Jornal de Biomarcadores Moleculares e Diagnóstico

Marine natural products are valuable sources that could produce potential chemotherapeutic agents, and marinederived organisms are widely recognized as important sources of these natural products with interesting biological activities. Furthermore, Red sea was recognized as a rich source of microbial diversity with unique metabolites that can be of pharmaceutical and medicinal importance. The discovery of novel active metabolites provides an intellectual challenge to examine new products for medicinal purposes. Although many bacterial strains were isolated from Red sea with potent bioactivities; however, the microbial diversity of marine environment such Red sea remained largely un-explored. Lately, it has been possible to easily collect marine samples, isolate, and further identify diverse marine organisms (e.g. bacteria, fungi, and algae and marine invertebrate) by modern molecular techniques. Based on a wide range of screening and extraction methods, a vast number of metabolites have been extracted from marine sources with potential biological activities such as antibacterial, anticancer, anti-inflammatory agents and many others. In this article, we have reviewed the previous studies that have been conducted to explore marine-derived bioactives of Red sea. In addition, we have illustrated the following aspects: (i) Red sea microbial diversity for antibacterial and anticancer agents; (ii) the conventional and molecular approach used for screening and characterization marine microorganisms; (iii) characterization of natural products of microbial origin, and (iv) drug development from novel marine-derived metabolites and clinical trials. Moreover, modern molecular technologies, meta-genomic, proteomic and bio-chemo-informatics approaches are adding more potency to the targeted search of bioactive compounds derived from marine microbes. The novel marine derived drug discovery is aimed to improve our understanding of natural resources, to improve public health awareness about the environmental microbial diversity and their importance for nutraceuticals, pharmaceutical, agrochemicals and food processing. Recently, the research area of microbial diversity of the Red sea and their metabolites has opened a new access for significant sources of more effective drug entities with low coast.

Leishmaniasis are zoonotic diseases caused by a protozoa from Trypanosoma family and of the genus Leishmania, being transmitted by sandfly vectors. Leishmania genus comprise 30 species, including 20 species able to cause disease with different clinical manifestations in humans, ranging from asymptomatic, cutaneous and mucocutaneous lesions, to the severe visceral form. According to the World Health Organization, visceral leishmaniasis, caused by Leishmania infantum chagasi in the Americas, is the most severe form of the disease, and is lethal if not treated. Brazil is part of the group of countries with the highest prevalence of this disease, concentrating 90% of the cases registered in Latin America. A rapid and accurate diagnostic method is of great importance to detect and treat specifically L. i. chagasi in the American continent where others trypanosomiasis circulate, making a specific diagnostic difficult, due to cross reaction. In this work, a new conventional molecular diagnostic method was developed, based on the single copy L. infantum chitinase encoding gene, which presented high specificity and showed increased sensitivity when compared to the method based on the gene encoding the internal transcribed spacer 1 of the Leishmania rRNA (rDNA ITS-1) to diagnose L. i. chagasi on human clinical samples.

Background: N-terminal pro-Brain Natriuretic Peptide(NT-proBNP)is associated with atrial fibrillation(AF) in the setting of acute ST-elevation myocardial infarction (STEMI), and the present study was aimed at assessing the temporal association between NT-proBNP and incident AF.

Methods: 830 patients enrolled in On-TIME II were included. NT-proBNP was assessed at baseline, 24 h and 72 h after admission for STEMI. Patients with new-onset AF <30 days after STEMI were divided among 3 subgroups: AF on admission, AF 24-72 h after admission and AF >72 h after admission. NT-proBNP serum levels at the three assessment intervals was used to predict the timing of AF with a receiver-operator characteristic, and a binary logistic model was created to predict the AF at the various timings.

Results: Mean age was 62 ±12 years and 76% were male. 73 patients developed incident AF, 41 developed AF on admission, 14 patients developed AF 24-72 h after admission and 18 patients developed AF >72 h after admission. NT-proBNP at baseline (area under curve (AUC) 0.657, P<0.001), after 24 h (AUC 0.829, P<0.001) and after 72 h (AUC 0.891, P<0.001) predicted AF. However, NT-proBNP at baseline did not predict AF on admission (AUC 0.591, P=0.058). NT-proBNP after 24 h and 72 h were stronger predictors of AF compared to NT-proBNP at baseline. In regression analysis, NT-proBNP after 24 h (OR:1.220, P<0.001) and 72 h (OR:1.290, P<0.002) showed a significant association with postinfarction AF.

Conclusion: This study shows serial NT-proBNP plasma level assessments enhance risk stratification for incident AF in STEMI patients.

Introduction: Developed from centuries of oral knowledge passed from generation to generation, African traditional medicines (ATM) are at a crossroads. In order for these ATMs to evolve with time similarly to modern medical sciences, there is an urgent need to scientifically evaluate their mechanism of action, safety and efficacy.

Case report: In this short commentary we report on the progress we have made in scientifically evaluating traditional herbal immune boosters at a period where the African continent finds itself ravaged by a plethora of infectious diseases.

Discussion: While the South African government has gone a long way in building an effective modern health system, many people still use ATMs such as immune boosters for a variety of infectious diseases and general wellbeing. The high prevalence of HIV infections is one of the reasons that have led to an increase in the use of ATMs which purport to have immune boosting capabilities. In our laboratory we have developed various models and carried out extensive in vitro and in vivo biochemical and molecular experiments on the immunomodulatory effects of these immune boosters and have shown that these products can modulate the expression and secretion of both cytokines and chemokines. Therefore the potential uses of immune boosters in clinical medicine does not only apply in treating immunodeficiency caused by HIV but can be useful in managing tuberculosis (TB), various forms of cancer and various other diseases that can be managed by modulating the immune response. Such research studies are very promising and present opportunities for further clinical studies to develop unique ATMs.

Conclusion: As medicines meant to stimulate the body’s immune system to defend itself, immune boosters can be useful alone or as immune adjuvants along with pharmaceutical drugs. Therefore further studies on the effectiveness of these immune boosters are justified along with those that will ensure that there are no drug interactions with other pharmaceutical products.

Although it remains difficult to treat advanced cancers affecting organs with distant metastasis, therapeutic cancer vaccination is conducted for the induction of an efficient immune response against tumor-associated antigens. Wilms’ tumor 1 (WT1) shown to be the most potent tumor-associated antigens may have potentially strong therapeutic activity against cancers. WT1 expression using immunohistochemistry (IHC) can be evaluated on paraffin-embedded tissues and is proportional to mRNA levels. The standardized IHC would be useful for personalized cancer immunotherapy.

Stem cell therapy for lung disorders has turned a new leaf, several recent reports have highlighted the promising role of stem cells as a potential therapeutic for CF, however there a several challenges ahead which need to been resolved for its effective translation into the clinic. The present review focusses on understanding the progress made in this cutting edge field so far and the potential challenges which lie ahead.

Peroxynitrite, a toxic product of the free radicals, NO and superoxide, has been implicated in the pathologies of central nervous system, inflammatory diseases, including multiple sclerosis. Peroxynitrite leads to sulfhydryl oxidation and lipid peroxidation as well as structural and functional alteration of proteins. Endogenous peroxynitrite has been found to mediate various effects, including DNA single-strand breakage. Peroxynitrite is a relatively longlived oxidant that may serve as an important cytotoxic agent. Its biological effects are due to its reactivity toward a large number of molecules including lipids, amino acids and nucleic acids. It is involved in tissue damage in a number of pathophysiological conditions such as neurodegenerative diseases, cardiovascular disorders. A change in the structure of DNA could either be due to radiation or interaction with free radicals. Free radical species such as peroxynitrite make either native DNA or DNA-adducts immunogenic leading to the production of autoantibodies in autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis.

Prostate cancer (PCa) is one of the most common cancer in men and most common causes of male cancerrelated deaths. Over many years, biomarkers have been extensively studied for screening, diagnosis, prediction of (PCa) behavior and outcome and for assigning the patients during treatments. Molecular biomarkers could also help scientists to attain better understanding for the molecular basis of the disease and prediction of the patient response to therapies. Early detection of PCa was made possible about 30 years ago by the introduction of prostate specific antigen (PSA) in the clinical practice. However, PCa screening remains controversial, because of the risk of over diagnosis and/or over treatment and the inability to detect a significant proportion of advanced tumors. Several novel biomarkers have shown promises in preliminary studies. This review will focus on traditional biomarkers approved by FDA as PSA, PSA isoforms, Prostate health index (phi) and prostate cancer antigen 3 (PCA3), also novel and promising PCa biomarkers as Prostate stem cell antigen (PSCA) and Urokinase plasminogen activator (uPA), emphasizing on their molecular and biochemical basis, clinical implication and prospective role.