JMJD6 Autoantibodies as a Potential Biomarker for Inflammation-Related Diseases.

Inflammation is closely associated with cerebrovascular diseases, cardiovascular diseases, diabetes, and cancers, and it is accompanied by the development of autoantibodies in the early stage of inflammation-related diseases. Hence, it is meaningful to discover novel antibody biomarkers targeting inflammation-related diseases. In this study, Jumonji C-domain-containing 6 (JMJD6) was identified by the serological identification of antigens through recombinant cDNA expression cloning. In particular, JMJD6 is an antigen recognized in serum IgG from patients with unstable angina pectoris (a cardiovascular disease). Then, the serum antibody levels were examined using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay and a purified recombinant JMJD6 protein as an antigen. We observed elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with inflammation-related diseases such as ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers (including esophageal cancer, EC; gastric cancer; lung cancer; and mammary cancer), compared with the levels in healthy donors. The s-JMJD6-Ab levels were closely associated with some inflammation indicators, such as C-reactive protein and intima-media thickness (an atherosclerosis index). A better postoperative survival status of patients with EC was observed in the JMJD6-Ab-positive group than in the negative group. An immunohistochemical analysis showed that JMJD6 was highly expressed in the inflamed mucosa of esophageal tissues, esophageal carcinoma tissues, and atherosclerotic plaques. Hence, JMJD6 autoantibodies may reflect inflammation, thereby serving as a potential biomarker for diagnosing specific inflammation-related diseases, including stroke, AMI, DM, and cancers, and for prediction of the prognosis in patients with EC.

Stage-Specific Alteration and Prognostic Relationship of Serum Fumarate Hydratase Autoantibodies in Gastric Cancer.

The relationship between energy production and cancer is attracting attention. This study aimed to investigate the clinicopathological significance of fumarate hydratase (FH), a tricarboxylic acid cycle enzyme, in gastric cancer using autoantibodies as biomarkers. The study analyzed 116 patients who underwent gastric cancer surgery and 96 healthy controls. Preoperative serum FH autoantibody (s-FH-Ab) titers were analyzed using an immunosorbent assay with an amplified luminescent proximity homogeneous assay. Receiver operating characteristic analysis was used to determine the cutoff s-FH-Ab titer. Clinicopathological factors and prognosis were compared between the high and low s-FH-Ab groups. The s-FH-Ab levels were significantly higher in the gastric cancer group than in the control group (p = 0.01). Levels were elevated even in patients with stage I gastric cancer compared with healthy controls (p = 0.02). A low s-FH-Ab level was significantly associated with distant metastasis (p = 0.01), peritoneal dissemination (p < 0.05), and poor overall survival (p < 0.01). Multivariate analysis revealed that low s-FH-Ab levels were an independent risk factor for poor prognosis (p < 0.01). Therefore, s-FH-Ab levels may be a useful biomarker for early diagnosis and the prediction of prognosis in patients with gastric cancer.

Combination of high anti-SKI and low anti-TMED5 antibody levels is preferable prognostic factor in esophageal carcinoma.

Given that esophageal cancer is highly malignant, the discovery of novel prognostic markers is eagerly awaited. We performed serological identification of antigens by recombinant cDNA expression cloning (SEREX) and identified SKI proto-oncogene protein and transmembrane p24 trafficking protein 5 (TMED5) as antigens recognized by serum IgG antibodies in patients with esophageal carcinoma. SKI and TMED5 proteins were expressed in Escherichia coli, purified by affinity chromatography, and used as antigens. The serum anti-SKI antibody (s-SKI-Ab) and anti-TMED5 antibody (s-TMED5-Ab) levels were significantly higher in 192 patients with esophageal carcinoma than in 96 healthy donors. The presence of s-SKI-Abs and s-TMED5-Abs in the patients' sera was confirmed by western blotting. Immunohistochemical staining showed that the TMED5 protein was highly expressed in the cytoplasm and nuclear compartments of the esophageal squamous cell carcinoma tissues, whereas the SKI protein was localized predominantly in the nuclei. Regarding the overall survival in 91 patients who underwent radical surgery, the s-SKI-Ab-positive and s-TMED5-Ab-negative statuses were significantly associated with a favorable prognosis. Additionally, the combination of s-SKI-Ab-positive and s-TMED5-Ab-negative cases showed an even clearer difference in overall survival as compared with that of s-SKI-Ab-negative and s-TMED5-Ab-positive cases. The s-SKI-Ab and s-TMED5-Ab biomarkers are useful for diagnosing esophageal carcinoma and distinguishing between favorable and poor prognoses.

Breathing changes following mini-implant-supported maxillary skeletal expander treatment in late adolescent or adult patients : Assessment of objective and subjective functional breathing changes.

PURPOSE: The aim of this study was to assess objective and subjective breathing changes in adult patients who underwent maxillary skeletal expansion with the mini-implant-supported maxillary skeletal expander (MSE). METHODS: Twenty-nine patients (mean age 18.1 ± 4.3 years) who underwent expansion using the MSE were compared pre- and posttreatment and with a control group (mean age 19.9 ± 2.6 years) to assess objective and subjective functional breathing changes. Objective measurements of the airway including peak nasal inspiratory flow (PNIF) and peak oral inspiratory flow (POIF) were measured utilizing the In-Check medical device (Clement Clarke, Harlow, United Kingdom). Patients reported subjective breathing assessment utilizing the visual analog scale (VAS). Intragroup comparisons were performed with Wilcoxon tests and intergroup comparison with Mann-Whitney U tests. Spearman correlation coefficients were calculated among the studied variables (P < 0.05). RESULTS: Following MSE treatment, there were significantly higher values for PNIF total (P < 0.0001), PNIF right (P < 0.0001), PNIF left (P < 0.0001), and POIF (P < 0.01) compared to pretreatment and control group results. Also, patients reported a significant decrease in troubled breathing as measured by the VAS for breathing through the right nostril (P < 0.01), left nostril (P < 0.001), and both nostrils (P < 0.01). Comparing the objective and subjective variables for both the pre-MSE or post-MSE groups, the results indicated no significant correlation between total PNIF and total VAS. However, the values had significant correlations between PNIF and VAS on each side when the patients were asked to block one nostril. CONCLUSIONS: Objective functional breathing measurements were increased immediately after treatment with MSE. Subjective functional breathing measurements changes were significantly higher after MSE treatment and compared with the control group. MSE presents a nonsurgical alternative to achieving orthopedic expansion in adult patients which may provide a benefit for patients with nasal airway obstruction.

Long-term effects of maxillary skeletal expander treatment on functional breathing.

Objective: : To investigate the long-term effects of maxillary skeletal expander (MSE) treatment on functional breathing. Objective: measures of breathing, the peak nasal inspiratory flow (PNIF), and peak oral inspiratory flow (POIF), and subjective measures of breathing, the visual analog scale (VAS) and nasal obstruction symptom evaluation (NOSE) survey, were used to investigate the long-term effects of MSE in functional breathing. Seventeen patients, mean age 19.4 ± 3.9 years treated at the UCLA Orthodontics Clinic were assessed on their functional breathing at 3 timepoints: pre-expansion (T0), post-expansion (T1), and post-orthodontic treatment (T2). Results: : Immediately after expansion (T1), all the objective functional breathing values were significantly increased in comparison to T0 (P < 0.05). The VAS total, VAS right and VAS left were significantly lower at T1 in comparison to T0 (P < 0.05). At 26.8 ± 3.9 months after MSE expansion (T2), PNIF total, PNIF right, PNIF left, and POIF were significantly higher when compared to T0 (P < 0.05). Also, VAS total, VAS right and VAS left were significantly lower at T2 when compared to T0 (P < 0.05). Additionally, there was a positive correlation between PNIF and the magnitude of expansion at anterior nasal spine and zygomaticomaxillary point (ZMA). There was a positive correlation between total VAS and the magnitude of expansion at the ZMA. There were no significant changes for the NOSE subjective breathing measurement at all time comparisons. Conclusions: : Overall, MSE treatment produces an increased objective and subjective airway improvement that continues to remain stable in the long-term post expansion.

Serum anti-PCK1 antibody levels are a prognostic factor for patients with diabetes mellitus.

BACKGROUND: Autoantibodies develop in autoimmune diseases, cancer, diabetes mellitus (DM), and atherosclerosis-related diseases. However, autoantibody biomarkers have not been successfully examined for diagnosis and therapy. METHODS: Serological identification of antigens through recombinant cDNA expression cloning (SEREX) was used for primary screening of antigens. The cDNA product was expressed in bacteria and purified. Amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) was used to evaluate antibody levels in serum samples. RESULTS: Phosphoenolpyruvate carboxykinase 1 (PCK1) was recognized as an antigen by serum IgG antibodies in the sera of patients with atherosclerosis. AlphaLISA showed significantly higher serum antibody levels against recombinant PCK1 protein in patients with DM and cardiovascular disease than in healthy donors, but not in those with acute ischemic stroke, transient ischemic attack, or obstructive sleep apnea syndrome. The area under the receiver operating characteristic curve for anti-PCK1 antibodies was 0.7024 for DM. The serum anti-PCK1 antibody levels were associated with age, platelet count, and blood pressure. Anti-PCK1-antibody-positive patients showed significantly lower overall survival than the negative patients. CONCLUSIONS: Serum anti-PCK1 antibody levels were found to be associated with DM. The anti-PCK1 antibody marker is useful for predicting the overall survival of patients with DM.

Prognostic and diagnostic significance of preoperative Jumonji domain­containing 6 antibodies in colorectal cancer.

Jumonji domain-containing 6 (JMJD6) protein has been reported to be upregulated in different cancer cells; however, to the best of our knowledge, no report has analyzed serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with cancer. Therefore, the present study evaluated the clinical significance of s-JMJD6-Abs in patients with colorectal cancer. Preoperative serum samples were analyzed from 167 patients with colorectal cancer who underwent radical surgery between April 2007 and May 2012. The pathological stages were as follows Stage I (n=47), stage II (n=56), stage III (n=49) and stage IV (n=15). In addition, 96 healthy participants were analyzed as controls. s-JMJD6-Abs were analyzed by amplified luminescent proximity homology assay-linked immunosorbent assay. The cutoff value of s-JMJD6-Abs for detecting colorectal cancer was calculated to be 5,720 using the receiver operating characteristic curve. The positive rate of s-JMJD6-Abs was 37% in patients with colorectal cancer (61 of 167), independent of carcinoembryonic antigen or carbohydrate antigen 19-9 and p53-Abs. Clinicopathological factors and prognosis were compared between the s-JMJD6-Abs-positive group and the s-JMJD6-Abs-negative group. The s-JMJD6-Ab-positive status was significantly associated with older age (P=0.03), but was not associated with other clinicopathological variables. Regarding recurrence-free survival, the s-JMJD6-positive status was a significant poor prognostic factor in both univariate (P=0.02) and multivariate (P<0.01) analyses. Similarly, regarding overall survival, the s-JMJD6-Abs-positive status was a significant poor prognostic factor in both univariate (P=0.03) and multivariate (P=0.01) analyses. In conclusion, preoperative s-JMJD6-Abs was positive in 37% of patients with colorectal cancer and may be considered an independent poor prognostic biomarker.

Utility of atherosclerosis-associated serum antibodies against colony-stimulating factor 2 in predicting the onset of acute ischemic stroke and prognosis of colorectal cancer.

Introduction: Autoantibodies against inflammatory cytokines may be used for the prevention of atherosclerosis. Preclinical studies consider colony-stimulating factor 2 (CSF2) as an essential cytokine with a causal relationship to atherosclerosis and cancer. We examined the serum anti-CSF2 antibody levels in patients with atherosclerosis or solid cancer. Methods: We measured the serum anti-CSF2 antibody levels via amplified luminescent proximity homogeneous assay-linked immunosorbent assay based on the recognition of recombinant glutathione S-transferase-fused CSF2 protein or a CSF2-derived peptide as the antigen. Results: The serum anti-CSF2 antibody (s-CSF2-Ab) levels were significantly higher in patients with acute ischemic stroke (AIS), acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic kidney disease (CKD) compared with healthy donors (HDs). In addition, the s-CSF2-Ab levels were associated with intima-media thickness and hypertension. The analyzes of samples obtained from a Japan Public Health Center-based prospective study suggested the utility of s-CSF2-Ab as a risk factor for AIS. Furthermore, the s-CSF2-Ab levels were higher in patients with esophageal, colorectal, gastric, and lung cancer than in HDs but not in those with mammary cancer. In addition, the s-CSF2-Ab levels were associated with unfavorable postoperative prognosis in colorectal cancer (CRC). In CRC, the s-CSF2-Ab levels were more closely associated with poor prognosis in patients with p53-Ab-negative CRC despite the lack of significant association of the anti-p53 antibody (p53-Ab) levels with the overall survival. Conclusion: S-CSF2-Ab was useful for the diagnosis of atherosclerosis-related AIS, AMI, DM, and CKD and could discriminate poor prognosis, especially in p53-Ab-negative CRC.

Serum anti­TSTD2 antibody as a biomarker for atherosclerosis­induced ischemic stroke and chronic kidney disease.

Autoantibodies can be used in the early diagnosis and treatment of atherosclerosis-related diseases. Using ProtoArray® screening of samples from patients with atherosclerosis, the present study identified thiosulfate sulfurtransferase-like domain-containing 2 (TSTD2) as a novel atherosclerosis antigen. The serum TSTD2 antibody levels were then quantified using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay. This demonstrated the levels of TSTD2 antibodies (TSTD2-Abs) to be significantly higher in patients with acute cerebral infarction or chronic kidney disease than in healthy donors. The TSTD2-Ab levels were also found to be higher in males, older adults, smokers, in those who consumed alcohol regularly, and in those with hypertension. Furthermore, Spearman's rank correlation analysis revealed TSTD2-Ab levels to be strongly associated with measures of atherosclerosis severity, including plaque scores, intima-media thickness of the carotid artery and the cardio-ankle vascular index. Thus, TSTD2-Abs may thus be a promising novel biomarker for atherosclerosis-related cerebral infarction and kidney disease.

Analysis for global characteristics of Lyapunov exponents in vehicle plane motion system.

In the field of vehicle system dynamics, it is significant to propose an appropriate quantitative indicator for system stability or dynamics characteristics. Lyapunov exponents method is an excellent quantitative indicator for analysing nonlinear system characteristics. It was used to studied the stable region of nonlinear vehicle plane motion system. However, the effect of Lyapunov exponents method in revealing the global dynamics characteristics has not been fully studied. Aiming at this key problem, this paper analyses the global characteristics of Lyapunov exponents with different degrees of freedom nonlinear models. The results show that Lyapunov exponents can well reflect the global layer characteristics for vehicle system. However, the value characteristic under different DOF models is not unified. The research and analysis in this paper supplement the quantitative analysis theory for vehicle system dynamics.

Serum anti-SERPINE1 antibody as a potential biomarker of acute cerebral infarction.

The presence of disease-specific antigens and autoantibodies in the sera of patients with atherosclerosis-related diseases has been widely reported and is considered to result from inflammation of the arterial wall and the involvement of immune factors. The aim of this study was to identify a novel antibody in patients with ischemic stroke by serological identification of antigens using recombinant cDNA expression cloning from patients who had a transient ischemic attack (TIA). We identified the serpin peptidase inhibitor, clade E member 1 (SERPINE1), as a candidate antigen. The serum anti-SERPINE1 antibody levels quantified using amplified luminescent proximity homogeneous assay-linked immunosorbent assay were significantly higher in patients with ischemic stroke, including those with acute cerebral infarction (aCI), TIA, and chronic cerebral infarction, than in healthy donors. The antibody levels were strongly associated with old age, female sex, and presence of hypertension, diabetes mellitus, and cardiovascular disease. Age and intima-media thickness of the carotid artery were positively correlated with antibody levels, which suggests that SERPINE1 may reflect the progression of atherosclerosis. In a multivariate analysis, SERPINE1 antibody level was an independent predictor of aCI. Thus, the serum levels of anti-SERPINE1 antibody could potentially serve as a biomarker of atherothrombotic infarction.

Differential assessment of skeletal, alveolar, and dental components induced by microimplant-supported midfacial skeletal expander (MSE), utilizing novel angular measurements from the fulcrum.

BACKGROUND: In order to assess skeletal expansion, alveolar bone bending, and dental tipping after maxillary expansion, linear and angular measurements have been performed utilizing different craniofacial references. Since the expansion with midfacial skeletal expander (MSE) is archial in nature, the aim of this paper is to quantify the differential components of MSE expansion by calculating the fulcrum locations and applying a novel angular measurement system. METHODS: Thirty-nine subjects with a mean age of 18.2 ± 4.2 years were treated with MSE. Pre- and post-expansion CBCT records were superimposed and compared. The rotational fulcrum of the zygomaticomaxillary complex was identified by localizing the interfrontal distance and modified interfrontal distance. Based on the fulcrum, a novel angular measurement method is presented and compared with a conventional linear method to assess changes of the zygomaticomaxillary complex, dentoalveolar bone, and maxillary first molars. RESULTS: From 39 patients, 20 subjects have the rotational fulcrum of the zygomaticomaxillary complex at the most distant points of the interfrontal distance (101.6 ± 4.7 mm) and 19 subjects at the most distant points of the modified interfrontal distance (98.9 ± 5.7 mm). Linear measurements accounted for 60.16% and 56.83% of skeletal expansion, 16.15% and 16.55% of alveolar bone bending, and 23.69% and 26.62% of dental tipping for right and left side. Angular measurements showed 96.58% and 95.44% of skeletal expansion, 0.34% and 0.33% alveolar bone bending, and 3.08% and 4.23% of dental tipping for the right and left sides. The frontozygomatic, frontoalveolar, and frontodental angles were not significant different (P > 0.05). CONCLUSIONS: In the coronal plane, the center of rotation for the zygomaticomaxillary complex was located at the most external and inferior point of the zygomatic process of the frontal bone or slightly above and parallel to the interfrontal distance. Due to the rotational displacement of the zygomaticomaxillary complex, angular measurements should be a preferred method for assessing the expansion effects, instead of the traditional linear measurement method.

Matrix Metalloproteinase 13 from Satellite Cells is Required for Efficient Muscle Growth and Regeneration.

BACKGROUND/AIMS: Cell migration and extracellular matrix remodeling underlie normal mammalian development and growth as well as pathologic tumor invasion. Skeletal muscle is no exception, where satellite cell migration replenishes nuclear content in damaged tissue and extracellular matrix reforms during regeneration. A key set of enzymes that regulate these processes are matrix metalloproteinases (MMP)s. The collagenase MMP-13 is transiently upregulated during muscle regeneration, but its contribution to damage resolution is unknown. The purpose of this work was to examine the importance of MMP-13 in muscle regeneration and growth in vivo and to delineate a satellite cell specific role for this collagenase. METHODS: Mice with total and satellite cell specific Mmp13 deletion were utilized to determine the importance of MMP-13 for postnatal growth, regeneration after acute injury, and in chronic injury from a genetic cross with dystrophic (mdx) mice. We also evaluated insulin-like growth factor 1 (IGF-1) mediated hypertrophy in the presence and absence of MMP-13. We employed live-cell imaging and 3D migration measurements on primary myoblasts obtained from these animals. Outcome measures included muscle morphology and function. RESULTS: Under basal conditions, Mmp13-/- mice did not exhibit histological or functional deficits in muscle. However, following acute injury, regeneration was impaired at 11 and 14 days post injury. Muscle hypertrophy caused by increased IGF-1 was blunted with minimal satellite cell incorporation in the absence of MMP-13. Mmp13-/- primary myoblasts displayed reduced migratory capacity in 2D and 3D, while maintaining normal proliferation and differentiation. Satellite cell specific deletion of MMP-13 recapitulated the effects of global MMP-13 ablation on muscle regeneration, growth and myoblast movement. CONCLUSION: These results show that satellite cells provide an essential autocrine source of MMP-13, which not only regulates their migration, but also supports postnatal growth and resolution of acute damage.

Herbal Medicine in the Mitigation of Reactive Oxygen Species, Autophagy, and Cancer: A Review.

Since the discovery of autophagy in the mid-2000s, the interest in autophagy-related processes within the scientific community has been burgeoning. Countless authors have investigated its function in cellular homeostasis, but arguably of higher importance is its role during pathology. Although primarily a catabolic process, in cancer cells autophagy has numerous downstream effects, being observed to be both pro- and anti-apoptotic. One of the primary factors mediating this differential role of autophagy is the accumulation or sequestration of reactive oxygen species (ROS). Until recently, despite its increasing popularity in the Western world, the efficacy of herbal supplements has been largely anecdotal. Herein, we reviewed the ten most commonly studied herbs in cancer research and their impact on ROS regulation, on the activation and inhibition of autophagy, and ultimately on cancer cell death.

Prescription Opioid Abuse and its Potential Role in Gross Dental Decay.

INTRODUCTION: Prescription opioid abuse may have adverse dental effects that are irreversible, leaving younger populations with substantially decayed dentitions. This article explores the damaging effects of three years of prescription opioid abuse to a twenty-six-year-old's dentition and oral health. CASE PRESENTATION: A twenty-six-year-old Caucasian male presented to the University of Pennsylvania School of Dental Medicine with a past medical history of Percocet® abuse. He was consuming approximately twenty tablets per day for three years, and he had neglected to visit a dentist for over five years before arriving to the School of Dental Medicine. Management and Outcome: Intraoral examination revealed gross generalized decay along with generalized plaque accumulation. He was diagnosed with severe plaque induced gingivitis with localized chronic periodontitis and xerostomia. The dental treatment for this patient included periodontal maintenance and control, caries excavation, root canal therapy, extractions of non-restorable teeth, and continuous dental education. DISCUSSION: Prescription opioids are addictive, have high abuse potential, and dentists contribute to this problem by overprescribing these drugs.