Molecular genetic study of novel biomarkers for early diagnosis of oral squamous cell carcinoma

Objectives: Early detection and treatment of an oral squamous cell carcinoma (OSCC) is critical because of its rapid growth, frequent lymph-node metastasis, and poor prognosis. However, no clinically-valuable methods of early diagnosis exist, and genetic analysis of OSCCs has yielded no biomarkers. Study D esign: We investigated the expression of genes associated with inflammation in OSCCs via a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis of microarray data. Tumor and normal tissues from five patients with an OSCC were used for microarray analysis. Differentially-expressed genes, identified using permutation, local pooled error (LPE), t-tests, and significance analysis of microarrays (SAM), were selected as candidate genetic markers. Results: Two groups corresponding to tissue identity were evident, implying that their differentially-expressed genes represented biological differences between tissues. Fifteen genes were identified using the Student’s paired t-test ( p< 0.05) and the SAM, with a false discovery rate of less than 0.02. Based on gene expression, these 15 genes can be used to classify an OSCC. A genetic analysis of functional networks and ontologies, validated by using a qRT-PCR analysis of the tissue samples, identified four genes, ADAM15, CDC7, IL12RB2 and TNFRSF8, that demonstrated excellent concordance with the microarray data. Conclusions: Our study demonstrated that four genes (ADAM15, CDC7, IL12RB2 and TNFRSF8) had potential as novel biomarkers for the diagnosis and the treatment of an OSCC

The influence of waist circumference on insulin resistance and nonalcoholic fatty liver disease in apparently healthy Korean adults

Background/AimsWaist circumference (WC) is a risk factor for metabolic syndrome and is related to insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to determine the association between WC and IR and NAFLD in apparently healthy Korean adults.MethodsThe volunteers included in this cross-sectional study comprised 9,159 adults (5,052 men, 4,107 women) who participated in a comprehensive health checkup program. IR was evaluated by the homeostasis model assessment of IR (HOMA-IR) and was considered to be present when the HOMA-IR score was >2. NAFLD was evaluated by ultrasound examination. Elevated alanine aminotransferase (ALT) was defined as >40 IU/L in men and >35 IU/L in women. Logistic regression was performed to determine the odds ratios (ORs) and 95% confidence intervals (95% CIs) for NAFLD, IR, and ALT according to categorized levels of WC.ResultsNAFLD was found in 2,553 (27.9%) of the participants (82.6% men, 17.4% women), while IR and elevated ALT were found in 17.2% (68.1% men, 31.9% women) and 10% (83% men, 17% women), respectively. After adjusting for confounding factors, the prevalence of NAFLD, IR, and elevated ALT was significantly associated with increases in WC quartile: highest quartile for NAFLD in men, OR=15.539, 95% CI=12.687-19.033; highest quartile for NAFLD in women, OR=48.732, 95% CI=23.918-99.288 (P<0.001); and highest quartile for IR in men, OR=17.576, 95% CI=13.283-23.255; highest quartile for IR in women, OR=11.078, 95% CI=7.813-15.708 (P<0.001); highest quartile for elevated ALT in men, OR=7.952, 95% CI=6.046-10.459; and highest quartile for elevated ALT in women, OR=8.487, 95% CI=4.679-15.395 (P<0.001).ConclusionsWC contributes to IR and NAFLD in apparently healthy Korean adults, and thus may be an important factor in the development of IR and NAFLD

Interaction of Veratrum nigrum

Obesity has become a major health threat in developed countries. However, current medications for obesity are limited because of their adverse effects. Interest in natural products for the treatment of obesity is thus rapidly growing. Korean Medicine (KM) is characterized by the wide use of herbal formulas. However, the combination rule of herbal formulas in KM lacks experimental evidence. According to Shennong’s Classic of Materia Medica, the earliest book of herbal medicine, Veratrum nigrum (VN) has antagonistic features against Panax ginseng (PG), and the PG-VN pair is strictly forbidden. In this study, we have shown the effects of PG, VN, and their combination on obesity in high-fat (HF) diet-induced obese mice and in 3T3-L1 cells. PG, VN, and PG-VN combination significantly reduced weight gain and the fat pad weight in HF diet-induced obese mice. They also significantly decreased lipid accumulation and the expressions of two major adipogenesis factors, PPARγ and C/EBPα, in 3T3-L1 cells. In addition, the PG-VN combination had synergistic effects compared with the mixture of extracts of PG and VN on inhibition of PPARγ and C/EBPα expressions at lower doses. These results indicate a new potential anti-obese pharmacotherapy and also provide scientific evidence supporting the usage of herbal combinations instead of mixtures in KM

An Essential Regulatory Role of Downstream of Kinase-1 in the Ovalbumin-Induced Murine Model of Asthma

The downstream of kinase (DOK)-1 is involved in the protein tyrosine kinase (PTK) pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases

Motherwort (Leonurus japonicus Houtt.) extends the lifespan and healthspan of Caenorhabditis elegans via sir-2.1 and daf-16 activation

Introduction: As a traditional medicine, the aerial parts of Leonurus japonicus Houtt. (Lamiaceae), aka motherwort, have been extensively used to treat gynecological diseases. The current study was designed to investigate the longevity properties of the methanolic extract of L. japonicus (MLJ) using Caenorhabditis elegans model system. Methods: The longevity effect of MLJ was determined by lifespan assay. Lipofuscin accumulation, thermotolerance, and body movement were measured to test the effects on the healthspan. The antioxidant capacity of MLJ was investigated by analyzing antioxidant enzyme activities, intracellular reactive oxygen species (ROS) levels, and the survival rate against oxidative stress conditions. Pharyngeal pumping rate and body length were observed to determine the effect of MLJ on aging-related factors. Transcriptional activity of daf-16 was observed under fluorescence microscopy using a transgenic mutant carrying DAF-16::GFP transgene. Results: MLJ could significantly prolong the median and maximum lifespan of worms. In addition, MLJ reduced the accumulation of lipofuscin in aged worms and delayed the age-dependent decrease in locomotion and thermotolerance suggesting its beneficial role in the healthspan. Also, MLJ increased the stress resistance of worms against oxidative stress and decreased intracellular ROS generation by up-regulating the activities of antioxidant enzymes. Additional genetic studies showed that MLJ failed to prolong the lifespan of worms lacking daf-2, age-1, daf-16, and sir-2.1 genes. Moreover, in the presence of MLJ, the nuclear translocation of daf-16 was significantly increased. Conclusion: Collectively, our results demonstrate that the anti-aging properties of MLJ might be attributed to sir-2.1 and insulin/IGF signaling-dependent daf-16/FOXO activation

Changes and Remodeling of Intersegmental Interferences following Bilateral Sagittal Split Ramus Osteotomy in Patients with Mandibular Prognathism

Purpose: This study aimed to measure the amount of change in the mandibular angle, intergonial width, and ramus angulation due to intersegmental interference and changes in condyle position after mandibular bilateral sagittal split ramus osteotomy (BSSRO) in patients with mandibular prognathism and to evaluate the correlation between them. Materials and Methods: A total of 32 patients who underwent mandibular setback using the BSSRO of the mandible to manage skeletal prognathism during the years 2018 to 2020 at the Department of Oral and Maxillofacial Surgery, Pusan National University were followed both clinically and with cone beam computed tomography (CBCT) for at least one year. Those who were also treated with genioplasty or other orthognathic surgery were excluded from the study. The mandibular angle (gonial angle: Ar&ndash;Go&ndash;Me), intergonial width (Go&ndash;Go), and total angle (sum of left and right proximal segmental angle) were recorded. Changes in the ramus were compared and analyzed before surgery (T1), immediately after surgery (T2), and one year following surgery (T3). Results: The mandibular angle increased by an average of 0.14 degrees immediately after surgery (T2&ndash;T1) and increased by 0.97 degrees at 12 months postoperatively (T3&ndash;T2). No correlation was observed with the amount of change in each group relative to the amount of mandibular setback. The mandibular width decreased by 0.01 mm on average immediately after surgery (T2&ndash;T1), and by 4.2 mm on average at 12 months after surgery (T3&ndash;T2). The angle of the mesial fragment of the mandible increased by 1.04 degrees immediately after surgery (T2&ndash;T1), compared to the preoperative state. It decreased by 0.86 degrees at 12 months postoperatively (T3&ndash;T2). Conclusion: The increase in the mandibular angle from immediately after surgery to 12 months after BSSRO reflects the counterclockwise rotational tendency to prevent opening restriction when intentionally selecting the condylar position. The decrease in the intergonial width immediately after surgery is thought to be due to the effect of internal trimming to minimize the bone interference between the outer surface of the distal bone fragment and the inner surface of the mesial fragment, and the decrease 1 year after surgery can be considered to be due to bone remodeling. Interosseous interference during mandibular setback osteotomy does not necessarily cause an increase in the width of the mandibular angle after surgery

Rheoforging of thin case for IT devices with optimal process parameters and new type die design

The latest trend in the cell phone component industry to use aluminium and magnesium alloys has resulted in the advanced processing technologies. Semi-solid forming process that is advantageous for the mass production of thin parts with complex shapes have been of interest as a promising tool for near net-shape manufacturing. This study describes a semi-solid forming process for the development of a 1 mm-thick cell phone case by using the rheological material prepared by electromagnetic stirring equipment. Thus, a new type of die design for indirect rheoforging was proposed to efficiently control the primary α-Al phase particles in the thin part under rheological conditions. Their microstructure and mechanical properties were investigated and compared to parts produced without electromagnetic stirring. Those products fabricated by electromagnetic stirring had better mechanical properties and globular microstructures than those fabricated without electromagnetic stirring. Several processing parameters such as punch velocity (30 mm/s), punch pressure (75-250 MPa), stirring time (10 s), and solid fraction (0-20%) were used. The optimal condition that resulted in a defect-free component with the improved mechanical properties was explained and discussed. © 2013 IMechE

Lingonberry Fruit Ethanol Extract Ameliorates DSS-Induced Ulcerative Colitis In Vivo and In Vitro

Ulcerative colitis (UC) is an inflammatory chronic intestinal disease with pathological characteristics, including imbalanced immune function and the overexpression of inflammatory cytokines and mediators. Inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6) were oversecreted in UC condition. Cyclooxygenase (COX)-2 and prostaglandin (PG)E2 were also overexpressed in colon tissue. Lingonberry (LB) (Vaccinium vitis-idaea L.) possesses pharmacological activities, including anti-oxidant, anti-cancer, and anti-obesity effects. To explore LB’s effects on UC, BALB/c mice were administered with 3% (w/v) dextran sulphate sodium (DSS) and LB extract (70% ethanol) orally for nine days. The severity of UC was measured by the change in body weight and colon length. To evaluate LB’s regulatory effect on inflammatory cytokines, the enzyme-linked immunosorbent assay (ELISA) kit was used to measure the inflammatory cytokines in mouse serum. Mouse peritoneal microphages were used to detect LB’s anti-inflammatory effect. The results showed that LB treatment ameliorated less weight loss and longer colon length compared to the DSS-treated group. LB treatment also ameliorated the secretion of inflammatory cytokines. These results indicated that LB has potential as an herbal medicine to treat UC