Ireneusz Ryszkiel

Gastric organoids are advanced three-dimensional models generated from adult or pluripotent stem cells. By reproducing key structural, cellular, and functional features of gastric tissue, they overcome several limitations of conventional two-dimensional cultures and animal models. Gastric organoids provide physiologically relevant platforms for studying stomach development, cellular differentiation, and the molecular mechanisms underlying gastric diseases. This review summarizes the principal cell sources and protocols used to generate gastric organoids and discusses recent advances in culture systems, including two-dimensional organoid-derived monolayers, air–liquid interface cultures, co-culture systems, and organoid-on-a-chip technologies. Particular attention is given to the application of gastric organoids in modeling Helicobacter pylori infection, SARS-CoV-2 infection, and gastric cancer, as well as in evaluating therapeutic responses. Their roles in developmental biology, the investigation of congenital disorders, drug screening, potential precision-medicine application, biobanking, and regenerative medicine are also discussed. Despite their considerable potential, current gastric organoid models remain limited: conventional epithelial organoids lack stromal, immune, neural, and vascular components; PSC-derived organoids contain only a limited mesenchymal population; and more complex engineered multicellular tissues still depend largely on in vivo engraftment for maturation. Variable maturation, dependence on poorly defined extracellular matrices, and insufficient standardization further limit their translation.

Background/Objectives: The response of complete blood count (CBC)-derived inflammatory indices to whole-body cryotherapy (WBC) in ankylosing spondylitis (AS) remains unknown. This exploratory post hoc secondary analysis examined whether adding WBC to kinesiotherapy was associated with differences in these indices and explored their associations with disease activity, pain, and high-sensitivity C-reactive protein (hsCRP) levels. Prospectively collected data from 32 men with AS were analyzed. Participants were allocated by alternation, rather than randomization, to WBC combined with kinesiotherapy (WBC + K; n = 16) or kinesiotherapy alone (KT; n = 16). Methods: Prospectively collected data from 32 men with ankylosing spondylitis (AS) who participated in a prior study were analyzed. Participants were allocated to whole-body cryotherapy combined with kinesiotherapy (WBC + K; n = 16) or kinesiotherapy alone (KT; n = 16). Complete blood count parameters, high-sensitivity C-reactive protein (hsCRP) levels, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and visual analogue scale (VAS) pain scores were assessed prospectively before and after the intervention. Previously unpublished complete blood count data were used to calculate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) post hoc and to explore their associations with hsCRP, BASDAI, and VAS pain. The primary intervention effects were assessed using baseline-adjusted analysis of covariance, and the five treatment-effect p-values were subjected to Benjamini–Hochberg correction. Comparisons of changes from baseline were performed as sensitivity analyses. Results: None of the baseline-adjusted between-group treatment effects for NLR, PLR, MLR, SII, or SIRI were statistically significant before or after false discovery rate correction. The adjusted between-group difference for MLR was −0.033 (95% confidence interval: −0.074 to 0.008; p = 0.115; q = 0.329). In the change-score sensitivity analysis, the between-group difference in MLR change was nominally significant (p = 0.012) but did not meet the multiplicity-adjusted significance threshold (q = 0.060). Within the WBC + K group, PLR, MLR, and SIRI decreased significantly, whereas no corresponding within-group changes were observed in the KT group; however, these within-group findings were descriptive and did not establish an additional effect of WBC. Changes in the indices were not significantly correlated with changes in hsCRP, BASDAI, or VAS pain. None of the exploratory post-treatment correlations remained significant after multiple-testing correction. Conclusions: This study did not provide baseline-adjusted or multiplicity-adjusted evidence that adding WBC to kinesiotherapy affected any of the investigated CBC-derived inflammatory indices in men with AS. The nominal MLR signal identified in the change-score sensitivity analysis and the within-group reductions in PLR, MLR, and SIRI should be considered exploratory and hypothesis-generating. Larger, prospectively designed, adequately powered randomized studies with prespecified outcomes and baseline-adjusted analyses are required.

Leukemia represents a heterogeneous group of hematologic malignancies characterized by the dysregulated proliferation, differentiation, and survival of hematopoietic cells. Vitamin D (VD), a fat-soluble secosteroid hormone, is increasingly recognized not only as a regulator of calcium–phosphate metabolism but also as an important immune–metabolic modulator involved in hematopoietic homeostasis, inflammatory signaling, and cellular fate determination. Growing evidence suggests that VD deficiency may influence leukemogenesis, disease progression, treatment responsiveness, and supportive-care outcomes in patients with leukemia. Mechanistic studies indicate that the active metabolite, 1,25-dihydroxyvitamin D₃ (calcitriol), modulates leukemic cell biology by activating the vitamin D receptor (VDR) and regulating genomic and non-genomic signaling pathways, including MAPK, PI3K/AKT/mTOR, JAK/STAT, NF-κB, and β-catenin. Through these pathways, VD may affect transcriptional programs governing proliferation, differentiation, apoptosis, autophagy, immune regulation, and treatment resistance. Clinical and observational studies suggest that low 25-hydroxyvitamin D levels may be associated with adverse outcomes in selected leukemia subtypes, including poorer treatment responses, shorter overall survival and relapse-free survival, and shorter time to treatment. However, the available data remain heterogeneous, and causality has not been established. This review provides an integrated translational synthesis of VD deficiency in leukemia, linking molecular mechanisms with subtype-specific clinical evidence and supportive-care implications. Although VD supplementation should not be considered an independent anti-leukemic therapy, individualized assessment and correction of deficiency may represent a rational, low-toxicity component of supportive care. Further prospective and interventional studies are needed to define optimal supplementation strategies, identify responsive patient subgroups, and clarify the clinical relevance of VD status in leukemia.

Graft-versus-host disease (GVHD) is one of the principal complications seen in the recipients of allogenic hematopoietic stem cell transplantation (allo-HSCT), and persists as a leading cause of post-transplant morbidity and mortality. Increasing evidence highlights the crucial influence of the gut microbiome (GM) on transplant outcomes. Microbial dysbiosis, characterized by reduced bacterial diversity and pathogenic overgrowth, is strongly associated with higher rates of complications and mortality. Patients with lower microbial diversity exhibit poorer overall survival (OS) and an increased incidence of acute GVHD (aGVHD). Conversely, restoration of beneficial commensal communities has been shown to enhance immune homeostasis, mitigate GVHD severity, and decrease infection risk. Emerging therapeutic strategies now focus on modulating the intestinal microbiome through dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation (FMT). It has been demonstrated that bacterial metabolites, such as short-chain fatty acids (SCFAs) from the diet, especially a diet rich in fibers, reduce the occurrence/severity of GVHD by inducing regulatory T cells (Tregs), which release anti-inflammatory cytokines and regulate the host immune system. Hence, the implementation of dietary fibers (DFs) could increase beneficial commensals, Treg induction, and improve outcomes such as GVHD and OS in recipients of allo-HCT. Hereupon, this review addresses how a fiber-rich diet modulates GM composition, reinforces epithelial barrier integrity, and improves the efficacy of Treg-based immunotherapy by stabilizing their regulatory phenotype and increasing their functional persistence, ultimately leading to a reduction in GI complications associated with GVHD. Unlike prior reviews that primarily cover the microbiome–GVHD axis or Treg therapies in isolation, this review emphasizes fermentable dietary fibers as a mechanistically grounded, clinically actionable strategy to support Treg stability and persistence via microbiota-derived metabolites. We integrate mechanistic evidence with emerging clinical feasibility data and ongoing trials of prebiotic supplementation in allogeneic HSCT.

Ovarian cancer remains one of the leading causes of cancer-related mortality among women, underscoring the need for novel combination strategies that effectively inhibit tumor cell growth while limiting adverse effects. N-acetylcysteine (NAC) and alpha-ketoglutarate (AKG) are biologically active compounds with reported anticancer properties; however, their combined effects in ovarian cancer are not well characterized. In this study, we applied an integrative approach combining network pharmacology analysis with in vitro experiments to investigate the effects of NAC and AKG on OVCAR3 ovarian cancer cells. Common molecular targets of NAC and AKG were identified by intersecting predicted compound targets with ovarian cancer-associated genes, followed by protein–protein interaction network construction and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Experimental validation assessed the effects of NAC and AKG, alone and in combination, on cell viability, apoptosis, migration, and clonogenic capacity. Network analysis identified 70 shared target genes enriched in pathways related to apoptosis, cellular stress responses, and cell migration. In vitro experiments demonstrated that combined treatment with NAC (10 mM) and AKG (100 µM) significantly reduced cell viability, increased apoptotic cell death, and markedly suppressed cell migration and colony formation compared with single-agent treatments. Overall, these findings indicate that the combination of NAC and AKG exerts enhanced inhibitory effects on ovarian cancer cell growth and motility in vitro.

The human gut microbiome and its relationship with both physiological and pathological functions have long intrigued researchers. One of the most fascinating and important areas within this domain is cognitive function. Given that a substantial number of studies, especially interventional ones, have been conducted on animal models, the findings of which are not fully generalizable to humans and may therefore be misinterpreted, the purpose of this study is to synthesize evidence from the most recent human research. Current evidence indicates that the gut microbiota is linked to cognitive function in both healthy and diseased states, with numerous studies suggesting a potential causal relationship between the two. Although the majority of these studies associate changes in cognitive function with differences in the composition of the gut microbiota, some findings also indicate an inverse relationship.

Metabolic syndrome (MetS) is defined by a combination of metabolic abnormalities, such as central obesity, insulin resistance, hypertension, and dyslipidemia, and significantly increases the risk of cardiovascular diseases and type 2 diabetes. The high prevalence of MetS is a public health concern, necessitating rapid identification and intervention strategies to prevent this emerging epidemic. Diagnosing MetS requires the presence of three or more of these abnormalities, underscoring the need for effective management approaches. Despite a growing body of literature, limited reviews have critically evaluated the complex interplay between metabolic dysfunction, inflammation, and coagulation, particularly in the context of dietary interventions. Therefore, this article reviews the relationship between metabolic syndrome, inflammation, and thrombotic diseases, with an emphasis on their impacts on hematological health. Furthermore, this review explores the potential role of vegetarian and vegan dietary patterns in controlling these processes and improving hematological outcomes. This narrative review aims to critically evaluate current research on the inflammatory and thrombotic implications of MetS and assess the potential modulating role of vegan and plant-based diets within this context.

The purpose of this study was to evaluate the effects of contrast heat and cold pressure therapy (CHCP) on muscle tone, elasticity, stiffness, perfusion unit, and muscle fatigue indices after plyometric training consisting of five sets of jumping on a 50-cm high box until exhaustion. A prospective, randomized, controlled single-blind study design was used. Twenty professional MMA fighters were included in the study. The experimental group (n = 10) was subjected to the CHCP protocol (eGR), while the control group (cGR) (n = 10) was subjected to sham therapy. Both protocols consisted of three CHCP sessions performed immediately after plyometric exercise, 24 and 48 h afterwards. Measurements were taken at the following time points: 1) at rest; 2) 1 min post-exercise; 3) 1 min post-CHCP therapy; 4) 24 h post-CHCP therapy; 5) 48 h post-CHCP therapy. The results of the eGR compared to the cGR showed significantly higher perfusion at time point 5 (p < 0.001), higher muscle tone at time points 1, and 3–5 (p < 0.001 for all), higher stiffness at time points 1, 3–5 (p < 0.001 for all) and a higher pain threshold at time points 1 and 5 (p < 0.001 for all). This study suggests a positive effect of CHCP therapy on muscle biomechanics, the pain threshold, and tissue perfusion, which may contribute to increasing the effectiveness of post-exercise muscle recovery in MMA athletes.

Leczenie ran jest sztuką, której początki sięgają początków ludzkości. Można przypuszczać, że dobór różnych materiałów o właściwościach wspomagających gojenie ran następował metodą prób i błędów przez długi okres. W rezultacie, gdy około 6000 lat temu zaczęły powstawać pierwsze cywilizacje, pojawiło się wiele skutecznych metod miejscowego leczenia ran. Od zarania dziejów rany i owrzodzenia skóry stanowiły przedmiot zainteresowania mędrców i medyków, ponieważ były nie tylko poważnym problemem dla chorych, ale również wyzwaniem dla osób zajmujących się ich leczeniem. Ogromny postęp w tej dziedzinie, dokonany w ciągu ostatnich 150 lat, nie byłby możliwy bez wcześniejszych osiągnięć i doświadczeń, które uczyniły zaopatrywanie ran jednym z głównych bodźców do rozwoju medycyny. Pomysłowość ludzi oraz ich dążenie do rozwiązywania problemów związanych z trudno gojącymi się ranami przyczyniały się do nieustannego doskonalenia metod leczenia. Już starożytni Rzymianie, Grecy oraz Babilończycy usystematyzowali objawy stanu zapalnego ran. Wśród pionierów w tej dziedzinie należy wymienić Hipokratesa z Kos, Aulusa Corneliusa Celsusa oraz arabskiego lekarza znanego pod łacińskim imieniem Abulcasis. Leczenie opierało się głównie na obserwacji i doświadczeniu. W terapii wykorzystywano różnorodne naturalne substancje, takie jak rośliny, miód, wino, pajęczyny czy mleko. Rany opatrywano materiałami pochodzenia naturalnego, m.in. lnem, wełną, jedwabiem czy gliną. Zioła stosowano w formie maści lub okładów, a wśród roślin o właściwościach ściągających lub antybakteryjnych używano m.in. dziurawca zwyczajnego, żywokostu oraz rdestu. Znaczący postęp w technikach leczenia ran nastąpił w XVII wieku, dzięki odkryciom w zakresie anatomii naczyń krwionośnych dokonanym przez Hieronima de Fabritiusa, Marcella Malpighiego oraz Benjamina Brodiego. W tym okresie zaczęto stosować bardziej zaawansowane procedury, takie jak podwiązywanie naczyń krwionośnych. Pojawiły się również innowacyjne metody opatrywania ran, w tym bandażowanie kończyn dolnych z wykorzystaniem materiałów nasączonych lekami, co znacząco przyczyniło się do poprawy skuteczności terapii.