Combined protective effects of icariin and selenomethionine on novel chronic tubulointerstitial nephropathy models in vivo and in vitro.

Chronic tubulointerstitial nephropathy (CTIN) is one of the most common kidney diseases. However, treatment for CTIN has multiple limits. Adjuvant therapy through nutritional regulation has become a hot research topic at present. Icariin (ICA), an extraction of Chinese herbal medicine epimedium, has many pharmacological functions including anti-inflammation and tonifying kidney. Selenomethionine (SeMet) possesses the effects of antioxidant and lightening nephrotoxicity. However, little is known about the combined nephroprotection of them. This study was investigated to evaluate the joint effects of ICA and SeMet on CTIN and explore the mechanism. Based on a novel CTIN model developed in our previous study, mice were randomly divided into five groups (a: control; b: model; c: model + ICA; d: model + SeMet; e: model + ICA + SeMet). Renal tubule epithelial cells were treated with cyclosporine A and ochratoxin A without/with ICA or/and SeMet. The results showed that ICA or/and SeMet ameliorated CTIN by inhibiting the uptrends of blood urine nitrogen, serum creatinine, urine protein, urine gravity, histopathological damage degree and collagen I deposition. ICA or/and SeMet also increased cell proliferation and decreased apoptosis and the expression of transforming growth factor-beta 1 and α-smooth muscle actin. Emphatically, ICA and SeMet joint had better nephroprotection than alone in most indexes including fibrosis. Furthermore, ICA and SeMet joint decreased the activation of toll-like receptor 4 (TLR4)/NFκB pathway induced by CTIN. TLR4 overexpression counteracted the joint protection of ICA and SeMet. Therefore, ICA and SeMet in combination could protect against CTIN through blocking TLR4/NFκB pathway. The study will provide novel insights to explore an adjuvant therapeutic orientation.

Combination of zinc and selenium alleviates ochratoxin A-induced fibrosis via blocking ROS-dependent autophagy in HK-2 cells.

BACKGROUND: Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium. The key target organ of OTA toxicity is the kidney, which has a significant impact on human health. Recently, nutrition regulation is suggested to be an effective protection against mycotoxins contamination. The current study investigated the combined protective effects of zinc and selenomethionine (SeMet) (a major component of organic selenium) on OTA-induced renal fibrosis and their potential mechanisms in human renal proximal tubule epithelial cells (HK-2 cells). METHODS: Cytotoxicity of different concentrations of OTA, zinc and SeMet on HK-2 cells was detected by cell viability, lactate dehydrogenase (LDH) and apoptotic nuclei assays. The expression of fibrosis biomarkers was detected by Real-Time PCR, western blotting and indirect immunofluorescence assays. The production of reactive oxygen species (ROS) was detected by ROS assay kit. The protein expression of autophagy biomarkers was detected by western blotting assay. RESULTS: Cytotoxicity was induced by OTA treatment in a dose-dependent manner, and it was attenuated by zinc or SeMet application in HK-2 cells. Zinc or SeMet application also down-regulated the expression of fibrosis biomarkers, and the combination of them displayed better effects. In addition, OTA increased intracellular ROS level and activated autophagy in a dose-dependent manner, and it was reversed by zinc and SeMet combined application. With the treatment of hydrogen peroxide (H2O2) or rapamycin (the specific activator of autophagy), the combined protective effects of zinc and SeMet were abolished. CONCLUSIONS: Zinc and SeMet application alleviated OTA-induced cytotoxicity and fibrosis in HK-2 cells. Combination of them was more effective than its individual application. The present study manifest novel insight about the alleviation of OTA-induced nephrotoxicity by nutrition regulation, and had a guiding effect on the clinical supplementation of nutritional elements.

Effects of Selenium-enriched probiotics on ochratoxin A-induced kidney injury and DNMTs expressions in piglets.

Effects of Selenium-enriched probiotics (SP) on ochratoxin A-induced kidney injury, growth performance, antioxidant injury, selenoprotein and DNA methylation transferases (DNMTs) expression of piglets were investigated in the article. A total of 48 piglets were randomly divided into 4 groups and fed with basal diet (Con, 0.15 mg Se/kg and OTA at 0.00 mg/kg), basal diets added with OTA (OTA, 0.40 mg OTA/kg), SP and OTA (SP1, 0.15 mg Se/kg and 0.40 mg OTA/kg), SP and OTA (SP2, 0.30 mg Se/kg and 0.40 mg OTA/kg) respectively for 42 days. From each group, six piglets were randomly selected for blood collection on Days 0 and 42 and three piglets were selected for tissue collection on Day 42.The results showed that OTA at 0.40 mg /kg significantly decreased growth performance of pigs, induced the histopathological lesions of kidney and increased urea and creatine levels of serum, decreased GPx and SOD activities, and increased MDA levels. OTA decreased GPx1, GPx4 and SelS expressions, and increased TR1, DNMT 1, DNMT3a and SOCS3 expressions. Both SP1 and SP2 improved OTA-induced poor growth performance, kidney injury, poor antioxidant statues, GPx1, SelS, TR1, SOCS3, DNMT1 and DNMT3a expressions in kidney of pigs. The effects of SP2 on the above parameters changes were better than that of SP1. SP increased GPx and SOD activities and decreased MDA levels changes induced by OTA treatment. These results suggest that SP may serve as a better feed additive for piglets under mycotoxin contamination environments.

Study on the Improvement of Behavioral and Cognitive Dysfunction of Children with OSAHS by Vitamin D.

OBJECTIVE: This study is aimed at exploring the role of vitamin D in the treatment of children with OSAHS by comparing the clinical symptoms, serum indicators, and behavioral changes of vitamin D intervention. METHOD: Healthy children who were examined physically in Rizhao People's Hospital were selected as the control group, and their sex, age, triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, serum 25-OHD levels, and Conners' parental scale were measured. In addition, children diagnosed as OSAHS in the otolaryngology department of Rizhao People's Hospital were selected as experimental subjects. Their body mass index, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, serum 25-OHD levels, sleep apnea hypopnea index, minimum oxygen saturation, and Conners' parental scale were measured. The experimental subjects were treated with Rocaltrol intervention therapy (0.25 g/QD) for 4 weeks and reanalyzing their triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, serum 25-OHD levels, sleep apnea hypopnea index, minimum oxygen saturation, and Conners' parental scale. RESULT: OSAHS children commonly have the situation of obesity, dyslipidemia, and vitamin D deficiency. Behavioral and cognitive dysfunction is common in OSAHS children. There were no significant changes in body mass index, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, sleep apnea, hypopnea index, and minimum oxygen saturation for OSAHS children after vitamin D treatment, but the serum 25-OHD level is significantly improved, and children with conduct problems, learning problems, and hyperactivity index decrease. CONCLUSION: (1) OSAHS children commonly have the situation of obesity, dyslipidemia, vitamin D deficiency, and behavioral and cognitive impairment. (2) Vitamin D supplementation has no therapeutic effect on obesity and dyslipidemia of OSAHS children, but has obvious protective and improving effects on neuron damage caused by hypoxia. Obstructive sleep apnea syndrome (OSAHS) is a common disease. Patients with OSAHS usually have many clinical features, such as obesity, metabolic syndrome, and cardiovascular disease. The decline of cognitive function and learning ability is one of the serious complications of OSAHS patients [1]. Vitamin D (VitD) deficiency is associated with many diseases. Recent studies have shown that the serum 25-OHD level of OSAHS patients is relatively insufficient and related to the disease severity. However, there are few reports on explaining whether vitamin D supplementation can alleviate the clinical symptoms and improve serum indicators and behavioral and cognitive dysfunction in children with OSAHS.

In situ growth of nano-gold on anodized aluminum oxide with tandem nanozyme activities towards sensitive electrochemical nanochannel sensing.

Electrochemical nanochannel sensors have attracted extensive interest due to their potential applications in biosensing systems. In this work, porous anodized aluminum oxide (AAO) nanochannels are coupled with gold nanoparticles (AuNPs) through a polydopamine (PDA)-induced in situ growth process. It is found that the resulting hybrid nanochannel (denoted as Au-PDA-AAO) can act as both glucose oxidase- and peroxidase-like nanozymes to catalyze the cascade reaction involving glucose. To the best of our knowledge, this is the first report on the synthesis of nanozymes in an AAO nanochannel. Moreover, apart from the nanozyme-catalyzed colorimetric reaction, the Au-PDA-AAO nanochannel could simultaneously serve as a sensitive signal reporter for an electrochemical sensing platform. In such an approach, the glucose oxidation reaction boosts the resistance of the Au-PDA-AAO nanochannel towards ion transport based on the H2O2-mediated size enlargement of AuNPs, resulting in the varied transmembrane ionic current signal of the Au-PDA-AAO nanochannel. On the basis of the changed current-potential properties, the label-free detection of glucose can be achieved with a low detection limit, good reproducibility, and high stability. This work demonstrates the feasibility of the incorporation of versatile nanozymes into AAO nanochannels for mimicking multi-enzymatic catalysis reactions and detecting target analytes.

Docosahexaenoic Acid Serving As Sensitizing Agents And Gefitinib Resistance Revertants In EGFR Targeting Treatment.

OBJECTIVE: Due to the resistance of cancer cells, chemotherapy has been severely restricted. Docosahexaenoic acid (DHA) has been broadly identified as the chemo-sensitizing agent and revertant of multidrug resistance owing to its pleiotropic characteristics; however, it has not been well interpreted. The purpose of this research was to identify the anticancer role of DHA and its combination with the chemotherapeutic agent Gefitinib in non-small cell lung cancer (NSCLC). METHODS: Human chemo-sensitive NSCLC PC-9 cells and the Gefitinib-resistant counterpart PC-9/GR cells were adopted to assess the effects of the integrated DHA and Gefitinib treatments in vitro and vivo, for which the combination index (CI), apoptosis rate and the epithelial growth factor receptor (EGFR) pathway were analyzed. RESULTS: Comparing with the control cells, the DHA-treated PC-9/GR cells triggered the increase of drug absorption and sensitivity, suggesting that the sensitivity of chemotherapeutic drug could be induced by DHA. Moreover, the elevation of phosphorylation levels of EGFR and the downstream extracellular signal-regulated kinase (ERK) in the cellular lysates were induced by the DHA+Gefitinib treatment. Additionally, the long-term Gefitinib stimulated PC-9 model revealed that DHA could revert the Gefitinib resistance. CONCLUSION: This is the first research that indicated the novel biochemical effect of DHA, which can help in overcoming the resistance of EGFR-TKI in NSCLC cells and broaden the horizon of the DHA supplementation during the NSCLC therapy.

Sodium nitrite negatively affects reproductive ability and offspring survival in female mice.

Sodium nitrite (NaNO2) is an industrial chemical that is frequently used as a food additive to prevent botulism and enhance glossiness, such as curing meat. In addition, in some regions, water source NaNO2 concentrations exceed standard regulatory levels. Whether the excessive intake of NaNO2 has toxic effects on female fertility and fetal development remain unknown. In this study, we administered ICR mice control saline, low-dose NaNO2 (60 mg/kg/day), or high-dose NaNO2 (120 mg/kg/day) by intragastric gavage for 21 days. We then assessed oocyte morphology, spindle-chromosome dynamics, mitochondrial distribution, ATP content, apoptotic cell numbers, DNA damage levels, histone modifications, reactive oxygen species (ROS) levels, and offspring survival. Results showed that NaNO2 treatment decreased oocyte number, impaired polar body extrusion, and increased zona pellucida thickness in oocytes. Furthermore, NaNO2 disrupted MII spindle integrity, caused abnormal mitochondrial distribution, decreased ATP content, and increased levels of ROS and H3K4me2. Moreover, the number of oocytes in early stages of apoptosis and with levels of DNA damage increased in NaNO2-treated mice along with decreased offspring numbers and survival rates. We demonstrated the negative effects of NaNO2 on female reproductive abilities in mice.

Capecitabine versus 5-fluorouracil in neoadjuvant chemoradiotherapy of locally advanced rectal cancer: A meta-analysis.

BACKGROUND: The differences in efficacy between capecitabine and 5-fuorouracil (5-FU) in neoadjuvant chemoradiotherapy (CRT) of locally advanced rectal cancer (LARC) are not well recognized. We performed this meta-analysis to analyze the effect of capecitabine and 5-FU on neoadjuvant CRT to more accurately understand the differences between the 2 drugs. METHODS: MEDLINE, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database were performed to identify all published studies investigating the efficacy of capecitabine in neoadjuvant CRT of LARC versus 5-FU before August, 2017. Primary endpoint was the odds ratio (OR) for improving pathological complete response (pCR) rate of patients with LARC. Secondary endpoints were the ORs of efficiency for downstaging tumor and increasing R0 resection in patients with LARC. Safety analyses were also performed. The OR was the principal measurement of effect, which was calculated as capecitabine group versus 5-FU group, and was presented as a point estimate with 95% confidence intervals (CIs). All calculations and statistical tests were performed using RevMan 5.3 software. RESULTS: In all, 2916 patients with LARC enrolled in the 10 studies were divided into capecitabine group (n = 1451) and 5-FU group (n = 1465). The meta-analysis showed that capecitabine improved pCR (OR 1.34, 95% CI 1.10-1.63), and R0 resection rate (OR 1.92, 95% CI 1.10-3.36). There were no statistically significant differences either in overall downstaging rate (OR 1.31, 95% CI 0.79-2.16) or in the tumor downstaging rate (OR 1.24, 95% CI 0.79-1.92), but there was a significant difference of the nodal downstaging rate between the 2 groups (OR 1.68, 95% CI 1.11-2.54). There was no statistically significant difference in sphincter preservation rate between the 2 groups (OR 1.36, 95% CI 0.96-1.92). No obvious safety concerns about mortality and complications were raised in these studies. There were no statistically significant differences in 3-year disease-free-survival (OR 1.29, 95% CI 0.75-2.20), and in grade 3 to 4 acute toxicity during CRT (OR 0.63, 95% CI 0.31-1.30). CONCLUSIONS: Compared with 5-FU-based neoadjuvant CRT, capecitabine-based neoadjuvant CRT can safely improve pCR, nodal down-staging, ad R0 resection of patients with LARC.

Efficacy and safety of traditional Chinese medicine on thromboembolic events in patients with atrial fibrillation: A systematic review and meta-analysis.

OBJECTIVES: Traditional Chinese medicine (TCM) in combination with Western medicine (WM) has been widely used worldwide. This systematic review aimed to evaluate the efficacy and safety of TCM in prevention of thromboembolic events in patients with atrial fibrillation (AF). METHODS: Potential studies were searched through the Cochrane Library, PubMed, EMBASE, CBM, VIP, CNKI, and Wanfang databases up to February 2016. Randomized controlled trials (RCTs) investigating the thromboembolic events and/or safety outcome of TCM in patients with AF were included. RESULTS: A total of 905 AF patients from 9 RCTs were identified. Meta-analysis showed that TCM in combination with warfarin was better than warfarin alone for preventing total thromboembolic events with a 68% reduction of risk (risk ratio [RR] 0.32; 95% confidence interval [CI] 0.13-0.78) without increasing the risk of total bleeding (RR 0.71; 95% CI 0.29-1.72). Compared with warfarin, TCM therapy was associated with lower risk of total bleeding (RR 0.13; 95% CI 0.04-0.47), but increased the risk of total thromboembolic events (RR 1.84; 95% CI 1.03-3.27). CONCLUSIONS: This meta-analysis suggests that TCM combined with warfarin is superior to warfarin alone for the prevention of total thromboembolic events in patients with AF, with equal risk of bleeding as warfarin alone.

Using "dioscorea batatas bean"-like silver nanoparticles based localized surface plasmon resonance to enhance the fluorescent signal of zinc oxide quantum dots in a DNA sensor.

We reported here the preparation of "dioscorea batatas bean"-like silver nanoparticles (AgNPs) and the unique structure provided the AgNPs good localized surface plasmon resonance (LSPR) property. In addition, zinc oxide quantum dots (ZnO QDs) were also synthesized and found with good fluorescent property. Furthermore, the ZnO QDs decorated exfoliated graphene oxide (EGO-ZnO) was prepared via electrostatic interaction. The named nanomaterials were applied in a LSPR-induced fluorescent DNA sensor. To fabricate the DNA sensor, the EGO-ZnO was modified on the silica glass as the supporter for the capture probe ssDNA, and the complementary ssDNA was labeled on the surface of the AgNPs. After the hybridization step by step, the AgNPs was fastened on the surface of the EGO-ZnO, and the fluorescent intensity of the EGO-ZnO increased as a result. The prepared DNA sensor enabled the target ssDNA to be detected in the concentration range of 10(-19)-10(-14)M, and the limit of detection was 4.3 × 10(-20)M.

Effectiveness of 5-flurouracil-based neoadjuvant chemotherapy in locally-advanced gastric/gastroesophageal cancer: a meta-analysis.

AIM: To investigate the effectiveness of 5-flurouracil-based neoadjuvant chemotherapy (NAC) for gastroesophageal and gastric cancer by meta-analysis. METHODS: MEDLINE and manual searches were performed to identify all published randomized controlled trials (RCTs) investigating the efficacy of the flurouracil-based NAC for gastroesophageal and gastric cancer, and RCTs of NAC for advanced gastroesophageal and gastric cancer vs no therapy before surgery. Studies that included patients with metastases at enrollment were excluded. Primary endpoint was the odds ratio (OR) for improving overall survival rate of patients with gastroesophageal and gastric cancer. Secondary endpoints were the OR of efficiency for down-staging tumor and increasing R0 resection in patients with gastroesophageal and gastric cancer. Safety analyses were also performed. The OR was the principal measurement of effect, which was calculated as the treatment group (NAC plus surgery) vs control group (surgery alone) and was presented as a point estimate with 95% confidence intervals (CI). All calculations and statistical tests were performed using RevMan 5.1 software. RESULTS: Seven RCTs were included for the analysis. A total of 1249 patients with advanced gastroesophageal and gastric cancer enrolled in the seven trials were divided into treatment group (n = 620) and control group (n = 629). The quality scores of the RCTs were assessed according to the method of Jadad. The RCT quality scores ranged from 2 to 7 (5-point scale), with a mean of 3.75. The median follow-up time in these studies was over 3 years. The meta-analysis showed that NAC improved the overall survival rate (OR 1.40, 95%CI 1.11-1.76; P = 0.005), which was statistically significant. The 3-year progression-free survival rate was significantly higher in treatment group than in control group (37.7% vs 27.3%) (OR 1.62, 95%CI 1.21-2.15; P = 0.001). The tumor down-stage rate was higher in treatment group than in control group (55.76% vs 41.38%) (OR 1.77, 95%CI 1.27-2.49; P = 0.0009) and the R0 resection rate of the gastroesophageal and gastric cancer was higher in treatment group than in control group (75.11% vs 68.56%) (OR 1.38, 95%CI 1.03-1.85; P = 0.03), with significant differences. No obvious safety concerns about mortality and complications were raised in these trials. There were no statistically significant differences in perioperative mortality (5.08% vs 4.86%) (OR 1.05, 95%CI 0.57-1.94; P = 0.87 fixed-effect model) and in the complication rate between the two groups (13.25% vs 9.66%) (OR 1.40, 95%CI 0.91-2.14; P = 0.12 fixed-effect model). Trials showed that patients from Western countries favored NAC compared with those from Asian countries (OR 1.40, 95%CI 1.07-1.83). Monotherapy was inferior to multiple chemotherapy (OR 1.40, 95%CI 1.07-1.83). Intravenous administration of NAC was more advantageous than oral route (OR 1.41, 95%CI 1.09-1.81). CONCLUSION: Flurouracil-based NAC can safely improve overall survival rate of patients with gastroesophageal/gastric cancer. Additionally, NAC can down the tumor stage and improve R0 resection.

Studies on the effects of fpf1 gene on Artemisia annua flowering time and on the linkage between flowering and artemisinin biosynthesis.

The flowering promoting factor1 ( fpf1) from Arabidopsis thaliana was transferred into Artemisia annua L. via Agrobacterium tumefaciens. The fpf1 gene was firstly inserted in the binary vector pBI121 under the control of CaMV 35S promoter to construct the plant expression vector pBIfpf1, then leaf explants of A. annua were infected with A. tumefaciens LBA4404 containing pBIfpf1, and induced shoots. Transgenic plants were obtained through the selection with kanamycin. PCR, PCR-Southern and Southern blot analyses confirmed that the foreign fpf1 gene had been integrated into the A. annua genome. RT-PCR and RT-PCR-Southern analyses suggested that the foreign fpf1 gene had expressed at the transcriptional level. Under short-day conditions, the flowering time of fpf1 transgenic plants was about 20 days earlier than the non-transformed plants; however, no significant differences were detected in artemisinin content between the flowering transgenic plants and the non-flowering non-transgenic plants. These results showed that flowering is not a necessary factor for increasing the artemisinin content, furthermore, there may be no direct linkage between flowering and artemisinin biosynthesis.