Transplantation of various types of stem cells as a possible therapy for stroke has been tested for years, and the results are promising. Recent investigations have shown that the administration of the conditioned media obtained after stem cell cultivation can also be effective in the therapy of the central nervous system pathology (hypothesis of their paracrine action). The aim of this study was to evaluate the therapeutic effects of the conditioned medium of hiPSC-derived glial and neuronal progenitor cells in the rat middle cerebral artery occlusion model of the ischemic stroke. Secretory activity of the cultured neuronal and glial progenitor cells was evaluated by proteomic and immunosorbent-based approaches. Therapeutic effects were assessed by overall survival, neurologic deficit and infarct volume dynamics, as well as by the end-point values of the apoptosis- and inflammation-related gene expression levels, the extent of microglia/macrophage infiltration and the numbers of formed blood vessels in the affected area of the brain. As a result, 31% of the protein species discovered in glial progenitor cells-conditioned medium and 45% in neuronal progenitor cells-conditioned medium were cell type specific. The glial progenitor cell-conditioned media showed a higher content of neurotrophins (BDNF, GDNF, CNTF and NGF). We showed that intra-arterial administration of glial progenitor cells-conditioned medium promoted a faster decrease in neurological deficit compared to the control group, reduced microglia/macrophage infiltration, reduced expression of pro-apoptotic gene Bax and pro-inflammatory cytokine gene Tnf, increased expression of anti-inflammatory cytokine genes (Il4, Il10, Il13) and promoted the formation of blood vessels within the damaged area. None of these effects were exerted by the neuronal progenitor cell-conditioned media. The results indicate pronounced cytoprotective, anti-inflammatory and angiogenic properties of soluble factors secreted by glial progenitor cells.

The gut microbiota plays an essential role in maintaining immune homeostasis and influencing the immune landscape within the tumor microenvironment. This review aims to elucidate the interactions between gut microbiota and tumor immune dynamics, with a focus on colorectal cancer (CRC). The review spans foundational concepts of immuno-microbial interplay, factors influencing microbiome composition, and evidence linking gut microbiota to cancer immunotherapy outcomes. Gut microbiota modulates anti-cancer immunity through several mechanisms, including enhancement of immune surveillance and modulation of inflammatory responses. Specific microbial species and their metabolic byproducts can significantly influence the efficacy of cancer immunotherapies. Furthermore, microbial diversity within the gut microbiota correlates with clinical outcomes in CRC, suggesting potential as a valuable biomarker for predicting response to immunotherapy. Conclusions: Understanding the relationship between gut microbiota and tumor immune responses offers potential for novel therapeutic strategies and biomarker development. The gut microbiota not only influences the natural history and treatment response of CRC but also serves as a critical modulator of immune homeostasis and anti-cancer activity. Further exploration into the microbiome’s role could enhance the effectiveness of existing treatments and guide the development of new therapeutic modalities.

This comprehensive review elucidates the intricate roles of long non-coding RNAs (lncRNAs) within the colorectal cancer (CRC) microenvironment, intersecting the domains of immunity, intercellular communication, and therapeutic potential. lncRNAs, which are significantly involved in the pathogenesis of CRC, immune evasion, and the treatment response to CRC, have crucial implications in inflammation and serve as promising candidates for novel therapeutic strategies and biomarkers. This review scrutinizes the interaction of lncRNAs with the Consensus Molecular Subtypes (CMSs) of CRC, their complex interplay with the tumor stroma affecting immunity and inflammation, and their conveyance via extracellular vesicles, particularly exosomes. Furthermore, we delve into the intricate relationship between lncRNAs and other non-coding RNAs, including microRNAs and circular RNAs, in mediating cell-to-cell communication within the CRC microenvironment. Lastly, we propose potential strategies to manipulate lncRNAs to enhance anti-tumor immunity, thereby underlining the significance of lncRNAs in devising innovative therapeutic interventions in CRC.

Preeclampsia is a gestation-associated hypertensive syndrome that threatens the life and health of the mother and the child. The condition is presumably caused by systemic failure with a strong involvement of innate immunity. In particular, it has been associated with flexible phenotypes of macrophages, which depend on the molecules circulating in the blood and tissue fluid, such as cytokines and hormones. This study aimed at a comparative evaluation of pro-inflammatory (TNFα) and anti-inflammatory (CD206, MMP9, HGF) markers, as well as the levels of estrogen receptor α, expressed by decidual macrophages in normal pregnancy and in patients with early- and late-onset preeclampsia. The tissue samples of decidua basalis were examined by immunohistochemistry and Western blotting. Isolation of decidual macrophages and their characterization were performed using cultural methods, flow cytometry and real-time PCR. Over 50% of the isolated decidual macrophages were positive for the pan-macrophage marker CD68. In the early-onset preeclampsia group, the levels of estrogen receptor α in decidua were significantly decreased. Furthermore, significantly decreased levels of HGF and CD206 were observed in both preeclampsia groups compared with the control group. The observed downregulation of estrogen receptor α, HGF and CD206 may contribute to the balance of pro- and anti-inflammatory macrophages and thereby to pathogenesis of preeclampsia.

We present EndoNuke, an open dataset consisting of tiles from endometrium immunohistochemistry slides with the nuclei annotated as keypoints. Several experts with various experience have annotated the dataset. Apart from gathering the data and creating the annotation, we have performed an agreement study and analyzed the distribution of nuclei staining intensity.

Introduction. Colorectal cancer (CRC) is one of the most common oncological diseases, the pathogenesis of which is closely associated with the development of inflammation. The study of inflammation regulation, including the balance of pro- and antiinflammatory cytokines, is a promising topic for research, allowing for a deeper understanding of the pathogenesis of CRC and improving clinical approaches to the treatment for and diagnosis of this disease. This study investigates the altered secretion of proinflammatory cytokines, i.e., TNF-α and IL-1β, in CRC patients, aiming to elucidate immune dysregulation mechanisms. We sought to investigate the secretion characteristics of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), in patients with CRC. Materials and methods. We enrolled 25 newly diagnosed CRC patients and 20 age- and sex-matched controls. Monocytes were isolated from the peripheral blood of participants using magnetic separation based on the CD14 marker. The isolated monocytes were cultured and subjected to dual stimulation with bacterial lipopolysaccharide at 24 hours and 7 days, followed by quantitative measurement of basal and stimulated cytokine levels using an enzyme-linked immunosorbent assay (ELISA). Results. We revealed a significant reduction in TNF-α secretion in CRC monocytes after initial LPS stimulation, with no subsequent recovery upon restimulation. In contrast, IL-1β secretion elevated markedly in CRC patients, particularly after restimulation. These results suggest an impaired TNF-α response and an exacerbated IL-1β response in CRC, indicating a potential immune tolerance mechanism that may contribute to tumor progression. The distinct cytokine dynamics observed point at complex immune dysregulation within the CRC microenvironment. Conclusion. The observed cytokine secretion patterns may indicate immune dysregulation in the microenvironment of CRC. Our study underscores the importance of understanding the specific roles of cytokines in CRC pathogenesis and highlights the potential for targeted therapeutic interventions to modulate these immune responses. Further research is necessary to explore the underlying signaling pathways and the broader implications of these findings for CRC treatment strategies. This work provides critical insights into the pro-inflammatory cytokine profiles in CRC, advancing our understanding of the immune landscape in cancer and opening new avenues for therapeutic exploration. Keywords: colorectal cancer, cytokines, tumor necrosis factor-alpha, interleukin-1 beta, immune tolerance