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Inflammation is an important driver of atherosclerosis, and the favourable outcomes of the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial revealed the large potential of anti-inflammatory drugs for the treatment of cardiovascular disease, especially in patients with a pro-inflammatory constitution. However, the complex immune reactions driving inflammation in the vascular wall in response to an atherosclerotic microenvironment are still being unravelled. Novel insights into the cellular processes driving immunity and inflammation revealed that alterations in intracellular metabolic pathways are strong drivers of survival, growth, and function of immune cells. Therefore, this position paper presents a brief overview of the recent developments in the immunometabolism field, focusing on its role in atherosclerosis. We will also highlight the potential impact of immunometabolic markers and targets in clinical cardiovascular medicine., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Purpose: This paper outlines the theoretical and empirical basis for compassion focused therapy (CFT) for psychosis, the gaps in the current knowledge and research, as well as some of the challenges for addressing gaps. It will guide the direction of future work and the steps needed to develop and advance this approach. Method: This paper reviews evidence of how evolutionary models such as social rank theory and attachment theory have greatly contributed to our understanding of psychosis and provide a clear rationale and evidence base for the mechanisms of change in CFT for psychosis. It reviews the evidence for outcomes of compassion training more generally, and early feasibility evaluations of CFT for psychosis. Results: The process evidence shows that people with psychosis have highly active social rank and threat systems, and the benefits of switching into attachment and care systems, which can support emotion regulation and integrative mind states. The outcomes evidence shows that compassion training impacts not only psychological outcomes, but also physiological outcomes such as neural circuits, immune system, and the autonomic nervous system. Within the psychosis field, outcomes research is still in the early days, but there are good indications of feasibility and a clear path forward for the next steps. Conclusions: CFT for psychosis is an approach that integrates biopsychosocial processes, an integration that's evidenced across each aspect of the model, from theoretical foundations (evolution‐informed) to interventions (e.g., body/breath training and relational techniques), to evaluation. Future RCTs are required to understand the effects on biopsychosocial outcomes for people with psychosis. [ABSTRACT FROM AUTHOR]

Objective: The level of immunological reactivity of the indigenous inhabitants of the Far North may depend on the extreme-discomfort factors of the climatic environment and genetic traits of the population. Therefore, the aim of this study was to identify the distinctive elements of the immune status of the Kola Saami and Russians living in the Far North (Murmansk Region)., Methods: A complex immunological study of peripheral venous blood composition was performed and involved 67 Saami and 81 Russian inhabitants of the Far North (Murmansk Region) who were aged 21-55. Blood was collected from the cubital vein on an empty stomach in the morning. For the peripheral venous blood, we obtained a hemogram and phagocytic activity of neutrophils, determined the content of lymphocytes with CD4, CD8, CD16, and CD71 phenotypes by indirect immunoperoxidase reaction and flow cytometry using an Epics XL apparatus (Beckman Coulter, United States), obtained concentrations of IL-6, IFN-γ, IL-10, IgA, M, G, E, sCD54, and sCD62L, transferrin, and sCD71 by enzyme immunoassay using the "Evolis" enzyme immunoassay analyzer from Bio-RAD (Germany), and obtained circulating immune complexes by precipitation using 3.5%, 4.0%, and 7.5% PEG-6000. The sIgA content was determined in morning saliva, urine, and gastrointestinal tract secretions. The results were analyzed using descriptive statistics, independent sample t-criterion, and Pearson correlation coefficient., Results: A decrease in the total number of leukocyte cells in the Saami was associated with a high incidence of leukopenia, lymphopenia, and neutropenia. Deficiency in active phagocytes and serum IgA and sIgA concentrations was revealed as well as increased contents of CD4+ and CD8+ receptor lymphocytes, membrane and free adhesion molecules, and transferrin. Leukocytosis, lymphocytosis, neutrophilia, monocytosis, and eosinophilia with increased contents of natural killer cells, IL-6, and IL-10 were recorded more frequently in the Russians. High levels of IgE and IFN-γ, which have the most pronounced cytotoxicity and are indicative of strained immune mechanisms, were characteristic of the Saami and Russians., Conclusion: The distinctive aspects of the immune status of the Kola Saami is related to the deficit in the active phagocyte and serum IgA and sIgA concentrations as well as the increase in the contents of cytotoxic lymphocytes, intercellular adhesion molecules, transferrin, and IFN-γ proinflammatory cytokines. The Russian inhabitants of the Far North are characterized by an adaptive response manifested by an increase in antibody-dependent cytotoxicity, involving IL-6 and IL-10., (© 2023 Wiley Periodicals LLC.)

Plain language summary: A uterine transplant, or womb transplant, provides a potential treatment for women who cannot become pregnant or carry a pregnancy because they do not have a womb, or have a womb that is unable to maintain a pregnancy. This is estimated to affect one in 500 women. Options for those who wish to start a family include adoption and surrogacy, but these are associated with legal, cultural, ethical and religious implications that may not be appropriate for some women and their families. A womb transplant is undertaken when the woman is ready to start a family, and is removed following the completion of their family. Womb transplants have been performed all over the world, with more than 70 procedures carried out so far. At least 23 babies have been born as a result, demonstrating that womb transplants can work. While the procedure offers a different option to adoption and surrogacy, it is associated with significant risks, including multiple major surgeries and the need to take medications that help to dampen the immune system to prevent rejection of the womb. To date there has been a 30% risk of a transplant being unsuccessful. Although the number of transplants to date is still relatively small, the number being performed globally is growing, providing an opportunity to learn from the experience gained so far. This paper looks at the issues that have been encountered, which may arise at each step of the process, and proposes a framework for the future. However, long term follow‐up of cases will be essential to draw reliable conclusions about any overall benefits of this procedure. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to present evidence that supports the notion that the primary reason behind marginal bone loss and implant failure is immune-based and that bacterial actions in the great majority of problematic cases are of a secondary nature. Materials and Methods: The paper is written as a narrative review. Results: Evidence is presented that commercially pure titanium is not biologically inert, but instead activates the innate immune system of the body. For its function, the clinical implant is dependent on an immune/inflammatory defense against bacteria. Biologic models such as ligature studies have incorrectly assumed that the primary response causing marginal bone loss is due to bacterial action. In reality, bacterial actions are secondary to an imbalance of the innate immune system caused by the combination of titanium implants and ligatures, ie, nonself. This immunologic imbalance may lead to marginal bone resorption even in the absence of bacteria. Conclusion: Marginal bone loss and imminent oral implant failure cannot be properly analyzed without a clear understanding of immunologically caused tissue responses. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibition therapy (ICIT) is an emerging field in oncology especially opening new horizons to chemotherapy refractory patients. However, immune-related adverse events (irAEs) and undesired response patterns such as progression after the initial good response in a subset of patients pose a major challenge and drawback to ICIT. This paper provides deep insight into ICIT related bottlenecks and corresponding effective management and combat strategies for very complex complications., Methods: The relevant literatures from PubMed have been reviewed. Based on obtained information, rigorous and exhaustive analyses have been made to present novel methods and strategies against ICIT drawbacks and bottlenecks., Results: The results show that baseline biomarker tests are very crucial to identify suitable candidates for ICIT and frequent assessments throughout ICIT help to recognize possible irAEs at early stages. Equally important are the necessity for mathematical definitions for the ICIT success rate and optimum duration, and the development of combat mechanisms against loss of sensitivity within the tumor microenvironment (TME)., Conclusion: Rigorous management approaches are presented for mostly observed irAEs. Furthermore, for the first time in the literature, a non-linear mathematical model is invented to measure the ICIT success rate and to decide about the optimum ICIT duration. Finally, a strategy against tumor plasticity is introduced., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The paper mulberry (Broussonetia papyrifera) leaf is rich in alkaloids and flavonoids, which has high medicinal and feeding value. We aimed to analyze the effects of B. papyrifera leaf extract on growth performance, antioxidant capacity, immune functions, and fecal microflora of weaned piglets. Thirty healthy, 28-day-old piglets were randomly assigned to three groups and fed with a basal diet supplemented with 0, 150, and 300 g/t B. papyrifera leaf extract for 42 days (control group, group I, and group II) separately. The result revealed that the final weight of piglets in group II was higher than the other groups, and the diarrhea rate in this group was 62.9% lower than in the control group. The feed conversion ratio in group I was significantly lower than the other two groups. Higher blood urine nitrogen concentration was noted in group II, higher glutathione peroxidase and catalase in group II, higher superoxide dismutase in the control group, and higher immune globulins (Ig) IgG, IgA, and IgM in group II. There was no significant difference in community richness and community diversity among the three groups of fecal samples. The relative level of Roseburia was higher in groups I and II, while Lactobacillus was higher in the control group. In conclusion, supplementation with B. papyrifera leaf extract at a certain dosage can increase growth performance and antioxidant capacity of weaned piglets, reduce the occurrence of diarrhea, enhance immune functions and disease resistance, and affect the composition of fecal microflora. [ABSTRACT FROM AUTHOR]

Abstract Background Our current understanding of the pathophysiology and management of sepsis is associated with a lack of progress in clinical trials, which partly reflects insufficient appreciation of the heterogeneity of this syndrome. Consequently, more patient-specific approaches to treatment should be explored. Aims To summarize the current evidence on precision medicine in sepsis, with an emphasis on translation from theory to clinical practice. A secondary objective is to develop a framework enclosing recommendations on management and priorities for further research. Sources A global search strategy was performed in the MEDLINE database through the PubMed search engine (last search December 2017). No restrictions of study design, time, or language were imposed. Content The focus of this Position Paper is on the interplay between therapies, pathogens, and the host. Regarding the pathogen, microbiologic diagnostic approaches (such as blood cultures (BCs) and rapid diagnostic tests (RDTs)) are discussed, as well as targeted antibiotic treatment. Other topics include the disruption of host immune system and the use of biomarkers in sepsis management, patient stratification, and future clinical trial design. Lastly, personalized antibiotic treatment and stewardship are addressed (Fig. 1). Implications A road map provides recommendations and future perspectives. RDTs and identifying drug-response phenotypes are clear challenges. The next step will be the implementation of precision medicine to sepsis management, based on theranostic methodology. This highly individualized approach will be essential for the design of novel clinical trials and improvement of care pathways. [ABSTRACT FROM AUTHOR]

Unlike other cells in the body, immune cells have to be able to enter and adapt to life within diverse tissues. Immune cells develop within dedicated immune system organs, such as the bone marrow, thymus and lymphoid tissues, but also inhabit other tissues, wherein they not only provide defense against infection and malignancies but also contribute to homeostatic tissue function. Because different tissues have widely divergent metabolic rates and fuel requirements, this raises interesting questions about the adaptation of immune cells in specific tissues. When immune cells take up residence in different tissues, they develop a transcriptional signature that reflects adaptation to life and function within that tissue. Genes encoding metabolic-pathway proteins are strongly represented within these signatures, reflective of the importance of metabolic adaptation to tissue residence. In this Review, we discuss the available data on the metabolic adaptation of immune cells to life in different tissue sites, within the broader framework of how functional adaptation versus maladaptation in the niche can affect tissue homeostasis.

Smartphone detection of Escherichia coli from field water samples is successfully demonstrated using paper microfluidics. A three-channel paper chip is designed and fabricated, with a negative control channel preloaded with bovine serum albumin (BSA)-conjugated beads and two E. coli detection channels preloaded with anti-E. coli-conjugated beads, for low- and high-concentration detection. Field water samples are introduced to the paper chip by dipping or pipetting, and the antigens from E. coli travel through the paper fibers by capillary action while the dust/soil or algae particles are effectively filtered. Antibody-conjugated beads, confined within the paper fibers, immunoagglutinate in the presence of E. coli antigens, while BSA-conjugated beads do not. The extent of immunoagglutination is quantified by evaluating Mie scatter intensity from the digital images taken at an optimized angle and distance using a smartphone. The assay results show excellent agreement with the MacConkey plate results, i.e., the count of viable E. coli. The scatter simulation procedure is introduced to substitute for experimental optimization, such that the proposed method can be easily adapted to the other types of samples. A smartphone application is developed, incorporating the internal gyroscope of a smartphone, to allow the user to position the smartphone at an optimized angle of scatter detection. The detection limit is single-cell-level and the total assay time is 90 s. [ABSTRACT FROM PUBLISHER]

Aging is associated with substantial physiological changes and constitutes a major risk factor for neurological disorders including dementia. Alterations in gene expression upon aging have been extensively studied; however, an in-depth characterization of post-transcriptional regulatory events remains elusive. Here, we profiled the age-related changes of the transcriptome and translatome in the female mouse hippocampus by RNA sequencing of total RNA and polysome preparations at four ages (3-, 6-, 12-, 20-month-old); and we implemented a variety of bioinformatics approaches to unravel alterations in transcript abundance, alternative splicing, and polyadenylation site selection. We observed mostly wellcoordinated transcriptome and translatome expression signatures across age including upregulation of transcripts related to immune system processes and neuroinflammation, though transcripts encoding ribonucleoproteins or associated with mitochondrial functions, calcium signaling and the cell-cycle displayed substantial discordant profiles, suggesting translational control associated with age-related deficits in hippocampal-dependent behavior. By contrast, alternative splicing was less preserved, increased with age and was associated with distinct functionally-related transcripts encoding proteins acting at synapses/dendrites, RNA-binding proteins; thereby predicting regulatory roles for RBM3 and CIRBP. Only minor changes in polyadenylation site selection were identified, indicating pivotal 3'-end selection in young adults compared to older groups. Overall, our study provides a comprehensive resource of age-associated post-transcriptional regulatory events in the mouse hippocampus, enabling further examination of the molecular features underlying age-associated neurological diseases. [ABSTRACT FROM AUTHOR]

Introduction and aim. In the literature, blood is described as a body fluid that circulates in a closed vascular system that makes up about 10% of the body weight. The morphotic elements of blood are suspended in this fluid, which is why we can define blood as liquid tissue. Blood in the organization helped to play a role, performing a transport, hemodynamic and protective-defensive function. Its main components are red blood cells, white blood cells and platelets. Erythrocytes due to the ability to connect to the source, participate in the delivery from the lungs to the source. Leukocytes include a group of blood cells that include monocytes, lymphocytes and granulocytes that participate in the body's reactions. Platelets are referred to in the literature as thrombocytes, as non-nucleated blood components. The main component of blood samples is participation in hemostatic processes in the composition. They play one key role in the blood clotting process. At some point, when the continuity of the straight line is interrupted, platelets pass to the subendothelial matrix, the formation of a platelet plug, a clot is formed. Until the beginning of the twentieth, blood functions are provided only for hemostatic activities. Recent scientific research that blood cells are involved in non-hemostatic processes. Including the immune system. Collecting information on the role of blood in an independent team, enabling review work. Material and methods. Literature search from 1989 up to 2022 has been conducted on PubMed, Google Scholar databases and the Practical Medicine for Physicians. For the final analysis, 10 research papers and 9 review papers were used. Following keywords were used to search articles: platelets, in- flammation, immune system, hemostasis. The articles were from the years 1989-2022. Results. Platelets are one of the main morphotic elements of blood, when it comes to size, they are the smallest of all components of peripheral blood, but they are very reactive. They participate in the processes of coagulation and maintaining hemostasis in the body. The characteristic properties of platelets are the presence of dense granules δ and α, their compactness during hemostasis or inflammation are released into the body. Platelets, in addition to active participation in hemostasis processes, take part in immune processes. Platelets have been shown to be regulators of immune processes through the presence of TLRs that trigger the initiation of an immune system response. In addition to the regulatory properties, platelets are involved in the innate immunity and inflammation of the body. Platelets with the participation of endothelial cells lead to the recruitment of leukocytes to the site of inflammation. Platelets participate in the recognition of a foreign pathogen that is in the body, the mechanisms that lead to this are presented in the paper. In addition to the function of platelets in the immune system, the topic of autoimmune diseases, where platelets play a role, is discussed. The work deals with the subject of the influence of platelets on the immune system and their role in immune processes. Through the progress of scientific research, platelets have been shown to play a significant role in immune mechanisms. The work is a review of literature dealing with topics related to the immune system and platelets and aims to explain the mechanisms that lead to the active participation of platelets in the immune system. Conclusion. Platelets are involved in the immune system, it has been shown at the same time that platelets perform regulatory functions in the immune system through the CD154 molecule and additionally participate in inflammation. Where are the first cells that are responsible for fighting in the body's non-specific immune response. In addition, TLR receptors that are found on the surface of platelets play a key role in recognizing a threat and initiating an immune response. Through these receptors, platelets recognize pathogens in the body. Scientists continue to study the non-haemostatic functions of platelets and discover their significant role in the body, which is not only based on blood coagulation processes, but to a large extent in the body's immune defense. [ABSTRACT FROM AUTHOR]

In the pursuit of point-of-care systems that present high sensitivity and fast turnaround time, lateral flow is considered a remarkable promising class of in vitro diagnostics, and popularized by the pregnancy tests. A variety of lateral flow tests have emerged able to provide cardiac panels in emergency conditions, infectious disease screening, drug abuse, among others. However, most commercial tests only provide qualitative results, limiting their applicability for quantification thresholds of most biomarkers. In this paper, we propose a novel detection architecture for quantification of biomolecules labeled with magnetic nanoparticles employing two spin valve sensors. The main goal of this paper is to demonstrate that this architecture can detect and monitor MNPs flowing in a LFT strip for detection and quantification of different solutions varying in MNP concentration. In addition, we present preliminary analytical results that support our strategy for achieving biomolecular quantification using the proposed solution. [ABSTRACT FROM AUTHOR]

In 2019, the SARS-CoV-2 virus caused one of the biggest virus pandemics called Coronavirus disease-19 (COVID-19). This virus has been responsible for the death of millions of people around the world. The biological function of SARS-CoV-2 and its pathophysiology mechanisms, as well as the host immunity against this virus, has attracted the attention of the scientific community all over the world. The current study reviewed innate and acquired immune responses following COVID-19 infection. These immune responses are probably involved in the severity of the disease and death. Also, the cause and consequence of potential clinical strategies to treat or prevent SARS-CoV-2 infection have been proposed. [ABSTRACT FROM AUTHOR]

The comparison of methylomes from immune cells enables the identification of differentially methylated regions and thereby region-associated gene loci. Those regions can be used to discriminate one immune cell population from the other, as well as help to identify key molecules and major pathways determining the unique phenotypes of immune cell lineages. The combination of bisulfite treatment of genomic DNA and next-generation sequencing provides the basis for studying epigenetic changes in different immune cell populations. Further development of whole-genome bisulfite sequencing resulted in a protocol for sequencing libraries that accept both single- or double-stranded DNA from fixed or nonfixed cells, respectively. Therefore, researchers can include immune cell populations in their methylation studies whose isolation depends on the staining of intracellular molecules.

Over the past decade, solving complex optimization problems with metaheuristic algorithms has attracted many experts and researchers. Nature has always been a model for humans to draw the best mechanisms and the best engineering out of it and use it to solve their problems. The concept of optimization is evident in several natural processes, such as the evolution of species, the behavior of social groups, the immune system, and the search strategies of various animal populations. For this purpose, the use of nature-inspired optimization algorithms is increasingly being developed to solve various scientific and engineering problems due to their simplicity and flexibility. Anything in a particular situation can solve a significant problem for human society. This paper presents a comprehensive overview of the metaheuristic algorithms and classifications in this field and offers a novel classification based on the features of these algorithms. [ABSTRACT FROM AUTHOR]

The objective of the present study is to identify and evaluate informative indicators for the welfare of rainbow trout exposed to (A) a water temperature of 27 °C and (B) a stocking density of 100 kg/m 3 combined with a temperature of 27 °C. The spleen-somatic and condition index, haematocrit and the concentrations of haemoglobin, plasma cortisol and glucose revealed non-significant differences between the two stress groups and the reference group 8 days after the onset of the experiments. The transcript abundance of almost 1,500 genes was modulated at least twofold in in the spleen of rainbow trout exposed to a critical temperature alone or a critical temperature combined with crowding as compared to the reference fish. The number of differentially expressed genes was four times higher in trout that were simultaneously challenged with high temperature and crowding, compared to trout challenged with high temperature alone. Based on these sets of differentially expressed genes, we identified unique and common tissue- and stress type-specific pathways. Furthermore, our subsequent immunologic analyses revealed reduced bactericidal and inflammatory activity and a significantly altered blood-cell composition in challenged versus non-challenged rainbow trout. Altogether, our data demonstrate that heat and overstocking exert synergistic effects on the rainbow trout's physiology, especially on the immune system.

Polyinosinic:polycytidylic acid [poly (I:C)] was administered in vivo to Chinook salmon (Oncorhynchus tshawytscha) post-smolts to determine the immune responses on haematological and cellular functional parameters, including spleen (SP), head kidney (HK) and red blood cell (RBC) cytokine expression, as well as serum metabolomics. Poly (I:C) in vivo (24 h exposure) did not affect fish haematological parameters, leucocyte phagocytic activity and phagocytic index, reactive oxygen species and nitric oxide production. Gas chromatography-mass spectrometry-based metabolomics revealed that poly (I:C) significantly altered the serum biochemistry profile of 25 metabolites. Metabolites involved in the branched-chain amino acid/glutathione and transsulphuration pathways and phospholipid metabolism accumulated in poly (I:C)-treated fish, whereas those involved in the glycolytic and energy metabolism pathways were downregulated. At cytokine transcript level, poly (I:C) induced a significant upregulation of antiviral ifnγ in HK and Mx1 protein in HK, SP and RBCs. This study provides evidence for poly (I:C)-induced, immune-related biomarkers at metabolic and molecular levels in farmed O. tshawytscha in vivo. These findings provide insights into short-term effects of poly (I:C) at haematological, innate and adaptive immunity and metabolic levels, setting the stage for future studies., (© 2020 The Fisheries Society of the British Isles.)

Simple Summary: Myeloid-derived suppressor cells (MDSCs) are immature cells that expand in the circulation of patients with cancer, sepsis or chronic inflammation, modulate the immune response against cancer (favoring tumor onset and progression) and promote neoangiogenesis. These premises suggest that MDSCs could be involved in the pathogenesis of primary myelofibrosis (PMF) (a myeloproliferative neoplasm characterized by chronic inflammation and extensive neoangiogenesis in bone marrow and spleen). In this paper, we found that (1) MDSCs are increased both in the circulation and in the spleen of PMF patients and strongly correlate with disease progression; and (2) reduced CXCR4 expression on MDSCs along with increased plasmatic SDF-1α can be involved in their mobilization. These findings suggest that circulating MDSCs can be considered a parameter of disease severity and set MDSCs as potential new targets for cancer therapy. Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by a chronic inflammatory state that plays a relevant role in the disease pathogenesis (as proven by high levels of inflammatory cytokines with prognostic significance and by a persistent oxidative stress) and by extensive neoangiogenesis in bone marrow (BM) and spleen. Myeloid-derived suppressor cells (MDSCs) are immature cells that expand in patients with cancer, sepsis or chronic inflammation, favoring tumor onset and progression mainly through the decrease in immune surveillance and the promotion of neoangiogenesis. In this paper, we evaluated the presence of circulating MDSCs in PMF patients, the plasmatic factors involved in their mobilization/expansion and the correlations with laboratory, genetic and clinical parameters. The data indicated that MDSCs could have a relevant role in PMF as a new pathogenic mechanism contributing to explaining the phenotypic diversity observed during the clinical course of the disease, or a potential new target for personalized treatment. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a severe psychiatric illness known to be highly complex due to its difficulty in identifying genetic factors and its polygenic nature. While genetic studies and research into epigenetic changes have advanced our understanding of MDD, the precise role of genetics in MDD's manifestation remains elusive. This paper reviews the current state of research on MDD genetics, encompassing findings on MDD's biological blueprint and investigations into epigenetic modifications associated with MDD development. Furthermore, this paper explores the interplay between depression and the immune system and the impact of inflammation on the disorder. Neuroimaging studies have also impacted comprehension of MDD, revealing alterations in brain size and chemistry. These insights shed light on the biological underpinnings of MDD and hold promise for developing more effective treatments and therapies for patients. [ABSTRACT FROM AUTHOR]

Medulloblastoma (MB) is a highly malignant childhood brain tumor. Group 3 MB (Gr3 MB) is considered to have the most metastatic potential, and tailored therapies for Gr3 MB are currently lacking. Gr3 MB is driven by PRUNE-1 amplification or overexpression. In this paper, we found that PRUNE-1 was transcriptionally regulated by lysine demethylase LSD1/KDM1A. This study aimed to investigate the therapeutic potential of inhibiting both PRUNE-1 and LSD1/KDM1A with the selective inhibitors AA7.1 and SP-2577, respectively. We found that the pharmacological inhibition had a substantial efficacy on targeting the metastatic axis driven by PRUNE-1 (PRUNE-1-OTX2-TGFβ-PTEN) in Gr3 MB. Using RNA seq transcriptomic feature data in Gr3 MB primary cells, we provide evidence that the combination of AA7.1 and SP-2577 positively affects neuronal commitment, confirmed by glial fibrillary acidic protein (GFAP)-positive differentiation and the inhibition of the cytotoxic components of the tumor microenvironment and the epithelial–mesenchymal transition (EMT) by the down-regulation of N-Cadherin protein expression. We also identified an impairing action on the mitochondrial metabolism and, consequently, oxidative phosphorylation, thus depriving tumors cells of an important source of energy. Furthermore, by overlapping the genomic mutational signatures through WES sequence analyses with RNA seq transcriptomic feature data, we propose in this paper that the combination of these two small molecules can be used in a second-line treatment in advanced therapeutics against Gr3 MB. Our study demonstrates that the usage of PRUNE-1 and LSD1/KDM1A inhibitors in combination represents a novel therapeutic approach for these highly aggressive metastatic MB tumors. [ABSTRACT FROM AUTHOR]

The innate immune system is the first line of defense against pathogens. Its composition includes barriers, mucus, and other substances as well as phagocytic and other cells. The purpose of the present paper is to compare tissues with regard to their immune response to infections and to cancer. Simple ideas and the qualitative theory of differential equations are used along with general principles such as the minimization of the pathogen load and economy of resources. In the simplest linear model, the annihilation rate of pathogens in any tissue should be greater than the pathogen's average replication rate. When nonlinearities are added, a stability condition emerges, which relates the strength of regular threats, barrier height, and annihilation rate. The stability condition allows for a comparison of immunity in different tissues. On the other hand, in cancer immunity, the linear model leads to an expression for the lifetime risk, which accounts for both the effects of carcinogens (endogenous or external) and the immune response. The way the tissue responds to an infection shows a correlation with the way it responds to cancer. The results of this paper are formulated in the form of precise statements in such a way that they could be checked by present-day quantitative immunology. [ABSTRACT FROM AUTHOR]

The cells presented in this work are not classified as cells that make up the immune system. They, however, present functions and molecules, which are characteristic of immune cells. These characteristic functions are, for example, sensing threat, performing phagocytosis, presentation of foreign antigens, cytokine release or enhancing immune memory. The enlisted immune response mechanisms are carried out by the possession of molecules such as Toll-like receptors, receptors for the Fc fragment of IgG, major histocompatibility complex class II molecules, costimulatory CD80/CD86 proteins and molecules needed for NLRP3 (NOD-like family pyrin domain containing 3) inflammasome activation. Thanks to these properties, the described nonimmune cells play an important role in the local immune response and support of the entire body in the fight against pathogens. They constitute the first line of defense of tissues and organs against pathogens and molecules recognized as harmful. The cells described in this article are particularly important in immunologically privileged places (e.g. the Bowman's capsule in the kidney), where "typical" immune cells normally do not have access. In this paper, we present immune-like functions and molecule suites of resident kidney cells (podocytes and mesangial cells), cochlear resident cells, fibrocytes and fibroblasts, as well as some stem cells (mesenchymal stem cells and umbilical cord Wharton's jelly-derived cells)., (© 2024 the Australian and New Zealand Society for Immunology, Inc.)