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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.)

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). [ABSTRACT FROM AUTHOR]

In this paper, we study a delayed HIV infection model with nonmonotonic immune response and perform stability and bifurcation analysis. Our results show that the delayed HIV infection system with nonmonotonic immune response has bistability and stable periodic solution appear. We find that both the uninfected and immune-free equilibria are globally asymptotically stable under certain conditions which are not affected by time delay. However, the time delay makes one immune equilibrium always unstable for τ ≥ 0 and also makes another immune equilibrium appear stability switches; meanwhile, the system will exhibit local Hopf bifurcation, global Hopf bifurcation, and saddle-node-Hopf bifurcation. Numerical simulations are carried out to verify our results. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to review papers that assessed the vitamin D intake of children living in Norway, as research has suggested that it has remained below the recommended daily allowance of 10 μg/day. Methods: This mini review examined the vitamin D status of Norwegian children aged 0–18 years by systematically searching the PubMed, Google Scholar and Scopus databases from 1 January 2009 to 1 July 2020. Results: The review comprised six studies published in English between 2009 and 2020 on native‐born and non‐Western immigrant children. Most studies defined satisfactory vitamin D status as a plasma 25‐hydroxyvitamin D (25(OH)D) concentration of 50 nmol/L, with 25–50 nmol/L being classified as insufficient and below 25 nmol/L being classified as deficient. A study of healthy children found that 21% had insufficient levels and a further 1% were deficient, but this second finding was only among adolescents. Other studies showed that 47% of Norwegian children with a non‐Western immigrant background were deficient, and so were 19% of overweight children, mainly adolescents. Conclusion: Vitamin D concentrations were often insufficient among children living in Norway, particularly adolescents and those with a non‐Western immigrant background. Higher recommended supplements may be needed. [ABSTRACT FROM AUTHOR]

The colon is the largest compartment of the immune system, with innate immune cells exposed to antigens in the environment. However, the mechanisms by which the innate immune system is instigated are poorly defined in colorectal cancer (CRC). Here, a population of CD16+ neutrophils that specifically accumulate in CRC tumor tissues by imaging mass cytometry (IMC), immune fluorescence, and flow cytometry, which demonstrated pro‐tumor activity by disturbing natural killer (NK) cells are identified. It is found that these CD16+ neutrophils possess abnormal cholesterol accumulation due to activation of the CD16/TAK1/NF‐κB axis, which upregulates scavenger receptors for cholesterol intake including CD36 and LRP1. Consequently, these region‐specific CD16+ neutrophils not only competitively inhibit cholesterol intake of NK cells, which interrupts NK lipid raft formation and blocks their antitumor signaling but also release neutrophil extracellular traps (NETs) to induce the death of NK cells. Furthermore, CD16‐knockout reverses the pro‐tumor activity of neutrophils and restored NK cell cytotoxicity. Collectively, the findings suggest that CRC region‐specific CD16+ neutrophils can be a diagnostic marker and potential therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

Posttranslational modifications play a crucial role in governing cellular functions and protein behavior. Researchers have implicated dysregulated posttranslational modifications in protein misfolding, which results in cytotoxicity, particularly in neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and Huntington disease. These aberrant posttranslational modifications cause proteins to gather in certain parts of the brain that are linked to the development of the diseases. This leads to neuronal dysfunction and the start of neurodegenerative disease symptoms. Cognitive decline and neurological impairments commonly manifest in neurodegenerative disease patients, underscoring the urgency of comprehending the posttranslational modifications' impact on protein function for targeted therapeutic interventions. This review elucidates the critical link between neurodegenerative diseases and specific posttranslational modifications, focusing on Tau, APP, α‐synuclein, Huntingtin protein, Parkin, DJ‐1, and Drp1. By delineating the prominent aberrant posttranslational modifications within Alzheimer disease, Parkinson disease, and Huntington disease, the review underscores the significance of understanding the interplay among these modifications. Emphasizing 10 key abnormal posttranslational modifications, this study aims to provide a comprehensive framework for investigating neurodegenerative diseases holistically. The insights presented herein shed light on potential therapeutic avenues aimed at modulating posttranslational modifications to mitigate protein aggregation and retard neurodegenerative disease progression. [ABSTRACT FROM AUTHOR]

Immune dysregulation is a pivotal factor in the onset and progression of various diseases. In cancer, the immune system's inability to discern and eliminate abnormal cells leads to uncontrolled tumor growth. When faced with resilient pathogens or harmful toxins, the immune system encounters challenges in clearance and neutralization. Achieving a delicate balance of pro‐inflammatory and anti‐inflammatory signals is essential in managing a range of disorders and diseases. Like in other biomedical research domains, nanotechnology has provided innovative approaches for rebalancing host immunity. Among the plethora of nanotechnology‐based interventions, the concept of cell membrane‐coated nanoparticles holds significant potential for immunomodulatory applications owing to their biomimetic properties that allow for precise interaction with the compromised immune system. This review thoroughly examines the potential of novel nanosystems for immune modulation. The exploration covers crucial elements, including the origins and characteristics of cell membranes, the methods employed for their procurement and coating, physicochemical/biological characterization techniques, and enhancement of their therapeutic efficacy via functionalization. Subsequently, case studies‐based analysis of utilizing these bioinspired nanosystems in tackling different conditions caused by immune disturbance has been comprehensively discussed. [ABSTRACT FROM AUTHOR]

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Regulatory T cells (Tregs) are essential for maintaining immune homeostasis by serving as negative regulators of adaptive immune system effector cell responses. Reduced production or function of Tregs has been implicated in several human autoimmune diseases. The cytokine interleukin 2 plays a central role in promoting Treg differentiation, survival, and function in vivo and may therefore have therapeutic benefits for autoimmune diseases. mRNA‐6231 is an investigational, lipid nanoparticle‐encapsulated, mRNA‐based therapy that encodes a modified human interleukin 2 mutein fused to human serum albumin (HSA‐IL2m). Herein, we report the development of a semi‐mechanistic kinetic‐pharmacodynamic model to quantify the relationship between subcutaneous dose(s) of mRNA‐6231, HSA‐IL2m protein expression, and Treg expansion in nonhuman primates. The nonclinical kinetic‐pharmacodynamic model was extrapolated to humans using allometric scaling principles and the physiological basis of pharmacological mechanisms to predict the clinical response to therapy a priori. Model‐based simulations were used to inform the dose selection and design of the first‐in‐human clinical study (NCT04916431). The modeling approach used to predict human responses was validated when data became available from the phase I clinical study. This validation indicates that the approach is valuable in informing clinical decision‐making. [ABSTRACT FROM AUTHOR]

Despite being some of the most anecdotally well‐known roads to pathogenesis, the mechanisms governing autoimmune rheumatic diseases are not yet fully understood. The overactivation of the cellular immune system and the characteristic development of autoantibodies have been linked to oxidative stress. Typical clinical manifestations, such as joint swelling and deformities and inflammation of the skin and internal organs, have also been connected directly or indirectly to redox mechanisms. The differences in generation and restraint of oxidative stress provide compelling evidence for the broad variety in pathology among rheumatic diseases and explain some of the common triggers and discordant manifestations in these diseases. Growing evidence of redox mechanisms in pathogenesis has provided a broad array of new potential therapeutic targets. Here, we explore the mechanisms by which oxidative stress is generated, explore its roles in autoimmunity and end‐organ damage, and discuss how individual rheumatic diseases exhibit unique features that offer targets for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Summary: Plants have evolved a multi‐layered immune system to fight off pathogens. However, immune activation is costly and is often associated with growth and development penalty. In crops, yield is the main breeding target and is usually affected by high disease resistance. Therefore, proper balance between growth and defence is critical for achieving efficient crop improvement. This review highlights recent advances in attempts designed to alleviate the trade‐offs between growth and disease resistance in crops mediated by resistance (R) genes, susceptibility (S) genes and pleiotropic genes. We also provide an update on strategies for optimizing the growth–defence trade‐offs to breed future crops with desirable disease resistance and high yield. [ABSTRACT FROM AUTHOR]

The primary objective of this meta‐analysis was to provide the comprehensive understanding of the intricate correlation that existed between immune senescence and its effects on the advancement of lung cancer as well as recovery of cutaneous wounds. By conducting this systematic review of six rigorous studies utilizing databases such as PubMed and Web of Science, this research examined the multitude of facets pertaining to immune aging and consequences it bear on the health outcomes. The incorporated studies encompassed wide range of geographical and methodological viewpoints, with the specific emphasis on non‐small‐cell lung cancer and diverse scenarios related to wound recovery. This analysis synthesized discoveries regarding therapeutic responses, cellular and molecular mechanisms and impact of lifestyle factors on immune senescence. The findings suggested that immune senescence has substantial impact on the effectiveness of treatments for lung cancer and cutaneous wounds healing process; therefore, targeted therapies and holistic approaches may be able to mitigate these effects. By following the revised PRISMA guidelines, this meta‐analysis guarantee thorough and ethically sound methodology for amalgamating pre‐existing literature. The study concluded by emphasizing the critical nature of comprehending immune senescence in the context of clinical practice and proposed avenues for further investigation to enhance health results among the elderly. [ABSTRACT FROM AUTHOR]