Identification of biomarkers for periodontal disease using the immunoproteomics approach

BackgroundPeriodontitis is one of the most common oral diseases associated with the host’s immune response against periodontopathogenic infection. Failure to accurately diagnose the stage of periodontitis has limited the ability to predict disease status. Therefore, we aimed to look for reliable diagnostic markers for detection or differentiation of early stage periodontitis using the immunoprotemic approach.MethodIn the present study, patient serum samples from four distinct stages of periodontitis (i.e., mild chronic, moderate chronic, severe chronic, and aggressive) and healthy controls were subjected to two-dimensional gel electrophoresis (2-DE), followed by silver staining. Notably, we consistently identified 14 protein clusters in the sera of patients and normal controls.ResultsOverall, we found that protein levels were comparable between patients and controls, with the exception of the clusters corresponding to A1AT, HP, IGKC and KNG1 (p < 0.05). In addition, the immunogenicity of these proteins was analysed via immunoblotting, which revealed differential profiles for periodontal disease and controls. For this reason, IgM obtained from severe chronic periodontitis (CP) sera could be employed as a suitable autoantibody for the detection of periodontitis.DiscussionTaken together, the present study suggests that differentially expressed host immune response proteins could be used as potential biomarkers for screening periodontitis. Future studies exploring the diagnostic potential of such factors are warranted.

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Evaluation of Diagnostic Potential of Epigenetically Deregulated MiRNAs in Epithelial Ovarian Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.681872 ◽

2021 ◽

Vol 11 ◽

Author(s):

Vivek Kumar ◽

Sameer Gupta ◽

Amrita Chaurasia ◽

Manisha Sachan

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cancer Progression ◽

Early Stage ◽

Ovarian Tissue ◽

Characteristic Curve ◽

Mirna Gene ◽

Serum Samples ◽

Cancer Management ◽

Diagnostic Potential

BackgroundEpithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies among women worldwide. Early diagnosis of EOC could help in ovarian cancer management. MicroRNAs, a class of small non-coding RNA molecules, are known to be involved in post-transcriptional regulation of ~60% of human genes. Aberrantly expressed miRNAs associated with disease progression are confined in lipid or lipoprotein and secreted as extracellular miRNA in body fluid such as plasma, serum, and urine. MiRNAs are stably present in the circulation and recently have gained an importance to serve as a minimally invasive biomarker for early detection of epithelial ovarian cancer.MethodsGenome-wide methylation pattern of six EOC and two normal ovarian tissue samples revealed differential methylation regions of miRNA gene promoter through MeDIP-NGS sequencing. Based on log2FC and p-value, three hypomethylated miRNAs (miR-205, miR-200c, and miR-141) known to have a potential role in ovarian cancer progression were selected for expression analysis through qRT-PCR. The expression of selected miRNAs was analyzed in 115 tissue (85 EOC, 30 normal) and 65 matched serum (51 EOC and 14 normal) samples.ResultsAll three miRNAs (miR-205, miR-200c, and miR-141) showed significantly higher expression in both tissue and serum cohorts when compared with normal controls (p < 0.0001). The receiver operating characteristic curve analysis of miR-205, miR-200c, and miR-141 has area under the curve (AUC) values of 87.6 (p < 0.0001), 78.2 (p < 0.0001), and 86.0 (p < 0.0001), respectively; in advance-stage serum samples, however, ROC has AUC values of 88.1 (p < 0.0001), 78.9 (p < 0.0001), and 86.7 (p < 0.0001), respectively, in early-stage serum samples. The combined diagnostic potential of the three miRNAs in advance-stage serum samples and early-stage serum samples has AUC values of 95.9 (95% CI: 0.925–1.012; sensitivity = 96.6% and specificity = 80.0%) and 98.1 (95% CI: 0.941–1.021; sensitivity = 90.5% and specificity = 100%), respectively.ConclusionOur data correlate the epigenetic deregulation of the miRNA genes with their expression. In addition, the miRNA panel (miR-205 + miR-200c + miR-141) has a much higher AUC, sensitivity, and specificity to predict EOC at an early stage in both tissue and serum samples.

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A Review of Oxidative Stress Products and Related Genes in Early Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-210497 ◽

2021 ◽

pp. 1-25

Author(s):

Federica Cioffi ◽

Rayan Hassan Ibrahim Adam ◽

Ruchi Bansal ◽

Kerensa Broersen

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Mechanisms ◽

Early Stage ◽

Disease Status ◽

Diagnostic Value ◽

Oxidation Products ◽

Protein Levels ◽

Stress Levels

Oxidative stress is associated with the progression of Alzheimer’s disease (AD). Reactive oxygen species can modify lipids, DNA, RNA, and proteins in the brain. The products of their peroxidation and oxidation are readily detectable at incipient stages of disease. Based on these oxidation products, various biomarker-based strategies have been developed to identify oxidative stress levels in AD. Known oxidative stress-related biomarkers include lipid peroxidation products F2-isoprostanes, as well as malondialdehyde and 4-hydroxynonenal which both conjugate to specific amino acids to modify proteins, and DNA or RNA oxidation products 8-hydroxy-2’-deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8-OHG), respectively. The inducible enzyme heme oxygenase type 1 (HO-1) is found to be upregulated in response to oxidative stress-related events in the AD brain. While these global biomarkers for oxidative stress are associated with early-stage AD, they generally poorly differentiate from other neurodegenerative disorders that also coincide with oxidative stress. Redox proteomics approaches provided specificity of oxidative stress-associated biomarkers to AD pathology by the identification of oxidatively damaged pathology-specific proteins. In this review, we discuss the potential combined diagnostic value of these reported biomarkers in the context of AD and discuss eight oxidative stress-related mRNA biomarkers in AD that we newly identified using a transcriptomics approach. We review these genes in the context of their reported involvement in oxidative stress regulation and specificity for AD. Further research is warranted to establish the protein levels and their functionalities as well as the molecular mechanisms by which these potential biomarkers are involved in regulation of oxidative stress levels and their potential for determination of oxidative stress and disease status of AD patients.

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The Thomsen-Friedenreich Antigen-Specific Antibody Signatures in Patients with Breast Cancer

BioMed Research International ◽

10.1155/2018/9579828 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Oleg Kurtenkov ◽

Kaire Innos ◽

Boris Sergejev ◽

Kersti Klaamas

Keyword(s):

Breast Cancer ◽

Sialic Acid ◽

Specific Antibody ◽

Early Stage ◽

Ammonium Thiocyanate ◽

Sambucus Nigra ◽

Serum Samples ◽

Naturally Occurring ◽

Diagnostic Potential ◽

Antibody Isotypes

Alterations in the glycosylation of serum total immunoglobulins show these antibodies to have a diagnostic potential for cancer but the disease-related Abs to the tumor-associated antigens, including glycans, have still poorly been investigated in this respect. We analysed serum samples from patients with breast carcinoma (n = 196) and controls (n = 64) for the level of Thomsen-Friedenreich (TF) antigen-specific antibody isotypes, their sialylation, interrelationships, and the avidity by using ELISA with the synthetic TF-polyacrylamide conjugate as an antigen and the sialic acid-specificSambucus nigraagglutinin (SNA) and ammonium thiocyanate as a chaotrope. An increased sialylation of IgG and IgM, but a lower SNA reactivity of IgA TF antibodies, and a higher level and avidity of the TF-specific IgA were found in cancer patients. Other cancer-related signatures were the highly significant increase of the IgG/IgA ratio and the very low SNA/IgA index in cancer, including patients with an early stage of the disease. These changes showed a good diagnostic potential with about 80% accuracy. Thus, the level of naturally occurring anti-TF antigen antibodies, their sialylation profile, isotype distribution, and avidity displayed cancer-specific changes that could serve as novel noninvasive Ab-based biomarkers for early breast cancer.

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PERIODONTAL DISEASE STATUS, KNOWLEDGE, ATTITUDE, PRACTICE AND TREATMENT NEEDS OF PREGNANT WOMEN

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2018.6.18 ◽

2018 ◽

Vol 8 (6) ◽

pp. 138-144

Author(s):

Thien Nguyen Duc ◽

Tai Tran Tan

Keyword(s):

Periodontal Disease ◽

Pregnant Women ◽

Oral Hygiene ◽

Disease Status ◽

Incidence Rates ◽

Gestation Period ◽

Treatment Needs ◽

Cross Sectional ◽

Mean Values ◽

The Mean

Background: Periodontal disease is a prominent and important issue of public health, especially in pregnant women. The objective of this study is to describe the clinical characteristics; learn knowledge, attitudes, practice oral hygiene and assess the need for treatment of periodontal disease in pregnant women. Subjects and Methods: A cross-sectional study of 210 pregnant women who visited the Department of Obstetrics and Gynecology at the Hue University of Medicine and Pharmacy Hospital. Clinical examination and interview questions on knowledge, attitudes and practice of oral care for all subjects. Results: The incidence of gingivitis was 100%, with mild gingivitis of 4,3% and moderate gingivitis of 95.7%. There was a difference in incidence rates of gingivitis in the gestational period (p<0.001). The incidence of periodontitis is 17.6% and there is no difference in gestational age (p>0.05). The mean values of GI and BOP indices differed by gestation period (p<0.05) and PD, OHI-S, PlI have statistically significant relationship with gestation period (p>0.05). The incidence of periodontal disease is 80.5%; The percentage of pregnant women who abstain from brushing their teeth after birth is 61.4%. Prevalence of brushing once a day: 7.1%; Twice a day: 70.5% and 3 times daily: 22.4%; The mean values of GI, PD, BOP, OHI-S and PlI were inversely proportional to the number of brushing (p<0.001). The rate of dental hygiene is just 3.3%; The rate of oral hygiene, dental plaque and plaque removal was 94,3%; The proportion of subjects required for intensive treatment is 2.4%. Conclusion: Periodontal disease, especially for pregnant women, is high. It is necessary to educate the knowledge, attitudes and practice of proper oral hygiene and to better meet the demand for periodontal disease treatment for pregnant women. Key words: Periodontal disease, pregnant women, knowledge, attitude, practice for oral hygiene, treatment needs

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Fluoxetine Protects against Dendritic Spine Loss in Middle-aged APPswe/PSEN1dE9 Double Transgenic Alzheimer’s Disease Mice

Current Alzheimer Research ◽

10.2174/1567205017666200213095419 ◽

2020 ◽

Vol 17 (1) ◽

pp. 93-103 ◽

Cited By ~ 1

Author(s):

Jing Ma ◽

Yuan Gao ◽

Wei Tang ◽

Wei Huang ◽

Yong Tang

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Dendritic Spines ◽

Dendritic Spine ◽

Early Stage ◽

Learning Ability ◽

Middle Aged ◽

Protein Levels ◽

Spine Pathology ◽

The Impact

Background: Studies have suggested that cognitive impairment in Alzheimer’s disease (AD) is associated with dendritic spine loss, especially in the hippocampus. Fluoxetine (FLX) has been shown to improve cognition in the early stage of AD and to be associated with diminishing synapse degeneration in the hippocampus. However, little is known about whether FLX affects the pathogenesis of AD in the middle-tolate stage and whether its effects are correlated with the amelioration of hippocampal dendritic dysfunction. Previously, it has been observed that FLX improves the spatial learning ability of middleaged APP/PS1 mice. Objective: In the present study, we further characterized the impact of FLX on dendritic spines in the hippocampus of middle-aged APP/PS1 mice. Results: It has been found that the numbers of dendritic spines in dentate gyrus (DG), CA1 and CA2/3 of hippocampus were significantly increased by FLX. Meanwhile, FLX effectively attenuated hyperphosphorylation of tau at Ser396 and elevated protein levels of postsynaptic density 95 (PSD-95) and synapsin-1 (SYN-1) in the hippocampus. Conclusion: These results indicated that the enhanced learning ability observed in FLX-treated middle-aged APP/PS1 mice might be associated with remarkable mitigation of hippocampal dendritic spine pathology by FLX and suggested that FLX might be explored as a new strategy for therapy of AD in the middle-to-late stage.

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Vaccination strategy and anti - SARS-CoV-2 S titers in healthcare workers of the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy)

Infectious Agents and Cancer ◽

10.1186/s13027-021-00375-2 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Ernesta Cavalcanti ◽

Maria Antonietta Isgrò ◽

Domenica Rea ◽

Lucia Di Capua ◽

Giusy Trillò ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Healthcare Workers ◽

Geometric Mean ◽

Vaccination Strategy ◽

Antibody Responses ◽

Cancer Center ◽

Serum Samples ◽

Humoral Immune ◽

History Of

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously infected to SARS-CoV-2 subjects and not infected to SARS-CoV-2 subjects. Methods We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated. Results Both previously infected and not infected to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-infected subjects in comparison to titers of not infected subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously infected to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ($$ \overline{x} $$ x ¯ =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose. Conclusions The results showed that, as early as the first dose, SARS-CoV-2-infected individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-infected subjects. FC for previously infected subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not infected subjects, after the second dose, were = 3.8 in > 45.0% of vaccinees, and ≤ 3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.

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The APAC Score: A Novel and Highly Performant Serological Tool for Early Diagnosis of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

Journal of Clinical Medicine ◽

10.3390/jcm10153392 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3392

Author(s):

Joeri Lambrecht ◽

Mustafa Porsch-Özçürümez ◽

Jan Best ◽

Fabian Jost-Brinkmann ◽

Christoph Roderburg ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

At Risk ◽

Liver Cirrhosis ◽

Early Stage ◽

Treatment Options ◽

Growth Factor Receptor ◽

Serum Samples ◽

Disease Etiology ◽

Risk Patients ◽

Scoring Tool

(1) Background: Surveillance of at-risk patients for hepatocellular carcinoma (HCC) is highly necessary, as curative treatment options are only feasible in early disease stages. However, to date, screening of patients with liver cirrhosis for HCC mostly relies on suboptimal ultrasound-mediated evaluation and α-fetoprotein (AFP) measurement. Therefore, we sought to develop a novel and blood-based scoring tool for the identification of early-stage HCC. (2) Methods: Serum samples from 267 patients with liver cirrhosis, including 122 patients with HCC and 145 without, were collected. Expression levels of soluble platelet-derived growth factor receptor beta (sPDGFRβ) and routine clinical parameters were evaluated, and then utilized in logistic regression analysis. (3) Results: We developed a novel serological scoring tool, the APAC score, consisting of the parameters age, sPDGFRβ, AFP, and creatinine, which identified patients with HCC in a cirrhotic population with an AUC of 0.9503, which was significantly better than the GALAD score (AUC: 0.9000, p = 0.0031). Moreover, the diagnostic accuracy of the APAC score was independent of disease etiology, including alcohol (AUC: 0.9317), viral infection (AUC: 0.9561), and NAFLD (AUC: 0.9545). For the detection of patients with (very) early (BCLC 0/A) HCC stage or within Milan criteria, the APAC score achieved an AUC of 0.9317 (sensitivity: 85.2%, specificity: 89.2%) and 0.9488 (sensitivity: 91.1%, specificity 85.3%), respectively. (4) Conclusions: The APAC score is a novel and highly accurate serological tool for the identification of HCC, especially for early stages. It is superior to the currently proposed blood-based algorithms, and has the potential to improve surveillance of the at-risk population.

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Synovium-Synovial Fluid Axis in Osteoarthritis Pathology: A Key Regulator of the Cartilage Degradation Process

Genes ◽

10.3390/genes12070989 ◽

2021 ◽

Vol 12 (7) ◽

pp. 989

Author(s):

Dhanashri Ingale ◽

Priya Kulkarni ◽

Ali Electricwala ◽

Alpana Moghe ◽

Sara Kamyab ◽

...

Keyword(s):

Synovial Fluid ◽

Early Stage ◽

Challenge Test ◽

Degradation Process ◽

Cartilage Degradation ◽

Gene Expressions ◽

Inflammatory Microenvironment ◽

Protein Levels ◽

Advanced Stages ◽

Inflammatory Milieu

Failure of conventional anti-inflammatory therapies in osteoarthritis (OA) underlines the insufficient knowledge about inflammatory mechanisms, patterns and their relationship with cartilage degradation. Considering non-linear nature of cartilage loss in OA, a better understanding of inflammatory milieu and MMP status at different stages of OA is required to design early-stage therapies or personalized disease management. For this, an investigation based on a synovium-synovial fluid (SF) axis was planned to study OA associated changes in synovium and SF along the progressive grades of OA. Gene expressions in synovial-biopsies from different grades OA patients (N = 26) revealed a peak of IL-1β, IL-15, PGE2 and NGF in early OA (Kellgren–Lawrence (KL) grade-I and II); the highest MMP levels were found in advanced stages (KL grade-III and IV). MMPs (MMP-1, 13, 2 and 9) abundance and FALGPA activity estimated in forty SFs of progressive grades showed the maximum protein levels and activity in KL grade-II and III. In an SF challenge test, SW982 and THP1 cells were treated with progressive grade SFs to study the dynamics of MMPs modulation in inflammatory microenvironment; the test yielded a result pattern, which matched with FALGPA and the protein-levels estimation. Inflammatory mediators in SFs served as steering factor for MMP up-regulation. A correlation-matrix of IL-1β and MMPs revealed expressional negative correlation.

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Racial inequality and periodontal condition in Brazilian adolescents

European Journal of Public Health ◽

10.1093/eurpub/ckaa166.812 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

R S Moreira ◽

L D R Santos

Keyword(s):

Oral Health ◽

Periodontal Disease ◽

Sex Education ◽

Multinomial Logistic Regression ◽

Permanent Teeth ◽

Multiple Model ◽

Oral Diseases ◽

Socioeconomic Variables ◽

Periodontal Index ◽

Dmft Index

Abstract Background Oral health, such as other health conditions, reflects social inequalities. These inequalities are fed back by oral diseases, generating a vicious and sustainable circle. Racial issues play a prominent role, once they are associated with oral diseases as risk markers. Among the different oral diseases, periodontal disease associated with racial inequalities in adolescents is emblematic. Thus, this study aimed to analyse the race differentials associated with the levels of periodontal disease, regardless of other risk factors. Methods Data from the 2010 national epidemiological survey on oral health were used, with 5445 adolescents (15 to 19 years old). Multinomial logistic regression models were used. Dependent variable was the Community Periodontal Index. Independent variable was self-declared race/colour, categorized as white, pardo (mixed-race identity) and preto (black). The effect of race was controlled in the presence of the covariates sex, years of study, decayed, missing and filled permanent teeth (DMFT index), toothache and self-reported need for dental treatment. Odds Ratio (OR) was estimated and sample weights were considered. Results The simple model showed preto with 2.7 (p < 0.05) and 8 (p < 0.05) times more likely to have shallow and deep periodontal pockets, respectively, compared to white. Pardo was 1.5 (p < 0.05) times more likely to have periodontal calculus. In the multiple model, even in the presence of all independent covariates, preto showed association with shallow pockets (OR = 2.51, p < 0.05) and pardo showed association with the presence of calculus (OR = 1.37, p < 0.05). Conclusions Regardless of sex, education, perception of pain and need for treatment and the DMFT index, race/colour was associated with periodontal problems. It should be noted that skin colour is not a biological risk factor for periodontal disease. However, the findings of this study revealed racial inequities regardless of socioeconomic variables. Key messages Raises the need to guarantee health as a resource for social development, with science having a fundamental role in recovering the citizenship of this historically forgotten population. The findings of this study revealed racial inequities regardless of socioeconomic variables.

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Automated Assay of a Four-Protein Biomarker Panel for Improved Detection of Ovarian Cancer

Cancers ◽

10.3390/cancers13020325 ◽

2021 ◽

Vol 13 (2) ◽

pp. 325

Author(s):

Christopher Walker ◽

Tuan-Minh Nguyen ◽

Shlomit Jessel ◽

Ayesha B. Alvero ◽

Dan-Arin Silasi ◽

...

Keyword(s):

Ovarian Cancer ◽

Early Detection ◽

Predictive Value ◽

Early Stage ◽

Ca 125 ◽

Healthy Controls ◽

Classification Models ◽

Serum Samples ◽

Protein Biomarker ◽

Biomarker Panel

Background: Mortality from ovarian cancer remains high due to the lack of methods for early detection. The difficulty lies in the low prevalence of the disease necessitating a significantly high specificity and positive-predictive value (PPV) to avoid unneeded and invasive intervention. Currently, cancer antigen- 125 (CA-125) is the most commonly used biomarker for the early detection of ovarian cancer. In this study we determine the value of combining macrophage migration inhibitory factor (MIF), osteopontin (OPN), and prolactin (PROL) with CA-125 in the detection of ovarian cancer serum samples from healthy controls. Materials and Methods: A total of 432 serum samples were included in this study. 153 samples were from ovarian cancer patients and 279 samples were from age-matched healthy controls. The four proteins were quantified using a fully automated, multi-analyte immunoassay. The serum samples were divided into training and testing datasets and analyzed using four classification models to calculate accuracy, sensitivity, specificity, PPV, negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). Results: The four-protein biomarker panel yielded an average accuracy of 91% compared to 85% using CA-125 alone across four classification models (p = 3.224 × 10−9). Further, in our cohort, the four-protein biomarker panel demonstrated a higher sensitivity (median of 76%), specificity (median of 98%), PPV (median of 91.5%), and NPV (median of 92%), compared to CA-125 alone. The performance of the four-protein biomarker remained better than CA-125 alone even in experiments comparing early stage (Stage I and Stage II) ovarian cancer to healthy controls. Conclusions: Combining MIF, OPN, PROL, and CA-125 can better differentiate ovarian cancer from healthy controls compared to CA-125 alone.

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