Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde dehydrogenase/disialoganglioside identify their tumor stem cells.

IntroductionAlthough breast phyllodes tumors are rare, there is no effective therapy other than surgery. Little is known about their tumor biology. A malignant phyllodes tumor contains heterologous stromal elements, and can transform into rhabdomyosarcoma, liposarcoma and osteosarcoma. These versatile properties prompted us to explore their possible relationship to mesenchymal stem cells (MSCs) and to search for the presence of cancer stem cells (CSCs) in phyllodes tumors.MethodsParaffin sections of malignant phyllodes tumors were examined for various markers by immunohistochemical staining. Xenografts of human primary phyllodes tumors were established by injecting freshly isolated tumor cells into the mammary fat pad of non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. To search for CSCs, xenografted tumor cells were sorted into various subpopulations by flow cytometry and examined for their in vitro mammosphere forming capacity, in vivo tumorigenicity in NOD-SCID mice and their ability to undergo differentiation.ResultsImmunohistochemical analysis revealed the expression of the following 10 markers: CD44, CD29, CD106, CD166, CD105, CD90, disialoganglioside (GD2), CD117, Aldehyde dehydrogenase 1 (ALDH), and Oct-4, and 7 clinically relevant markers (CD10, CD34, p53, p63, Ki-67, Bcl-2, vimentin, and Globo H) in all 51 malignant phyllodes tumors examined, albeit to different extents. Four xenografts were successfully established from human primary phyllodes tumors. In vitro, ALDH+ cells sorted from xenografts displayed approximately 10-fold greater mammosphere-forming capacity than ALDH- cells. GD2+ cells showed a 3.9-fold greater capacity than GD2- cells. ALDH+/GD2+cells displayed 12.8-fold greater mammosphere forming ability than ALDH-/GD2- cells. In vivo, the tumor-initiating frequency of ALDH+/GD2+ cells were up to 33-fold higher than that of ALDH+ cells, with as few as 50 ALDH+/GD2+ cells being sufficient for engraftment. Moreover, we provided the first evidence for the induction of ALDH+/GD2+ cells to differentiate into neural cells of various lineages, along with the observation of neural differentiation in clinical specimens and xenografts of malignant phyllodes tumors. ALDH+ or ALDH+/GD2+ cells could also be induced to differentiate into adipocytes, osteocytes or chondrocytes.ConclusionsOur findings revealed that malignant phyllodes tumors possessed many characteristics of MSC, and their CSCs were enriched in ALDH+ and ALDH+/GD2+ subpopulations

Increased Risk for Invasive Breast Cancer Associated with Hormonal Therapy: A Nation-Wide Random Sample of 65,723 Women Followed from 1997 to 2008

BACKGROUND: Hormonal therapy (HT) either estrogen alone (E-alone) or estrogen plus progesterone (E+P) appears to increase the risk for breast cancer in Western countries. However, limited information is available on the association between HT and breast cancer in Asian women characterized mainly by dietary phytoestrogens intake and low prevalence of contraceptive pills prescription. METHODOLOGY: A total of 65,723 women (20-79 years of age) without cancer or the use of Chinese herbal products were recruited from a nation-wide one-million representative sample of the National Health Insurance of Taiwan and followed from 1997 to 2008. Seven hundred and eighty incidents of invasive breast cancer were diagnosed. Using a reference group that comprised 40,052 women who had never received a hormone prescription, Cox proportional hazard models were constructed to determine the hazard ratios for receiving different types of HT and the occurrence of breast cancer. CONCLUSIONS: 5,156 (20%) women ever used E+P, 2,798 (10.8%) ever used E-alone, and 17,717 (69%) ever used other preparation types. The Cox model revealed adjusted hazard ratios (HRs) of 2.05 (95% CI 1.37-3.07) for current users of E-alone and 8.65 (95% CI 5.45-13.70) for current users of E+P. Using women who had ceased to take hormonal medication for 6 years or more as the reference group, the adjusted HRs were significantly elevated and greater than current users and women who had discontinued hormonal medication for less than 6 years. Current users of either E-alone or E+P have an increased risk for invasive breast cancer in Taiwan, and precautions should be taken when such agents are prescribed

Analysis of the High Conversion Efficiencies β

Both β-FeSi2 and BaSi2 are silicides and have large absorption coefficients; thus they are very promising Si-based new materials for solar cell applications. In this paper, the dc I-V characteristics of n-Si/i-βFeSi2/p-Si and n-Si/i-BaSi2/p-Si thin film solar cells are investigated by solving the charge transport equations with optical generations. The diffusion current densities of free electron and hole are calculated first. Then the drift current density in the depletion regions is obtained. The total current density is the sum of diffusion and drift current densities. The conversion efficiencies are obtained from the calculated I-V curves. The optimum conversion efficiency of n-Si/i-βFeSi2/p-Si thin film solar cell is 27.8% and that of n-Si/i-BaSi2/p-Si thin film solar cell is 30.4%, both are larger than that of Si n-i-p solar cell (η is 20.6%). These results are consistent with their absorption spectrum. The calculated conversion efficiency of Si n-i-p solar cell is consistent with the reported researches. Therefore, these calculation results are valid in this work

Overweight worsens apoptosis, neuroinflammation and blood-brain barrier damage after hypoxic ischemia in neonatal brain through JNK hyperactivation

<p>Abstract</p> <p>Background</p> <p>Apoptosis, neuroinflammation and blood-brain barrier (BBB) damage affect the susceptibility of the developing brain to hypoxic-ischemic (HI) insults. c-Jun N-terminal kinase (JNK) is an important mediator of insulin resistance in obesity. We hypothesized that neonatal overweight aggravates HI brain damage through JNK hyperactivation-mediated upregulation of neuronal apoptosis, neuroinflammation and BBB leakage in rat pups.</p> <p>Methods</p> <p>Overweight (OF) pups were established by reducing the litter size to 6, and control (NF) pups by keeping the litter size at 12 from postnatal (P) day 1 before HI on P7. Immunohistochemistry and immunoblotting were used to determine the TUNEL-(+) cells and BBB damage, cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP), and phospho-JNK and phospho-Bim_ELlevels. Immunofluorescence was performed to determine the cellular distribution of phospho-JNK.</p> <p>Results</p> <p>Compared with NF pups, OF pups had a significantly heavier body-weight and greater fat deposition on P7. Compared with the NF-HI group, the OF-HI group showed significant increases of TUNEL-(+) cells, cleaved levels of caspase-3 and PARP, and ED1-(+) activated microglia and BBB damage in the cortex 24 hours post-HI. Immunofluorescence of the OF-HI pups showed that activated-caspase 3 expression was found mainly in NeuN-(+) neurons and RECA1-(+) vascular endothelial cells 24 hours post-HI. The OF-HI group also had prolonged escape latency in the Morris water maze test and greater brain-volume loss compared with the NF-HI group when assessed at adulthood. Phospho-JNK and phospho-Bim_ELlevels were higher in OF-HI pups than in NF-HI pups immediately post-HI. JNK activation in OF-HI pups was mainly expressed in neurons, microglia and vascular endothelial cells. Inhibiting JNK activity by AS601245 caused more attenuation of cleaved caspase-3 and PARP, a greater reduction of microglial activation and BBB damage post-HI, and significantly reduced brain damage in OF-HI than in NF-HI pups.</p> <p>Conclusions</p> <p>Neonatal overweight increased HI-induced neuronal apoptosis, microglial activation and BBB damage, and aggravated HI brain damage in rat pups through JNK hyperactivation.</p

New Plasma Separation Glucose Oxidase-based Glucometer in Monitoring of Blood With Different PO2 Levels

BackgroundThe PalmLab glucometer is a newly designed plasma separation glucose oxidase (GO)-based glucometer. Past studies have shown that the accuracy of GO-based glucometers is compromised when measurements are taken in patients with high PO2 levels. We performed a two-arm study comparing the fitness of the PalmLab blood glucometer with that of a standard glucose analyzer in monitoring blood glucose levels in pediatric patients, especially when arterial partial pressure of oxygen (PO2) was high.MethodsIn the first arm of the study, arterial blood samples from pediatric patients were measured by the PalmLab blood glucometer and the YSI 2302 Plus Glucose/Lactate analyzer. In the second arm of the study, venous blood samples from adult volunteers were spiked with glucose water to prepare three different levels of glucose (65, 150, and 300mg/dL) and then oxygenated to six levels of PO2 (range, 40–400mmHg). The biases of the PalmLab glucometer were calculated.ResultsA total of 162 samples were collected in the first arm of the study. Results of linear regression showed that the coefficient of determination (R2) between PalmLab glucometer and standard glucose analyzer was 0.9864. Error grid analysis revealed that all the results were within Zone A (clinically accurate estimate zone). The biases between the two systems were low at different PO2 levels. In the second arm of the study, the results were also unaffected by changes in PO2.ConclusionThe PalmLab glucometer provides accurate results in samples with high PO2 and is suitable for measuring arterial glucose levels in pediatric patients

Garlic Oil Alleviates MAPKs- and IL-6-mediated Diabetes-related Cardiac Hypertrophy in STZ-induced DM Rats

Garlic oil has been reported to protect the cardiovascular system; however, the effects and mechanisms behind the cardioprotection of garlic oil on diabetes-induced cardiaomyopathy are unclear. In this study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether garlic oil could protect the heart from diabetes-induced cardiomyopathy. Wistar STZ-induced diabetic rats received garlic oil (0, 10, 50 or 100 mg kg_1 body weight) by gastric gavage every 2 days for 16 days. Normal rats without diabetes were used as control. Cardiac contractile dysfunction and cardiac pathologic hypertrophy responses were observed in diabetic rat hearts. Cardiac function was examined using echocardiography. In addition to cardiac hypertrophy-related mitogen-activated protein kinases (MAPK) pathways (e.g., p38, c-Jun N-terminal kinases (JNK) and extracellularly responsive kinase (ERK1/2)), the IL-6/MEK5/ERK5 signaling pathway was greatly activated in the diabetic rat hearts, which contributes to the up-regulation of cardiac pathologic hypertrophy markers including atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), and leads to cardiac contractile dysfunction. Garlic oil treatment significantly inhibited the up-regulation in MAPK (e.g., p38, JNK and ERK1/2) and IL-6/MEK5/ERK5 signaling pathways in the diabetic rat hearts, reducing the levels of cardiac pathologic hypertrophy markers such as ANP and BNP, and improving the cardiac contractile function. Collectively, data from these studies demonstrate that garlic oil shows the potential cardioprotective effects for protecting heart from diabetic cardiomyopathy

Strong Gravitational Lensing Parameter Estimation with Vision Transformer

Quantifying the parameters and corresponding uncertainties of hundreds of strongly lensed quasar systems holds the key to resolving one of the most important scientific questions: the Hubble constant ($H_{0}$) tension. The commonly used Markov chain Monte Carlo (MCMC) method has been too time-consuming to achieve this goal, yet recent work has shown that convolution neural networks (CNNs) can be an alternative with seven orders of magnitude improvement in speed. With 31,200 simulated strongly lensed quasar images, we explore the usage of Vision Transformer (ViT) for simulated strong gravitational lensing for the first time. We show that ViT could reach competitive results compared with CNNs, and is specifically good at some lensing parameters, including the most important mass-related parameters such as the center of lens $\theta_{1}$ and $\theta_{2}$, the ellipticities $e_1$ and $e_2$, and the radial power-law slope $\gamma'$. With this promising preliminary result, we believe the ViT (or attention-based) network architecture can be an important tool for strong lensing science for the next generation of surveys. The open source of our code and data is in \url{https://github.com/kuanweih/strong_lensing_vit_resnet}.Comment: Accepted by ECCV 2022 AI for Space Worksho

Molecular events associated with epithelial to mesenchymal transition of nasopharyngeal carcinoma cells in the absence of Epstein-Barr virus genome

Epithelial-mesenchymal transition (EMT) is an important process in tumor metastasis. The EMT-related events associated with metastasis of NPC in the absence of EBV have not been elucidated. We established an EBV-negative NPC cell line from a bone marrow biopsy of an NPC patient. Using a Matrigel system we isolated an invasive and non-invasive sublines, designated NPC-BM29 and NPC-BM00. NPC-BM29 acquired an invasive-like phenotype characterized by EMT, marked by down-regulation of E-cadherin and β-catenin with concomitant increased expression of Ets1. NPC-BM29 cells expressed ≥ 10-fold higher of MMP-9 than NPC-BM00 cells. NPC-BM29 cells grew better in 2% serum than NPC-BM00 cells, with a population doubling-time of 26.8 h and 30.7 h, respectively. A marked reduction in colony-formation ability of NPC-BM00 cells compared to NPC-BM29 was observed. Wound-healing assay revealed that NPC-BM29 cells displayed higher motility than NPC-BM00 and the motility was further enhanced by cell treatment with TPA, a PKC activator. Cell surface markers and tumor-associated molecules, AE3, MAK6 and sialyl-Tn, were up-regulated in NPC-BM29 cells, whereas the expression of HLA-DR and CD54 was significantly increased in NPC-BM00 cells. NPC-BM29 consistently released higher levels of IL-8 and IL-10 than NPC-BM00, with low levels of IL-1α expression in both cell lines. Higher level of VEGF production was detected in NPC-BM00 than NPC-BM29 cells. These data show that EBV is not required for exhibiting multiple metastatic phenotypes associated with EMT. More studies that target right molecules/signalings associated with the EMT may offer new therapeutic intervention options for NPC invasion and metastasis