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Membrane-type metalloproteinases (including MMP-14 and MMP-15) are enzymes involved in the degradation of extracellular matrix components. In cancer, they are involved in processes such as cellular invasion, angiogenesis and metastasis. Therefore, the aim of this study was to evaluate the expression, content and activity of MMP-14 and MMP-15 in human renal cell carcinoma. Samples of healthy kidney tissue (n = 20) and tissue from clear-cell kidney cancer (n = 20) were examined. The presence and contents of the MMPs were assessed using Western blot and ELISA techniques, respectively. Their activity-both actual and specific-was evaluated using fluorimetric analysis. Both control and cancer human kidney tissues contain MMP-14 and MMP-15 enzymes in the form of high-molecular-weight complexes. Moreover, these enzymes occur in both active and latent forms. Their content in cancer tissues is very similar, but with a noteworthy decrease in content with an increase in the kidney cancer grade for both membrane-type metalloproteinases. Even more notable is the highest content of the investigated enzymes represented by MMP-14 in the control tissues. Considering the actual and specific activity outcomes, MMP-14 dominates over MMP-15 in all of the investigated tissues. Nevertheless, we also noted a significant enhancement of the activity of both metalloproteinases with an increase in the grade of renal cancer. The expression and activity of both enzymes were detected in all examined renal cancer tissues. However, our findings suggest that transmembrane metalloproteinase 14 (MMP-14) plays a much more significant and essential role than MMP-15 in the studied renal carcinoma tissues. Therefore, it seems that MMP-14 could be a promising target in the diagnosis, prognosis and therapy of renal cell carcinoma.
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Carcinoma de Células Renais , Neoplasias Renais , Metaloproteinase 14 da Matriz , Metaloproteinase 15 da Matriz , Humanos , Metaloproteinase 14 da Matriz/metabolismo , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/enzimologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/enzimologia , Metaloproteinase 15 da Matriz/metabolismo , Metaloproteinase 15 da Matriz/genética , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , AdultoRESUMO
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.
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COVID-19 , Diabetes Mellitus Tipo 2 , Humanos , SARS-CoV-2 , Cadeias Leves de Imunoglobulina , Cadeias lambda de Imunoglobulina , Biomarcadores , InflamaçãoRESUMO
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.
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COVID-19 , Esclerose Múltipla , Humanos , Imunidade Celular , SARS-CoV-2 , VacinaçãoRESUMO
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.
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COVID-19 , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , SARS-CoV-2 , Acetato de Glatiramer/uso terapêutico , Fumarato de Dimetilo/uso terapêutico , Interferon beta , N,N-Dimetiltriptamina , Imunoglobulina A , Imunoglobulina G , Anticorpos AntiviraisRESUMO
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.
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COVID-19 , Quimiocina CXCL10 , Síndrome da Liberação de Citocina , Citocinas , Humanos , SARS-CoV-2RESUMO
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.
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COVID-19/patologia , NF-kappa B/metabolismo , COVID-19/imunologia , Humanos , Inflamação/patologia , SARS-CoV-2 , Tratamento Farmacológico da COVID-19RESUMO
The aim of this study is to assess the synthesis of kappa (κ) and lambda (λ) free light chains (FLCs) in the serum of patients with COVID-19. All the 120 serum samples were collected from patients with COVID-19 and from healthy controls (vaccinated and non-vaccinated against SARS-CoV-2). FLCs, IgG total, IgG4, IgG anti-Nucleocapsid (N), anti-spike S1 receptor binding domain (S-RBD) antibodies and IL-6 were measured according to the manufacturers' instructions. The concentrations of anti-N IgG, IgG total, IgG4 and IL-6 were elevated in the COVID-19 group in comparison to the vaccinated and non-vaccinated controls. The levels of anti-S-RBD IgG and κFLC were increased in COVID-19 and healthy vaccinated patients when compared to non-vaccinated controls. λFLC concentration was higher in the COVID-19 group than in the non-vaccinated group. The κ:λ ratio was lower in both COVID-19 and non-vaccinated groups in comparison to vaccinated controls. κFLC correlated with all tested parameters (anti-S-RBD IgG, anti-N IgG, λFLC, κ:λ ratio, IgG total, IgG4 and IL-6) except CRP, whereas λFLC correlated with all examined parameters except IgG4. Elevated levels of FLCs in COVID-19 and healthy vaccinated against SARS-CoV-2 patients, as well as the correlation between free light chains with specific anti-SARS-CoV-2 antibodies and IL-6, reflect hyperactivation of the immune system after contact with coronavirus. Furthermore, it seems that serum levels of FLCs might be used as predictive markers of COVID-19. Our findings suggest that free light chains are involved in SARS-CoV-2 infection. However, understanding the exact mechanism requires further investigation.
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COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Humanos , Imunoglobulina G , Cadeias Leves de Imunoglobulina , Interleucina-6RESUMO
Tick-borne encephalitis (TBE) is an acute disease caused by the tick-borne encephalitis virus. Due to the viral nature of the condition, there is no effective causal treatment for full-blown disease. Current and nonspecific TBE treatments only relieve symptoms. Unfortunately, the first phase of TBE is characterized by flu-like symptoms, making diagnosis difficult during this period. The second phase is referred to as the neurological phase as it involves structures in the central nervous system-most commonly the meninges and, in more severe cases, the brain and the spinal cord. Therefore, it is important that early markers of TBE that will guide clinical decision-making and the choice of treatment are established. In this review, we performed an extensive search of literature reports relevant to biomarkers associated with TBE using the MEDLINE/PubMed database. We observed that apart from routinely determined specific immunoglobulins, free light chains may also be useful in the evaluation of intrathecal synthesis in the central nervous system (CNS) during TBEV infection. Moreover, selected metalloproteinases, chemokines, or cytokines appear to play an important role in the pathogenesis of TBE as a consequence of inflammatory reactions and recruitment of white blood cells into the CNS. Furthermore, we reported promising findings on tau protein or Toll-like receptors. It was also observed that some people may be predisposed to TBE. Therefore, to understand the role of selected tick-borne encephalitis biomarkers, we categorized these factors and discussed their potential application in the diagnosis, prognosis, monitoring, or management of TBE.
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Vírus da Encefalite Transmitidos por Carrapatos , Encefalite Transmitida por Carrapatos/sangue , Encefalite Transmitida por Carrapatos/líquido cefalorraquidiano , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/líquido cefalorraquidiano , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Barreira Hematoencefálica/patologia , Quimiocinas/sangue , Quimiocinas/líquido cefalorraquidiano , Encefalite Transmitida por Carrapatos/diagnóstico , Encefalite Transmitida por Carrapatos/genética , Encefalite Transmitida por Carrapatos/virologia , Predisposição Genética para Doença , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Imunoglobulina M/sangue , Imunoglobulina M/líquido cefalorraquidiano , Cadeias lambda de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/líquido cefalorraquidiano , Metaloproteinase 9 da Matriz/sangue , Metaloproteinase 9 da Matriz/líquido cefalorraquidianoRESUMO
Neuroborreliosis (NB) and neurosyphilis (NS) are abnormal conditions caused by spirochetal bacteria which affect the nervous system. Diagnosis of neuroborreliosis and neurosyphilis is determined by clinical examination of visible symptoms, serum and cerebrospinal fluid (CSF) analysis, and serological detection of antibodies against Borrelia burgdorferi sensu lato and Treponema pallidum, respectively. Establishing a diagnosis may sometimes pose a number of diagnostic difficulties. A potential role of chemokine ligand 13 (CXCL13) as an accurate diagnostic biomarker of intrathecal inflammation has been suggested. In this review, we focused on changes in serum and cerebrospinal fluid concentration of chemokine ligand 13 in selected spirochetal neurological diseases neuroborreliosis and neurosyphilis reported in the available literature. We performed an extensive search of the literature relevant to our investigation via the MEDLINE/PubMed database. It has been proven that CXCL13 determination can provide rapid information regarding central nervous system inflammation in patients with selected spirochetosis. We described that neuroborreliosis and neurosyphilis are associated with an elevated CXCL13 concentration, mainly in the cerebrospinal fluid. Moreover, literature data suggest that CXCL13 determination is the most interesting additional marker for diagnosis and monitoring of neuroborreliosis and neurosyphilis thanks to its high sensitivity. Based on these published findings, we suggest that CXCL13 has high diagnostic utility and may be applied in laboratory diagnostics as a potential diagnostic marker in human spirochetal neurologic diseases.
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Biomarcadores , Quimiocina CXCL13/líquido cefalorraquidiano , Neuroborreliose de Lyme/líquido cefalorraquidiano , Neuroborreliose de Lyme/diagnóstico , Neurossífilis/líquido cefalorraquidiano , Neurossífilis/diagnóstico , Gerenciamento Clínico , Humanos , Neuroborreliose de Lyme/etiologia , Neuroborreliose de Lyme/terapia , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/etiologia , Neurossífilis/etiologia , Neurossífilis/terapia , PrognósticoRESUMO
The major invasive subtype of kidney cancer is renal cell carcinoma (RCC). The essential components of cancer development are chronic inflammation and neoangiogenesis. It has been suggested that the chemokine ligand 9, -10, -11 (CXCL9-11) and chemokine receptor 3 (CXCR3) chemokines receptor expressed on monocytes, T and NK cells may be involved in the inhibition of angiogenesis. However, to date, little is known about the potential clinical significance of these chemokines and their receptor in renal cell carcinoma. Therefore, in this review, we described the role of CXCR3 and its ligands in pathogenesis of RCC. We performed an extensive search of the current literature in our investigation, using the MEDLINE/PubMed database. The changes of chemokines and their specific receptor in renal cell carcinoma were observed. Published studies revealed an increased expression of CXCR3 and elevated concentration of its ligands in RCC. The association between treatment of RCC and CXCL9-11/CXCR3 concentration and expression was also observed. Moreover, CXCR3 and its ligands levels were related to patient's prognosis, risk of metastasis and tumor growth. This review describes the potential role of CXCR3 and its ligands in pathogenesis of RCC, as well as their potential immune-therapeutic significance. However, future studies should aim to confirm the clinical and prognostic role of CXCL9-11/CXCR3 in renal cell carcinoma.
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Carcinoma de Células Renais/metabolismo , Quimiocinas CXC/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/metabolismo , Proteínas de Neoplasias/metabolismo , Receptores CXCR3/metabolismo , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Ligantes , PrognósticoRESUMO
INTRODUCTION: The aim of this study was to evaluate the concentration of interleukin-6 and N-terminal propeptide of procollagen type I and their relationship in liver diseases of different etiologies. MATERIAL AND METHODS: Serum samples were obtained from 30 healthy volunteers and patients suffering from alcoholic cirrhosis (AC) - 31, non-alcoholic cirrhosis (NAC) - 28 and toxic hepatitis (HT) - 23 patients. Cirrhotic patients were classified according to Child-Pugh score. IL-6 and PINP concentrations were determined according to the electrochemiluminescence immunoassay. RESULTS: The mean serum IL-6 concentration was significantly higher in AC (mean ± SD:21.52 ± 15.01 pg/mL), NAC (20.07 ± 32.12 pg/mL) and HT (15.14 ± 17.18 pg/mL) when compared to the control group (C) (1.67 ± 0.42 pg/mL) (Mann-Whitney U test: p < .001 for all comparisons). The mean serum PINP concentration was significantly higher only in patients with AC (104.32 ± 54.50 ng/mL) in comparison with the control group (54.70 ± 19.83 ng/mL; p < .001). The mean values of IL-6 and PINP significantly differed between liver diseases (ANOVA rank Kruskal-Wallis test: p = .020 and p < .001, respectively). Accordingly, the serum levels of IL-6 and PINP were significantly higher in patients with AC than that in NAC (p < .001 and p = .022, respectively). IL-6 and PINP concentrations appeared to vary depending on the severity of liver damage (p < .001 for both). The concentrations of IL-6 and PINP were significantly higher in class C (31.88 ± 21.51 pg/mL; 132.73 ± 65.63 ng/mL, respectively) than that in class A (6.12 ± 9.00 pg/mL; 57.32 ± 28.85 ng/mL, respectively) (p < .001 for both). There were also significant differences in IL-6 concentrations between Child-Pugh class B (27.88 ± 24.45 pg/mL) and class A (6.12 ± 9.00 pg/mL; p < .001). CONCLUSIONS: We conclude that serum concentrations of IL-6 and PINP change in liver diseases, and those changes reflect the severity of liver disease.
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Interleucina-6/sangue , Hepatopatias/sangue , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROCRESUMO
It is reported that alterations in protein glycosylation are present in adult rheumatic diseases; however, the data related to pediatric rheumatic conditions are very scarce. The aim of this study was to assess the effect of juvenile idiopathic arthritis (JIA) on the serum glycosylation profile of transferrin isoforms. Twenty-five patients with different clinical forms of an active JIA and 22 healthy controls were studied. Serum samples were analyzed by capillary electrophoresis on MINICAP electrophoretic system (Sebia, France) to determine the levels of transferrin isoforms. In patients with JIA, tetrasialotransferrin (median 82.6%; range 68.8-99.5) concentration was lower (P = 0.032), and pentasialotransferrin (median 14%; range 0.5-31.2) was higher (P = 0.020) in comparison to controls (median 84.45; range 79.8-87.4; median 11.55; range 9.7-16.1, respectively). No significant correlations between concentration of transferrin isoforms and disease activity score (JADAS 27) or the degree of disability (VAS and CHAQ) were found. Erythrocyte sedimentation rate and CRP levels correlated positively with disialotransferrin (R = 0.493, P = 0.017; R = 0.850, P < 0.001, respectively) and pentasialotransferrin (R = 0.533, P = 0.006; R = 0.491, P = 0.045, respectively), and negatively with trisialotransferrin (R = - 0.546, P = 0.007; R = - 0.515, P = 0.049, respectively) and tetrasialotransferrin (R = - 0.436, P = 0.029; R = - 0.504, P = 0.039, respectively). This preliminary study shows the shifts in transferrin isoforms profile among patients with JIA. Our data indicate a potential clinical utility of the transferrin isoforms measurement, especially tetrasialotransferrin and pentasialotransferrin. Further prospective studies on larger groups of patients should be conducted to validate the results.
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Artrite Juvenil/sangue , Transferrina/análise , Adolescente , Artrite Juvenil/diagnóstico , Sedimentação Sanguínea , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
Despite the fact that the global COVID-19 pandemic has officially ended, we continue to feel its effects and discover new correlations between SARS-CoV-2 infection and changes in the organism that have occurred in patients. It has been shown that the disease can be associated with a variety of complications, including disorders of the nervous system such as a characteristic loss of smell and taste, as well as less commonly reported incidents such as cranial polyneuropathy or neuromuscular disorders. Nervous system diseases that are suspected to be related to COVID-19 include Guillain-Barré syndrome, which is frequently caused by viruses. During the course of the disease, autoimmunity destroys peripheral nerves, which despite its rare occurrence, can lead to serious consequences, such as symmetrical muscle weakness and deep reflexes, or even their complete abolition. Since the beginning of the pandemic, case reports suggesting a relationship between these two disease entities have been published, and in some countries, the increasing number of Guillain-Barré syndrome cases have also been reported. This suggests that previous contact with SARS-CoV-2 may have had an impact on their occurrence. This article is a review and summary of the literature that raises awareness of the neurological symptoms' prevalence, including Guillain-Barré syndrome, which may be impacted by the commonly occurring COVID-19 disease or vaccination against it. The aim of this review was to better understand the mechanisms of the virus's action on the nervous system, allowing for better detection and the prevention of its complications.
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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.
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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.
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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.
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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.
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INTRODUCTION: Urinary bladder cancer is a serious oncological problem that is the cause of many deaths worldwide. The processes of metastasis and origination of local tumor invasion depend on the extracellular matrix (ECM) degradation. The cancer microenvironment, particularly the ECM, may be considered a key factor in cancer progression. Matrix metalloproteinases (MMPs) are classified as the main factors responsible for the degradation of ECM components. Therefore, the aim of the study was to evaluate the expression and activity of matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9) in urinary bladder cancer according to different stages. MATERIAL AND METHODS: Urinary bladder tissue samples were analyzed. Cancer patients were divided into two groups: low-grade tumors (LG; Group I) and high-grade tumors (HG; Group II). Control tissue was obtained from the opposite site to the tumor. MMPs content and activity (actual and specific) were evaluated using ELISA and Western blot methods, respectively. RESULTS: Both MMPs are present in high and low molecular complexes in healthy or bladder cancer tissues. The content of MMP-9 is enhanced in comparison with MMP-2, particularly in HG cancer tissue. The actual activity of MMP-2 was highest in LG cancer tissue whereas the actual activity of MMP-9 was highest in HG cancer. Specific activity of both MMPs was highest in LG cancer, but the activity of MMP-9 was higher in comparison with MMP-2. CONCLUSIONS: In conclusion, the content and specific activity of MMP-9 were increased in comparison with MMP-2. The revealed differences in content and activity of both MMPs demonstrate their different participation in ECM remodeling at different stages of cancer development. Moreover, it seems that MMP-9 has higher clinical utility than MMP-2 as a potential therapeutic option and a diagnostic biomarker of urinary bladder cancer.
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Stromelysin-1 and stromelysin-2 (matrix metalloproteinase 3; MMP-3 and matrix metalloproteinase 10; MMP-10, respectively) are enzymes that activate other metalloproteinases. Apart from collagen, they also degrade elastin, fibronectin, gelatin and laminin. In carcinogenic processes, they are involved in angiogenesis and metastasis. Therefore, the aim of this study was to evaluate the DNA content, expression and activity of both stromelysines in cancers of human kidney. Renal carcinoma tissue samples were analyzed. Low- and high-grade cancer tissues were collected. Control material was collected from part of the kidney opposite to the tumor. DNA content, stromelysines content and stromelysin-1 and stromelysin-2 activity were measured using ELISA and Western blot methods. A higher content of deoxyribonucleic acid in low- and high-grade cancer tissues in comparison to the respective control tissue was observed. Both stromelysines were presented in control and cancer tissues in high-molecular-weight complexes. The content of MMP-10 was significantly higher in comparison to MMP-3 in all investigated tissues. Moreover, the content of stromelysin-2 was significantly higher in high-grade (G3) tissues compared to grade 2 (G2) kidney cancer. A significant decrease in the actual and specific activities of both stromelysines was observed with the increase in renal cancer grade. The presented results may indicate that the degradation of extracellular matrix increases with a higher grade of cancer. Moreover, the elevated content and decreased specific activity of stromelysin-2 in cancer tissue indicate that MMP-10 is mainly present in an inactive form in renal carcinoma. Detailed knowledge of the mechanism and participation of stromelysines in extracellular matrix degradation may be important in understanding the pathomechanism of renal cancer development. Therefore, the potential application of stromelysines in the monitoring or prognosis of kidney cancer should be discussed.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Metaloproteinase 10 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Colágeno , DNA , Elastina , Fibronectinas/metabolismo , Gelatina , Humanos , Laminina , Metaloendopeptidases/genética , Metaloendopeptidases/metabolismoRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovered in 2019, is responsible for the global coronavirus disease 19 (COVID-19) pandemic. The main protein that interacts with the host cell receptor is the Spike-1 (S1) subunit of the coronavirus. This subunit binds with receptors present on the host cell membrane. It has been identified from several studies that neuropilin-1 (NRP-1) is one of the co-receptors for SARS-CoV-2 entry. Therefore, in this review, we focus on the significance of NRP-1 in SARS-CoV-2 infection. MEDLINE/PubMed database was used for a search of available literature. In the current review, we report that NRP-1 plays many important functions, including angiogenesis, neuronal development, and the regulation of immune responses. Additionally, the presence of this glycoprotein on the host cell membrane significantly augments the infection and spread of SARS-CoV-2. Literature data suggest that NRP-1 facilitates entry of the virus into the central nervous system through the olfactory epithelium of the nasal cavity. Moreover, published findings show that interfering with VEGF-A/NRP-1 using NRP-1 inhibitors may produce an analgesic effect. The review describes an association between NRP-1, SARS-CoV-2 and, inter alia, pathological changes in the retina. Based on the published findings, we suggest that NRP-1 is a very important mediator implicated in, inter alia, neurological manifestations of SARS-CoV-2 infection. Additionally, it appears that the use of NRP-1 inhibitors is a promising therapeutic strategy for the treatment of SARS-CoV-2 infection.