Current Biomarkers - Current Issue

The psoriatic disease has a multi-factorial determinism being generated by a complex array of genetic, immunologic, and environmental factors. In this array, cellular interplay takes place maintaining the epidermal equilibrium. Psoriasis pathophysiology is characterized by keratinocytes hyperproliferation and immune cell infiltration in the dermis and epidermis. Innate and adaptive immune cells are highly involved, the main cellular players being dendritic and T lymphocytes, among other cells. Th17-type cytokines (e.g.,, IL-17A, IL-17F, IL-22, IL-21) as regulatory are at the core of psoriasis pathogenesis. Cytokines that emerge due to the activation of lymphocytes maintain a chronic inflammatory response acknowledged in the psoriatic skin. In vivo and in vitro cellular models, along with clinical trials that acknowledge cytokines as biomarkers and therapy targets are presented.

Background: Canine parvovirus (CPV) enteritis is an important cause of high morbidity and mortality in pups. The high incidence of parvoviral enteritis is due to high capability of CPV to evolve into more virulent and resistant variants. The condition may be worsening in case of local gastrointestinal and systemic inflammation. In addition to CPV enteritis less common is the cardiac form, which attacks the heart muscles of very young puppies and often leading to death. Therefore, early and confirmed diagnosis of CPV is essential for suitable treatment of infected dogs. Objective: The prime objective of this review paper is to extend scientific knowledge on CPV as well as cardiac biomarkers in order to efficiently diagnose intestinal and cardiac forms of CPV in dogs. The information would eventually be helpful in proper treatment of suffering dogs falling in different age groups. Methods: The current review is based on extensive information search, analysis and compilation of CPV biomarker data from much authentic published literature available in several scientific databases including PubMed. The information also includes current knowledge of several clinical factors such as biochemical, haematological and endocrine parameters used as diagnostics as well as prognostic biomarkers in CPV enteritis. The review is also supplemented with cardiac biomarkers to assess the heart health in infected dogs where cardiac ailment may occur as consequences of viral enteritis. Results: In this review, we have elaborated current views of some CPV specific biomarkers along with cardiac biomarkers which would improve prognostic efficiency as well as diagnostic accuracy among canine patients. Conclusion: The current review discussed the CPV specific several biomarkers such as season, body weight, breed, lymphopaenia, leukopaenia, thrombocytopaenia, hypercoagulability, hypothyroxinaemia, hypoalbuminaemia, hypocholesterolaemia, hypocitrullinaemia, C-reactive protein level, tumour necrosis factors for assessment of disease condition. The severity and outcome of CPV infection are also dependent on host (breed), pathogen, secondary bacterial and viral infections, stress and environment. Application of biomarkers is based on several prognosticators such as hematology, coagulation abnormalities and serum biochemistry changes that can identify the patients at high risk of death and their targeted management in easier way. Recently, cardiac biomarkers including cardiac troponins and natriuretic peptides are being applied as diagnostic and prognostic biomarkers in dogs.

Background: Cancer is one of the most deadly diseases in the world. Cervical cancer is the second most common cancer in women worldwide. The major cause of cervical cancer has been found to be the infection with Human Papillomavirus (HPV). Out of over 100 types of HPV, the two types, which are considered high-risk HPV types, are HPV-16 and HPV-18. Several vaccines are available commercially which comprise Cervarix (Recombinant HPV Bivalent Vaccine), Gardasil (Recombinant HPV Quadrivalent Vaccine) etc. for the prevention of cervical cancer. In spite of the availability of many therapeutics for cervical cancer, the incidence of cervical cancer is increasing annually. Hence there is a strong need for new technologies for diagnosis, treatment and prevention to fight against this deadly disease. Objective: The paper presents a review of patenting scenario of therapeutics for cervical cancer to provide an insight into the technological trends during 2006-2016. Methods: The patent literature review spanning 10 years (2006-2016) was carried out in USPTO (www.uspto.gov) database, WIPO Patentscope database (www.wipo.int/patentscope), and EPO (www.espacenet.net) and relevant non-patent literature was searched using Scopus (www.scopus.com) and PUBMED (ncbi.nlm.nih.gov) databases and the World Wide Web. Relevant published patent applications, issued patents and non-patent literature were reviewed and excerpts were included in the present article. Results/Conclusions: Study of the patent profile of cervical cancer therapeutics during 2006-2016 reveals that much R worldwide has been focused on the development of therapeutics against cervical cancer resulting in the emergence of several potential therapies in various technological fields including DNA/RNA, peptide/protein-based therapy, nano-technological and phytochemical drugs, biomarkers oriented drugs and immune-therapeutics. In the end of the review article, the current and future directions of cervical cancer therapeutics are provided.

Background: The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis are a heterogeneous group of autoimmune diseases that predominantly affects small vessels. Churg Strauss Syndrom (CSS), Wegener's Granulomatosis (WG) and Microscopic polyangiitis (MPA) are the three clinical entities associated to this group. Marked eosinophilia, pulmonary involvement associated with dense eosinophilic infiltration in tissue biopsy and increase of circulating IgE were considered the clinical hallmark of CSS. On a cellular level, a strong shift towards a Th2-like response with massive T cell activation is prominent. CCL17/thymus and activation-regulated chemokine (TARC) is a chemokine responsible for the recruitment of Th2 cells. Objective: Taking into consideration the ability of TARC to recruit and modulate the trafficking of Th2 cellular elements we hypothesized that TARC plays an essential role in the pathogenesis of this disease and we investigated the role of TARC as potential biomarker. Methods: TARC levels in serum from patients with active or remitted CSS, hypereosinophilic syndrome, other ANCA associated vasculitis other than CSS, and healthy controls were determined by enzyme-linked immunosorbent assay. Results: We demonstrated that TARC concentration in active CSS was significantly higher than the healthy control groups and patients with inactive disease. This concentration reflected the clinical disease course and was correlated with the absolute eosinophilic count as well as IgE and CRP levels. ROC curve analysis was used to determine the best cut-off point (800 pg/mL) with a good sensitivity and specificity. Elevated TARC levels were also noted in patients with hypereosinophilic syndrome but not in other ANCA associated disease and other diseases under exam. Conclusions: TARC could be considered a good candidate as CSS biomarker, because of its specificity and the direct correlation with disease activity. Although the role of TARC in CSS pathophysiology is not yet entirely clear, future studies are needed to understand the effective roles and the possible uses of TARC as a biomarker.

Background: Epstein Barr Virus (EBV) infection has been associated with the Rheumatoid Arthritis (RA) etiopathology, thus, considering it a relevant etiological agent in the disease development. We have previously observed the Hyaluronic Acid (HA) serum increase in active RA patients (DAS 28-4 > 2.6) which might be responsible for the erythrocyte deformability, estimated by the erythrocyte Rigidity Index (RI). Objective: In the present study, we analyzed in one hundred RA patients if anti-EBV serum antibodies (TsEBV) and HA and RI levels are related with the disease activity. Results: [HA] s [[controls]]: 20.0 ± 9; [HA] s [[AR]]: 155.8 ± 44 (p< 0.00001 vs. controls (n:40). Antibodies anti-EBV (1/ TsEBV) [[controls]]: 2.55 ± 0.49; [[RA]]: 1.85 ± 0.35 (p< 0.00001 vs. controls). There were significant correlations between DAS 28-4 vs. log2 1/TsEBV (r: 0.70, p < 0.00001) and DAS 28-4 vs. RI (r: 0.75, p < 0.00001) in active RA patients. However, we observed a strong positive correlation between [HA] s in active RA patients vs. log2 1/TsEBV (r: 0.83, p < 0.00001) and [HA] s vs. RI (r: 0.91, p < 0.00001). Conclusion: The correlation obtained points out that the TsEBV may be related with the degree of RA activity determined by DAS28-4 and [HA]s in these patients. There was also a decrease in erythrocyte deformability estimated as RI, which is correlated with the DAS 28-4 activity index. Therefore, RI can be used as a reliable marker of RA activity. These findings might suggest a role of EBV infection regarding an autoimmune mechanism present in RA.

Background: Celery (Apium graveolens L.) is considered one of the most important cash crops of Apiaceae family. However, due to minimal genetic and genomic resources, most of the past studies were based on physiological and biochemical analysis rather than molecular breeding. Objective: The present in silico molecular study is an attempt to develop dbEST derived simple sequence repeats in celery. Method: Implementation of computational tools and analysis for the development and identification of EST-SSR markers of celery. Developed microsatellite markers were verified using biotechnological techniques. Results: We derived 118 SSRs, of which 103 (87.3%) were simple and 15 SSRs (12.7%) were compound in nature. Of the various SSRs 34 (33%) were mononucleotide, 44 (43%) dinucleotide, 20 (19%) trinucleotide, 3 (3%) tetranucleotide and 2 were penta-nucleotides. Genetic diversity and relationship among 35 local cultivars of celery were identified. Experiments were also conducted to investigate the competence of primers generated for celery genotypes. Conclusion: Thirty nine microsatellite makers were recognized best for distinguishing celery genotypes. This study provides a scientific ground for celery genotype identification and differentiation, evolutionary genetics, phylogenetics studies, breeding and protection of breeders' rights on celery as well as on different Apiaceae species in future.