Survival and reproductive outcome of childbearing age ovarian cancer patients taking fertility-sparing surgery

Background: Surgical management of ovarian cancer includes total hysterectomy and bilateral salpingo-oophorectomy which results in the loss of fertility. Fertility-sparing surgery in the reproductive aged women with early-stage ovarian cancer with favourable histology has been proposed by American College of Obstetrics and Gynecology and European Society for Medical Oncology. We sought to access the survival and fertility outcome of Korean women in their reproductive age who undertook fertility-sparing surgery.Methods: Based on the Korean National Insurance Claims Data and the National Health Information Database, 328 women with newly developed ovarian cancer in 2010 were followed up for the survival and pregnancy outcome until 2020. Patients who were diagnosed with cancer or underwent hysterectomy before 2010 were excluded. The control group consisted of 552 women matched by age, economic status and place of living.Results: Out of 120, 10 deaths occurred in the fertility-sparing surgery group showing a survival rate of 91.7%. Women undertaking fertility-sparing surgery had a lower chance of delivering a new-born compared to the control group (OR 0.46; 95% CI 0.26-0.81). Diagnosis of infertility, ectopic pregnancy, and abortion appeared higher in the fertility-sparing surgery group, but it did not reach a statistical significance.Conclusions: The pregnancy rate of the ovarian cancer patients with fertility-sparing surgery was lower than that of women without ovarian cancer. Undergoing fertility-sparing surgery per se should not deter women of trying to get pregnant as the pregnancy outcome indicators do not show statistically significant differences compared to the control group

Cell type–dependent variation in paracrine potency determines therapeutic efficacy against neonatal hyperoxic lung injury

AbstractBackground aimsThe aim of this study was to determine the optimal cell type for transplantation to protect against neonatal hyperoxic lung injury. To this end, the in vitro and in vivo therapeutic efficacies and paracrine potencies of human umbilical cord blood–derived mesenchymal stromal cells (HUMs), human adipose tissue–derived mesenchymal stromal cells (HAMs) and human umbilical cord blood mononuclear cells (HMNs) were compared.MethodsHyperoxic injury was induced in vitro in A549 cells by challenge with H2O2. Alternatively, hyperoxic injury was induced in newborn Sprague-Dawley rats in vivo by exposure to hyperoxia (90% oxygen) for 14 days. HUMs, HAMs or HMNs (5 × 105 cells) were given intratracheally at postnatal day 5.ResultsHyperoxia-induced increases in in vitro cell death and in vivo impaired alveolarization were significantly attenuated in both the HUM and HAM groups but not in the HMN group. Hyperoxia impaired angiogenesis, increased the cell death and pulmonary macrophages and elevated inflammatory cytokine levels. These effects were significantly decreased in the HUM group but not in the HAM or HMN groups. The levels of human vascular endothelial growth factor and hepatocyte growth factor produced by donor cells were highest in HUM group, followed by HAM group and then HMN group.ConclusionsHUMs exhibited the best therapeutic efficacy and paracrine potency than HAMs or HMNs in protecting against neonatal hyperoxic lung injury. These cell type-dependent variations in therapeutic efficacy might be associated or mediated with the paracrine potency of the transplanted donor cells

Matrix Metalloproteinase-3 Causes Dopaminergic Neuronal Death through Nox1-Regenerated Oxidative Stress

In the present study we investigated the interplay between matrix metalloproteinase 3 (MMP3) and NADPH oxidase 1 (Nox1) in the process of dopamine (DA) neuronal death. We found that MMP3 activation causes the induction of Nox1 via mitochondrial reactive oxygen species (ROS) production and subsequently Rac1 activation, eventually leading to Nox1-derived superoxide generation in a rat DA neuronal N27 cells exposed to 6-OHDA. While a MMP3 inhibitor, NNGH, largely attenuated mitochondrial ROS and subsequent Nox1 induction, both apocynin, a putative Nox inhibitor and GKT137831, a Nox1 selective inhibitor failed to reduce 6-OHDA-induced mitochondrial ROS. However, both inhibitors for MMP3 and Nox1 similarly attenuated 6-OHDA-induced N27 cell death. RNAi-mediated selective inhibition of MMP3 or Nox1 showed that knockdown of either MMP3 or Nox1 significantly reduced 6-OHDA-induced ROS generation in N27 cells. While 6-OHDA-induced Nox1 was abolished by MMP3 knockdown, Nox1 knockdown did not alter MMP3 expression. Direct overexpression of autoactivated MMP3 (actMMP3) in N27 cells or in rat substantia nigra (SN) increased expression of Nox1. Selective knockdown of Nox1 in the SN achieved by adeno-associated virus-mediated overexpression of Nox1-specific shRNA largely attenuated the actMMP3-mediated dopaminergic neuronal loss. Furthermore, Nox1 expression was significantly attenuated in Mmp3 null mice treated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Together we established novel molecular mechanisms underlying oxidative stress-mediated dopaminergic neuronal death in which MMP3 activation is a key upstream event that leads to mitochondrial ROS, Nox1 induction and eventual dopaminergic neuronal death. Our findings may lead to the development of novel therapeutic approach

Matrix Metalloproteinase-3 Causes Dopaminergic Neuronal Death through Nox1-Regenerated Oxidative Stress

In the present study we investigated the interplay between matrix metalloproteinase 3 (MMP3) and NADPH oxidase 1 (Nox1) in the process of dopamine (DA) neuronal death. We found that MMP3 activation causes the induction of Nox1 via mitochondrial reactive oxygen species (ROS) production and subsequently Rac1 activation, eventually leading to Nox1-derived superoxide generation in a rat DA neuronal N27 cells exposed to 6-OHDA. While a MMP3 inhibitor, NNGH, largely attenuated mitochondrial ROS and subsequent Nox1 induction, both apocynin, a putative Nox inhibitor and GKT137831, a Nox1 selective inhibitor failed to reduce 6-OHDA-induced mitochondrial ROS. However, both inhibitors for MMP3 and Nox1 similarly attenuated 6-OHDA-induced N27 cell death. RNAi-mediated selective inhibition of MMP3 or Nox1 showed that knockdown of either MMP3 or Nox1 significantly reduced 6-OHDA-induced ROS generation in N27 cells. While 6-OHDA-induced Nox1 was abolished by MMP3 knockdown, Nox1 knockdown did not alter MMP3 expression. Direct overexpression of autoactivated MMP3 (actMMP3) in N27 cells or in rat substantia nigra (SN) increased expression of Nox1. Selective knockdown of Nox1 in the SN achieved by adeno-associated virus-mediated overexpression of Nox1-specific shRNA largely attenuated the actMMP3-mediated dopaminergic neuronal loss. Furthermore, Nox1 expression was significantly attenuated in Mmp3 null mice treated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Together we established novel molecular mechanisms underlying oxidative stress-mediated dopaminergic neuronal death in which MMP3 activation is a key upstream event that leads to mitochondrial ROS, Nox1 induction and eventual dopaminergic neuronal death. Our findings may lead to the development of novel therapeutic approach

Probing the Importance of Charge Balance and Noise Current in WSe2/WS2/MoS(2)van der Waals Heterojunction Phototransistors by Selective Electrostatic Doping

Heterojunction structures using 2D materials are promising building blocks for electronic and optoelectronic devices. The limitations of conventional silicon photodetectors and energy devices are able to be overcome by exploiting quantum tunneling and adjusting charge balance in 2D p–n and n–n junctions. Enhanced photoresponsivity in 2D heterojunction devices can be obtained with WSe2 and BP as p-type semiconductors and MoS2 and WS2 as n-type semiconductors. In this study, the relationship between photocurrent and the charge balance of electrons and holes in van der Waals heterojunctions is investigated. To observe this phenomenon, a p-WSe2/n-WS2/n-MoS2 heterojunction device with both p–n and n–n junctions is fabricated. The device can modulate the charge carrier balance between heterojunction layers to generate photocurrent upon illumination by selectively applying electrostatic doping to a specific layer. Using photocurrent mapping, the operating transition zones for the device is demonstrated, allowing to accurately identify the locations where photocurrent generates. Finally, the origins of flicker and shot noise at the different semiconductor interfaces are analyzed to understand their effect on the photoresponsivity and detectivity of unit active area (2.5 µm2, λ = 405 nm) in the p-WSe2/n-WS2/n-MoS2 heterojunction device. © 2020 The Authors. Published by Wiley-VCH GmbH1

Replication of the genetic effects of IFN regulatory factor 5 (IRF5) on systemic lupus erythematosus in a Korean population

Recently, two studies provided convincing evidence that IFN regulatory factor 5 (IRF5) gene polymorphisms are significantly associated with systemic lupus erythematosus (SLE) in several white populations. To replicate the association with SLE in an Asian population, we examined the genetic effects in our SLE cohort from a Korean population. A total of 1,565 subjects, composed of 593 cases and 972 controls, were genotyped using the TaqMan® (Applied Biosystems, Foster City, CA, USA) method. The genetic effects of polymorphisms on the risk of SLE were evaluated using χ2 tests and a Mantel–Haenszel meta-analysis. Statistical analysis revealed results in the Korean population were similar to the previous reports from white populations. The rs2004640 T allele had a higher frequency in SLE cases (0.385) than controls (0.321; odds ratio (OR) = 1.32, P = 0.0003). In combined analysis, including all seven independent cohorts from the three studies so far, robust and consistent associations of the rs2004640 T allele with SLE were observed. The estimate of risk was OR = 1.44 (range, 1.34–1.55), with an overall P = 1.85 × 10-23 for the rs2004640 T allele. The haplotype (rs2004640T–rs2280714T) involved in both the alternative splice donor site and the elevated expression of IRF5 also had a highly significant association with SLE (pooled, P = 2.11 × 10-16). Our results indicate that the genetic effect on the risk of SLE mediated by IRF5 variants can be generally accepted in both white and Asian populations

Role of Neuronal NADPH Oxidase 1 in the Peri-Infarct Regions after Stroke

The molecular mechanism underlying the selective vulnerability of neurons to oxidative damage caused by ischemia-reperfusion (I/R) injury remains unknown. We sought to determine the role of NADPH oxidase 1 (Nox1) in cerebral I/R-induced brain injury and survival of newborn cells in the ischemic injured region. Male Wistar rats were subjected to 90 min middle cerebral artery occlusion (MCAO) followed by reperfusion. After reperfusion, infarction size, level of superoxide and 8-hydroxy-20-deoxyguanosine (8-oxo-2dG), and Nox1 immunoreactivity were determined. RNAi-mediated knockdown of Nox1 was used to investigate the role of Nox1 in I/R-induced oxidative damage, neuronal death, motor function recovery, and ischemic neurogenesis. After I/R, Nox1 expression and 8-oxo-2dG immunoreactivity was increased in cortical neurons of the peri-infarct regions. Both infarction size and neuronal death in I/R injury were significantly reduced by adeno-associated virus (AAV)-mediated transduction of Nox1 short hairpin RNA (shRNA). AAV-mediated Nox1 knockdown enhanced functional recovery after MCAO. The level of survival and differentiation of newborn cells in the peri-infarct regions were increased by Nox1 inhibition. Our data suggest that Nox-1 may be responsible for oxidative damage to DNA, subsequent cortical neuronal degeneration, functional recovery, and regulation of ischemic neurogenesis in the peri-infarct regions after stroke

Changes of empathy in medical college and medical school students: 1-year follow up study

BACKGROUND: This study aims to determine the correlation between medical education systems, medical college (MC) and medical school (MS), and empathy by investigating the changes in empathy among students with each additional year of medical education. METHODS: The subjects were MC and MS students who had participated in the same study the previous year. All participants completed the same self-report instruments: a questionnaire on sociodemographic characteristics, and the Korean edition of the Student Version of the Jefferson Scale of Empathy (JSE-S-K), Among 334 students, the final analysis was conducted on the data provided by 113 MC and 120 MS students, excluding 101 with incomplete data. RESULTS: The age and sex did not affect the changes in empathy. Though the JSE-S-K score of MS was significantly higher than that of MC in initial investigation, this study found no difference of empathy between MC and MS. CONCLUSION: Empathy increased significantly after one year of medical education. The difference between two education systems, MC and MS, did not affect the changes in empathy