Circulating Biomarkers in Cardiovascular Disease

Cardiovascular diseases (CVD) are one of the the primary causes of morbidity and mortality worlwide. Therefore, more accurate Blood cardiac biomarkers (CB) are needed for a correct handling of patients, at the diagnostic and prognostic level. CVDs are a myriad of diseases with different molecular mechanisms, so it is important to have CBs specific for each pathology.

Toray's 3D-Gene sensitive and accurate miRNA and mRNA microarray service by tebu-bio

Toray’s 3D-Gene technology enables sensitive and accurate miRNA and mRNA analysis through tebu-bio services

Biomarkers are a significant tool to better identify high-risk individuals, to diagnose disease conditions promptly and accurately, and to efficiently prognose and treat patients with disease. Circulating biomarkers, such as miRNAs, have been used in other fields (e.g. Oncology), but their use in clinical practice for CVD patients is still scarce. [Read more…]

miRNAs and Autoimmune Glomerulonephritis

Correlation of findings in animal models (e.g. mouse) and its validation in human samples lies at the basis of Translational medicine. Nowadays, hypothesis established in mouse models must, at some stage, be validated in a cohort of patients. [Read more…]

mTOR revisited

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Figure taken from Ref. 1.

The PI3K/Akt/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. It is directly related to cellular quiescence, proliferation, cancer, and longevity. This pathway can be regulated by genes involved in response to hypoxia. Discoveries that have been made over the last decade show that the mTOR pathway is activated during various cellular processes (e.g. tumour formation and angiogenesis, insulin resistance, adipogenesis and T-lymphocyte activation) and is deregulated in human diseases such as cancer and type 2 diabetes (1). [Read more…]

Circulating biomarkers – there’s more than human

In a previous post, we discussed about how important it is to have research tools that allow to study secretome biomarkers outside the usual human and rodents. Either because other species are important research models, or more importantly, because they are the final patient that will be treated, such as pets or cattle.

miRNAs are key mediators in cell processes, allowing to activate or inhibit the expression of certain genes important in different physiological processes. How miRNAs work, and which ones are relevant, are a hot topic of research nowadays, and important advances are being made in areas such as Oncology and the Immune response. [Read more…]

New Clinical Research trends in Oncology

A symposium on trends in Clinical Oncology was recently held in Madrid, Spain. The symposium gathered actors from the private health system (Hospital Madrid – Clara Campal, Onkologikoa, Clínica Universidad de Navarra), as well as pharmaceutical companies (Roche, Novartis).

The interest of this symposium is that it had a look at the research on cancer from the perspective of clinicians coming from private hospitals, and not from the National Health Systems. [Read more…]

Discovery of functional serum biomarkers

Lung cancer is one of the most common malignancies, and the leading cause of cancer-related fatality. Current diagnostic practices for common cancers rely heavily on imaging technologies. These methods are quite accurate, but still have a probability of having false-positive findings. Also, there is a substantial need for non-invasive ways to test whether the nodules are benign or malignant.

Blood-based biomarkers have potential in cancer screening, and their role could extend further from general population risk assessment to treatment response evaluation and recurrence monitoring. However, despite much research effort, biomarkers able to predict disease onset and evolution are not always easy to find, or distinctive enough. [Read more…]

Biomarker profiling: Diluting samples case studies (II)

Back to dilution of samples. After our post on whether samples should be diluted or not, let’s discuss today about how much they should be diluted.

Case # 1 – ELISA or simplex assays

Most ELISA manufacturers indicate the dilution range for different types of samples (serum, plasma, cell culture supernatants, etc.) to be used in their products. However, the dilution range can sometimes be from 1:2 to 1:2,000. How to choose the right dilution factor?

The honest answer is: nobody knows. That is,  nobody knows what is the right dilution factor in your specific research project, for your specific biomarker. [Read more…]

Multiplex assays in profiling biomarkers in eye disease

Cytokines are important cell mediators in a variety of processes, including cancer, obesity, and many other processes where inflammation plays a role.

Today, our spotlight is set on eye diseases. A recent publication by Nassar et al. depicts the importance of serum c00417_253_002ytokines as biomarkers for age-related macular degeneration. Serum samples from 30 age-related macular degeneration (AMD) patients and 15 age-matched controls were examined for 16 inflammatory cytokines using multiplex ELISA. Patients were divided into three subgroups (improvement/no change/deterioration during anti-VEGF treatment) by OCT and funduscopy, and correlated to the cytokine levels.

It was seen that elevation of IL-1α, IL-1β, IL-4, IL-5, IL-10, IL-13, and IL-17 in the serum of AMD patients supports the hypothesis of AMD as an inflammatory disease. Patients with high IL-17 and TNF-α serum levels were more likely to have a favourable course under VEGF therapy, allowing to use these cytokines both as diagnostic and prognostic biomarkers.

Another process where cytokines seem to play a role is Dry Eye Disease (DED). The main problem for analysis of cytokines in this case is that the ideal sample are tears… and in dry eye disease, obtaining high volumes of tears is quite challenging. So, for studies on cohorts of patients, oftentimes we have to work with tear samples volumes of maximum 1 or 2 microlitres.

The multiplex ELISA technology used in Nassar’s study has also been validated for its use in tears, using modified buffers. There are also tools allowing to perform a broader profiling (up to 40 by cytokines) in limited amounts of tear samples.

It is important to check that whatever tool we choose, it has been validated with tears, and especially, with small amounts!

Are you studying biomarkers on tears, or does your research on biomarkers make you cry?

Feel free to leave your comment!

PBMCs & drug development

Use of human samples including peripheral blood mononuclear cells (PBMCs) in drug discovery is critical for increasing the chances of success for a small molecule screen hit. A review based on recent published data!

PBMCs DD 1Several theories try to explain why many drug discovery and development projects have a moderate success rate. Even with the advances made in methods (HTS, HCA, library managment, etc), there are many hurdles for a small molecule on the long road to FDA or EMA approval.

One way that may improve predicted efficacy and toxicity of drug leads is to use human samples, such as blood, early on in drug discovery programs. Peripheral blood mononuclear cells  (PBMCs) can be easily used in a variety of ways during the drug discovery process to gain a better understanding of the effects of a small molecule. [Read more…]

Biomarkers of micronutrient malnutrition

Unfortunately, and still in the XXIst century, micronutrient (MN) malnutrition is a problem in all countries, in all segments of society. While part of the world starves, another part is obese. And a balanced diet is still far from being real for many people. Something to think about…

This is a real public health concern, and policies in this area are aimed at preventing, among others, mild, moderate an severe MN malnutrition. Deficiencies in MNs such as iron, vitamin A (VA), iodine, zinc and folic acid are associated with adverse health outcomes, especially in pregnant women and children. For example, VA is critical for embryonic development, adult growth and development, cellular differentiation, immune function, reproduction and vision. On the other hand, low iron levels lead to reduced physical activity in adults and impaired brain development in children. [Read more…]