Hairy cell leukemia - etiopathogenesis, diagnosis and modern therapeutic approach.

Hairy cell leukemia (HCL) represents 2% of all leukemia cases, with men aged above 55 years being the most affected. The most common symptoms of this type of leukemia include splenomegaly, monocytopenia, and neutropenia. In the basic blood count examination, leukopenia with monocytopenia and granulocytopenia, as well as aplastic anemia and/or thrombocytopenia occur. The mutation of ß-rapidly accelerated fibrosarcoma (BRAF) proto-oncogene, which can be found in nearly 100% of patients, is an important feature of HCL. Immunophenotypic analysis of the HCL cells reveals high expression of B-lineage antigens, including CD19, CD20, and CD22. Additionally, CD11c, CD25, CD103, and CD123 belong to specific markers of HCL. Lactate dehydrogenase activity and ß-2-microglobulin concentration are also important in the patient's assessment. The differential diagnosis between HCL, hairy cell leukemia variant (HCL-V) and splenic marginal zone lymphoma (SMZL) is of first importance. Currently, the main treatment for HCL involves the use of purine analogues, excluding pregnant women, individuals with severe infections, and those with relapsing HCL.

Exploring the Link between Inflammatory Biomarkers and Head and Neck Cancer: Understanding the Impact of Smoking as a Cancer-Predisposing Factor.

Head and neck cancer (HNC) is associated with significant morbidity globally, with smoking recognized as a key risk factor. This study investigates the interplay between smoking and inflammatory biomarkers in HNC development. The study involved 50 HNC patients, divided into smoking and non-smoking groups, and a control group of 30 healthy individuals. Serum levels of 48 cytokines, chemokines, growth factors, and other inflammatory markers were meticulously assessed. Significant differences in the levels of an extensive panel of inflammatory markers were observed between the patient groups and healthy controls. Elevated macrophage colony-stimulating factor (M-CSF) in both HNC groups implicated increased activity in pathways known for immunomodulation, proliferation, and angiogenesis during HNC cancerogenesis. In contrast, non-smokers with HNC demonstrated higher levels of interleukin 10 (IL-10) and interleukin 15 (IL-15), suggesting a more robust immune response. Platelet-derived growth factor BB (PDGF-BB) levels were particularly high in smokers with HNC. Smoking seems to alter the levels of crucial biomarkers in HNC, potentially affecting disease progression and responses to treatment. The data indicate that smokers may experience a more aggressive cancer phenotype, while non-smokers maintain a profile suggestive of a more active and effective immune response against HNC.

Evaluating p-tau217 and p-tau231 as Biomarkers for Early Diagnosis and Differentiation of Alzheimer's Disease: A Narrative Review.

The escalating prevalence of Alzheimer's disease (AD) highlights the urgent need to develop reliable biomarkers for early diagnosis and intervention. AD is characterized by the pathological accumulation of amyloid-beta plaques and tau neurofibrillary tangles. Phosphorylated tau (p-tau) proteins, particularly p-tau217 and p-tau231, have been identified as promising biomarker candidates to differentiate the disease progression from preclinical stages. This narrative review is devoted to a critical evaluation of the diagnostic accuracy, sensitivity, and specificity of p-tau217 and p-tau231 levels in the detection of AD, measured in plasma, serum, and cerebrospinal fluid, compared to established biomarkers. Additionally, the efficacy of these markers in distinguishing AD from other neurodegenerative disorders is examined. The significant advances offered by p-tau217 and p-tau231 in AD diagnostics are highlighted, demonstrating their unique utility in early detection and differential diagnosis. This comprehensive analysis not only confirms the excellent diagnostic capabilities of these markers, but also deepens the understanding of the molecular dynamics of AD, contributing to the broader scientific discourse on neurodegenerative diseases. This review is aimed to provide key information for researchers and clinicians across disciplines, filling interdisciplinary gaps and highlighting the role of p-tau proteins in revolutionizing AD research and clinical practice.

Adipokines, Vitamin D, and Selected Inflammatory Biomarkers among Parkinson's Disease Patients with and without Dyskinesia: A Preliminary Examination.

Parkinson's disease (PD), a widely recognized neurodegenerative disorder, is characterized by a spectrum of symptoms including motor fluctuations and dyskinesia. Neuroinflammation and dysregulation of adipokines are increasingly implicated in the progression of PD. This preliminary study investigated the levels of inflammatory biomarkers and adipokines, namely interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), C-reactive protein (CRP), visfatin, progranulin, and 25(OH)-vitamin D in 52 PD patients, divided equally between those with and without dyskinesia and 26 healthy controls. Significant differences in the levels of IL-6, TNF-α, visfatin, and progranulin were noted between the groups. Patients with dyskinesia exhibited notably higher IL-6 levels compared to controls, and TNF-α was significantly elevated in both PD patient groups relative to the control group. Additionally, visfatin levels were higher in PD patients without dyskinesia as opposed to those with dyskinesia, and progranulin levels were elevated in the non-dyskinetic PD group compared to controls. The findings highlight the potential role of the examined biomarkers in the pathophysiology of PD. Changes in levels of the tested inflammatory biomarkers and adipokines might be associated with Parkinson's disease and its symptoms such as dyskinesia.

30-Min Exposure to Tobacco Smoke Influences Airway Ion Transport-An In Vitro Study.

Introduction: Smoking is one of the most important causes of cancer in humans. However, it has not been proven how long exposure to cigarette smoke is sufficient to induce cancerogenesis. Cigarette smoke can cause changes in ion and water transport and the maintenance of mucociliary transport. The conducted research concerned the assessment of changes in ion transport in rabbit tracheal specimens after 30 min of exposure to cigarette smoke. Materials and Methods: A modified Ussing chamber was used to measure the transepithelial electrical potential under stationary conditions (PD) and during mechanical stimulation (PDmin), and the transepithelial electrical resistance (R) in control and cigarette smoke-exposed tracheal fragments. Results: Significant changes in PD (-2.53 vs. -3.92 mV) and PDmin (-2.74 vs. -0.39 mV) were noted for the samples exposed to smoke, which can be associated with a rise in reactivity after applying a mechanical stimulus. In addition, the measured R (108 vs. 136 Ω/cm2) indicated no changes in the vitality of the samples, but an increase in their permeability to ions in the experimental conditions. Conclusions: A single 30-min exposure to cigarette smoke has been shown to be associated with increased permeability of the tracheal epithelium to ions and thus to substances emitted during smoking, which might be sufficient to create the possibility of initiating procarcinogenic processes.

Effective Interventions in Obesity: Current Evidence and Concepts.

This Special Issue, entitled "Specialized Diet, Obesity and Associated Metabolic Disorders" in the section "Clinical Nutrition" of Nutrients, addresses the metabolic changes that occur in humans as a result of the so-called western lifestyle [...].

Dietary Interventions in Obesity and Metabolic Syndrome.

Here, we present a Special Issue of Nutrients entitled "Specialized Diet, Obesity and Associated Metabolic Diseases" containing up-to-date scientific data important to both researchers and the public [...].

Changes in the Secretion of Melatonin and Selected Adipokines during the Progression of Parkinson's Disease-Preliminary Studies.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases affecting elderly people. Considering the gap in the literature on melatonin and adipokine levels in PD patients at various stages of the disease, we conducted a study to investigate the levels of selected parameters in PD patients at the disease's early (ES) and advanced (AS) stages. Melatonin, leptin, adiponectin, and resistin concentrations were measured in the blood serum of 20 PD patients without dyskinesia (ES), 24 PD patients with dyskinesia (AS), and 20 healthy volunteers as a control group (CG). The data were analyzed using ANOVA. Melatonin was significantly lower in ES (p < 0.05) and higher in AS patients (p < 0.05) compared to CG. The level of leptin was increased both in ES (p < 0.001) and AS (p < 0.001) versus CG, while resistin was increased only in patients with dyskinesia (p < 0.05). Higher melatonin (p < 0.001) and resistin (p < 0.05) and lower leptin (p < 0.05) levels were found in AS versus ES. The main findings of the study include the changes in inflammatory markers' levels during PD and a surprising increase in melatonin level in dyskinesia patients. Further research is necessary, which will be aimed at modulating the secretion of melatonin and adipokines as a treatment target for PD.

The Influence of Selected Factors on the Detection of Giardia intestinalis by Microscopic and Immunoenzymatic Methods.

Background: Giardia intestinalis is one of the most common parasites in humans. Contaminated food and water can be a source of infection. Substances added to food are intended to increase its safety. We aimed to determination of the influence of various microorganisms and compounds that stimulate digestive functions, as well as preservatives and antioxidants on the detection of G. intestinalis by microscopic and immunoenzymatic methods. Methods: Twenty stool samples, archived in 1998-2018 in the Provincial Sanitary and Epidemiological Station in Bydgoszcz (Poland), collected both from patients referred for parasitic examinations by a doctor of a medical facility and from private individuals, were used to assess the impact of selected factors (such as bacterial strains, viruses and substances added to food) on the detection of G. intestinalis by microscopic and immunoenzymatic methods. Results: G. intestinalis was detected by both microscopic and immunoenzymatic methods with the same sensitivity (100%). The result of the G. intestinalis determination was positive in 90% of the samples after the addition of potassium sorbate, and in 25% of the samples after the addition of citric acid. Conclusion: The presence of other microorganism such as bacteria and viruses does not influence on the detection of G. intestinalis by microscopic and immunoenzymatic methods in stool samples. Citric acid as an antioxidant added to foods affects the detection of G. intestinalis. Due to the small number of samples used, it is necessary to continue research on the impact of various factors on the detection of protozoa.

Nickel ions influence the transepithelial sodium transport in the trachea, intestine and skin.

Measurements of transepithelial potential and resistance in tissue and organ model systems enable the evaluation of the Ni2+ effect on the epithelial sodium channels, aquaporin 3, and the sodium-potassium pump in the epithelial cells. The aim of the presented study was to assess the immediate and prolonged effect of nickel ions on the transport of sodium ions in tissues exposed to direct contact with nickel, including airways, digestive tract and the skin. The influence of 0.1 mM nickel solution was performed on the trachea (n = 34), intestine (n = 44), and skin (n = 51) samples descended from 16 New Zealand albino rabbits. The electrophysiological parameters were measured in a modified Ussing chamber in stationary conditions and during a 15-s mechanical-chemical stimulation. A statistically significant decrease in the electric resistance values and the smallest range of the measured potential were observed for the Ni-treated trachea specimens. The use of nickel solution did not affect the sodium transport in the intestine epithelium. The skin fragments showed altered sodium ion transport, as demonstrated by the lower range and intensity of the measured potential. The gastrointestinal tract seems to be an organ best adapted to contact with nickel ions. In airways, nickel ions most likely enter epithelial cells and the space between them, modifying proteins and the airway surface liquid. The skin turned out to be the most sensitive tissue to the intensification of sodium ion transport through nickel ions.

Evaluation of Serum Iron Parameters among Men Performing Regular Physical Activity-A Preliminary Study.

Iron deficiency anemia is one of the most common issues in clinical practice. It can be caused by intense physical activity, among other things. The aim of the study was to assess serum iron parameters in a group of men who engage in regular physical activity. The study group was composed of 20 men who regularly perform strength or endurance sports, whereas the control group consisted of 20 men without any sports activity. The red blood cell (RBC) parameters, platelet count (PLT), and white blood cell (WBC) count in venous blood samples were assessed with an automated hematology analyzer. The serum concentration of ferritin was determined through an immunology assay. There were no statistically significant differences between groups comparing RBC parameters and WBC. However, statistical analysis showed dissimilarity in PLT count and serum ferritin concentration comparing control and study groups (p < 0.05). It was shown that lower serum ferritin concentration concerns men with regular physical activity, whereas other blood parameters were not affected in this group.

Evaluation of Selected Parameters of Oxidative Stress and Adipokine Levels in Hospitalized Older Patients with Diverse Nutritional Status.

Malnutrition is classified as one of the Giant Geriatric Syndromes. It carries serious consequences, such as sarcopenia or depression, which lead to functional disability. The main objective of this study was to identify parameters of oxidative stress and adipokines, which may be potential biomarkers of malnutrition in hospitalized older patients. During the study, selected parameters were determined in 137 senile patients, taking into account their nutritional status determined according to the Mini Nutritional Assessment (MNA), as well as an additional tool, namely the Geriatric Nutritional Risk Index (GNRI). Leptin and resistin were determined as the parameters with statistically significant differences between the patients classified according to the MNA. This phenomenon was confirmed using the GNRI classification. However, additional parameters for which differences were observed include the oxidized low-density lipoprotein level and activity of glutathione peroxidase. In conclusion, the determination of the mentioned markers in hospitalized senile patients as an adjunct to the routine assessment of nutritional status might be suggested to identify the early risk of malnutrition so that a personalized nutritional therapy can be implemented as early as possible.

The Influence of Winter Swimming on Oxidative Stress Indicators in the Blood of Healthy Males.

Baths in cold water are a popular physical activity performed to improve health. This study aimed to determine whether repeated cold-water exposure leads to the up-regulation of antioxidant defenses and whether or not this leads to a reduction in basal and/or acute pulses of oxidative distress in humans. The study group consisted of 28 healthy male members of the WS club (average age 39.3 ± 6.1 years). The study sessions occurred at the beginning and the end of the WS season. During the WS season, the participants took 3-min cold-water baths in a cold lake once a week. Blood samples were collected three times during each session: before the bath, 30 min after the bath, and 24 h after the bath. The activity of selected antioxidant enzymes, including superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), as well as the concentration of lipid peroxidation (LPO) products, including thiobarbituric acid-reactive substances (TBARS) and conjugated dienes (CD), were determined in erythrocytes. The concentration of TBARS, CD, retinol, and α-tocopherol were determined in the blood plasma, whereas the level of other LPO products, including 4-hydroxynonenal and 8-iso-prostaglandin F2α, were determined in the blood serum. The repeated cold exposure up-regulated most antioxidant defenses, and this led to an attenuation of most indicators of oxidative stress at the baseline and acute pulses in response to cold exposure. In conclusion, due to regular cold exposure, the antioxidant barrier of winter swimmers was stimulated. Thus, short cold-bath sessions seem to be an effective intervention, inducing promoting positive adaptive changes such as the increased antioxidant capacity of the organism.

The Impact of Diclofenac Gel on Ion Transport in the Rabbit (Oryctolagus cuniculus) Skin: An In Vitro Study.

Diclofenac belongs to the non-steroidal anti-inflammatory drugs with analgesic, antipyretic and anti-inflammatory effects. Diclofenac administration on the skin may be associated with the appearance of side effects. The study aimed to evaluate the impact of diclofenac gel on transepithelial electrophysiological parameters of the 55 rabbit abdomen skin specimens. The electric parameters were analyzed in a modified Ussing chamber. The resistance (R) of the skin specimens treated with diclofenac gel significantly increased, which could be related to the reduction in the water content in intercellular spaces and, consequently, tighter adhesion of the cells. Increased electric potential (PD) was also observed in the skin specimens treated with diclofenac gel. The increase in both R and PD measured under stationary conditions was most likely caused by a transient and reversible increase in sodium ion transport, as the R and PD values decreased after the diclofenac gel was washed away. However, diclofenac gel did not affect the maximum and minimum PDs measured during stimulations. Therefore, it seems that diclofenac gel does not affect the perception of stimuli in the model system used.

Concentration of Selected Adipokines and Factors Regulating Carbohydrate Metabolism in Patients with Head and Neck Cancer in Respect to Their Body Mass Index.

Head and neck cancers (HNCs) are a group of tumors not common in European populations. So far, not much is known about the role of obesity, adipokines, glucose metabolism, and inflammation in the pathogenesis of HNC. The aim of the study was to determine the concentrations of ghrelin, omentin-1, adipsin, adiponectin, leptin, resistin, visfatin, glucagon, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), plasminogen activator inhibitor-1 (PAI-1), and gastric inhibitory peptide (GIP) in the blood serum of HNC patients depending on their body mass index (BMI). The study included 46 patients divided into two groups according to their BMI values: the normal BMI group (nBMI) included 23 patients with BMI < 25 kg/m2 and the increased BMI group (iBMI) included patients with BMI ≥ 25 kg/m2. A control group (CG) included 23 healthy people (BMI < 25 kg/m2). Statistically significant differences in the levels of adipsin, ghrelin, glucagon, PAI-1, and visfatin were shown between nBMI and CG. In the case of nBMI and iBMI, statistically significant differences were observed in the concentrations of adiponectin, C-peptide, ghrelin, GLP-1, insulin, leptin, omentin-1, PAI-1, resistin, and visfatin. The obtained results indicate a disruption of endocrine function of adipose tissue and impaired glucose metabolism in HNC. Obesity, which is not a typical risk factor for HNC, may aggravate the negative metabolic changes associated with this type of neoplasm. Ghrelin, visfatin, PAI-1, adipsin, and glucagon might be related to head and neck carcinogenesis. They seem to be promising directions for further research.

Advances and Challenges in Diagnostics of Toxoplasmosis in HIV-Infected Patients.

Toxoplasma gondii is a worldwide distributed protozoan parasite. This apicomplexan parasite infects one-third of the population worldwide, causing toxoplasmosis, considered one of the neglected parasitic infections. In healthy humans, most infections are asymptomatic. However, in immunocompromised patients, the course of the disease can be life-threatening. Human immunodeficiency virus (HIV)-infected patients have a very high burden of Toxoplasma gondii co-infection. Thus, it is essential to use modern, sensitive, and specific methods to properly monitor the course of toxoplasmosis in immunodeficient patients.

The Influence of Ambient Temperature Changes on the Indicators of Inflammation and Oxidative Damage in Blood after Submaximal Exercise.

Physical activity has a positive effect on human health and well-being, but intense exercise can cause adverse changes in the organism, leading to the development of oxidative stress and inflammation. The aim of the study was to determine the effect of short-term cold water immersion (CWI) and a sauna bath as methods of postexercise regeneration on the indicators of inflammation and oxidative damage in the blood of healthy recreational athletes. Forty-five male volunteers divided into two groups: 'winter swimmers' who regularly use winter baths (n = 22, average age 43.2 ± 5.9 years) and 'novices' who had not used winter baths regularly before (n = 23, mean age 25 ± 4.8 years) participated in the study. The research was divided into two experiments, differing in the method of postexercise regeneration used, CWI (Experiment I) and a sauna bath (Experiment II). During Experiment I, the volunteers were subjected to a 30-min aerobic exercise, combined with a 20-min rest at room temperature (RT-REST) or a 20-min rest at room temperature with an initial 3-min 8 °C water bath (CWI-REST). During the Experiment II, the volunteers were subjected to the same aerobic exercise, followed by a RT-REST or a sauna bath (SAUNA-REST). The blood samples were taken before physical exercise (control), immediately after exercise and 20 min after completion of regeneration. The concentrations of selected indicators of inflammation, including interleukin 1ß (IL-1ß), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 8 (IL-8), interleukin 10 (IL-10), transforming growth factor ß1 (TGF-ß1) and tumor necrosis factor α (TNF-α), as well as the activity of indicators of oxidative damage: α1-antitrypsin (AAT) and lysosomal enzymes, including arylsulfatase A (ASA), acid phosphatase (AcP) and cathepsin D (CTS D), were determined. CWI seems to be a more effective post-exercise regeneration method to reduce the inflammatory response compared to a sauna bath. A single sauna bath is associated with the risk of proteolytic tissue damage, but disturbances of cellular homeostasis are less pronounced in people who regularly use cold water baths than in those who are not adapted to thermal stress.

Inflammation Related to Obesity in the Etiopathogenesis of Gastroenteropancreatic Neuroendocrine Neoplasms.

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare neoplasms, which, due to their heterogeneous nature, non-specific symptoms, and lack of specific tumor markers pose many diagnostic and clinical challenges. In recent years, the effectiveness of GEP-NEN diagnosis has increased, which is probably associated with the greater availability of diagnostic tests and the cooperation of many experienced specialists in various scientific disciplines. In addition to the possible genetic etiology, the cause of GEP-NET development is not fully understood. Inflammation and obesity are known risks that contribute to the development of many diseases. Chronic inflammation accompanying obesity affects the hormonal balance and cell proliferation and causes the impairment of the immune system function, leading to neoplastic transformation. This review explores the role of inflammation and obesity in GEP-NETs. The exact mechanisms inducing tumor growth are unknown; however, the profile of inflammatory factors released in the GEP-NET tumor microenvironment is responsible for the progression or inhibition of tumor growth. Both the excess of adipose tissue and the impaired function of the immune system affect not only the initiation of cancer but also reduce the comfort and lifetime of patients.

Quantitative Structure-Activity Relationship Analysis of Isosteviol-Related Compounds as Activated Coagulation Factor X (FXa) Inhibitors.

Stevioside, one of the natural sweeteners extracted from stevia leaves, and its derivatives are considered to have numerous beneficial pharmacological properties, including the inhibition of activated coagulation factor X (FXa). FXa-PAR signaling is a possible therapeutic target to enhance impaired metabolism and insulin resistance in obesity. Thus, the goal of the investigation was a QSAR analysis using multivariate adaptive regression splines (MARSplines) applied to a data set of 20 isosteviol derivatives bearing thiourea fragments with possible FXa inhibitory action. The best MARS submodel described a strong correlation between FXa inhibitory activity and molecular descriptors, such as: B01[C-Cl], E2m, L3v, Mor06i, RDF070i and HATS7s. Five out of six descriptors included in the model are geometrical descriptors quantifying three-dimensional aspects of molecular structure, which indicates that the molecular three-dimensional conformation is of high significance for the MARSplines modeling procedure and obviously for FXa inhibitory activity. High model performance was confirmed through an extensive validation protocol. The results of the study not only confirmed the enhancement in pharmacological activity by the presence of chlorine in a phenyl ring, but also, and primarily, may provide the basis for searching for new active isosteviol analogues, which may serve as drugs or health-beneficial food additives in patients suffering from obesity and comorbidities.

Effect of Low High-Density Lipoprotein Level on Endothelial Activation and Prothrombotic Processes in Coronary Artery Disease-A Pilot Study.

High-density lipoproteins (HDL) play an important role in the prevention of atherosclerosis. The aim of the study was to assess the relationship between serum HDL-C concentration and proinflammatory/prothrombic activation in coronary artery disease (CAD) patients. The study group included 27 acute myocardial infarction (AMI) patients and 30 stable angina pectoris (SA) patients. The control group consisted of 23 people without cardiac symptoms. In the AMI and SA groups, a lower HDL-C and a higher LDL-C/HDL-C index were observed. The SA patients had lower total cholesterol, LDL-C, sE-selectin ligand, as well as higher triglycerides and CD40 concentration in comparison with both the control and AMI groups. A higher von Willebrand Factor and intercellular adhesion molecule-1 were found in both study groups. Low HDL-C concentration in the CAD patients may intensify pro-inflammatory endothelial activation and prothrombotic processes. A low concentration of HDL-C and a high value of the LDL-C/HDL-C index seem to be better indices of atherogenic processes than the LDL-C concentration alone.