The protective effects of icariin against testicular dysfunction in type 1 diabetic mice Via AMPK-mediated Nrf2 activation and NF-κB p65 inhibition.

BACKGROUND: Owing to the early suffering age and the rising incidence of type 1 diabetes (T1D), the resulting male reproductive dysfunction and fertility decline have become a disturbing reality worldwide, with no effective strategy being available. Icariin (ICA), a flavonoid extracted from Herba Epimedium, has been proved its promising application in improving diabetes-related complications including diabetic nephropathy, endothelial dysfunction and erectile dysfunction. Ensuring the future reproductive health of children and adolescents with T1D is crucial to improve global fertility. However, its roles in the treatment of T1D-induced testicular dysfunction and the potential mechanisms remain elusive. PURPOSE: The purpose of this present study was to investigate whether ICA ameliorates T1D-induced testicular dysfunction as well as its potential mechanisms. METHODS: T1D murine model was established by intraperitoneal injection of STZ with or without treated with ICA for eleven weeks. Morphological, pathological and serological experiments were used to determine the efficacy of ICA on male reproductive function of T1D mice. Western blotting, Immunohistochemistry analysis, qRT-PCR and kit determination were performed to investigated the underlying mechanisms. RESULTS: We found that replenishment of ICA alleviated testicular damage, promoted testosterone production and spermatogenesis, ameliorated apoptosis and blood testis barrier impairment in streptozotocin-induced T1D mice. Functionally, ICA treatment triggered adenosine monophosphate protein kinase (AMPK) activation, which in turn inhibited the nuclear translocation of nuclear factor kappa B p65 (NF-κB p65) to reduce inflammatory responses in the testis and activated nuclear factor erythroid 2-related factor 2(Nrf2), thereby enhancing testicular antioxidant capacity. Further studies revealed that supplementation with the AMPK antagonist Compound C or depletion of Nrf2 weakened the beneficial effects of ICA on testicular dysfunction of T1D mice. CONCLUSION: Collectively, these results demonstrate the feasibility of ICA in the treatment of T1D-induced testicular dysfunction, and reveal the important role of AMPK-mediated Nrf2 activation and NF-κB p65 inhibition in ICA-associated testicular protection during T1D.

Iodine status and associated dietary factors among preschool children in Shanghai.

Children aged 3-6 years undergo a critical stage of growth and development and are irreversibly affected by their iodine status. In order to reveal iodine status in preschool children, we detected iodine concentrations in urine samples from 1382 children aged 3-6 years based on a cross-sectional study. The median urinary iodine concentration (UIC) of children was 193.36 µg/L and was 336.96 µg/g·Cr corrected for creatinine. The study developed a link between dietary habits and iodine status, revealing that regular calcium supplement (OR: 1.79, (95% CI: 1.03, 3.12)) increased deficiency risk, while moderate seafood consumption (OR: 0.60, (95% CI: 0.38, 0.95)) decreased it. Additionally, modest intake of shellfish (OR: 0.58, (95% CI: 0.33, 1.00)), vegetables (OR: 0.61, (95% CI: 0.38, 0.97)), and eggs (OR: 0.53, (95% CI: 0.30, 0.95)) was found to protect against excess iodine. The findings underline the importance of balanced diets and various nutrients' roles in preschoolers' iodine status.

Removal effects of aquatic plants on high-concentration phosphorus in wastewater during summer.

Aquatic plants are widely used in depth treatment of wastewater; however, the phosphorus (P) removal mechanisms of aquatic plants at high temperatures in summer are not well understood. Eight aquatic plants, including two floating species (Ludwigia peploides and Hydrocharis dubia) and six emergent species (Lythrum salicaria, Sagittaria sagittifolia, Canna indica, Sparganium stoloniferum, Rotala rotundifolia, and Ludwigia ovalis), were treated with five P solutions (3.0, 3.5, 4.0, 4.5, and 5.5 mg L-1) for 5 weeks in a greenhouse during summer at air temperatures ranging from 25 to 35 °C. H. dubia, L. peploides, L. salicaria, and S. sagittifolia showed high water P removal efficiencies (exceeded 95%). Furthermore, their corresponding residual P concentrations in water were almost lower than the limit value of 0.2 mg L-1 of Grade III in the Chinese Environmental Quality Atandards for Surface Water (GB3838-2002). Plants have different water P removal paths. For example, H. dubia enriched more P with water P concentration increasing significantly. As the culture time increased, the water pH fluctuated significantly in the fall, and then H. dubia used the produced H+ enrich P. L. peploides did not enrich P, but proliferated rapidly, to remove P from water by increasing its fresh weight (FW). L. salicaria and S. sagittifolia showed two paths of enrich-P and FW increase. During the growth process of L. salicaria, the stem diameter and leaf length increased with an increase in P concentration in water or plant or both; however, the height and root length of L. peploides were reduced. Moreover, SOD and CAT activities responded to high P concentrations in water or high temperatures or both, which protected against oxidative damage. These findings could offer theoretical foundation and practical guidance for selection of aquatic plant species in depth treatment of wastewater during summer.

Gender differences in trace element exposures with cognitive abilities of school-aged children: a cohort study in Wujiang city, China.

Trace elements persist in the environment, and their early exposure may adversely affect children's intellectual development. To clarify the influence of blood trace element levels in newborns and school-aged children, we used Wechsler Intelligence Scale for children (WISC-CR) to explore intellectual development level of 148 school-aged children based on a population cohort study. Lead (Pb), selenium (Se), arsenic (As), copper (Cu), manganese (Mn) and chromium (Cr) in cord blood and Pb, As, Cu in venous blood were determined by inductively coupled plasma mass spectrometry (ICP-MS) and atomic absorption spectrometer (AAS). Our analysis of the correlation between children's mental development and trace element content found children's cognitive abilities negatively correlate with Pb (PIQ: ß=-0.109, P=0.03737) and Cu (PIQ: ß=-0.031, P=0.04431; FISQ: ß=-0.031, P=0.02137) levels in cord blood. Prenatal low-level As exposure may negatively affect girls' performance intelligence quotient (PIQ) and verbal intelligence quotient (VIQ). There were differences in Se levels in cord blood and venous blood between boys and girls (P=0.010; P=0.073). High Se levels were associated with a lower VIQ in boys and a higher VIQ in girls. Prenatal exposure to Pb, As and Cu may weaken children's cognitive abilities at school age. Se exposure may have opposite effects on cognitive abilities affected by dose and gender.

Ratiometric Dual Signal-Enhancing-Based Electrochemical Biosensor for Ultrasensitive Kanamycin Detection.

Based on the signal amplification elements of planar VS2/AuNPs nanocomposites and CoFe2O4 nanozyme, we herein developed an electrochemical biosensor for sensitive kanamycin (Kana) quantification. A ratiometric sensing platform was presented by incorporating VS2/AuNPs nanocomposites as a support material with excellent conductivity and high specific surface area, as well as hairpin DNA (hDNA) with complementary hybridization of biotinylated Kana-aptamer. In addition, streptavidin-functionalized CoFe2O4 nanozyme with superior peroxidase-like catalytic activity were immobilized onto the aptasensor, hence the peroxidase-like catalytic reaction could yield amplified electrochemical signals. With the presence of Kana, the aptamer-biorecognition resulted in a quantitative decrease of nanozyme accumulation and an increase of methylene blue response. Under optimal conditions, the electrochemical signal ratio of the aptasensor revealed a linear relation along with the logarithmic concentration of Kana from 1 pM to 1 µM, with the limit of detection reaching to 0.5 pM. Moreover, this aptasensor exhibited excellent precision, as well as high repeatability, hence possessing potentials in real samples and for diverse targets detection by easy replacement of the matched aptamer.

Dietary Fermented Soy Extract and Oligo-Lactic Acid Alleviate Chronic Kidney Disease in Mice via Inhibition of Inflammation and Modulation of Gut Microbiota.

Chronic kidney disease (CKD) is a global epidemic with an increasing prevalence worldwide. Effective preventive strategies are urgently needed. This study aimed to investigate the effect of nutraceutical components, a fermented soybean product (ImmuBalance, IMB) and an oligo-lactic acid product (LAP), on the prevention of adenine-induced CKD in mice. Female C57BL/6 mice were randomly assigned into following experimental groups: negative control; model control; and models treated with IMB at 250 or 1000 mg/kg body weight (BW), LAP at 1000 or 2000 mg/kg BW, and IMB/LAP combinations. The CKD model was established by intraperitoneal injection of adenine daily for 4 weeks, and treatments started 2 weeks before adenine injection and ended after 10 weeks. Compared with the model control, the treatments did not significantly alter the body weight or food intake. Both IMB and LAP, especially their combination, significantly inhibited tubular dilation, tubulointerstitial degeneration or atrophy, interstitial chronic inflammation and acute inflammation in the kidneys of CKD mice, and significantly decreased serum cystatin C levels. IMB or LAP significantly reversed CKD-associated increases of circulating and kidney levels of inflammatory cytokines, circulating levels of kidney injury biomarkers, and kidney levels of stem cell biomarkers, and significantly reversed CKD-associated reduction of cecum Clostridium leptum group. Our results suggest that dietary supplementation of IMB or LAP may significantly delay the development and/or progression of CKD.

Combinatorial effect of non-steroidal anti-inflammatory drugs and NF-κB inhibitors in ovarian cancer therapy.

Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID) with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24) is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda-7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor growth. A combination of these agents results in a synergistic effect. Furthermore, mda-7/IL-24 induction by NSAIDs is essential for programmed cell death, since inhibition of mda-7/IL-24 by small interfering RNA abrogates apoptosis. mda-7/IL-24 activation leads to upregulation of growth arrest and DNA damage inducible (GADD) 45 α and γ and JNK activation. The NF-κB family of transcription factors has been implicated in ovarian cancer development. We previously established NF-κB/IκB signaling as an essential step for cell survival in cancer cells and hypothesized that targeting NF-κB could potentiate NSAID-mediated apoptosis induction in ovarian cancer cells. Indeed, combining NSAID treatment with NF-κB inhibitors led to enhanced apoptosis induction. Our results indicate that inhibition of NF-κB in combination with activation of mda-7/IL-24 expression may lead to a new combinatorial therapy for ovarian cancer.

Rapid induction of regulatory and transporter genes in response to phosphorus, potassium, and iron deficiencies in tomato roots. Evidence for cross talk and root/rhizosphere-mediated signals.

Mineral nutrient deficiencies constitute major limitations for plant growth on agricultural soils around the world. To identify genes that possibly play roles in plant mineral nutrition, we recently generated a high-density array consisting of 1,280 genes from tomato (Lycopersicon esculentum) roots for expression profiling in nitrogen (N) nutrition. In the current study, we used the same array to search for genes induced by phosphorus (P), potassium (K(+)), and iron (Fe) deficiencies. RNA gel-blot analysis was conducted to study the time-dependent kinetics for expression of these genes in response to withholding P, K, or Fe. Genes previously not associated with P, K, and Fe nutrition were identified, such as transcription factor, mitogen-activated protein (MAP) kinase, MAP kinase kinase, and 14-3-3 proteins. Many of these genes were induced within 1 h after withholding the specific nutrient from roots of intact plants; thus, RNA gel-blot analysis was repeated for specific genes (transcription factor and MAP kinase) in roots of decapitated plants to investigate the tissue-specific location of the signal triggering gene induction. Both genes were induced just as rapidly in decapitated plants, suggesting that the rapid response to the absence of P, K, or Fe in the root-bathing medium is triggered either by a root-localized signal or because of root sensing of the mineral environment surrounding the roots. We also show that expression of Pi, K, and Fe transporter genes were up-regulated by all three treatments, suggesting coordination and coregulation of the uptake of these three essential mineral nutrients.