Morphometric Measurements of the Incomplete Partition Type II (IP-II) Cochlea and Implications on Cochlear Implantation.

Hypothesis: The objective of this study is to obtain comprehensive morphometric measurements of the incomplete partition type II (IP-II) cochlea to provide a better understanding of intracochlear anatomy and important considerations for electrode selection and insertion.

Background: IP-II is the most common bony inner ear malformation that often requires cochlear implantation. Currently, there is significant controversy on electrode selection due to a lack of research that can provide reliable, high-resolution measurements.

Expression of TGFβ-1 and CTGF in the Implanted Cochlea and its Implication on New Tissue Formation.

Hypothesis: Transforming growth factor beta-1 (TGFβ-1) and connective tissue growth factor (CTGF) are upregulated in the implanted human cochlea.

Background: Cochlear implantation can lead to insertion trauma and intracochlear new tissue formation, which can detrimentally affect implant performance. TGFβ-1 and CTGF are profibrotic proteins implicated in various pathologic conditions, but little is known about their role in the cochlea.

Identification of microRNA-mRNA regulatory network associated with oxidative DNA damage in human astrocytes.

The high lipid content of the brain, coupled with its heavy oxygen dependence and relatively weak antioxidant system, makes it highly susceptible to oxidative DNA damage that contributes to neurodegeneration. This study is aimed at identifying specific ROS-responsive miRNAs that modulate the expression and activity of the DNA repair proteins in human astrocytes, which could serve as potential biomarkers and lead to the development of targeted therapeutic strategies for neurological diseases. Oxidative DNA damage was established after treatment of human astrocytes with 10μM sodium dichromate for 16 h.

4NQO enhances differential activation of DNA repair proteins in HPV positive and HPV negative HNSCC cells.

Tobacco exposure and human papillomavirus (HPV) infection are among the main risk factors for the development of head and neck squamous cell carcinoma (HNSCC). Interestingly, recent studies show that tumors from HPV positive (HPV+) smokers and non-smokers have similar mutational profiles, which suggests that HPV could prevent mutation induction or accumulation in the intermediate risk group composed of HPV+ smokers. Hence, we tested this observation by analyzing the effects of 4-Nitroquinoline N-oxide (4NQO), a mutagen and smoking mimetic, in NOK (normal oral keratinocytes), NOK (NOK cells transfected with E6.

Ym155 Induces Oxidative Stress-Mediated DNA Damage and Cell Cycle Arrest, and Causes Programmed Cell Death in Anaplastic Thyroid Cancer Cells.

Anaplastic thyroid cancer (ATC) is one of the most lethal malignancies with a median survival time of about 4 months. Currently, there is no effective treatment, and the development of new therapies is an important and urgent issue for ATC patients. YM155 is a small molecule that was identified as the top candidate in a high-throughput screen of small molecule inhibitors performed against a panel of ATC cell lines by the National Cancer Institute.

Inhibition of CD147 improves oligodendrogenesis and promotes white matter integrity and functional recovery in mice after ischemic stroke.

White matter damage is an important contributor to long-term neurological deficit after stroke. Our previous study has shown that inhibition of CD147 ameliorates acute ischemic stroke in mice. In this study, we aimed to investigate whether inhibition of CD147 promotes white matter repair and long-term functional recovery after ischemic stroke.

Induction of Neuronal PI3Kγ Contributes to Endoplasmic Reticulum Stress and Long-Term Functional Impairment in a Murine Model of Traumatic Brain Injury.

Phosphoinositide 3-kinase γ (PI3Kγ) expressed in immune cells is linked to neuroinflammation in several neurological diseases. However, the expression and role of PI3Kγ in preclinical traumatic brain injury (TBI) have not been investigated. In WT mice, we found that TBI induced rapid and extensive expression of PI3Kγ in neurons within the perilesional cortex and the ipsilateral hippocampal subfields (CA1, CA3), which peaked between 1 and 3 days and declined significantly 7 days after TBI.

Sodium sulfide selectively induces oxidative stress, DNA damage, and mitochondrial dysfunction and radiosensitizes glioblastoma (GBM) cells.

Glioblastoma (GBM) has a poor prognosis despite intensive treatment with surgery and chemoradiotherapy. Previous studies using dose-escalated radiotherapy have demonstrated improved survival; however, increased rates of radionecrosis have limited its use. Development of radiosensitizers could improve patient outcome.

PI3Kγ (Phosphoinositide 3-Kinase-γ) Inhibition Attenuates Tissue-Type Plasminogen Activator-Induced Brain Hemorrhage and Improves Microvascular Patency After Embolic Stroke.

Genetic and pharmacological inhibition of the PI3Kγ (phosphoinositide 3-kinase-γ) exerts anti-inflammatory and protective effects in a number of inflammatory and autoimmune diseases. SHRs (spontaneously hypertensive rats) subjected to embolic middle cerebral occlusion were treated with AS605240 (30 mg/kg) at 2 or 4 hours, tPA (tissue-type plasminogen activator; 10 mg/kg) at 2 or 6 hours, or AS605240 at 4 hours plus tPA at 6 hours. Infarct volume, brain hemorrhage, neurological function, microvascular thrombosis, and cerebral microvessel patency were examined.

Three-Dimensional Printing of Cell Exclusion Spacers (CES) for Use in Motility Assays.

Purpose: Cell migration/invasion assays are widely used in commercial drug discovery screening. 3D printing enables the creation of diverse geometric restrictive barrier designs for use in cell motility studies, permitting on-demand assays. Here, the utility of 3D printed cell exclusion spacers (CES) was validated as a cell motility assay.

Taurine Reduces tPA (Tissue-Type Plasminogen Activator)-Induced Hemorrhage and Microvascular Thrombosis After Embolic Stroke in Rat.

Background And Purpose: Taurine (2-aminoethansulfolic amino acid) exerts neuroprotective actions in experimental stroke. Here, we investigated the effect of taurine in combination with delayed tPA (tissue-type plasminogen activator) on embolic stroke.

Methods: Rats subjected to embolic middle cerebral artery occlusion were treated with taurine (50 mg/kg) at 4 hours in combination with tPA (10 mg/kg) at 6 hours.

Inhibition of CD147 (Cluster of Differentiation 147) Ameliorates Acute Ischemic Stroke in Mice by Reducing Thromboinflammation.

Background And Purpose: Inflammation and thrombosis currently are recognized as critical contributors to the pathogenesis of ischemic stroke. CD147 (cluster of differentiation 147), also known as extracellular matrix metalloproteinase inducer, can function as a key mediator of inflammatory and immune responses. CD147 expression is increased in the brain after cerebral ischemia, but its role in the pathogenesis of ischemic stroke remains unknown.

Platelet CD40 Mediates Leukocyte Recruitment and Neointima Formation after Arterial Denudation Injury in Atherosclerosis-Prone Mice.

The role of platelets in the development of thrombosis and abrupt closure after angioplasty is well recognized. However, the direct impact of platelets on neointima formation after arterial injury remains undetermined. Herein, we show that neointima formation after carotid artery wire injury reduces markedly in CD40 apolipoprotein E-deficient (apoE) mice but only slightly in CD40 ligandapoE mice, compared with apoE mice.