Exploring Potential Biomarkers in Oesophageal Cancer: A Comprehensive Analysis.

Oesophageal cancer (OC) is the sixth leading cause of cancer-related death worldwide. OC is highly aggressive, primarily due to its late stage of diagnosis and poor prognosis for patients' survival. Therefore, the establishment of new biomarkers that will be measured with non-invasive techniques at low cost is a critical issue in improving the diagnosis of OC. In this review, we summarize several original studies concerning the potential significance of selected chemokines and their receptors, including inflammatory proteins such as interleukin-6 (IL-6) and C-reactive protein (CRP), hematopoietic growth factors (HGFs), claudins (CLDNs), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), adamalysines (ADAMs), as well as DNA- and RNA-based biomarkers, in OC. The presented results indicate the significant correlation between the CXCL12, CXCR4, CXCL8/CXCR2, M-CSF, MMP-2, MMP-9 ADAM17, ADAMTS-6, and CLDN7 levels and tumor stage, as well as the clinicopathological parameters of OC, such as the presence of lymph node and/or distant metastases. CXCL12, CXCL8/CXCR2, IL-6, TIMP-2, ADAM9, and ADAMTS-6 were prognostic factors for the overall survival of OC patients. Furthermore, IL-6, CXCR4, CXCL8, and MMP-9 indicate higher diagnostic utility based on the area under the ROC curve (AUC) than well-established OC tumor markers, whereas CLDN18.2 can be used in novel targeted therapies for OC patients.

Biomarkers of Activity-Dependent Plasticity and Persistent Enhancement of Synaptic Transmission in Alzheimer Disease: A Review of the Current Status.

Alzheimer disease (AD) is a chronic and heterogeneous neurodegenerative disorder characterized by complex pathological processes involving neuroinflammation, neurodegeneration, and synaptic dysfunction. Understanding the exact neurobiological mechanisms underlying AD pathology may help to provide a biomarker for early diagnosis or at least for assessment of vulnerability to dementia development. Neural plasticity is defined as a capability of the brain to respond to alterations including aging, injury, or learning, with a crucial role of synaptic elements. Long-term potentiation (LTP) and long-term depression (LTD) are important in regulating synaptic connections between neural cells in functional plasticity. Synaptic loss and impairment of the brain's plasticity in AD leads to cognitive impairment, and one of important roles of synaptic biomarkers is monitoring synaptic dysfunction, response to treatment, and predicting future development of AD. Synaptic biomarkers are undoubtedly very promising in developing novel approach to AD treatment and control, especially in the era of aging of societies, which is one of the most common risk factor of AD. Implementing a widespread measurement of synaptic biomarkers of AD will probably be crucial in early diagnosis of AD, early therapeutic intervention, monitoring progression of the disease, or response to treatment. One of the most important challenges is finding a biomarker whose blood concentration correlates with its level in the central nervous system (CNS). This review aims to present the current status of biomarkers of activity-dependent plasticity and persistent enhancement of synaptic transmission in Alzheimer disease.

Free Light Chains κ and λ as New Biomarkers of Selected Diseases.

Diagnostic and prognostic markers are necessary to help in patient diagnosis and the prediction of future clinical events or disease progression. As promising biomarkers of selected diseases, the free light chains (FLCs) κ and λ were considered. Measurements of FLCs are currently used in routine diagnostics of, for example, multiple myeloma, and the usefulness of FLCs as biomarkers of monoclonal gammopathies is well understood. Therefore, this review focuses on the studies concerning FLCs as new potential biomarkers of other disorders in which an inflammatory background has been observed. We performed a bibliometric review of studies indexed in MEDLINE to assess the clinical significance of FLCs. Altered levels of FLCs were observed both in diseases strongly connected with inflammation such as viral infections, tick-borne diseases or rheumatic disorders, and disorders that are moderately associated with immune system reactions, e.g., multiple sclerosis, diabetes, cardiovascular disorders and cancers. Increased concentrations of FLCs appear to be a useful prognostic marker in patients with multiple sclerosis or tick-borne encephalitis. Intensive synthesis of FLCs may also reflect the production of specific antibodies against pathogens such as SARS-CoV-2. Moreover, abnormal FLC concentrations might predict the development of diabetic kidney disease in patients with type 2 diabetes. Markedly elevated levels are also associated with increased risk of hospitalization and death in patients with cardiovascular disorders. Additionally, FLCs have been found to be increased in rheumatic diseases and have been related to disease activity. Furthermore, it has been suggested that inhibition of FLCs would reduce the progression of tumorigenesis in breast cancer or colitis-associated colon carcinogenesis. In conclusion, abnormal levels of κ and λ FLCs, as well as the ratio of κ:λ, are usually the result of disturbances in the synthesis of immunoglobulins as an effect of overactive inflammatory reactions. Therefore, it seems that κ and λ FLCs may be significant diagnostic and prognostic biomarkers of selected diseases. Moreover, the inhibition of FLCs appears to be a promising therapeutical target for the treatment of various disorders where inflammation plays an important role in the development or progression of the disease.

Molecular Aspects of a Diet as a New Pathway in the Prevention and Treatment of Alzheimer's Disease.

Alzheimer's disease is the most common cause of dementia in the world. Lack of an established pathology makes it difficult to develop suitable approaches and treatment for the disease. Besides known hallmarks, including amyloid ß peptides cumulating in plaques and hyperphosphorylated tau forming NFTs, inflammation also plays an important role, with known connections to the diet. In AD, adhering to reasonable nutrition according to age-related principles is recommended. The diet should be high in neuroprotective foods, such as polyunsaturated fatty acids, antioxidants, and B vitamins. In addition, foods capable of rising BDNF should be considered because of the known profitable results of this molecule in AD. Adhering to beneficial diets might result in improvements in memory, cognition, and biomarkers and might even reduce the risk of developing AD. In this review, we discuss the effects of various diets, foods, and nutrients on brain health and possible connections to Alzheimer's disease.

The Comprehensive Analysis of Specific Proteins as Novel Biomarkers Involved in the Diagnosis and Progression of Gastric Cancer.

Gastric cancer (GC) cases are predicted to rise by 2040 to approximately 1.8 million cases, while GC-caused deaths to 1.3 million yearly worldwide. To change this prognosis, there is a need to improve the diagnosis of GC patients because this deadly malignancy is usually detected at an advanced stage. Therefore, new biomarkers of early GC are sorely needed. In the present paper, we summarized and referred to a number of original pieces of research concerning the clinical significance of specific proteins as potential biomarkers for GC in comparison to well-established tumor markers for this malignancy. It has been proved that selected chemokines and their specific receptors, vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR), specific proteins such as interleukin 6 (IL-6) and C-reactive protein (CRP), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), as well as DNA- and RNA-based biomarkers, and c-MET (tyrosine-protein kinase Met) play a role in the pathogenesis of GC. Based on the recent scientific literature, our review indicates that presented specific proteins are potential biomarkers in the diagnosis and progression of GC as well as might be used as prognostic factors of GC patients' survival.

COVID-19: The Course, Vaccination and Immune Response in People with Multiple Sclerosis: Systematic Review.

When the Coronavirus Disease 2019 (COVID-19) appeared, it was unknown what impact it would have on the condition of patients with autoimmunological disorders. Attention was focused on the course of infection in patients suffering from multiple sclerosis (MS), specially treated with disease-modifying therapies (DMTs) or glucocorticoids. The impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on the occurrence of MS relapses or pseudo-relapses was important. This review focuses on the risk, symptoms, course, and mortality of COVID-19 as well as immune response to vaccinations against COVID-19 in patients with MS (PwMS). We searched the PubMed database according to specific criteria. PwMS have the risk of infection, hospitalization, symptoms, and mortality due to COVID-19, mostly similar to the general population. The presence of comorbidities, male sex, a higher degree of disability, and older age increase the frequency and severity of the COVID-19 course in PwMS. For example, it was reported that anti-CD20 therapy is probably associated with an increased risk of severe COVID-19 outcomes. After SARS-CoV-2 infection or vaccination, MS patients acquire humoral and cellular immunity, but the degree of immune response depends on applied DMTs. Additional studies are necessary to corroborate these findings. However, indisputably, some PwMS need special attention within the context of COVID-19.

Common and Trace Metals in Alzheimer's and Parkinson's Diseases.

Trace elements and metals play critical roles in the normal functioning of the central nervous system (CNS), and their dysregulation has been implicated in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). In a healthy CNS, zinc, copper, iron, and manganese play vital roles as enzyme cofactors, supporting neurotransmission, cellular metabolism, and antioxidant defense. Imbalances in these trace elements can lead to oxidative stress, protein aggregation, and mitochondrial dysfunction, thereby contributing to neurodegeneration. In AD, copper and zinc imbalances are associated with amyloid-beta and tau pathology, impacting cognitive function. PD involves the disruption of iron and manganese levels, leading to oxidative damage and neuronal loss. Toxic metals, like lead and cadmium, impair synaptic transmission and exacerbate neuroinflammation, impacting CNS health. The role of aluminum in AD neurofibrillary tangle formation has also been noted. Understanding the roles of these elements in CNS health and disease might offer potential therapeutic targets for neurodegenerative disorders. The Codex Alimentarius standards concerning the mentioned metals in foods may be one of the key legal contributions to safeguarding public health. Further research is needed to fully comprehend these complex mechanisms and develop effective interventions.

Investigating the Role of Serum and Plasma IL-6, IL-8, IL-10, TNF-alpha, CRP, and S100B Concentrations in Obstructive Sleep Apnea Diagnosis.

Obstructive sleep apnea (OSA) is a prevalent and underdiagnosed condition associated with cardiovascular diseases, depression, accidents, and stroke. There is an increasing need for alternative diagnostic tools beyond overnight sleep studies that measure the Apnea/Hypopnea Index (AHI). In this single-center, case-control study, we evaluated serum and plasma concentrations of IL-6, IL-8, IL-10, TNF-α, CRP, and S100B in 80 subjects, including 52 OSA patients (27 moderate [15 ≤ AHI ˂ 30], 25 severe [AHI ≥ 30]) and 28 non-OSA controls (AHI 0-5). Participants with OSA showed approximately 2 times higher median concentrations of CRP in plasma, and IL-6 in serum, as well as 1.3 to 1.7 times higher concentrations of TNF-α and IL-8 in plasma compared with the control group. Receiver Operator Characteristic (ROC) curve analysis was performed to evaluate the predictive capabilities of these serum and plasma biomarkers in distinguishing between the OSA and control groups, revealing varying sensitivity and specificity. In summary, in this study, serum and plasma biomarkers CRP, S100B, IL-6, TNF-α, and IL-8 have been shown to be elevated in patients with OSA, correlated positively with disease severity, age, and BMI. These results support the potential role of these biomarkers in diagnosing OSA, supplementing traditional methods such as overnight sleep studies.

The Relationships between Cerebrospinal Fluid Glial (CXCL12, CX3CL, YKL-40) and Synaptic Biomarkers (Ng, NPTXR) in Early Alzheimer's Disease.

In addition to amyloid and tau pathology in the central nervous system (CNS), inflammatory processes and synaptic dysfunction are highly important mechanisms involved in the development and progression of dementia diseases. In the present study, we conducted a comparative analysis of selected pro-inflammatory proteins in the CNS with proteins reflecting synaptic damage and core biomarkers in mild cognitive impairment (MCI) and early Alzheimer's disease (AD). To our knowledge, no studies have yet compared CXCL12 and CX3CL1 with markers of synaptic disturbance in cerebrospinal fluid (CSF) in the early stages of dementia. The quantitative assessment of selected proteins in the CSF of patients with MCI, AD, and non-demented controls (CTRL) was performed using immunoassays (single- and multiplex techniques). In this study, increased CSF concentration of CX3CL1 in MCI and AD patients correlated positively with neurogranin (r = 0.74; p < 0.001, and r = 0.40; p = 0.020, respectively), ptau181 (r = 0.49; p = 0.040), and YKL-40 (r = 0.47; p = 0.050) in MCI subjects. In addition, elevated CSF levels of CXCL12 in the AD group were significantly associated with mini-mental state examination score (r = -0.32; p = 0.040). We found significant evidence to support an association between CX3CL1 and neurogranin, already in the early stages of cognitive decline. Furthermore, our findings indicate that CXCL12 might be a useful marker for tract severity of cognitive impairment.

Antibodies against SARS-CoV-2 S and N proteins in relapsing-remitting multiple sclerosis patients treated with disease-modifying therapies.

CLINICAL RATIONALE FOR THE STUDY: The course of COVID-19 in people with multiple sclerosis (PwMS) has been described, while the serological status after SARS-CoV-2 infection or vaccination, especially in patients treated with disease-modifying therapies (DMT), is still under investigation. This is a significant clinical problem, as certain DMTs may predispose to a severe course of viral infections. AIM OF THE STUDY: We analyzed the presence of antibodies against spike (S) and nucleocapsid (N) proteins of SARS-CoV-2 in relapsing-remitting PwMS treated with DMT, especially dimethyl fumarate, interferon beta, and glatiramer acetate, in a single multiple sclerosis (MS) centre in north-eastern Poland (the Department of Neurology, Medical University of Bialystok). MATERIAL AND METHODS: The presence of antibodies against S and N proteins in PwMS was assessed twice: on visit one (between May and June 2020) (n = 186) and on visit two (between May and June 2021) (n = 88). Samples were taken from 68 individuals on both visits. Demographic and clinical data was collected: duration of MS, Expanded Disability Status Scale Score (EDSS), type of DMT, history of COVID-19 (positive PCR or antigen test in the past), vaccination status, and the type of vaccine. RESULTS: It was shown that on visit one: 3.7% (n = 7) PwMS were positive for IgA against S protein (IgA-S), 3.2% (n = 6) for IgG against S (IgG-S) protein, and none of those examined was positive for IgG against N protein (IgG-N). On visit two, the most common detected antibodies were IgG-S (71.3%; n = 62), then IgA-S (65.1%; n = 55), and the least common was IgG-N (18.2%; n = 16). On visit two: 20.45% of PwMS had a history of a positive SARS-CoV-2 PCR or antigen test during the last year. By the time of visit two, 42.05% (n = 37) of patients who participated in visit two had been full-course vaccinated against COVID-19. It was demonstrated that vaccination against SARS-CoV-2 significantly induces the production of IgG-S and IgA-S (p < 0.0001), while no difference between vaccinated and unvaccinated patients was shown in the detection of IgG-N. There was no correlation between COVID-19 infection and antibodies against proteins S and N in the study group. Moreover, the presented study did not show any relationship between the ability to produce antibodies against the S protein with any of the used DMTs. CONCLUSIONS AND CLINICAL IMPLICATIONS: According to our study, PwMS treated with dimethyl fumarate, interferon beta, or glatiramer acetate can efficiently produce antibodies against SARS-CoV-2 both after infection and after vaccination.

Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview.

INTRODUCTION: The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests. METHODS: We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients. RESULTS: The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis. DISCUSSION: This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD.

Molecular and Circulating Biomarkers of Gastric Cancer.

Gastric cancer (GC)-a common tumor that affects humans worldwide-is highly malignant with a poor prognosis. GC is frequently not diagnosed until a relatively advanced stage. Early detection and efficient monitoring of tumor dynamics are prerequisites for reducing disease burden and mortality. Minimally invasive methods are needed to establish a diagnosis or monitoring the response to treatment of gastric cancer. Blood-based biomarker assays for the detection of early-stage GC could be of great relevance both for the risk group or for population-wide based screening programs, The currently used tumor marker assays for detecting GC are simple and rapid, but their use is limited by their low sensitivity and specificity. In recent years, several markers have been identified and tested for their clinical relevance in the management of gastric cancer. Here we review the available literature on plasma classical tumor markers, circulating free microRNAs (cfmiRNAs), circulating cell-free DNA (cfDNA), circulating tumor cells (CTCs), autoantibodies against tumor associated antigens (TAAs), and circulating extracellular vesicles (EVs) for diagnosis and monitoring of gastric cancer. This review summarizes the present status and approaches for these biomarkers, which could be potentially used for early diagnosis and accurate prediction of therapeutic approaches. We also discuss the future perspective and challenges in the search for new biomarkers of gastric cancer.

Chemokines in Primary Liver Cancer.

The liver is responsible for extremely important functions in the human body. In the liver's structure, we distinguish between connective tissue (stroma) and parenchyma, the latter of which is formed from the basic structural and functional units of the liver-hepatocytes. There are many factors, that negatively affect the liver cells, contributing to their damage. This may lead to fibrosis, liver failure and, in consequence, primary liver cancer, which is the sixth most commonly diagnosed malignancy and the fourth leading cause of cancer death worldwide. Chemokines are a large family of secreted proteins. Their main role is to direct the recruitment and migration of cells to sites of inflammation or injury. Some authors suggest that these proteins might play a potential role in the development of many malignancies, including primary liver cancer. The aim of this study was to evaluate and summarize the knowledge regarding liver diseases, especially primary liver cancer (HCC) and the participation of chemokines in the development of this malignancy. Chemokines involved in the initiation of this type of tumor belong mainly to the CC and CXC chemokines. Their significant role in the course of hepatocellular carcinoma proves their usefulness in detecting and monitoring the course and treatment in patients with this disease.

New Possibilities in the Therapeutic Approach to Alzheimer's Disease.

Despite the fact that Alzheimer's disease (AD) is the most common cause of dementia, after many years of research regarding this disease, there is no casual treatment. Regardless of the serious public health threat it poses, only five medical treatments for Alzheimer's disease have been authorized, and they only control symptoms rather than changing the course of the disease. Numerous clinical trials of single-agent therapy did not slow the development of disease or improve symptoms when compared to placebo. Evidence indicates that the pathological alterations linked to AD start many years earlier than a manifestation of the disease. In this pre-clinical period before the neurodegenerative process is established, pharmaceutical therapy might prove invaluable. Although recent findings from the testing of drugs such as aducanumab are encouraging, they should nevertheless be interpreted cautiously. Such medications may be able to delay the onset of dementia, significantly lowering the prevalence of the disease, but are still a long way from having a clinically effective disease-modifying therapy.

The Role of Nuclear Factor Kappa B (NF-κB) in Development and Treatment of COVID-19: Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 19 (COVID-19), a disease that has affected more than 500 million people worldwide since the end of 2019. Due to its high complications and death rates, there is still a need to find the best therapy for SARS-CoV-2 infection. The dysregulation of the inflammatory response in COVID-19 plays a very important role in disease progression. It has been observed that abnormal activity of Nuclear Factor kappa B (NF-κB) is directly associated with, inter alia, increased synthesis of proinflammatory factors. Therefore, this review paper focuses on the functions of NF-κB in the development of SARS-CoV-2 infection and potential application of NF-κB inhibitors in COVID-19 immunotherapy. A comprehensive literature search was performed using the MEDLINE/PubMed database. In the current review, it is highlighted that NF-κB plays important functions in the modulation of an adaptive inflammatory response, including inducing the expression of proinflammatory genes. Increased activation of NF-κB in SARS-CoV-2 infection was observed. The association between NF-κB activation and the expression of SARS-CoV-2 structural and non-structural proteins were also reported. It was observed that modulation of NF-κB using, e.g., traditional Chinese medicine or glucocorticosteroids resulted in decreased synthesis of proinflammatory factors caused by SARS-CoV-2 infection. This review summarizes the role of NF-κB in COVID-19 and describes its potential immunotherapeutic target in treatment of SARS-CoV-2 infection. However, indisputably more studies involving patients with a severe course of COVID-19 are sorely needed.

What Is Currently Known about the Role of CXCL10 in SARS-CoV-2 Infection?

Dysregulation of the immune response plays an important role in the progression of SARS-CoV-2 infection. A "cytokine storm", which is a phenomenon associated with uncontrolled production of large amounts of cytokines, very often affects patients with COVID-19. Elevated activity of chemotactic cytokines, called chemokines, can lead to serious consequences. CXCL10 has an ability to activate its receptor CXCR3, predominantly expressed on macrophages, T lymphocytes, dendritic cells, natural killer cells, and B cells. So, it has been suggested that the chemokine CXCL10, through CXCR3, is associated with inflammatory diseases and may be involved in the development of COVID-19. Therefore, in this review paper, we focus on the role of CXCL10 overactivity in the pathogenesis of COVID-19. We performed an extensive literature search for our investigation using the MEDLINE/PubMed database. Increased concentrations of CXCL10 were observed in COVID-19. Elevated levels of CXCL10 were reported to be associated with a severe course and disease progression. Published studies revealed that CXCL10 may be a very good predictive biomarker of patient outcome in COVID-19, and that markedly elevated CXCL10 levels are connected with ARDS and neurological complications. It has been observed that an effective treatment for SARS-CoV-2 leads to inhibition of "cytokine storm", as well as reduction of CXCL10 concentrations. It seems that modulation of the CXCL10-CXCR3 axis may be an effective therapeutic target of COVID-19. This review describes the potential role of CXCL10 in the pathogenesis of COVID-19, as well as its potential immune-therapeutic significance. However, future studies should aim to confirm the prognostic, clinical, and therapeutic role of CXCL10 in SARS-CoV-2 infection.

Molecular Biomarkers and Their Implications for the Early Diagnosis of Selected Neurodegenerative Diseases.

The degeneration and dysfunction of neurons are key features of neurodegenerative diseases (NDs). Currently, one of the main challenges facing researchers and clinicians is the ability to obtain reliable diagnostic tools that will allow for the diagnosis of NDs as early as possible and the detection of neuronal dysfunction, preferably in the presymptomatic stage. Additionally, better tools for assessing disease progression in this group of disorders are also being sought. The ideal biomarker must have high sensitivity and specificity, be easy to measure, give reproducible results, and reflect the disease progression. Molecular biomarkers include miRNAs and extracellular microvesicles known as exosomes. They may be measured in two extracellular fluids of the highest importance in NDs, i.e., cerebrospinal fluid (CSF) and blood. The aim of the current review is to summarize the pathophysiology of the four most frequent NDs-i.e., Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)-as well as current progress in the research into miRNAs as biomarkers in these major neurodegenerative diseases. In addition, we discuss the possibility of using miRNA-based therapies in the treatment of neurodegenerative diseases, and present the limitations of this type of therapy.

Granzymes-Their Role in Colorectal Cancer.

Colorectal cancer (CRC) is among the most common malignancies worldwide. CRC is considered a heterogeneous disease due to various clinical symptoms, biological behaviours, and a variety of mutations. A number of studies demonstrate that as many as 50% of CRC patients have distant metastases at the time of diagnosis. However, despite the fact that social and medical awareness of CRC has increased in recent years and screening programmes have expanded, there is still an urgent need to find new diagnostic tools for early detection of CRC. The effectiveness of the currently used classical tumour markers in CRC diagnostics is very limited. Therefore, new proteins that play an important role in the formation and progression of CRC are being sought. A number of recent studies show the potential significance of granzymes (GZMs) in carcinogenesis. These proteins are released by cytotoxic lymphocytes, which protect the body against viral infection as well specific signalling pathways that ultimately lead to cell death. Some studies suggest a link between GZMs, particularly the expression of Granzyme A, and inflammation. This paper summarises the role of GZMs in CRC pathogenesis through their involvement in the inflammatory process. Therefore, it seems that GZMs could become the focus of research into new CRC biomarkers.

Relationship between VEGF Family Members, Their Receptors and Cell Death in the Neoplastic Transformation of Colorectal Cancer.

Colorectal cancer (CRC) is the second most common cause of cancer death in the world. Both modifiable and nonmodifiable risk factors play a significant role in the pathogenesis of this tumor. The diagnosis is usually made late due to limitations of screening tests; therefore, the scientists are looking for new diagnostic tools such as gene or miRNA expression or different proteins' concentrations, e.g., vascular endothelial growth factor (VEGF) family members. The VEGF family (VEGF-A, VEGF-B, VEGF-C, VEGF-D and PlGF) plays a key role in the processes of blood vessel formation in embryonic development as well as in pathological angiogenesis and lymphangiogenesis, which allow the tumor to grow exponentially. Blockage of VEGF-related pathways seems to be a valid therapeutic target. It was suggested in recent studies, that besides already used drugs, e.g., bevacizumab, there are other agents with potential usefulness in anticancer activity such as miRNAs, TMEA, granzyme K, baicalein and arginine. Moreover, VEGF proteins were assessed to induce the expression of anti-apoptotic proteins such as BCL-2 and BAX. Therefore, investigations concerning the usefulness of VEGF family members, not only in the development but also in the therapy of CRC, in order to fully elucidate their role in carcinogenesis, are extremely important.

Biomarkers for the Diagnosis of Alzheimer's Disease in Clinical Practice: The Role of CSF Biomarkers during the Evolution of Diagnostic Criteria.

Alzheimer's disease (AD) is a progressive condition and the most common cause of dementia worldwide. The neuropathological changes characteristic of the disorder can be successfully detected before the development of full-blown AD. Early diagnosis of the disease constitutes a formidable challenge for clinicians. CSF biomarkers are the in vivo evidence of neuropathological changes developing in the brain of dementia patients. Therefore, measurement of their concentrations allows for improved accuracy of clinical diagnosis. Moreover, AD biomarkers may provide an indication of disease stage. Importantly, the CSF biomarkers of AD play a pivotal role in the new diagnostic criteria for the disease, and in the recent biological definition of AD by the National Institute on Aging, NIH and Alzheimer's Association. Due to the necessity of collecting CSF by lumbar puncture, the procedure seems to be an important issue not only from a medical, but also a legal, viewpoint. Furthermore, recent technological advances may contribute to the automation of AD biomarkers measurement and may result in the establishment of unified cut-off values and reference limits. Moreover, a group of international experts in the field of AD biomarkers have developed a consensus and guidelines on the interpretation of CSF biomarkers in the context of AD diagnosis. Thus, technological advancement and expert recommendations may contribute to a more widespread use of these diagnostic tests in clinical practice to support a diagnosis of mild cognitive impairment (MCI) or dementia due to AD. This review article presents up-to-date data regarding the usefulness of CSF biomarkers in routine clinical practice and in biomarkers research.