The Influence of Retinol Ointment on Rabbit Skin (Oryctolagus cuniculus) Ion Transport-An In Vitro Study.

Retinoids are known to improve the condition of the skin. Transepithelial transport of sodium and chloride ions is important for proper skin function. So far, the effect of applying vitamin A preparations to the skin on ion transport has not been evaluated. In the study, electrophysiological parameters, including transepithelial electric potential (PD) and transepithelial resistance (R), of rabbit skin specimens after 24 h exposure to retinol ointment (800 mass units/g) were measured in a modified Ussing chamber. The R of the fragments incubated with retinol was significantly different than that of the control skin samples incubated in iso-osmotic Ringer solution. For the controls, the PD values were negative, whereas the retinol-treated specimens revealed positive PD values. Mechanical-chemical stimulation with the use of inhibitors of the transport of sodium (amiloride) or chloride (bumetanide) ions revealed specific changes in the maximal and minimal PD values measured for the retinol-treated samples. Retinol was shown to slightly modify the transport pathways of sodium and chloride ions. In particular, an intensification of the chloride ion secretion from keratinocytes was observed. The proposed action may contribute to deep hydration and increase skin tightness, limiting the action of other substances on its surface.

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.

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.

Application of Multivariate Adaptive Regression Splines (MARSplines) for Predicting Antitumor Activity of Anthrapyrazole Derivatives.

An approach using multivariate adaptive regression splines (MARSplines) was applied for quantitative structure-activity relationship studies of the antitumor activity of anthrapyrazoles. At the first stage, the structures of anthrapyrazole derivatives were subjected to geometrical optimization by the AM1 method using the Polak-Ribiere algorithm. In the next step, a data set of 73 compounds was coded over 2500 calculated molecular descriptors. It was shown that fourteen independent variables appearing in the statistically significant MARS model (i.e., descriptors belonging to 3D-MoRSE, 2D autocorrelations, GETAWAY, burden eigenvalues and RDF descriptors), significantly affect the antitumor activity of anthrapyrazole compounds. The study confirmed the benefit of using a modern machine learning algorithm, since the high predictive power of the obtained model had proven to be useful for the prediction of antitumor activity against murine leukemia L1210. It could certainly be considered as a tool for predicting activity against other cancer cell lines.

Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities.

Toxoplasma gondii is an apicomplexan parasite causing toxoplasmosis, a common disease, which is most typically asymptomatic. However, toxoplasmosis can be severe and even fatal in immunocompromised patients and fetuses. Available treatment options are limited, so there is a strong impetus to develop novel therapeutics. This review focuses on the role of oxidative stress in the pathophysiology and treatment of T. gondii infection. Chemical compounds that modify redox status can reduce the parasite viability and thus be potential anti-Toxoplasma drugs. On the other hand, oxidative stress caused by the activation of the inflammatory response may have some deleterious consequences in host cells. In this respect, the potential use of natural antioxidants is worth considering, including melatonin and some vitamins, as possible novel anti-Toxoplasma therapeutics. Results of in vitro and animal studies are promising. However, supplementation with some antioxidants was found to promote the increase in parasitemia, and the disease was then characterized by a milder course. Undoubtedly, research in this area may have a significant impact on the future prospects of toxoplasmosis therapy.

Redox State and Lysosomal Activity in Women with Ovarian Cancer with Tumor Recurrence and Multiorgan Metastasis.

The aim of the study is to evaluate oxidant-antioxidant balance as well as lysosomal and anti-protease activities in ovarian cancer since it has been emphasized that the crucial inducing factor of carcinogenesis may be reactive oxygen/nitrogen species or, more precisely, oxidative stress-induced inflammation. The study involved 15 women with ovarian cancer, aged 59.9 ± 7.8 years, and 9 healthy women aged 56.3 ± 4.3 years (controls). The study material was venous blood collected from fasting subjects. In erythrocytes, the activities of superoxide dismutase, glutathione peroxidase, and catalase, as well as concentrations of conjugated dienes (CDs) and thiobarbituric acid reactive substances (TBARS), were investigated. CD, TBARS, and vitamins A and E plasma concentrations were also determined. Moreover, total antioxidant capacity and concentrations of 4-hydroxynonenal adducts and 8-iso-prostaglandin F2α, as well as activities of acid phosphatase, arylsulfatase, cathepsin D, and α1-antitrypsin, were studied in serum. The vitamin E and 8-iso-prostaglandin F2α concentrations as well as arylsulfatase activity were lower in the women with cancer compared to the controls (p = 0.006, p = 0.03, p = 0.001, respectively). In contrast, cathepsin D activity was lower in the controls (p = 0.04). In the peripheral blood of the women with cancer, oxidant-antioxidant and lysosomal disturbances were observed.

Ionizing Radiation as a Source of Oxidative Stress-The Protective Role of Melatonin and Vitamin D.

Ionizing radiation (IR) has found widespread application in modern medicine, including medical imaging and radiotherapy. As a result, both patients and healthcare professionals are exposed to various IR doses. To minimize the negative side effects of radiation associated with oxidative imbalance, antioxidant therapy has been considered. In this review, studies on the effects of melatonin and vitamin D on radiation-induced oxidative stress are discussed. According to the research data, both substances meet the conditions for use as agents that protect humans against IR-induced tissue damage. Numerous studies have confirmed that melatonin, a hydro- and lipophilic hormone with strong antioxidant properties, can potentially be used as a radioprotectant in humans. Less is known about the radioprotective effects of vitamin D, but the results to date have been promising. Deficiencies in melatonin and vitamin D are common in modern societies and may contribute to the severity of adverse side effects of medical IR exposure. Hence, supporting supplementation with both substances seems to be of first importance. Interestingly, both melatonin and vitamin D have been found to selectively radiosensitise cancer cells, which makes them promising adjuvants in radiotherapy. More research is needed in this area, especially in humans.

Pyrethroids: How They Affect Human and Animal Health?

Pyrethroids are pesticides commonly used in crop protection; in the forestry, wood, and textile industries; as well as in medicine and veterinary medicine to treat parasitic crustacean infestations. They have been found to be relatively safe for humans and animals. Pyrethroids are recommended for personal protection against malaria and virus Zika by the World Health Organization. Pyrethroids act on voltage-gated sodium channels, which cause an influx of sodium ions into the nerve cells and permanent depolarization. They also influence activities of enzymes, especially in nerve and liver cells. Contact of pyrethroids with the skin, digestive tract, and respiratory tract results in their penetration into the body. Due to the importance of the subject, a summary of the current state of knowledge on the toxic effects of pyrethroids was presented in the comprehensive review by Chrustek et al, published in journal Medicina. Particular attention was paid to nephrotoxic, hepatotoxic, cardiotoxic, immunotoxic, neurotoxic, and behavioral effects of pyrethroids on human and animal bodies. It could be added that pyrethroids generate oxidative stress, which modifies DNA, RNA, protein, lipid and carbohydrate molecules. However, public awareness of the possible negative effects of the use of insecticides is still low. Further research should be carried out to clarify the molecular basis of the pathomechanism of pyrethroid detrimental action. Proper dissemination of the results seems to be of first importance for public health.

The immediate influence of deltamethrin on ion transport through rabbit skin. An in vitro study.

Deltamethrin can be absorbed into the respiratory tract, the gastrointestinal tract and through the skin. The study was designed to assess the effect of deltamethrin on electrophysiological parameters of rabbit's skin, studied in vitro, to identify the mechanism of action and effects of short-term dermal exposure to deltamethrin. The objective of the study was to investigate changes in electrophysiological parameters after exposure to 0.01 M deltamethrin under unchanged conditions, in the presence of amiloride (sodium transport blocker) and bumetanide (chloride transport blocker). Exposure to deltamethrin reduced the electrophysiological reaction of examined tissue in unchanged conditions and during the sodium reabsorption phase but did not influence the chloride ion secretion phase. The presented data show that the pyrethroide affects transepithelial ion transport in the external layers of the skin. The inhibition of chloride and sodium ions enabled evaluation of the impact of the pesticide on dermal transport.

Inter-relationships of the chronobiotic, melatonin, with leptin and adiponectin: implications for obesity.

Obesity and its medical complications represent a significant problem throughout the world. In recent decades, mechanisms underlying the progression of obesity have been intensively examined. The involvement of both the behavioral aspects, such as calorie-rich diet, low physical activity and sleep deprivation, and the intrinsic factors, including adipose tissue deregulation, chronic inflammation, oxidative stress, and chronodisruption, has been identified. The circadian disturbances of the adipose tissue endocrine function have been correlated with obesity. Leptin and adiponectin are adipokines strongly associated with glucose and lipid metabolism and with energy balance. Their synthesis and secretion display circadian rhythms that are disturbed in the obese state. Hyperleptinemia resulting in leptin resistance, and hypo-adiponectinemia have been linked to the pathophysiology of the obesity-related disorders. A deficiency of melatonin, one of the consequences of sleep deprivation, has also been demonstrated to correlate with obesity. Melatonin is a pineal secretory product involved in numerous actions, such as regulation of internal biological clocks and energy metabolism, and it functions as an antioxidant and as an anti-inflammatory agent. There exists a substantial amount of evidence supporting the beneficial effects of melatonin supplementation on obesity and its complications. In the current review, the results of studies related to the interactions between melatonin, and both leptin and adiponectin are discussed. Despite the existence of some inconsistencies, melatonin has been found to normalize the expression and secretion patterns of both adipokines. These results support the concept of melatonin as a potential therapeutic agent for obesity and related disorders.

Plasmodium knowlesi as a Threat to Global Public Health.

Malaria is a tropical disease caused by protozoans of the Plasmodium genus. Delayed diagnosis and misdiagnosis are strongly associated with higher mortality. In recent years, a greater importance is attributed to Plasmodium knowlesi, a species found mainly in Southeast Asia. Routine parasitological diagnostics are associated with certain limitations and difficulties in unambiguous determination of the parasite species based only on microscopic image. Recently, molecular techniques have been increasingly used for predictive diagnosis. The aim of the study is to draw attention to the risk of travelling to knowlesi malaria endemic areas and to raise awareness among personnel involved in the therapeutic process.

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.

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.

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.

Intersecting Pathways: The Role of Metabolic Dysregulation, Gastrointestinal Microbiome, and Inflammation in Acute Ischemic Stroke Pathogenesis and Outcomes.

Acute ischemic stroke (AIS) remains a major cause of mortality and long-term disability worldwide, driven by complex and multifaceted etiological factors. Metabolic dysregulation, gastrointestinal microbiome alterations, and systemic inflammation are emerging as significant contributors to AIS pathogenesis. This review addresses the critical need to understand how these factors interact to influence AIS risk and outcomes. We aim to elucidate the roles of dysregulated adipokines in obesity, the impact of gut microbiota disruptions, and the neuroinflammatory cascade initiated by lipopolysaccharides (LPS) in AIS. Dysregulated adipokines in obesity exacerbate inflammatory responses, increasing AIS risk and severity. Disruptions in the gut microbiota and subsequent LPS-induced neuroinflammation further link systemic inflammation to AIS. Advances in neuroimaging and biomarker development have improved diagnostic precision. Here, we highlight the need for a multifaceted approach to AIS management, integrating metabolic, microbiota, and inflammatory insights. Potential therapeutic strategies targeting these pathways could significantly improve AIS prevention and treatment. Future research should focus on further elucidating these pathways and developing targeted interventions to mitigate the impacts of metabolic dysregulation, microbiome imbalances, and inflammation on AIS.

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.

Searching for New Biomarkers of Neuroendocrine Tumors: A Comparative Analysis of Chromogranin A and Inflammatory Cytokines in Patients with Neuroendocrine Tumors.

Neuroendocrine neoplasms (NENs) present a diagnostic challenge due to their heterogeneous nature and non-specific clinical manifestations. This study aimed to explore novel biomarkers for NENs. Serum chromogranin A (CgA) levels and a panel of 48 inflammatory cytokines were analyzed in a cohort of 84 NEN patients and 40 healthy controls using enzyme-linked immunosorbent assay (ELISA) and multiplex ELISA. Significant alterations in cytokine levels were observed in the NEN patients compared to the controls, including elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNF-α), and reduced levels of angiogenic factors like platelet-derived growth factor-BB (PDGF-BB) and tumor necrosis factor beta (TNF-ß). Notably, cytokines such as growth-regulated alpha protein (GRO-α) and TNF-ß demonstrated strong potential as diagnostic markers, with receiver operating characteristic (ROC) curve analyses showing high sensitivity and specificity. Additionally, a positive correlation was found between CgA levels and several inflammatory cytokines, suggesting their synergistic role in tumor progression. These findings highlight the limited reliability of CgA alone as a diagnostic marker and underscore the importance of a multi-marker approach in diagnosing and monitoring NENs. Further research on a larger cohort is necessary to validate these biomarkers and their potential clinical applications.

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 [...].

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.