The Relationship between Coenzyme Q10, Oxidative Stress, and Antioxidant Enzymes Activities and Coronary Artery Disease

A higher oxidative stress may contribute to the pathogenesis of coronary artery disease (CAD). The purpose of this study was to investigate the relationship between coenzyme Q10 concentration and lipid peroxidation, antioxidant enzymes activities and the risk of CAD. Patients who were identified by cardiac catheterization as having at least 50% stenosis of one major coronary artery were assigned to the case group (n = 51). The control group (n = 102) comprised healthy individuals with normal blood biochemical values. The plasma coenzyme Q10, malondialdehyde (MDA) and antioxidant enzymes activities (catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx)) were measured. Subjects with CAD had significant lower plasma coenzyme Q10, CAT and GPx activities and higher MDA and SOD levels compared to those of the control group. The plasma coenzyme Q10 was positively correlated with CAT and GPx activities and negatively correlated with MDA and SOD. However, the correlations were not significant after adjusting for the potential confounders of CAD with the exception of SOD. A higher level of plasma coenzyme Q10 (≥0.52 μmol/L) was significantly associated with reducing the risk of CAD. Our results support the potential cardioprotective impact of coenzyme Q10

Anticancer drugs for the modulation of endoplasmic reticulum stress and oxidative stress

Prior research has demonstrated how the endoplasmic reticulum (ER) functions as a multifunctional organelle and as a well-orchestrated protein-folding unit. It consists of sensors which detect stress-induced unfolded/misfolded proteins and it is the place where protein folding is catalyzed with chaperones. During this folding process, an immaculate disulfide bond formation requires an oxidized environment provided by the ER. Protein folding and the generation of reactive oxygen species (ROS) as a protein oxidative byproduct in ER are crosslinked. An ER stress-induced response also mediates the expression of the apoptosis-associated gene C/EBP-homologous protein (CHOP) and death receptor 5 (DR5). ER stress induces the upregulation of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor and opening new horizons for therapeutic research. These findings can be used to maximize TRAIL-induced apoptosis in xenografted mice. This review summarizes the current understanding of the interplay between ER stress and ROS. We also discuss how damage-associated molecular patterns (DAMPs) function as modulators of immunogenic cell death and how natural products and drugs have shown potential in regulating ER stress and ROS in different cancer cell lines. Drugs as inducers and inhibitors of ROS modulation may respectively exert inducible and inhibitory effects on ER stress and unfolded protein response (UPR). Reconceptualization of the molecular crosstalk among ROS modulating effectors, ER stress, and DAMPs will lead to advances in anticancer therapy

Identification and characterisation of myofibroblast markers in human colon and colorectal cancer microenvironment

Myofibroblasts (MFs) are one of the most significant stromal cell types in epithelia such as in the gut. They play an important role in regulating the normal colorectal stem cell niche and facilitating tumour initiation, growth and progression through inter-cell signalling. Abundant presence of MFs is often associated with poor prognosis in cancers. The aim of this project is to identify new myofibroblast markers to distinguish them from others cells in the stroma, and also to establish patterns of myofibroblast gene regulation. First, we identify the membrane protein that home-raised IgG1 antibody PR2D3 recognises on myofibroblasts, by using immunoprecipitation and mass spectrometry based amino acid sequencing, as the AOC3 membrane primary amine oxidase, with additional reactivity to myosin heavy chain 11 (Chapter 3). The AOC3 expression in myofibroblasts in vivo and in vitro is validated by extensive expression profiling analyses. Our results demonstrate that AOC3 is expressed by myofibroblasts and that it functions as an SSAO enzyme (Chapter 4). Furthermore, we successfully separated primary myofibroblasts from fresh tissues by FACS sorting using AOC3 as a myofibroblast-specific surface marker (Chapter 5). Analysis of whole genome microarray mRNA expression profiles between myofibroblasts and fibroblasts revealed 4 candidate genes that were the most significantly differentially expressed in the two cell types; NKX2.3 and LRRC17 are highly expressed in myofibroblasts, while SHOX2 and TBX5 are highly expressed in fibroblasts (Chapter 6). NKX2.3 is essential for TGFβ-induced myofibroblast contraction and migration ability. Knockdown of NKX2.3 using siRNA caused a decrease of myofibroblast-related gene (ACTA2, MYH11 and AOC3) expression and an increased expression of fibroblast gene, SHOX2 in myofibroblasts. This suggests that NKX2.3 is a key mediator for maintaining myofibroblast characteristics and functions. Our work presented here shows that myofibroblasts and fibroblasts have significantly different expression profiles for a few key genes and that they differ in their response to TGFβ. In conclusion, the results clearly show that TGFβ activated fibroblasts and myofibroblasts, as defined by the expression of AOC3 and NKX2.3, are distinctly different cell types.</p

Facial Skincare Products’ Recommendation with Computer Vision Technologies

Acne is a skin issue that plagues many young people and adults. Even if it is cured, it leaves acne spots or acne scars, which drives many individuals to use skincare products or undertake medical treatment. On the contrary, the use of inappropriate skincare products can exacerbate the condition of the skin. In view of this, this work proposes the use of computer vision (CV) technology to realize a new business model of facial skincare products. The overall framework is composed of a finger vein identification system, skincare products’ recommendation system, and electronic payment system. A finger vein identification system is used as identity verification and personalized service. A skincare products’ recommendation system provides consumers with professional skin analysis through skin type classification and acne detection to recommend skincare products that finally improve skin issues of consumers. An electronic payment system provides a variety of checkout methods, and the system will check out by finger-vein connections according to membership information. Experimental results showed that the equal error rate (EER) comparison of the FV-USM public database on the finger-vein system was the lowest and the response time was the shortest. Additionally, the comparison of the skin type classification accuracy was the highest

The Antioxidant Status and Concentrations of Coenzyme Q10 and Vitamin E in Metabolic Syndrome

The purpose of this study was to investigate the levels of coenzyme Q10 and vitamin E and the antioxidant status in subjects with metabolic syndrome (MS). Subjects with MS (n=72) were included according to the criteria for MS. The non-MS group (n=105) was comprised of healthy individuals with normal blood biochemical values. The plasma coenzyme Q10, vitamin E concentrations, lipid profiles, and antioxidant enzymes levels (catalase, superoxide dismutase, and glutathione peroxidase) were measured. The subjects with MS had significantly higher concentrations of plasma coenzyme Q10 and vitamin E than those in the non-MS group, but these differences were not significant after being normalized for triglyceride level. The levels of antioxidant enzymes were significantly lower in the MS group than in the non-MS group. The subjects with the higher antioxidant enzymes activities had significant reductions in the risk of MS (P<0.01) after being adjusted for coenzyme Q10 and vitamin E. In conclusion, the subjects with MS might be under higher oxidative stress resulting in low levels of antioxidant enzyme activities. A higher level of antioxidant enzymes activities was significantly associated with a reduction in the risk of MS independent of the levels of coenzyme Q10 and vitamin E

γ-glutamyl transpeptidase in men and alanine aminotransferase in women are the most suitable parameters among liver function tests for the prediction of metabolic syndrome in nonviral hepatitis and nonfatty liver in the elderly

Background/Aims: Nonalchoholic fatty liver disease (NAFLD) has been reported as a hepatic manifestation of metabolic syndrome (MetS); it is common and accounts for 80% of the cases with abnormal liver function tests (LFTs). In addition, several studies have proved that there is a correlation between abnormal LFTs and MetS. Therefore, LFTs may represent the abnormal metabolic status of livers in the patients with MetS. To identify the early state of metabolic dysfunction, we investigate the value of LFTs for the future MetS development in the relatively healthy (non-NAFLD) elderly. Patients and Methods: A total of 16,912 subjects met the criteria for analysis. In the first stage of this study, subjects were enrolled in the cross-sectional study in order to find out the optimal cutoff value in different LFTs with higher chances to have MetS. In the second stage of the present study, subjects with MetS at baseline were excluded from the same study group, and a median 5.6-year longitudinal study was conducted on the rest of the group. Results: Among all LFTs, only aspartate aminotransferase in both genders and the α-fetal protein in women failed to show the significance in distinguishing subjects with MetS by the receiver operating characteristic curve. In the Kaplan-Meier plot, only γ-glutamyl transpeptidase (γ-GT) in men and the alanine aminotransferase (ALT) in women could be used to successfully separate subjects with higher risk of developing the MetS from those with lower risk. Finally, in the multivariant Cox regression model, similar results were identified. Still, the hazard ratio (HR) to have future MetS, γ-GT in men, and ALT in women showed significance (HR = 1.511 in men and 1.504 in women). Conclusion: Among all the different LFTs, γ-GT (>16 U/L) in male and ALT (>21 U/L) in female were the best predictors for the development of MetS in healthy elderly. These two liver markers could be an ancillary test in predicting future MetS development/diagnosis. Elevation of the LFTs without underlying liver diseases should be treated as a warning sign of the possible MetS development in the elderly

Computer-Aided Planning in Orthognathic Surgery: A Comparative Study with the Establishment of Burstone Analysis-Derived 3D Norms

Three-dimensional (3D) computer-aided simulation has revolutionized orthognathic surgery treatment, but scarce 3D cephalometric norms have been defined to date. The purposes of this study were to (1) establish a normative database of 3D Burstone cephalometric measurements for adult male and female Chinese in Taiwan, (2) compare this 3D norm dataset with the two-dimensional (2D) Burstone norms from Caucasian and Singaporean Chinese populations, and (3) apply these 3D norms to assess the outcome of a computer-aided simulation of orthognathic surgery. Three-dimensional Burstone cephalometric analysis was performed on 3D digital craniofacial image models generated from cone-beam computed tomography datasets of 60 adult Taiwanese Chinese individuals with normal occlusion and balanced facial profile. Three-dimensional Burstone analysis was performed on 3D image datasets from patients with skeletal Class III pattern (n = 30) with prior computer-aided simulation. Three-dimensional Burstone cephalometric measurements showed that Taiwanese Chinese males had significantly (p &lt; 0.05) larger anterior and posterior facial heights, maxillary length, and mandibular ramus height than females, with no significant (p &gt; 0.05) difference for facial soft-tissue parameters. The 3D norm dataset revealed Taiwanese Chinese-specific facial characteristics, with Taiwanese presenting (p &lt; 0.05) a more convex profile, protrusive maxillary apical bases, protruding mandible, protruding upper and lower lips, and a shorter maxillary length and lower facial height than Caucasians. Taiwanese had significantly (p &lt; 0.05) larger maxillary projection, vertical height ratio, lower face throat angle, nasolabial angle, and upper lip protrusion than Singaporean Chinese. No significant (p &gt; 0.05) difference was observed between 3D norms and computer-aided simulation-derived 3D patient images for horizontal skeletal, vertical skeletal, and dental measurements, with the exception of two dental parameters (p &lt; 0.05). This study contributes to literature by providing gender- and ethnic-specific 3D Burstone cephalometric norms, which can assist in the multidisciplinary-based delivery of orthodontic surgical care for Taiwanese Chinese individuals worldwide, including orthodontic management, computer-assisted simulation, and outcome assessment

Adlay (<i>Coix lachryma-jobi</i> L. var. <i>ma-yuen</i> Stapf.) Hull Extract and Active Compounds Inhibit Proliferation of Primary Human Leiomyoma Cells and Protect against Sexual Hormone-Induced Mice Smooth Muscle Hyperproliferation

Uterine leiomyomas, also known as fibroids, are benign neoplasms of the uterus and have a high incidence rate in women of reproductive age. Hysterectomy or myomectomy is the initial treatment, but fibroids will recur if the patient is still exposed to similar risk factors. Therefore, developing new therapeutic strategies are urgently necessary. In this study, the anti-proliferation effects of each fraction of adlay seeds were evaluated in uterine leiomyomas, and we identified the potential phytochemical compounds. We found that the ethyl acetate fraction of adlay hull (AHE-ea) appeared to be highly efficient in the anti-proliferation of rat uterine leiomyoma ELT3 cells and primary human uterine leiomyoma (hUL) cells. The proliferation of primary human normal uterine smooth muscle (UtSMC) and normal uterine myometrial (hUM) cells were also suppressed by AHE-ea. Two phytosterols, stigmasterol and &#946;-sitosterol, were identified from AHE-ea fraction. Mice treated with AHE-ea and stigmasterol alone demonstrated reduced diethylstilbestrol/medroxyprogesterone 17-acetate (DES/MPA)-induced uterine myometrial hyperplasia, which is the critical step for the development of leiomyoma. Taken together, our results suggest that the AHE-ea fraction could be considered as a natural plant-based medicine in the prevention or treatment of uterine leiomyoma growth

Myricetin as a promising inhibitor of platelet fibrinogen receptor in humans

Platelets play a vital role in the formation of dangerous arterial thrombosis. Platelets are activated by adhesive proteins or soluble agonists through their specific receptors. The receptor-mediated signaling pathways lead to common signaling events, which result in shape changes and inside–out signaling, leading fibrinogen binding to glycoprotein IIb/IIIa complex (integrin αIIbβ3). This interaction initiates integrin αIIbβ3-mediated outside-in signaling, subsequently culminating in granule secretion and aggregation. Myricetin is a flavonoid that occurs in a variety of plants. Although myricetin has been demonstrated to have several bioactive properties, its role in platelet activation has not been extensively studied. The present study demonstrated the ability of myricetin to inhibit platelet aggregation stimulated by collagen, thrombin, and U46619. Myricetin reduced the ATP-release, cytosolic Ca2+ mobilization, and P-selectin expression and the activation of PLCγ2/PKC, PI3K/Akt/GSK3β, and MAPK. Myricetin exerted a direct inhibitory effect on the activation of integrin αIIbβ3 by disrupting the binding between FITC-PAC-1 and the integrin. Moreover, myricetin suppressed integrin αIIbβ3-mediated outside–in signaling, such as integrin β3, Src, and Syk phosphorylation on immobilized fibrinogen. In animal studies, myricetin significantly prolonged the occlusion time of thrombotic platelet plug formation in mesenteric microvessels without extending bleeding time. This study concludes that myricetin is a natural integrin αIIbβ3 inhibitor and a novel antithrombotic agent

One-Jaw versus Two-Jaw Orthognathic Surgery for Patients with Cleft: A Comparative Study Using 3D Imaging Virtual Surgical Planning

Whether a one-jaw or two-jaw design is used in orthognathic surgery for patients with cleft remains varied and controversial. This study aimed to compare the two approaches using 3-dimensional imaging surgical simulation. This study was conducted on 41 consecutive patients with complete unilateral cleft lip and palate treated in the craniofacial center. All patients had original two-jaw virtual planning and orthognathic surgery. Simulation of one-jaw LeFort I surgery was performed using the same final dental occlusion on 3-dimensional images. Cephalometric data and asymmetry index were collected and compared among the designs. Average advancement of the maxilla was 7.46 mm in one-jaw and 4.80 mm in two-jaw design. SNA, SNB, and A-N perpendicular were significantly greater and close to normative data in the one-jaw design. ANB angles were similar in both designs. The anterior and posterior occlusal plane cants, the deviation of midline landmarks, and the asymmetry index were more improved in the two-jaw approach. It is concluded that the two-jaw cleft orthognathic surgery could significantly improve facial midline and symmetry compared with the one-jaw approach. However, the two-jaw surgery with mandibular setback produced less protrusive facial contour although a harmonious relationship between the maxilla and mandible was achieved