Type 1 diabetes (T1DM) is achronic autoimmune disease characterized by the progressive destruction of pancreatic beta-cells, leading to insulin deficiency and, consequently, hyperglycemia. Genetic predisposition, particularly genes related to the major histocompatibility complex, plays a significant role in the etiology of the disease, but the mere presence of a predisposition does not guarantee the development of the disease. Environmental factors, which can facilitate the initiation and acceleration of autoimmune processes, also play a significant role in the etiology of T1DM. Important environmental risk factors include viral infections, particularly enteroviruses (e.g., Coxsackie). The mechanism by which viral infections promote the development of T1DM is not fully understood. It appears that they may cause direct damage to beta-cells or initiate an autoimmune response through molecular mimicry mechanisms. Nutrition during infancy and early childhood may also influence the risk of developing the disease. There are indications that, for example, premature introduction of cow's milk or too early introduction of gluten into the diet may modulate the development of the immune system. There is also growing interest in the gut microbiota - the composition and diversity of the gut microbiota are crucial for maintaining immune balance. Another important aspect of T1DM development is environmental pollution. It has been suggested that many chemicals present in the environment (e.g., pesticides) may disrupt immune tolerance. Finally, increased psychological stress, particularly during childhood, is considered a potential factor intensifying inflammatory processes and disrupting immune regulation, which may indirectly increase the risk of developing T1DM. The importance of environmental factors in the etiology of type 1 diabetes is well documented, but current knowledge does not yet allow for modifications that would effectively reduce the number of new cases in the general population.
Acute ischemic stroke (AIS) remains one of the leading causes of disability and mortality worldwide. Timely reperfusion therapy is the cornerstone of management, aiming to restore cerebral blood flow and limit ischemic injury. Two main approaches-intravenous thrombolysis (IVT) with tissue plasminogen activator and mechanical thrombectomy (MT)-can be applied separately or in combination. This review presents current evidence regarding the clinical efficacy, safety, and economic impact of combined thrombolytic and mechanical reperfusion therapy compared with monotherapy in AIS. Combined IVT and MT (bridging therapy) showed slightly higher rates of successful reperfusion and favorable functional recovery compared to direct MT alone, especially in anterior and basilar artery occlusions. However, differences in mortality and symptomatic intracranial hemorrhage were not statistically significant. Triple therapy involving intra-arterial thrombolysis provided no additional benefit but was considered safe. Predictors of poor outcomes included high NIHSS scores on admission, posterior circulation stroke, and delayed treatment initiation. Economic evaluations from high-income countries demonstrated that MT-with or without IVT-is cost-effective, with potential cost savings through improved long-term outcomes. To conclude, the combination thrombolysis and mechanical thrombectomy offer modest but consistent improvements in reperfusion success and functional outcomes without increasing adverse events. Although direct MT remains effective, bridging therapy should be considered in eligible patients within therapeutic windows. Further studies are warranted to optimize patient selection, minimize futile reperfusion, and confirm cost-effectiveness across healthcare settings.
The paper describes a three-step synthesis that leads to dimeric heterocyclic compounds containing the indazole ring. The compounds were tested for their ability to inhibit the proliferation of the leukaemia K562 and colorectal cancer HCT116 cell lines. Two of them, namely the compounds with the 3,5-dimethylpyrazole or carbazole moiety, have been identified as potent proapoptotic agents.
Stroke in cancer patients represents an increasingly recognized clinical problem resulting from overlapping risk factors, complex pathophysiology, and treatment-related complications. Approximately 15% of patients with malignancies experience cerebrovascular disease, most frequently ischemic stroke, which may precede or reveal cancer. Cancer-associated strokes arise through multiple mechanisms, including tumor-induced hypercoagulability, inflammation, nonbacterial thrombotic endocarditis, and vascular injury secondary to chemotherapy or radiotherapy. Elevated D-dimer and fibrin degradation products are key laboratory indicators of cancer-related stroke. The cancers most commonly linked to ischemic stroke are those of the breast, genitourinary, and gastrointestinal systems, while lung cancer, melanoma and renal cell carcinoma more often cause hemorrhagic events. Treatment of acute stroke in cancer patients remains challenging. Current evidence suggests that cancer is not an absolute contraindication for reperfusion therapies. Intravenous thrombolysis with tissue plasminogen activator and mechanical thrombectomy may be effective and relatively safe in selected patients, provided bleeding risks are carefully evaluated. Outcomes, however, are often poorer due to systemic disease, infection, and increased mortality. The decision to initiate reperfusion therapy should consider tumor type, functional status, and life expectancy. Preventive strategies are limited by the absence of validated prediction models for stroke in cancer. The Khorana score, originally developed for venous thromboembolism, may assist in identifying high-risk patients initiating chemotherapy. Meta-analyses confirm that cancer survivors-particular ly women, younger patients, and those with head and neck, hematologic, or gastrointestinal cancers-face an elevated long-term risk of stroke. Dedicated clinical trials and biomarker-based approaches are essential to improve risk stratification, optimize antithrombotic therapy, and guide individualized management. Understanding the unique interplay between malignancy and cerebrovascular disease remains critical for reducing morbidity and mortality in this growing patient population.
Acute ischemic stroke (AIS) remains a main cause of disability in adults over 50 and the third leading cause of death worldwide. Despite advances in reperfusion therapies, such as intravenous thrombolysis and mechanical thrombectomy, up to two-thirds of patients experience futile reperfusion, where radiological efficacy does not translate into clinical recovery. Malnutrition and sarcopenia may contribute to these unfavorable outcomes. Malnutrition, present in up to half of hospitalized elderly patients and 16-49% of AIS cases, is associated with lower body mass index, reduced limb circumference, elevated C-reactive protein/albumin ratio (CAR), and increased mortality and disability at 90 days. Nutritional screening using tools such as NRS-2002, PNI, or CONUT should therefore be performed routinely in stroke units to guide early nutritional intervention. Sarcopenia, characterized by decreased of muscle strenght and low muscle mass, frequently coexists with malnutrition in AIS and is both a pre-and post-stroke condition. Its prevalence among stroke survivors ranges from 14% to over 50%, depending on the studied group. C-Reactive Protein to albumin ratio, age, and National Institutes of Health Stroke Scale (NIHSS) scores independently predict sarcopenia. Sarcopenia is also linked with frailty, prolonged hospitalization, cognitive decline, and higher risk of hemorrhagic complications following reperfusion or anticoagulant therapy. Integrating nutritional and muscle-mass assessments into acute and post-stroke care could help identify patients at risk of poor recovery and mortality. Comprehensive, interdisciplinary management targeting malnutrition and sarcopenia offers an opportunity to improve outcomes in AIS and reduce the burden of stroke-related disability.
Growing evidence supports the pivotal role of insulin resistance in the pathogenesis of Alzheimer's disease. Insulin, acting through widely distributed brain insulin receptors, regulates neuronal metabolism, neuroplasticity, and cognitive functions such as memory. In conditions of insulin resistance, impaired insulin signaling disrupts key pathways (PI3K/Akt, MAPK, mTOR), leading to neuronal survival deficits and protein homeostasis imbalance. This contributes to pathological beta-amy-o loid accumulation and tau hyperphosphorylation. Insulin resistance also promotes oxidative stress, which exacerbates neuroinflammation and activates kinases like GSK-3 beta, intensifying tau-related neurotoxicity. Additionally, the build-up of advanced glycation end-products (AGE) and their interaction with RAGE receptors amplifies beta-amyloid deposition, vascular damage, and chronic inflamomation. Insulin resistance is associated with blood-brain barrier dysfunction, synaptic and cognitive decline, and endoplasmic reticulum stress, which trigger maladaptive unfolded protein responses and neurodegeneration. Emerging data also highlight the role of gut microbiota dysbiosis in promoting neuroinflammation and neurotoxic metabolite production via the gut-brain axis. Understanding the mechanisms linking insulin resistance to Alzheimer's disease neuropathology opens new therapeutic avenues, including insulin-sensitizing agents (e.g., metformin, SGLT2 inhibitors), AGE-RAGE pathway modulators, and microbiota-targeted interventions (e.g., targeted probiotic therapies). Such strategies offer promising adjuncts to current molecular-targeted Alzheimer's disease treatments.
Vitain D functions both as a vitamin and a prohormone, exerting a crucial stimulatory effect on intestinal calcium absorption and skeletal remodeling-processes essential for a proper bone formation. The complex pathway of vitamin D synthesis and activation leads to its widespread deficiency, with currently affects nearly half of the global population. It resulted in vitamin D supplementation becoming broadly recommended and commonly used. In light of the widespread availability and routine use of vitamin D supplements, it is important to consider whether their use, in addition to their well-documented benefits, does not also carry risks such as tissue calcification (including vascular calcification) and the potential for cardiac arrhythmias. These concerns are especially relevant when vitamin D3 is co-formulated with vitamin K2, a compound known to promote blood coagulation. This paper addresses this dilemma by reviewing current scientific literature regarding the cardiovascular safety of vitamin D and K2 co-supplementation. Analysis indicates that the use of excessively high doses of vitamin D may indeed induce arterial calcification and arrhythmias. On the other hand, supplementation within recommended dosage range does not appear to be associated with these adverse effects. Moreover, simultaneous intake of vitamin K2 has been shown to enhance bone mineralization while additionally attenuating soft tissue calcification. A proper dosage of vitamin K2 not only does not increase the impact of thromboembolic events but may also contribute to the stabilization of the international normalized ratio (INR), a key marker of blood coagulability.
Summar: An abnormal form of the huntingtin (HTT) gene has been demonstrated to negatively influence the central nervous system and several peripheral organs, especially muscle tissue. Research studies based on mouse models of Huntington's disease (HD) have indicated that alterations in gene expression can impact different muscles throughout the body. However, no previously published study has been conducted on the HD subcutaneous muscles, which form part of the subcutaneous tissue and may exhibit a distinct transcriptional profile. The aim of our study was to explore differences in the subcutaneous muscles of R6/2 mice compared to controls. We performed microarray and immunohistochemical analyses using subcutaneous muscles from R6/2 model mice and control individuals. The resulting data were then subjected to bioinformatics analyses. Our analysis enabled us to identify a number of gene sets, to which the altered genes belonged, thus allowing the isolation of a set involved in the extracellular matrix (ECM) processes and components. The microarray data confirmed that an altered form of the human HTT was responsible for the observed changes. Our study has confirmed the effect of the altered form of HTT on gene expression in the subcutaneous muscle and has additionally highlighted the potential for changes in the ECM, which represents a promising direction for future research. To our knowledge, this is the first study to investigate transcriptomic alterations in subcutaneous muscles in the context of Huntington's disease.
Spatial transcriptomics (ST) represents a revolutionary methodological approach enabling gene expression analysis while preserving spatial context within tissues. The past decade has witnessed rapid development of ST technologies, encompassing both imaging-based methods (MER-FISH, seqFISH, Xenium) and sequencing-based approaches (Visium, Visium HD, Stereo-seq). This review provides a systematic overview of available technological platforms, bioinformatics tools for data analysis, and key applications of spatial transcriptomics in neurobiology, cancer research, and developmental biology. Methodological challenges, including signal deconvolution and integration of ST data with single-cell sequencing data, are also discussed. Spatial transcriptomics opens new possibilities in basic and translational research, offering unprecedented insights into the molecular architecture of tissues.
One of the many challenges of today's medicine are obesity and mental health disorders, which include eating disorders. In this paper we focused on binge-eating disorder as it stands as a significant public health problem, due to its increasing frequency and an association with obesity and other metabolic diseases. The aim of this article is to show a connection between compulsive eating and the development of obesity, taking into consideration epidemiological, diagnostic and neurobiological aspects. The role of dopaminergic, opioid, endocannabinoid and serotoninergic systems and some genetic, as well as hormonal factors and the treatment of mentioned disorders are discussed. Not only may the understanding of the molecular basis of BED contribute to a more effective treatment and prevention of this disorder, but also obesity as its consequence.
D-dimers, as a product of cross-linked fibrin clot degradation, are one of the most frequently measured laboratory parameters. Their formation requires the activation of both the coagulation cascade and the fibrinolysis system, providing valuable information about the body's coagulation state. Changes in D-dimers levels are observed in both pathological and physiological conditions. There are several methods used to evaluate D-dimers level but most of them rely on reactions with monoclonal antibodies. In the diagnosis of venous thromboembolism (VTE), D-dimers level below 500 mu g/L can, with high probability, rule out the disease in asymptomatic patients. D-dimers reach heightened levels in disseminated intravascular coagulation syndrome (DIC) and are a component of diagnostic scales. Their level within the normal range excludes the presence of this syndrome. The increase in D-dimers levels in the course of cancer is associated with the degree of progression, type and prognosis of cancer. The causes of the increase in D-dimers concentration can also be found in the course of a thromboembolic event associated with SARS-CoV-2 infection. Situations in which D-dimers can be elevated also include pregnancy, childbirth, inflammatory diseases or age-related changes.
Polycystic ovary syndrome (PCOS) is a multifactorial health condition and the most prevalent metabolic disorder among women of reproductive age. Due to its complexity, PCOS is often associated with other endocrinological disorders, including elevated prolactin levels. This article reviews the recent findings on the connection between PCOS and hyperprolactinemia, focusing on molecular, clinical, and therapeutic aspects.
Acute ischemic stroke (AIS) is one of the leading causes of disability and mortality worldwide. Its incidence is prognosed to rise significantly in Europe in the coming years. Despite advances in treatment, such as intravenous thrombolysis (IVT) and mechanical thrombectomy (MT), overall clinical outcomes remain unsatisfactory. Futile reperfusion is considered a disability persisting at 90 days after stroke onset despite successful radiological recanalization. It unmasks the complexity of AIS pathomechanisms and the need for reliable tools to quantify comorbidity-related risks. A major contributor to futile reperfusion is the high burden of comorbidities in stroke patients, which negatively affects prognosis and therapeutic efficacy. Comorbidity indexes, notably the Charlson Comorbidity Index (CCI), have become essential in evaluating the impact of concurrent diseases on outcomes in AIS. Increased CCI scores are independently associated with severe disability, prolonged hospitalization, higher readmission rates, and increased mortality. The predictive value of the CCI for short-and long-term outcomes following ischemic stroke was confirmed in studies performed across diverse populations. Adapted versions of the CCI, such as the ischemic stroke-specific Charlson Comorbidity Index (ISCCI), may offer more practical and disease-specific prognostic utility. Given the growing elderly population and the increasing prevalence of comorbid conditions, integrating comorbidity assessment into clinical decision-making is vital for improving AIS management. The tools quantitatively estimating comorbidities enable a more accurate prediction of treatment effectiveness, post-stroke disability, and survival outcomes. Moreover, they support ther apeutic decisions. Future research should focus on refining comorbidity scoring systems to optimize therapeutic strategies and healthcare resource allocation for patients with ischemic stroke.
Bone defects are challenging for both orthopaedists and dentists. Bone Tissue Engineering points on scaffold materials for improved bone regeneration. Such materials should create a 3-dimensional biocompatible scaffold for extracellular matrix and should support cell processes such as adhesion, proliferation, and differentiation. Scaffold materials should optimize conditions for bone regeneration, after which they should resorb and be replaced by the newly formed bone. Scaffolds can be fabricated from both natural and synthetic materials. Polycaprolactone is one of the synthetic materials. It is a synthetic, semi-crystalline, biodegradable polyester. To improve the bone tissue reaction nanoparticles can be added to polycaprolactone, creating a polymer. Such additives include calcium phosphates (hydroxyapatite, tricalcium phosphate, or biphasic calcium phosphates), metals (TiO2, Zn) or bioactive glass. We present a literature review concerning cell response to polycaprolactone base scaffold materials modified with nanoparticles in bone tissue regeneration.
The most common method of treating central nervous system (CNS) tumors in children is neurosurgical intervention, which may temporarily or permanently impair brain function, making independent eating impossible. In such cases, it is necessary to consider providing the patient with long-term access to the gastrointestinal tract. If the patient is found to be malnourished, steps to improve their nutritional status should be taken as soon as possible. Cachexia prolongs hospitalization, increases treatment costs, and raises the risk of postoperative complications. This study presents a literature review aimed at determining the effectiveness of percutaneous endoscopic gastrostomy (PEG) in malnourished patients suffering from head and neck cancers. Based on the data, it was concluded that the decision to place a PEG should be made by an interdisciplinary therapeutic team. The current health status of the patient should be assessed, and the treatment plan along with potential complications should be outlined. The treatment of malnutrition in pediatric patients with central nervous system tumors can be effectively managed with the use of PEG. Severe complications from a properly placed PEG are very rare, and the effectiveness of this method in treating malnutrition is high.
The kidney is the most frequently transplanted vascularised organ in the world. Transplantation is a complex, multi-stage process requiring the involvement of a multidisciplinary team and knowledge of medical law. This article presents the qualification process in kidney recipients, the basis of selecting living donor and deceased donor and it outlines the importance of education of patients and their families, as well as long-term post-transplant care in specialist centres. Transplantology is based on a sensitive field in terms of society perception and the lack of transparency in this environment may lead to a loss of public trust. The following article presents the complexity of legal and medical aspects of kidney transplantation in Poland.
Dexamethasone suppression tests are used to diagnose cortisol secretion disorders such as Cushing's syndrome and pseudo-Cushing's syndrome. The purpose of this study was to analyze the influence of various factors on the cut-off values of dexamethasone suppression tests. A literature re-view was conducted, which included clinical studies, review studies and scientific society guidelines. Analysis of these data showed that cytochrome P450 3A4 inducers, chronic diarrhea or celiac disease, elevated levels of corticosteroid-binding globulin due to pregnancy, oral contraceptives, hormone replacement therapy, alcohol abuse, liver disease may increase the proportion of false-positive 1 mg dexamethasone suppression test results, while cytochrome P450 3A4 inhibitors may increase the proportion of false-negative results. Polymorphisms of genes encoding the glucocorticoid receptor may predispose to false-positive or false-negative results. In addition, this review shows that conditions leading to abnormal cortisol levels in the body, such as chronic kidney disease, obesity, diabetes mellitus, metabolic syndrome, anorexia, starvation, neuropsychiatric disorders including depression and bipolar affective disorder lead to a lack of cortisol suppression in dexamethasone suppression tests, especially when using cut-off values that result in a decrease in test sensitivity, such as 5 mu g/dl. The influence of the above factors on the cut-off values of dexamethasone suppression tests shows that an individualized approach to the patient is essential when diagnosing cortisol secretion disorders.
Histology remains a fundamental component of medical education, providing essential insights into the microscopic structure of tissues and organs. Although traditional light microscopy has long served as the core instructional tool, contemporary educational challenges-including increased cohort sizes, limited contact hours and the abstract nature of the subject-have reduced its effectiveness. Virtual microscopy has emerged as a superior alternative, offering high-quality digital slides, ease of access, improved interactivity, and enhanced learning outcomes, while still acknowledging the educational value of hands-on microscopy. Despite technological advances, many curricula continue to rely on passive teaching formats, leading students to view histology as difficult, disconnected from clinical practice, and lacking relevance. Active learning strategies offer a response to these limitations. Methods such as flipped classroom, case-based learning, problem-based learning, and team-based learning have consistently demonstrated improved student engagement, deeper conceptual understanding, and better integration of histology with related disciplines, especially pathology. Gamification further enhances motivation, although its impact on measurable learning outcomes varies. Peer-assisted learning and near-peer teaching increase students' comfort and reduce anxiety, while providing mutual benefits for both learners and student-tutors. In parallel, blended learning and self-directed learning modules allow individualized pacing, flexible access to materials, and improved academic performance, particularly when integrated with virtual microscopy. Collectively, these active, technology-enhanced, and student-centered methods represent a modernized approach to histology education. They address key limitations of traditional instruction, support the development of clinical reasoning and observational skills, and better align histology teaching with the expectations of contemporary medical practice. A multimodal educational model-combining virtual microscopy with structured active learning strategies-offers the most effective pathway to improving both learning outcomes and student satisfaction in histology education.
Beside diabetes and thyroid diseases, parathyroid disorders are one of the most common among all endocrine malfunctions. Due to the difficulties in imaging parathyroid glands, caused by their size and location, the diagnosis of those pathologies is based mainly on laboratory findings. PTH-secreting glands control the body's calcium and phosphate homeostasis by influencing bone metabolism, production of the active form of vitamin D3 in kidneys and the excretion of calcium and phosphates with urine. Knowing these mechanisms is the basis for interpreting diagnostic test results. Various PTH tests, measuring both its active and inactive form, indicate significant relevance to clinical use. Moreover, depending on oxidation of different methionine in the PTH amino-acid sequence, current research reveal varied activity of this hormone. In addition, it appears that the choice of calcium levels determination is not indifferent in the diagnostic process, and ionized calcium seems to respond better to an increase in PTH than total calcium. The results of laboratory tests used in the diagnosis of parathyroid disorders might be affected by many different factors, such as abnormalities in magnesium levels, medications that alter the calcium-phosphate balance and co-existing diseases.
Hepcidin is an acute phase protein and peptide hormone participating in maintaining homeostasis of the body's iron metabolism. Increase in hepcidin production by hepatocytes takes place by induction of ferroportin degradation. This results in limited iron absorption in intestinal epithelial cells and releasing iron reserves from liver and macrophages and leads to a decreased plasma iron levels. Changes in hepcidin levels and other iron homeostasis parameters in plasma have been observed in some diseases, including pathologies of the endocrine glands. Those occur in both hyperthyroidism and hypothyroidism, in pathologies such as: Hashimoto's disease, Graves' disease and subacute thyroiditis. Decrease in hepcidin levels predisposes to diabetes development, by functional impairment in pancreatic beta cells. Hepcidin is also considered to be a prognostic factor in acute pancreatitis and pancreatic cancer. With reference to the gonads, changes in hepcidin levels have been observed in polycystic ovary syndrome, testicular and ovarian cancers and in men with testicular hypogonadism after testosterone treatment. Use of hepcidin more broadly as a diagnostic marker and for monitoring the course of treatment of endocrine gland diseases has been suggested. Presented review is an overview of current knowledge about the dependence between changes in hepcidin and other iron homeostasis parameters levels and pathologies of thyroid, pancreas and gonads.
