Mathematical Modeling of the Impact of Actin and Keratin Filaments on Keratinocyte Cell Spreading

AbstractKeratin intermediate filaments (IFs) form cross-linked arrays to fulfill their structural support function in epithelial cells and tissues subjected to external stress. How the cross-linking of keratin IFs impacts the morphology and differentiation of keratinocytes in the epidermis and related surface epithelia remains an open question. Experimental measurements have established that keratinocyte spreading area is inversely correlated to the extent of keratin IF bundling in two-dimensional culture. In an effort to quantitatively explain this relationship, we developed a mathematical model in which isotropic cell spreading is considered as a first approximation. Relevant physical properties such as actin protrusion, adhesion events, and the corresponding response of lamellum formation at the cell periphery are included in this model. Through optimization with experimental data that relate time-dependent changes in keratinocyte surface area during spreading, our simulation results confirm the notion that the organization and mechanical properties of cross-linked keratin filaments affect cell spreading; in addition, our results provide details of the kinetics of this effect. These in silico findings provide further support for the notion that differentiation-related changes in the density and intracellular organization of keratin IFs affect tissue architecture in epidermis and related stratified epithelia

Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes.

Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine in vivo. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH

Basaloid Squamous Cell Carcinoma in Nasal Cavity

Basaloid squamous cell carcinoma (BSCC) is often founded in the head and neck region. However, BSCC in the sinonasal tract is rare. We report here on the case of a 58-yr-old woman who presented with nasal obstruction and epistaxis. Computed tomography and examination of the nasal cavity revealed a tumor mass that originated from the right inferior turbinate with erosion of the nasal floor. The tumor that was attached to the inferior turbinate, the lateral nasal wall and the eroded right side hard palate, and so all this was resected. Histopathologic examination of the excised tumor confirmed BSCC in the nasal cavity. We report here on a nasal cavity BSCC that was treated with partial maxillectomy only

Black Hairy Tongue Associated with Erlotinib Treatment in a Patient with Advanced Lung Cancer

Erlotinib is a tyrosine kinase inhibitor that acts on the epidermal growth factor receptor (EGFR). There have been many reports of the mucocutaneous side effects related to several EGFR inhibitors (EGFRIs). However, no case of black hairy tongue (BHT) associated with EGFRI has been reported. Herein, we report the first case of erlotinib-induced BHT in a 61-year-old man with advanced lung cancer. Considering recent use of EGFRIs worldwide, dermatologists should recognize the possible occurrence of BHT associated with EGFRIs such as erlotinib

KINEMATIC ANALYSIS OF THE WOMEN’S JAVELIN THROW AT THE IAAF WORLD CHAMPIONSHIPS, DAEGU 2011

The purpose of this study was to analyze the kinematic variables for the women's javelin throw at the IAAF World Championships, Daegu 2011. Three-dimensional motion analyses of the eight players who qualified for the final round were carried out to obtain the data. The results showed that average release, attitude, and attack angles were 38.0±2.0°, 40.4±4.3°, and 3.7±1.1°, respectively. At the release, the average inclination angle of the trunk, upper arm, forearm were 60.8±8.3°, 47.3±10.1°, and 62.6±10.6°, respectively. Moreover, the release velocity and the release height results averaged 25.60±1.16 m/s and 1.86±0.05 m. The crossover phase and delivery phase had average distances of 1.88±0.31 m and 1.53±0.21 m. After release, the average distance between the landing foot and the foul line was 1.72±0.63 m

Hepatoprotective and Antioxidative Activities of Cornus officinalis against Acetaminophen-Induced Hepatotoxicity in Mice

The fruit of Cornus officinalis Sieb. et Zucc. is commonly prescribed in Asian countries as a tonic formula. In this study, the hepatoprotective effect of ethanolic extracts of the fruit of C. officinalis (ECO) was investigated in a mouse model of acetaminophen- (APAP-) induced liver injury. Pretreatment of mice with ECO (100, 250, and 500 mg/kg for 7 days) significantly prevented the APAP (200 mg/kg) induced hepatic damage as indicated by the serum marker enzymes (AST, ALT, and LDH). Parallel to these changes, ECO treatment also prevented APAP-induced oxidative stress in the mice liver by inhibiting lipid peroxidation (MDA) and restoring the levels of antioxidant enzymes (SOD, CAT, and HO-1) and glutathione. Liver injury and collagen accumulation were assessed using histological studies by hematoxylin and eosin staining. Our results indicate that ECO can prevent hepatic injuries associated with APAP-induced hepatotoxicity by preventing or alleviating oxidative stress

Diagnostic performance of the 2022 KLCA-NCC criteria for hepatocellular carcinoma on magnetic resonance imaging with extracellular contrast and hepatobiliary agents: comparison with the 2018 KLCA-NCC criteria

Background/Aim This study aimed to determine the diagnostic performance of 2022 Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) imaging criteria compared with the 2018 KLCA-NCC for hepatocellular carcinoma (HCC) in high-risk patients using magnetic resonance imaging (MRI). Methods This retrospective study included 415 treatment-naïve patients (152 patients who underwent extracellular contrast agent [ECA]-MRI and 263 who underwent hepatobiliary agent [HBA]-MRI; 535 lesions, including 412 HCCs) with a high risk of HCC who underwent contrast-enhanced MRI. Two readers evaluated all lesions according to the 2018 and 2022 KLCA-NCC imaging diagnostic criteria, and the per-lesion diagnostic performances were compared. Results In “definite” HCC category of both 2018 and 2022 KLCA-NCC, HBA-MRI showed a significantly higher sensitivity for the diagnosis of HCC than ECA-MRI (77.0% vs. 64.3%, P=0.006) without a significant difference in specificity (94.7% vs. 95.7%, P=0.801). On ECAMRI, “definite” or “probable” HCC categories of the 2022 KLCA-NCC had significantly higher sensitivity than those of the 2018 KLCA-NCC (85.3% vs. 78.3%, P=0.002) with identical specificity (93.6%). On HBA-MRI, the sensitivity and specificity of “definite” or “probable” HCC categories of both 2018 and 2022 KLCA-NCC were not significantly different (83.3% vs. 83.6%, P>0.999 and 92.1% vs. 90.8%, P>0.999, respectively). Conclusions In “definite” HCC category of both 2018 and 2022 KLCA-NCC, HBA-MRI provides better sensitivity than ECA-MRI without compromising specificity. On ECA-MRI, “definite” or “probable” HCC categories of the 2022 KLCA-NCC may improve sensitivity in the diagnosis of HCC compared with the 2018 KLCA-NCC

The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma

<p>Abstract</p> <p>Background</p> <p><it>Klotho </it>was originally characterized as an anti-aging gene that predisposed Klotho-deficient mice to a premature aging-like syndrome. Recently, KLOTHO was reported to function as a secreted Wnt antagonist and as a tumor suppressor. Epigenetic gene silencing of secreted Wnt antagonists is considered a common event in a wide range of human malignancies. Abnormal activation of the canonical Wnt pathway due to epigenetic deregulation of Wnt antagonists is thought to play a crucial role in cervical tumorigenesis. In this study, we examined epigenetic silencing of <it>KLOTHO </it>in human cervical carcinoma.</p> <p>Results</p> <p>Loss of <it>KLOTHO </it>mRNA was observed in several cervical cancer cell lines and in invasive carcinoma samples, but not during the early, preinvasive phase of primary cervical tumorigenesis. <it>KLOTHO </it>mRNA was restored after treatment with either the DNA demethylating agent 2'-deoxy-5-azacytidine or histone deacetylase inhibitor trichostatin A. Methylation-specific PCR and bisulfite genomic sequencing analysis of the promoter region of <it>KLOTHO </it>revealed CpG hypermethylation in non-<it>KLOTHO</it>-expressing cervical cancer cell lines and in 41% (9/22) of invasive carcinoma cases. Histone deacetylation was also found to be the major epigenetic silencing mechanism for <it>KLOTHO </it>in the SiHa cell line. Ectopic expression of the secreted form of KLOTHO restored anti-Wnt signaling and anti-clonogenic activity in the CaSki cell line including decreased active β-catenin levels, suppression of T-cell factor/β-catenin target genes, such as <it>c-MYC </it>and <it>CCND1</it>, and inhibition of colony growth.</p> <p>Conclusions</p> <p>Epigenetic silencing of <it>KLOTHO </it>may occur during the late phase of cervical tumorigenesis, and consequent functional loss of KLOTHO as the secreted Wnt antagonist may contribute to aberrant activation of the canonical Wnt pathway in cervical carcinoma.</p