Suppression of lymphoma growth by the xenoestrogens bisphenol A and genistein

Well-defined physiological functions of estrogens are mediated via nuclear estrogen receptors α (ESR1) and β (ESR2). With regard to hematological malignancies, expression of ESR2 has been found in both B and T cell lymphomas. In addition to endogenous estrogens or selective ESR2 agonists, ESR2 signaling may be affected by both environmental synthetic estrogen-mimicking compounds and dietary phytoestrogens. In the present study, we demonstrate that oral exposure with either the synthetic compound bisphenol A (BPA) or the dietary phytoestrogen genistein reduced the growth of grafted murine T cell (EG7) and human B cell (Granta-519 mantle cell) lymphomas which both express ESR2. Suppression of lymphoma growth was due to reduced proliferation (BPA and genistein) and induction of apoptosis (genistein). Inhibition of lymphoma growth was seen at a BPA dose of 50 μg/kg body weight (BW)/day considered to be safe human exposure dose or a genistein dose of 1 mg/kg BW/day orally, which is reached in soy-rich diets. Thus, our study indicates that the environmental xenoestrogens BPA and genistein have anti-proliferative effects on ESR2-expressing lymphomas. Our data suggest that phytoestrogens may be considered as a dietary supplement for lymphoma patients and possibly for prevention of lymphoid malignancies

Differences in Gene Expression between Mouse and Human for Dynamically Regulated Genes in Early Embryo

Peer reviewe

A Defined and Xeno-Free Culture Method Enabling the Establishment of Clinical-Grade Human Embryonic, Induced Pluripotent and Adipose Stem Cells

Peer reviewe

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Does Cryopreservation of Ovarian Tissue Affect the Distribution and Function of Germinal Vesicle Oocytes Mitochondria?

The aim of this study was to evaluate mitochondrial alteration and ATP content of germinal vesicle (GV) oocytes isolated from fresh and vitrified ovaries. After superovulation, the ovaries from adult mice were collected and divided into control and vitrified groups. GV oocytes were isolated mechanically from each group. Half were cultured for 24 hours and their maturation was assessed. Metaphase II oocytes were collected and submitted to in vitro fertilization and their fertilization rates and development to the blastocyst stage were evaluated. In the remaining GV oocytes, ATP levels were quantified, and mitochondrial distribution, mitochondrial membrane potential, and intracellular free calcium were detected with rhodamine 123, JC-1 and Flou-4 AM staining, using laser-scanning confocal microscopy. Maturation and fertilization rates of GV oocytes and the developmental rates of subsequent embryos were significantly lower in vitrified samples (P<0.05). The ATP content and Ca2+ levels differed significantly in fresh and vitrified GV oocytes (P<0.05). Most mitochondria were seen as large and homogenous aggregates (66.6%) in fresh GV oocytes compared to vitrified oocytes (50%). No significant differences in mitochondrial membrane potential were found between the groups. The lower maturation and fertilization rates of GV oocytes from vitrified ovaries may be due to changes in their mitochondrial function and distribution

Generation of nonviral integration-free human iPS cell line KISCOi001-A from normal human fibroblasts, under defined xeno-free and feeder-free conditions

KISCOi001-A is a healthy feeder-free and fully characterized human induced pluripotent stem (iPS) cell line cultured under xeno-free and defined conditions. The cell line is generated from normal human foreskin fibroblasts with non-integrating episomal plasmid vectors encoding OCT4, SOX2, KLF4, NANOG, LIN28, nontransforming L-MYC and dominant negative p53. The generated iPS cells are transgene-free and their pluripotency is confirmed by the expression of stem cell markers and capacity to differentiate into the cells of ectoderm, endoderm and mesoderm while their identity and karyotype stability is confirmed with Genomic assays

A Crest Factor Reduction Technique for LTE Signals with Target Relaxation in Power Amplifier Linearization

The signal conditioning treatment to achieve good relation of power with radio-frequency (RF) conversion in conventional transceiver systems require precise baseband models. A developed framework is built to provide a demonstration of the modeling figures of merit with orthogonal frequency division multiplexing (OFDM) support under signal conditioning and transmission restrictions to waveforms with high peak to average power ratio (PAPR) in practical applications. Therefore, peak and average power levels have to be limited to correct high PAPR for a better suited correction power from the amplifier that can lead to compression or clipping in the signal of interest. This work presents an alternative joint crest factor reduction (CFR) algorithm to correct the performance of PAPR. A real-time field-programmable gate array (FPGA) testbed is developed to characterize and measure the behavior of an amplifier using a single-carrier 64–QAM OFDM based on long-term evolution (LTE) downlink at 2.40 GHz as stimulus, across wide modulation bandwidths. The results demonstrate that the CFR accuracy capabilities for the signal conditioning show a reliable clipping reduction to give a smooth version of the clipping signal and provide a factor of correction for the unwanted out-of-band emission validated according to the adjacent channel power ratio (ACPR), PAPR, peak power, complementary cumulative distribution function (CCDF), and error vector magnitude (EVM) figures of merit

Motor Function Deficits in the Estrogen Receptor Beta Knockout Mouse : Role on Excitatory Neurotransmission and Myelination in the Motor Cortex

Background: Male estrogen receptor beta (ER beta) knockout (BERKO) mice display anxiety and aggression linked to, among others, altered serotonergic signaling in the basolateral amygdala and dorsal raphe, impaired cortical radial glia migration, and reduced GABAergic signaling. The effects on primary motor cortex (M1 cortex) and locomotor activity as a consequence of ER beta loss have not been investigated. Objective: The aim of this study was to determine whether locomotor activity is altered as a consequence of the changes in the M1 cortex. Methods: The locomotor activity of male wild-type (WT) and BERKO mice was evaluated using the open-field and rotarod tests. Molecular changes in the M1 cortex were analyzed by RNA sequencing, electron microscopy, electrophysiology, and immunohistological techniques. In addition, we established oligodendrocyte (OL) cultures from WT and BERKO mouse embryonic stem cells to evaluate OL function. Results: Locomotor profiling revealed that BERKO mice were more active than WT mice but had impaired motor coordination. Analysis of the M1 cortex pointed out differences in synapse function and myelination. There was a reduction in GABAergic signaling resulting in imbalanced excitatory and inhibitory neurotransmission as well as a defective OL differentiation accompanied by myelin defects. The effects of ER beta loss on OL differentiation were confirmed in vitro. Conclusion: ER beta is an important regulator of GABAergic interneurons and OL differentiation, which impacts on adult M1 cortex function and may be linked to increased locomotor activity and decreased motor coordination in BERKO mice.Peer reviewe

FPGA-based Chaotic Cryptosystem by Using Voice Recognition as Access Key

A new embedded chaotic cryptosystem is introduced herein with the aim to encrypt digital images and performing speech recognition as an external access key. The proposed cryptosystem consists of three technologies: (i) a Spartan 3E-1600 FPGA from Xilinx; (ii) a 64-bit Raspberry Pi 3 single board computer; and (iii) a voice recognition chip manufactured by Sunplus. The cryptosystem operates with four embedded algorithms: (1) a graphical user interface developed in Python language for the Raspberry Pi platform, which allows friendly management of the system; (2) an internal control entity that entails the start-up of the embedded system based on the identification of the key access, the pixels-entry of the image to the FPGA to be encrypted or unraveled from the Raspberry Pi, and the self-execution of the encryption/decryption of the information; (3) a chaotic pseudo-random binary generator whose decimal numerical values are converted to an 8-bit binary scale under the VHDL description of m o d ( 255 ) ; and (4) two UART communication algorithms by using the RS-232 protocol, all of them described in VHDL for the FPGA implementation. We provide a security analysis to demonstrate that the proposed cryptosystem is highly secure and robust against known attacks