Analysis of the Presence and Levels of IgG Antibodies Directed against the S1 Protein Receptor Binding Domain and the N Protein of SARS-CoV-2 in Patients with Multiple Sclerosis Treated with Immunomodulatory Therapies.

The coronavirus 2019 disease (COVID-19) course and serological statuses of patients with relapsing-remitting multiple sclerosis (RRMS), treated with disease-modifying therapies (DMTs) are generally parallel that of the general population. Over the pandemic's course, however, a notable increase in the number of RRMS patients who received vaccination against severe acute respiratory coronavirus 2 (SARS-CoV-2) and those who had COVID-19 (symptomatic and asymptomatic) was reported. This virus and/or vaccination likely influenced DMT-treated RRMS patients' serological statuses regarding the presence of SARS-CoV-2 antibodies and their quantitative expression. This investigation assesses the presence and levels of the antibody directed against the S1 protein receptor binding domain (SRBD) and against the N protein of SARS-CoV-2 in 38 DMT-treated RRMS patients. The findings indicate that people vaccinated against SARS-CoV-2 exhibited significantly higher levels of IgG antibodies against S1-RBD at both assessment points. Patients with a prior history of COVID-19 demonstrated statistically significant increases in anti-N antibodies at visit 1, whereas such statistical significance was not observed at visit 2. DMT-treated RRMS patients generated neutralizing antibodies following vaccination and/or COVID-19 infection. Nevertheless, it is noteworthy that antibody levels more accurately reflect the serological status and exhibit a stronger correlation with vaccination than just the presence of antibodies.

Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer's disease neuropathology.

Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer's disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize tau forms phosphorylated additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that is specific to p-tau212 without cross-reactivity to p-tau217. Here, we examined the diagnostic utility of plasma p-tau212. In five cohorts (n = 388 participants), plasma p-tau212 showed high performances for AD diagnosis and for the detection of both amyloid and tau pathology, including at autopsy as well as in memory clinic populations. The diagnostic accuracy and fold changes of plasma p-tau212 were similar to those for p-tau217 but higher than p-tau181 and p-tau231. Immunofluorescent staining of brain tissue slices showed prominent p-tau212 reactivity in neurofibrillary tangles that co-localized with p-tau217 and p-tau202/205. These findings support plasma p-tau212 as a peripherally accessible biomarker of AD pathophysiology.

The Role of Pentraxin 3 in Gastrointestinal Cancers.

Gastrointestinal cancers have become a huge problem worldwide as the number of new cases continues to increase. Due to the growing need to explore new biomarkers and therapeutic targets for the detection and treatment of cancerous lesions, we sought to elucidate the role of Pentraxin-3 in the progression of cancerous lesions, as it is involved in the process of angiogenesis and inflammation. Statistically significant changes in the concentration of this parameter have emerged in many gastrointestinal cancer patients. Moreover, it is related to the advancement of cancer, as well as processes leading to the development of those changes. In the case of studies concerning tissue material, both increased and decreased tissue expression of the tested parameter were observed and were dependent on the type of cancer. In the case of cell lines, both human and animal, a significant increase in Pentraxin 3 gene expression was observed, which confirmed the changes observed at the protein level. In conclusion, it can be assumed that PTX3, both at the level of gene expression and protein concentrations, is highly useful in the detection of gastrointestinal cancers, and its use as a biomarker and/or therapeutic target may be useful in the future.

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.

Higher Content but No Specific Activity in Gelatinase B (MMP-9) Compared with Gelatinase A (MMP-2) in Human Renal Carcinoma.

Gelatinases belong to a group of enzymes known as matrix metalloproteinases (MMPs). Gelatinases A and B (MMP-2 and MMP-9, respectively) are the enzymes with the highest ability to destroy collagen, primarily type IV collagen, which is an essential component of the base membrane. Hence, it can be assumed that they are involved, among other things, with the metastasis process of cancer. As a result, the objective of this study was to assess the presence, activity, and expression of selected gelatinases in human renal cancer. Healthy (n = 20) and clear-cell kidney cancer tissue samples (G2 n = 10, G3 n = 10) were analyzed. The presence and content of MMPs were measured using the Western blot and ELISA methods, respectively. The activity (actual and specific) was analyzed with a fluorimetric method. The presence of both investigated enzymes was demonstrated in the representative zymogram. MMP-9 showed the most intensive saturation. It has been observed that both gelatinases occur primarily in high molecular complexes in the human kidney, regardless of whether it is a control or tumor tissue. Both gelatinases were present in comparable amounts in healthy tissues of the kidney. MMP-9 showed a higher content than MMP-2 in both renal cancer grades, but we observed the enhanced activity of both gelatinases with an increase in the grade of renal cancer. A higher MMP-9 content and, on the other hand, lower specific activity in the cancer tissue suggest that MMP-9 is predominantly present in an inactive form in renal cancer. The higher activity of MMP-9 demonstrated using the zymography method may be a cause of different values of activity that depend on the phase of the carcinogenic process. The present study revealed changes in the tested gelatinases in healthy and cancerous tissues of renal cell carcinoma. Therefore, it can be concluded that matrix metalloproteinases 2 and 9 are enzymes directly involved in carcinogenesis, and hence, it seems that MMPs may have potential in the diagnosis and treatment of renal carcinoma.

The Effect of Antidepressant Treatment on Neurocognitive Functions, Redox and Inflammatory Parameters in the Context of COVID-19.

Inflammation is an important component of the etiopathology of depression that uses oxidative and nitrosative stress (O&NS) and elevated inflammatory markers. SARS-CoV-2 infection is also associated with abnormal inflammatory processes, which may impair effective treatment of depression in COVID-19 survivors. In the presented study, thirty-three hospitalized patients with major depressive disorder (MDD) were started on antidepressant treatment, and twenty-one were re-evaluated after 4-6 weeks. The control group consisted of thirty healthy volunteers. All participants underwent neuropsychiatric evaluation, biochemical blood and urine analyses. The results of the research demonstrated positive correlations of the Hamilton Depression Rating Scale (HAM-D) scores with serum catalase (CAT) and urinary S-Nitrosothiols levels, and the Beck Depression Inventory (BDI) scores with serum reduced glutathione (GSH) and superoxide dismutase (SOD) levels. Depressed patients with a history of COVID-19 prior to the treatment had higher urinary nitric oxide (NO) levels and lower serum glutathione peroxidase (GPx) levels. In the control group, COVID-19 survivors had higher levels of urinary N-formylkynurenine (NFK). Our results suggest that the antidepressant treatment has a modulating effect on O&NS, reduces depressive symptoms and improves cognitive functions The present study does not indicate that clinical response to antidepressant treatment is associated with COVID-19 history and baseline SARS-CoV-2 antibody levels. Nevertheless, further research in this area is needed to systematize antidepressant treatment in COVID-19 survivors.

Optimized RT-qPCR and a novel normalization method for validating circulating miRNA biomarkers in ageing-related diseases.

Circulating miRNAs have potential as minimally invasive biomarkers for diagnosing various diseases, including ageing-related disorders such as Alzheimer's disease (AD). However, the lack of standardization in the common analysis method, RT-qPCR, and specifically in the normalization step, has resulted in inconsistent data across studies, hindering miRNA clinical implementation as well as basic research. To address this issue, this study proposes an optimized protocol for key steps in miRNA profiling, which incorporates absorbance-based haemolysis detection for assessing sample quality, double spike-in controls for miRNA isolation and reverse transcription, and the use of 7 stable normalizers verified in an aging population, including healthy subjects and individuals at different stages of Alzheimer's disease (140 subjects). The stability of these 7 normalizers was demonstrated using our novel method called BestmiRNorm for identifying optimal normalizers. BestmiRNorm, developed utilizing the Python programming language, enables the assessment of up to 11 potential normalizers. The standardized application of this optimized RT-qPCR protocol and the recommended normalizers are crucial for the development of miRNAs as biomarkers for AD and other ageing-related diseases in clinical diagnostics and basic research.

CXCL5 and CXCL14, but not CXCL16 as potential biomarkers of colorectal cancer.

Experts emphasize that colorectal cancer (CRC) incidence and mortality are increasing. That is why its early detection is of the utmost importance. Patients with cancer diagnosed in earlier stages have a better prognosis and a chance for faster implementation of treatment. Consequently, it is vital to search for new parameters that could be useful in its diagnosis. Therefore, we evaluated the usefulness of CXCL5, CXCL14 and CXCL16 in serum of 115 participants (75 CRC patients and 40 healthy volunteers). Concentrations of all parameters were measured using Luminex. CRP (C-reactive protein) levels were determined by immunoturbidimetry, while levels of classical tumor markers were measured using CMIA (Chemiluminescence Microparticle Immunoassay). Concentrations of CXCL5 were statistically higher in the CRC group when compared to healthy controls. The diagnostic sensitivity, specificity, positive and negative predictive value, and area under the ROC curve (AUC) of CXCL5 and CXCL14 were higher than those of CA 19-9. Obtained results suggest the usefulness of CXCL5 and CXCL16 in the determination of distant metastases and differentiation between TNM (Tumor-Node-Metastasis) stages, as well as the usefulness of CXCL14 and CRP combination in CRC detection (primary or recurrence). However, further studies concerning their role in CRC progression are crucial to confirm and explain their diagnostic utility and clinical application as biomarkers.

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.

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.

Subfertility as Overlapping of Nutritional, Endocrine, Immune, and Cardiometabolic Dysregulations-A Study Focused on Biochemical Endophenotypes of Subfertile Couples.

Subfertility is a global health issue, and as many as 30% of cases are attributed to unexplained reasons. A hypercaloric, high-fat diet stimulates the expansion of pro-inflammatory gut microbiota with a consequent rise in circulating lipopolysaccharides. Adverse gut microbiota remodeling can exacerbate insulin resistance, while sex and thyroid hormones may influence the variability in gut microbiota. This cross-sectional study included 150 participants and was designed to determine a biochemical, nutritional-related pattern that may distinguish subfertile from fertile individuals and couples. A panel of 28 biomarkers was assessed. Four biochemical phenotypes of unexplained subfertility were found, including two metabolic and two immune, when assessed using binary logistic regression models. Two phenotypes were distinguished in women: cardio-metabolic with atherogenic dyslipidemia (LowHDL-cholesterol: OR = 10.9; p < 0.05) and autoimmune thyroid disorder (Highanti-thyroid-peroxidase: OR = 5.5; p < 0.05) and two in men: hepato-metabolic with elevated liver injury enzymes (HighHOMA-IR: OR = 6.1; p < 0.05) and immune type-2 response (HighIgE: OR = 6.4; p < 0.05). The chances of a couple's subfertility rose with the number of laboratory components of metabolic syndrome in the couple (OR = 1.7; p < 0.05) and if at least one partner had an elevated total IgE level (>100 kU/L) (OR = 6.5; p < 0.05). This study found that unexplained subfertility may be accompanied by mutually overlapping immune and metabolic dysregulations in individuals and couples. We propose one-time laboratory diagnostics taking into account the lipid profile, insulin resistance, anti-thyroid-peroxidase, and total IgE in both males and females with unexplained subfertility. This may allow for a one-time assessment of targeted medical and nutritional interventions and help optimize patients' health. The gut-organ axes related to subfertility are discussed in the context of the obtained results.

Potential Diagnostic Utility of microRNAs in Gastrointestinal Cancers.

Early detection of gastrointestinal cancers is beneficial for patient survival and prognosis. MiRNAs have been shown to be potential cancer biomarkers that can be used to diagnose cancers. MiRNAs are single-stranded, small non-coding RNAs that are involved in the post-transcriptional regulation of the expression of different oncogenes. Cancer tissues contain miRNAs that play a special role in the etiology of cancer development or limiting cancer suppression. Dysregulation of miRNAs occurs in a variety of malignancies, including gastrointestinal cancers. MiRNAs are stable and protected against degradation by RNase, which enables their detection in tissues and biological fluids. The results of many studies suggest that miRNAs have a relatively higher diagnostic efficiency in distinguishing cancer patients from healthy people. The researchers have identified many miRNA signature in the blood for the detection of gastrointestinal cancers. This review focuses on the role and potential utility of miRNAs in the early detection, prognosis and evaluation of the treatment effectiveness of gastrointestinal cancers.

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 Significance of CXCL1 and CXCR1 as Potential Biomarkers of Colorectal Cancer.

The CXCL1/CXCR2 and CXCL8-CXCR1/CXCR2 axes are under intensive investigation as they appear to regulate the progression and invasion of colorectal cancer (CRC). Growing evidence demonstrates the elevated expression of these proteins in CRC. However, a majority of relevant studies have been performed on CRC tissues using immunohistochemical techniques. Our study is the first to evaluate the diagnostic significance of serum CXCL1 and CXCR1 levels in CRC patients in comparison to well-established tumor markers, such as the carcinoembryonic antigen (CEA), and markers of inflammation, such as C-reactive protein (CRP). Thus, the aim of our study was to assess whether circulating serum levels of CXCL1 and CXCR1 might be candidates for novel biomarkers in the diagnosis and progression of CRC. The study was performed on 76 subjects, including patients with CRC and healthy volunteers as a control group. Serum concentrations of CXCL1, CXCR1, and the classical tumor marker (CEA) were measured using immunoenzyme assays, while CRP levels were assessed with the immunoturbidimetric method. Serum CXCL1 levels were statistically significantly increased in CRC patients when compared to healthy subjects, and similar results were found for CEA and CRP levels. The percentage of elevated concentrations of CXCL1 and CXCR1 was higher than that of the classical tumor biomarker and increased in the combined measurement of these proteins with CEA. In addition, among all proteins tested, serum CXCL1 seems to be the best indicator in the differentiation between CRC patients with nodal involvement and patients without the presence of lymph node metastasis. Our preliminary results indicate the role of serum CXCL1 and CXCR1 in the diagnosis of CRC, particularly in the combined measurement with CEA.

Potential Utility of Cerebrospinal Fluid Glycoprotein Nonmetastatic Melanoma Protein B as a Neuroinflammatory Diagnostic Biomarker in Mild Cognitive Impairment and Alzheimer's Disease.

Alzheimer's disease (AD) is a very common neurodegenerative disorder characterized by the gradual loss of neurons and extracellular amyloid-peptide buildup. There is compelling evidence that the disease process depends on neuroinflammatory alterations, such as the activation of astrocytes and microglia cells. A transmembrane glycoprotein known as glycoprotein nonmetastatic melanoma protein B (GPNMB) plays a neuroprotective role during the development of neurodegeneration. To the best of our knowledge, this is the first investigation discussing the potential clinical usefulness of this protein in the AD continuum, especially in the MCI (mild cognitive impairment) stage. A total of 71 patients with AD or MCI as well as controls were enrolled in this study. The concentrations of GPNMB, YKL-40, Aß1-42 (amyloid beta 1-42), Tau, and pTau and the Aß1-42/1-40 ratio in the CSF (cerebrospinal fluid) were tested using immunological methods. The concentrations of both GPNMB and YKL-40 in the cerebrospinal fluid were significantly higher in patients with AD and MCI compared to the controls. Moreover, both proteins were biochemically associated with classical biomarkers of AD and were especially associated with the Aß1-42/1-40 ratio and Tau and pTau levels in the whole study group. Elevated concentrations of GPNMB were observed in the Aß(+) group of AD patients compared to the Aß(-) subjects. Additionally, the diagnostic performance (AUC value) of GPNMB was higher than that of amyloid ß1-42 in MCI patients compared with controls. Our study indicates that GPNMB might be a promising neuroinflammatory biomarker for the early diagnosis and prognosis of the AD continuum, with potential utility as a therapeutic target.

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.

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.

The Clinical Significance of Serum Free Light Chains in Bladder Cancer.

This research aimed to assess the clinical usefulness of serum kappa (κ) and lambda (λ) free light chains (FLCs) in patients with bladder cancer (BC). One hundred samples were collected and analysed from healthy volunteers (C) and bladder cancer patients. Cancer patients were divided into two subgroups: low-grade (LG) and high-grade cancer (HG). Concentrations of FLCs, CEA, CA19-9, creatinine and urea were measured per manufacturers' guidelines. The concentrations of κ and λ FLCs and CEA were significantly higher in BC patients in comparison to the control group. Moreover, the concentrations of κ and λ FLCs and CEA were significantly higher in both low-grade as well as high-grade cancer in comparison to the controls. The levels of κ and λ FLCs differed between tumour grades, with patients presenting higher concentrations in high-grade compared to low-grade cancer. In the total study group, κFLC correlated with λFLC, the κ:λ ratio, CRP, CEA, CA19-9, creatinine and urea. There was also a correlation between λFLC and κFLC, CRP, CEA, creatinine and urea. The λFLC showed a higher ability (sensitivity and PPV) to detect bladder cancer in comparison to κFLC and CEA. In addition, λFLC had a higher ability to exclude BC (specificity and NPV) than κFLC and CEA. λFLC also showed the highest accuracy in the detection of bladder cancer. In conclusion, the revealed differences in the concentrations of both κ and λ FLCs suggest their potential participation in bladder cancer development. Increased concentrations of free light chains in bladder cancer patients and the association with the tumour grade suggest that κ and λ FLC measurements may be useful in the diagnosis and prognosis of bladder cancer. This is the first research that evaluates the concentration of FLCs in bladder cancer, so further studies are necessary to confirm their usefulness as tumour markers of this malignancy.

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.

A Novel Approach to Staging and Detection of Colorectal Cancer in Early Stages.

Colorectal cancer (CRC) is a significant problem affecting patients all over the world. Since it is the fourth most common cause of cancer-related deaths, many scientists aim to expand their knowledge on the detection in early stages and treatment of this disease. Chemokines, as protein parameters involved in many processes accompanying the development of cancer, constitute a group of potential biomarkers that could also be useful in the detection of CRC. For this purpose, our research team used the results of thirteen parameters (nine chemokines, one chemokine receptor and three comparative markers, i.e., CEA, CA19-9 and CRP) to calculate one hundred and fifty indexes. Moreover, for the first time, the relationship between these parameters during the ongoing cancer process and in comparison to a control group are presented. As a result of statistical analyses using patients' clinical data and the obtained indexes, it was established that several of the indexes have a diagnostic utility that is much higher than the tumor marker that is currently the most commonly used (CEA) currently. Furthermore, two of the indexes (CXCL14/CEA and CXCL16/CEA) showed not only extremely high usefulness in the detection of CRC in its early stages, but also the ability to determine whether the stage is low (stage I and II) or high (stage III and IV).