Cadmium suppresses the proliferation of piglet Sertoli cells and causes their DNA damage, cell apoptosis and aberrant ultrastructure

<p>Abstract</p> <p>Objective</p> <p>Very little information is known about the toxic effects of cadmium on somatic cells in mammalian testis. The objective of this study is to explore the toxicity of cadmium on piglet Sertoli cells.</p> <p>Methods</p> <p>Sertoli cells were isolated from piglet testes using a two-step enzyme digestion and followed by differential plating. Piglet Sertoli cells were identified by oil red O staining and Fas ligand (FasL) expression as assayed by immunocytochemistry and expression of transferrin and androgen binding protein by RT-PCR. Sertoli cells were cultured in DMEM/F12 supplemented with 10% fetal calf serum in the absence or presence of various concentrations of cadmium chloride, or treatment with p38 MAPK inhibitor SB202190 and with cadmium chloride exposure. Apoptotic cells in seminiferous tubules of piglets were also performed using TUNEL assay in vivo.</p> <p>Results</p> <p>Cadmium chloride inhibited the proliferation of Piglet Sertoli cells as shown by MTT assay, and it increased malondialdehyde (MDA) but reduced superoxide dismutase (SOD) and Glutathione peroxidase (GSH-Px) activity. Inhibitor SB202190 alleviated the proliferation inhibition of cadmium on piglet Sertoli cells. Comet assay revealed that cadmium chloride caused DNA damage of Piglet Sertoli cells and resulted in cell apoptosis as assayed by flow cytometry. The in vivo study confirmed that cadmium induced cell apoptosis in seminiferous tubules of piglets. Transmission electronic microscopy showed abnormal and apoptotic ultrastructure in Piglet Sertoli cells treated with cadmium chloride compared to the control.</p> <p>Conclusion</p> <p>cadmium has obvious adverse effects on the proliferation of piglet Sertoli cells and causes their DNA damage, cell apoptosis, and aberrant morphology. This study thus offers novel insights into the toxicology of cadmium on male reproduction.</p

Cell Pluripotency Levels Associated with Imprinted Genes in Human

Pluripotent stem cells are exhibited similarly in the morphology, gene expression, growth properties, and epigenetic modification with embryonic stem cells (ESCs). However, it is still controversial that the pluripotency of induced pluripotent stem cell (iPSC) is much inferior to ESC, and the differentiation capacity of iPSC and ESC can also be separated by transcriptome and epigenetics. miRNAs, which act in posttranscriptional regulation of gene expression and are involved in many basic cellular processes, may reveal the answer. In this paper, we focused on identifying the hidden relationship between miRNAs and imprinted genes in cell pluripotency. Total miRNA expression patterns in iPSC and ES cells were comprehensively analysed and linked with human imprinted genes, which show a global picture of their potential function in pluripotent level. A new CPA4-KLF14 region which locates in chromosomal homologous segments (CHSs) within mammals and include both imprinted genes and significantly expressed miRNAs was first identified. Molecular network analysis showed genes interacted with imprinted genes closely and enriched in modules such as cancer, cell death and survival, and tumor morphology. This imprinted region may provide a new look for those who are interested in cell pluripotency of hiPSCs and hESCs

Dietary DHA/EPA ratio affected tissue fatty acid profiles, antioxidant capacity, hematological characteristics and expression of lipid-related genes but not growth in juvenile black seabream (Acanthopagrus schlegelii)

An 8-week feeding trial was conducted to investigate the effects of dietary docosahexaenoic to eicosapentaenoic acid ratio (DHA/EPA) on growth performance, fatty acid profiles, anti- oxidant capacity, hematological characteristics and expression of some lipid metabolism related genes of juvenile black seabream (Acanthopagrus schlegelii) of initial weight 9.47 &plusmn; 0.03 g. Five isonitrogenous and isolipidic diets (45% crude protein and 14% crude lipid) were formulated to contain graded DHA/EPA ratios of 0.65, 1.16, 1.60, 2.03 and 2.67. There were no differences in growth performance and feed utilization among treatments. Fish fed higher DHA/EPA ratios had higher malondialdehyde (MDA) contents in serum than lower ratios. Serum triacylglycerol (TAG) content was significantly higher in fish fed the lowest DHA/EPA ratio. Tissue fatty acid profiles reflected the diets despite down-regulation of LC- PUFA biosynthesis genes, fatty acyl desaturase 2 (fads2) and elongase of very long-chain fatty acids 5 (elovl5), by high DHA/EPA ratios. Expression of acetyl-CoA carboxylase alpha (acc&alpha;) and carnitine palmitoyl transferase 1A (cpt1a) were up-regulated by high DHA/EPA ratio, whereas sterol regulatory element-binding protein-1 (srebp-1) and hormone-sensitive lipase (hsl) were down-regulated. Fatty acid synthase (fas), 6-phosphogluconate dehydro- genase (6pgd) and peroxisome proliferator-activated receptor alpha (ppar&alpha;) showed highest expression in fish fed intermediate (1.16) DHA/EPA ratio. Overall, this study indicated that dietary DHA/EPA ratio affected fatty acid profiles and significantly influenced lipid metabo- lism including LC-PUFA biosynthesis and other anabolic and catabolic pathways, and also had impacts on antioxidant capacity and hematological characteristics

Evolution of the edge states and corner states in a multilayer honeycomb valley-Hall topological metamaterial

The valley-Hall effect provides topological protection to a broad class of defects in valley-Hall photonic topological metamaterials. Unveiling precisely how such protection is achieved and its implications in practical implementations is paramount to move from fundamental science to applications. To this end, we investigate a honeycomb valley-Hall topological metamaterial and monitor the evolution of the topological valley-Hall edge states and higher-order corner states under different perturbation δR. The evolutions of the edge states of the armchair and zigzag interfaces are demonstrated, respectively. By adjusting the geometric parameters and introducing disturbances to break the inversion symmetry, we achieve the edge states with different modes including the conventional crossed edge state and the specific gapped edge state. It is found that the edge states of topological valley kinking will gradually separate with the increase of δR, and finally a complete gap between the edge states appears. The gap has rarely been reported previously in topological materials fabricated by printed circuit board technology. In addition, the higher-order topological corner states can also be observed in the proposed topological metamaterial. The higher-order topological phase is theoretically characterized by nontrivial bulk polarization and the Wannier centers. Our results show that the corner state localization becomes stronger with the increase of δR. It is expected that our results will provide a platform for the realization of optical topological insulators

Segmentation of Kidney and Renal Tumor in CT Scans Using Convolutional Networks

Accurate segmentation of kidney and renal tumor in CT images is a prerequisite step in surgery planning. However, this task remains a challenge. In this report, we use convolutional networks (ConvNet) to automatically segment kidney and renal tumor. Specifically, we adopt a 2D ConvNet to select a range of slices to be segmented in the inference phase for accelerating segmentation, while a 3D ConvNet is trained to segment regions of interest in the above narrow range. In localization phase, CT images from several publicly available datasets were used for learning localizer. This localizer aims to filter out slices impossible containing kidney and renal tumor, and it was fine-tuned from AlexNet pre-trained on ImageNet. In segmentation phase, a simple U-net with large patch size (160×160×80) was trained to delineate contours of kidney and renal tumor. In the 2019 MICCAI Kidney Tumor Segmentation (KiTS19) Challenge, 5-fold cross-validation was performed on the training set. 168 (80%) CT scans were used for training and remaining 42 (20%) cases were used for validation. The resulting average Dice similarity coefficients are 0.9662 and 0.7905 for kidney and renal tumor, respectively

DNA damage and decrease of cellular oxidase activity in piglet sertoli cells exposed to gossypol

The study was designated to explore the toxic effects of gossypol on piglet sertoli cells. Sertoli cells were isolated from piglet testes using a two-step enzyme digestion and followed by differential plating. Piglet sertoli cells were cultured and classified into five groups, that is, group A, the control without gossypol, group B with 2.5 μg/ml gossypol, group C with 5 μg/ml gossypol, group D with 10 μg/ml gossypol and group E with 20 μg/ml gossypol. We found that sertoli cells’ growth was inhibited by gossypol at dose 2.5 μg/ml when compared with the control group. The oxidase activity of sertoli cell also decreased at 2.5 μg/m gossypol. Moreover, DNA damage of sertoli cells was observed at 5 μg/ml gossypol. Putting this into consideration, our study suggests that exposure of gossypol to sertoli cells leads to an inhibition of sertoli cell growth and oxidase activity of sertoli cells at a low concentration, whereas gossypol results in DNA damage of sertoli cells at a higher concentration.Keywords: Gossypol, sertoli cells, oxidase, DNA damag

Genome-Wide Association Study of Tacrolimus Pharmacokinetics Identifies Novel Single Nucleotide Polymorphisms in the Convalescence and Stabilization Periods of Post-transplant Liver Function

After liver transplantation, the liver function of a patient is gradually restored over a period of time that can be divided into a convalescence period (CP) and a stabilizing period (SP). The plasma concentration of tacrolimus, an immunosuppressant commonly used to prevent organ rejection, varies as a result of variations in its metabolism. The effects of genetic and clinical factors on the plasma concentration of tacrolimus appear to differ in the CP and SP. To establish a model explaining the variation in tacrolimus trough concentration between individuals in the CP and SP, we conducted a retrospective, single-center, discovery study of 115 pairs of patients (115 donors and 115 matched recipients) who had undergone liver transplantation. Donors and recipients were genotyped by a genome-wide association study (GWAS) using an exome chip. Novel exons were identified that influenced tacrolimus trough concentrations and were verified with bootstrap analysis. In donors, two single-nucleotide polymorphisms showed an effect on the CP (rs1927321, rs1057192) and four showed an effect on the SP (rs776746, rs2667662, rs7980521, rs4903096); in recipients, two single-nucleotide polymorphisms showed an effect in the SP (rs7828796, rs776746). Genetic factors played a crucial role in tacrolimus metabolism, accounting for 44.8% in the SP, which was higher than previously reported. In addition, we found that CYP3A5, which is known to affect the metabolism of tacrolimus, only influenced tacrolimus pharmacokinetics in the SP

Causal association between lipid-lowering drugs and female reproductive endocrine diseases: a drug-targeted Mendelian randomization study

PurposeThe relationship between dyslipidemia and female reproductive endocrine diseases has been increasingly studied. The use of lipid-lowering drugs in treating various related diseases, including coronary heart disease, may affect female reproductive endocrine diseases. Therefore, our study aims to investigate the effects of lipid-lowering drugs on female reproductive endocrine diseases and provide a basis for the appropriate selection of drugs.MethodsIn this study, we focused on three drug targets of statins, namely HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase kexin 9 (PCSK9) inhibitors, and Niemann–Pick C1-Like 1 (NPC1L1) inhibitors. To identify potential inhibitors for these targets, we collected single nucleotide polymorphisms (SNPs) associated with HMGCR, PCSK9, and NPC1L1 from published genome-wide association study statistics. Subsequently, we conducted a drug target Mendelian randomization (MR) analysis to investigate the effects of these inhibitors on reproductive endocrine diseases mediated by low-density lipoprotein cholesterol (LDL-C) levels. Alongside coronary heart disease as a positive control, our main outcomes of interest included the risk of polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), premenstrual syndrome (PMS), abnormal uterine bleeding (including menorrhagia and oligomenorrhea), and infertility.ResultsPCSK9 inhibitors significantly increased the risk of infertility in patients (OR [95%CI] = 1.14 [1.06, 1.23], p&lt;0.05). In contrast, HMGCR inhibitors significantly reduced the risk of menorrhagia in female patients (OR [95%CI] = 0.85 [0.75, 0.97], p&lt;0.05), but had no statistical impact on patients with oligomenorrhea.ConclusionThe findings suggest that PCSK9 inhibitors may significantly increase the risk of infertility in patients. On the other hand, HMGCR inhibitors could potentially offer protection against menorrhagia in women. However, no effects of lipid-lowering drugs have been observed on other reproductive endocrine disorders, such as PCOS, POF, PMS and oligomenorrhea

Orbital parameters for an ELM white dwarf with a white dwarf companion: LAMOST J033847.06+413424.2

Double white dwarf systems are of great astrophysical importance in the field of gravitational wave and Type Ia supernova. While the binary fraction of CO core white dwarf is about a few percents, the extremely low mass white dwarfs are all thought to be within binary systems. In this work, we report the orbital solution of a double degenerate system: J033847.06+413424.24, an extremely low mass He core white dwarf orbiting a CO core white dwarf. With LAMOST and P200, time domain spectroscopic observations have been made and spectral atmosphere parameters are estimated to be $T_{\rm eff}\sim22500$ K and log $g\sim5.6$ dex. Combining Gaia parallax, 3D extinction, and evolution tracks, we estimate a radius of $\sim0.12$ $R_{\odot}$ and a mass of $\sim0.22$ $M_{\odot}$. With the 37 single exposure spectra, the radial velocities are measured and the orbital parameters are estimated to be $P=0.1253132(1)$ days, $K1=289\pm4$ km/s and $V_{sys}=-41\pm3$ km/s. The radial velocity based system ephemeris is also provided. The light curves from several photometric surveys show no orbital modulation. The orbital solution suggests that the invisible companion has a minimum mass of about 0.60 $M_{\odot}$ and is $\sim0.79$ $M_{\odot}$ for an inclination of $60.0^{\circ}$, indicating most probably a CO core white dwarf. The system is expected to merge in about 1 Gyr. With present period and distance ($\sim596$ pc) it can not irradiate strong enough gravitational wave for LISA. More double degenerate systems are expected to be discovered and parameterized as the LAMOST survey goes on.Comment: 12 pages, 11 figure