured by enzyme-linked immunosorbent assay. The rats were sacrificed 12 wk after operation. Subsequently, a superior mesenteric venous blood sample was taken to measure serum LPS levels by enzyme-linked immunosorbent assay. The cecal contents of the DO and DS groups were taken to extract metagenomic DNA per the genomic DNA standardization procedure. The V4 region of the 16 S rRNA was sequenced with the Illumina Hiseq sequencing platform to compare the structure and relative abundance of cecal microbiota between the DO and DS groups. RESULTS: Twelve weeks after operation in the DO group, fasting plasma glucose and body weight showed a significant decrease (P < 0.05). Moreover, the levels of peripheral serum LPS, IL-1, IL-6, and TNF-α were obviously decreased (P < 0.05). A change in the LPS level of superior mesenteric venous blood also revealed a dramatic decrease (P < 0.05). Additionally, RYGB resulted in a shift of cecal microbiota in obese rats with T2D. CONCLUSIONS: Hypoglycemic effects after RYGB may be associated with improved levels of LPS, IL-1, IL-6, and TNF-α. Changes in the structure of cecal microbiota may also play an important role.

Associations of TNFRSF1A Polymorphisms with Autoimmune Thyroid Diseases: A Case-Control Study.

Previous studies have shown associations of polymorphisms in the tumor necrosis factor (TNF) receptor super family member 1A (TNFRSF1A) gene with several groups of inflammatory and autoimmune related diseases, but associations of TNFRSF1A polymorphisms with autoimmune thyroid diseases (AITD), mainly including two sub-types of Hashimoto's thyroiditis (HT) and Graves' disease (GD), in the Chinese Han population is unclear. A case-control study of 1812 subjects (965 AITD patients and 847 unrelated healthy controls) was conducted to assess AITD associations with five single nucleotide polymorphisms (SNPs), including rs4149576, rs4149577, rs4149570, rs1800693, and rs767455 in the TNFRSF1A gene locus. Genotyping was performed and evaluated using the platform of ligase detection reaction. No significant difference was observed in the allele and genotype frequencies between HT or GD patients and controls in any of the five SNPs in the TNFRSF1A gene (all p values >0.05). However, a moderate association of rs4149570 with HT was found after adjusting for age and gender [odds ratio (OR)=1.40, p=0.03]. No obvious difference was found in the haplotype distribution of any of the five SNPs in the TNFRSF1A gene between the AITD patients and controls. These data suggest that these five SNPs in the TNFRSF1A gene are not associated with AITD in the Chinese Han population, but rs4149570 shows a weak association with HT after adjusting for gender and age.

TNFSF4 Gene Variations Are Related to Early-Onset Autoimmune Thyroid Diseases and Hypothyroidism of Hashimoto's Thyroiditis.

The aim of the current study was to examine whether the polymorphism loci of the tumor necrosis factor superfamily member 4 (TNFSF4) gene increase the risk of susceptibility to autoimmune thyroid diseases (AITDs) in the Han Chinese population, and a case-control study was performed in a set of 1,048 AITDs patients and 909 normal healthy controls in the study. A total of four tagging single nucleotide polymorphisms (SNPs) in the TNFSF4 region, including rs7514229, rs1234313, rs16845607 and rs3850641, were genotyped using the method of ligase detection reaction. An association between GG genotype of rs3850641 in TNFSF4 gene and AITDs was found (p = 0.046). Additionally, the clinical sub-phenotype analysis revealed a significant association between GG genotype in rs7514229 and AITDs patients who were ≤18 years of age. Furthermore, rs3850641 variant allele G was in strong association with hypothyroidism in Hashimoto's thyroiditis (HT) (p = 0.018). The polymorphisms of the TNFSF4 gene may contribute to the susceptibility to AITDs pathogenesis.

Treatment with a fusion protein of the extracellular domains of NKG2D to IL-15 retards colon cancer growth in mice.

Tumor-targeted cytokines are a new class of pharmaceutical anticancer agents often considered superior to the corresponding unconjugated cytokines for therapeutic purposes. We generated a new fusion protein, dsNKG2D-IL-15, in which double NKG2D extracellular domains were fused to IL-15, in Escherichia coli. This fusion protein promoted the activation, proliferation, and cytotoxicity of NK cells, and bound to NKG2D ligand-positive tumor cells. These tumor cells were also more susceptible to NK-cell attack when decorated with dsNKG2D-IL-15. The administration of mouse dsNKG2D-IL-15 protein in vivo significantly retarded the growth of transplanted colon cancers and prolonged the survival of tumor-bearing mice. Treatment with dsNKG2D-IL-15 increased the frequencies of NK and CD8 T cells in spleen and tumor tissues. The antitumor effect mediated by dsNKG2D-IL-15 was significantly decreased with in vivo depletion of NK cells or CD8 T cells. Recombinant dsNKG2D-IL-15 thus inhibited NKG2D ligand-positive tumor growth effectively by activating lymphocytes. This new biological fusion protein could potentially be used to elicit immunity in tumor-targeting treatments.