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Introduction In accordance with its mandate to provide normative guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations [...]

This document is a correction notice for a paper on the potential bioactive compound bromelain. The authors have identified errors in one section of the paper and provide revised references. The corrected table includes therapeutic studies of bromelain based on experimental studies. The document also includes a compilation of various scientific studies and articles related to the use of bromelain for various medical purposes. The studies explore the potential benefits of bromelain in treating conditions such as cancer, inflammation, thrombosis, and pain. The document provides a comprehensive overview of the scientific research on bromelain and its potential applications in medicine. [Extracted from the article]

The 80+ existing autoimmune disorders (ADs) affect billions with little prevention or treatment options, except for temporary symptomatic management, leading to enormous human suffering and a monumental financial burden. The autoantibodies formed in most ADs have been identified, allowing the development of novel anti-idiotypic antibodies to mute the autoantibodies using vaccines. Nucleoside vaccines have been successfully tested as antigen-specific immunotherapies (ASI), with mRNA technology offering multi-epitope targeting to mute multiple autoantibodies. This paper proposes using mRNA technology to produce anti-idiotypic antibodies with broad effectiveness in preventing and treating them. This paper delves into the state-of-the-art mRNA design strategies used to develop novel ASIs by selecting appropriate T cell and B cell epitopes to generate anti-idiotypic antibodies. The low cost and fast development of mRNA vaccines make this technology the most affordable for the global control of ADs. [ABSTRACT FROM AUTHOR]

Over the past century, the field of antibody discovery has undergone significant evolution, excluding the current exploration stage of artificial intelligence‐based antibody generation and the often overlooked non‐animal sourced antibody discovery, which typically requires mature in vitro affinity and the selection of high‐quality antigen formulations. This journey has traversed various stages, from methods involving serum‐based antibody acquisition, the isolation of B cells capable of perpetual antibody production through hybridoma technology, to the in‐depth exploration of genetic material using the phage display system, and the current stage involving diverse single B cell screening techniques. Additionally, the emergence of machine learning has brought impressive scientific and technological breakthroughs across research domains, proving to be a powerful application in the field of antibody discovery. However, each technique comes with its limitations, such as variability and control challenges in serum‐based acquisition, lengthy and difficult hybridoma‐derived antibody development, potential limitations in sequence and epitope diversity due to immunization biases in phage display techniques, and costly single B cell screening. Protein mass spectrometry sequencing, with shorter acquisition time and lower costs, is seen as a shortcut by diagnostic companies, impacting traditional antibody development. In diagnostic antibody development, methodological differences in downstream assays and the impact of constant regions outside the Fv core are often neglected. This paper deeply analyzes challenges, proposing innovative strategies for the next generation of diagnostic antibody development. Aimed at moving closer to the gold standard of antibody discovery, these strategies enhance the competitiveness of diagnostic reagent products. [ABSTRACT FROM AUTHOR]

Simple Summary: The B cell receptor (BCR) is a membrane-bound protein complex that is required for the normal development of B cells. BCR signalling is also involved in the pathogenesis of B cell cancers. While there is substantial literature on genomic analyses of the BCR, there are limited proteomic studies of receptor structure and its interactions with neighbouring proteins. This is partly due to the location of the BCR in the surface-membrane lipid environment that has limited the ability to enrich the complex for proteomic analysis. Here, we report an enrichment technique that can be used for mass spectrometry analyses of the BCR from live B cells. B cells are central to the adaptive immune response and provide long-lasting immunity after infection. B cell activation is mediated by the surface membrane-bound B cell receptor (BCR) following recognition of a specific antigen. The BCR has been challenging to analyse using mass spectrometry (MS) due to the difficulty of isolating and enriching this membrane-bound protein complex. There are approximately 120,000 BCRs on the B cell surface; however, depending on the B cell activation state, there may be hundreds-of-millions to billions of proteins in a B cell. Consequently, advanced proteomic techniques such as MS workflows that use purified proteins to yield structural and protein-interaction information have not been published for the BCR complex. This paper describes a method for enriching the BCR complex that is MS-compatible. The method involves a Protein G pull down on agarose beads using an intermediary antibody to each of the BCR complex subcomponents (CD79a, CD79b, and membrane immunoglobulin). The enrichment process is shown to pull down the entire BCR complex and has the advantage of being readily compatible with further proteomic study including MS analysis. Using intermediary antibodies has the potential to enrich all isotypes of the BCR, unlike previous methods described in the literature that use protein G-coated beads to directly pull down the membrane IgG (mIgG) but cannot be used for other mIg isotypes. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this data paper is to describe a collection of 33 genomic, transcriptomic and epigenomic sequencing datasets of the B-cell acute lymphoblastic leukemia (ALL) cell line REH. REH is one of the most frequently used cell lines for functional studies of pediatric ALL, and these data provide a multi-faceted characterization of its molecular features. The datasets described herein, generated with short- and long-read sequencing technologies, can both provide insights into the complex aberrant karyotype of REH, and be used as reference datasets for sequencing data quality assessment or for methods development. Data description: This paper describes 33 datasets corresponding to 867 gigabases of raw sequencing data generated from the REH cell line. These datasets include five different approaches for whole genome sequencing (WGS) on four sequencing platforms, two RNA sequencing (RNA-seq) techniques on two different sequencing platforms, DNA methylation sequencing, and single-cell ATAC-sequencing. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune condition frequently found in rheumatological patients that sometimes raises diagnosis and management problems. The pathogenesis of the disease is complex and involves the activation of many cells and intracellular signaling pathways, ultimately leading to the activation of the innate and acquired immune system and producing extensive tissue damage. Along with joint involvement, RA can have numerous extra-articular manifestations (EAMs), among which lung damage, especially interstitial lung disease (ILD), negatively influences the evolution and survival of these patients. Although there are more and more RA-ILD cases, the pathogenesis is incompletely understood. In terms of genetic predisposition, external environmental factors act and subsequently determine the activation of immune system cells such as macrophages, neutrophils, B and T lymphocytes, fibroblasts, and dendritic cells. These, in turn, show the ability to secrete molecules with a proinflammatory role (cytokines, chemokines, growth factors) that will produce important visceral injuries, including pulmonary changes. Currently, there is new evidence that supports the initiation of the systemic immune response at the level of pulmonary mucosa where the citrullination process occurs, whereby the autoantibodies subsequently migrate from the lung to the synovial membrane. The aim of this paper is to provide current data regarding the pathogenesis of RA-associated ILD, starting from environmental triggers and reaching the cellular, humoral, and molecular changes involved in the onset of the disease. [ABSTRACT FROM AUTHOR]

The Bursa of Fabricius, an avian unique humoral immune organ, is instrumental to B cell development. Bursal-derived peptide BP9 fosters B-cell development and formation. Yet, the exact mechanism wherein BP9 impacts B cell differentiation and antigenic presentation remains undefined. In this paper, B cell activation and differentiation in the spleen cells from mice immunized with the AIV vaccine and BP9 were detected following flow cytometry (FCM) analysis. Furthermore, the molecular mechanism of BP9 in B cell differentiation in vivo was investigated with RNA sequencing technology. To verify the potential functional mechanism of BP9 in the antigenic presentation process, the transcriptome molecular basis of chicken macrophages stimulated by BP9 was measured via high-throughput sequencing technology. The results proved that when given in experimental dosages, BP9 notably accelerated total B cells, and enhanced B-cell differentiation and plasma cell production. The gene expression profiles of B cells from mice immunized with 0.01 mg/mL BP9 and AIV vaccine disclosed that 0.01 mg/mL BP9 initiated the enrichment of several biological functions and significantly stimulated key B-cell pathways in immunized mice. Crucially, a total of 4093 differentially expressed genes were identified in B cells with BP9 stimulation, including 943 upregulated genes and 3150 downregulated genes. Additionally, BP9 induced various cytokine productions in the chicken macrophage HD11 cells and activated 9 upregulated and 20 downregulated differential miRNAs, which were involved in various signal and biological processes. Furthermore, BP9 stimulated the activation of multiple transcription factors in HD11 cells, which was related to antigen presentation processes. In summary, these results suggested that BP9 might promote B cell differentiation and induce antigen presentation, which might provide the valuable insights into the mechanism of B cell differentiation upon bursal-derived immunomodulating peptide stimulation and provide a solid experimental groundwork for enhancing vaccine-induced immunity. [ABSTRACT FROM AUTHOR]

Cadmium (Cd), a prevalent environmental contaminant, exerts widespread toxic effects on human health through various biochemical and molecular mechanisms. This review encapsulates the primary pathways through which Cd inflicts damage, including oxidative stress induction, disruption of Ca2+ signaling, interference with cellular signaling pathways, and epigenetic modifications. By detailing the absorption, distribution, metabolism, and excretion (ADME) of Cd, alongside its interactions with cellular components such as mitochondria and DNA, this paper highlights the extensive damage caused by Cd2+ at the cellular and tissue levels. The role of Cd in inducing oxidative stress—a pivotal mechanism behind its toxicity—is discussed with emphasis on how it disrupts the balance between oxidants and antioxidants, leading to cellular damage and apoptosis. Additionally, the review covers Cd's impact on signaling pathways like Mitogen-Activated Protein Kinase (MAPK), Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), and Tumor Protein 53 (p53) pathways, illustrating how its interference with these pathways contributes to pathological conditions and carcinogenesis. The epigenetic effects of Cd, including DNA methylation and histone modifications, are also explored to explain its long-term impact on gene expression and disease manifestation. This comprehensive analysis not only elucidates the mechanisms of Cd toxicity but also underscores the critical need for enhanced strategies to mitigate its public health implications. [ABSTRACT FROM AUTHOR]

Introduction: B cells play a pivotal role in adaptive immunity which has been extensively characterised primarily via flow cytometry-based gating strategies. This study addresses the discrepancies between flow cytometry-defined B cell subsets and their high-confidence molecular signatures using single-cell multiomics approaches. Methods: By analysing multi-omics single-cell data from healthy individuals and patients across diseases, we characterised the level and nature of cellular contamination within standard flow cytometric-based gating, resolved some of the ambiguities in the literature surrounding unconventional B cell subsets, and demonstrated the variable effects of flow cytometric-based gating cellular heterogeneity across diseases. Results: We showed that flow cytometric-defined B cell populations are heterogenous, and the composition varies significantly between disease states thus affecting the implications of functional studies performed on these populations. Importantly, this paper draws caution on findings about B cell selection and function of flow cytometric-sorted populations, and their roles in disease. As a solution, we developed a simple tool to identify additional markers that can be used to increase the purity of flow-cytometric gated immune cell populations based on multi-omics data (AlliGateR). Here, we demonstrate that additional non-linear CD20, CD21 and CD24 gating can increase the purity of both naïve and memory populations. Discussion: These findings underscore the need to reconsider B cell subset definitions within the literature and propose leveraging single-cell multi-omics data for refined characterisation. We show that single-cell multi-omics technologies represent a powerful tool to bridge the gap between surface marker-based annotations and the intricate molecular characteristics of B cell subsets. [ABSTRACT FROM AUTHOR]

Background: The tonsils operate as a protection ring of mucosa at the gates of the upper aero-digestive tract. They show similarities with lymph nodes and participate as inductive organs of systemic and mucosal immunity. Based on the reduction of their size since puberty, they are thought to experience involution in adulthood. In this context, we have used tonsillar mononuclear cells (TMC) isolated from patients at different stages of life, to study the effect of ageing and the concomitant persistent inflammation on these immune cells. Results: We found an age-dependent reduction in the proportion of germinal center B cell population (BGC) and its T cell counterpart (T follicular helper germinal center cells, TfhGC). Also, we demonstrated an increment in the percentage of local memory B cells and mantle zone T follicular helper cells (mTfh). Furthermore, younger tonsils rendered higher proportion of proliferative immune cells within the freshly isolated TMC fraction than those from older ones. We demonstrated the accumulation of a B cell subset (CD20+CD39highCD73+ cells) metabolically adapted to catabolize adenosine triphosphate (ATP) as patients get older. To finish, tonsillar B cells from patients at different ages did not show differences in their proliferative response to stimulation ex vivo, in bulk TMC cultures. Conclusions: This paper sheds light on the changing aspects of the immune cellular landscape, over the course of time and constant exposure, at the entrance of the respiratory and digestive systems. Our findings support the notion that there is a re-modelling of the immune functionality of the excised tonsils over time. They are indicative of a transition from an effector type of immune response, typically oriented to reduce pathogen burden early in life, to the development of an immunosuppressive microenvironment at later stages, when tissue damage control gets critical provided the time passed under immune attack. Noteworthy, when isolated from such histologic microenvironment, older tonsillar B cells seem to level their proliferation capacity with the younger ones. Understanding these features will not only contribute to comprehend the differences in susceptibility to pathogens among children and adults but would also impact on vaccine developments intended to target these relevant mucosal sites. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumour. Despite advancements in surgery, radiotherapy and chemotherapy, which have improved the prognosis of most patients, a subset of patients with poor prognoses still exist due to loss of surgical opportunities, postoperative recurrence, and metastasis, among other reasons. The tumour microenvironment (TME) is a complex organization composed of tumour, stromal, and endothelial cells. Communication and interaction between tumours and immune cells within the TME are increasingly being recognized as pivotal in inhibiting or promoting tumour development. Previous studies on T cells in the TME of HNSCC have yielded novel therapeutic possibilities. However, the function of B cells, another adaptive immune cell type, in the TME of HNSCC patients has yet to be determined. Recent studies have revealed various distinct subtypes of B cells and tertiary lymphoid structures (TLSs) in the TME of HNSCC patients, which are believed to impact the efficacy of immune checkpoint inhibitors (ICIs). Therefore, this paper focuses on B cells in the TME to explore potential directions for future immunotherapy for HNSCC. [ABSTRACT FROM AUTHOR]

Helminths are multicellular parasites that are a substantial problem for both human and veterinary medicine. According to estimates, 1.5 billion people suffer from their infection, resulting in decreased life quality and burdens for healthcare systems. On the other hand, these infections may alleviate autoimmune diseases and allergy symptoms. The immune system is programmed to combat infections; nevertheless, its effector mechanisms may result in immunopathologies and exacerbate clinical symptoms. This review summarizes the role of the immune response against worms, with an emphasis on the Th2 response, which is a hallmark of helminth infections. We characterize non-immune cells (enteric tuft cells—ETCs) responsible for detecting parasites, as well as the role of hematopoietic-derived cells (macrophages, basophils, eosinophils, neutrophils, innate lymphoid cells group 2—ILC2s, mast cells, T cells, and B cells) in initiating and sustaining the immune response, as well as the functions they play in granulomas. The aim of this paper is to review the existing knowledge regarding the immune response against helminths, to attempt to decipher the interactions between cells engaged in the response, and to indicate the gaps in the current knowledge. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What are the similarities and differences in endometrial B cells in the normal human endometrium and benign reproductive pathologies? SUMMARY ANSWER Endometrial B cells typically constitute <5% of total endometrial CD45+ lymphocytes, and no more than 2% of total cells in the normal endometrium, and while their relative abundance and phenotypes vary in benign gynaecological conditions, current evidence is inconsistent. WHAT IS KNOWN ALREADY B cells are vitally important in the mucosal immune environment and have been extensively characterized in secondary lymphoid organs and tertiary lymphoid structures (TLSs), with the associated microenvironment germinal centre. However, in the endometrium, B cells are largely overlooked, despite the crucial link between autoimmunity and reproductive pathologies and the fact that B cells are present in normal endometrium and benign female reproductive pathologies, scattered or in the form of lymphoid aggregates (LAs). A comprehensive summary of current data investigating B cells will facilitate our understanding of endometrial B cells in the endometrial mucosal immune environment. STUDY DESIGN, SIZE, DURATION This systematic review retrieved relevant studies from four databases (MEDLINE, EMBASE, Web of Science Core Collection and CINAHL) from database inception until November 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS The search strategy combined the use of subject headings and relevant text words related to 'endometrium', 'B cells' and B-cell derivatives, such as 'antibody' and 'immunoglobulin'. Non-benign diseases were excluded using cancer-related free-text terms, and searches were limited to the English language and human subjects. Only peer-reviewed research papers were included. Each paper was graded as 'Good', 'Fair' or 'Poor' quality based on the NEWCASTLE-OTTAWA quality assessment scale. Only 'Good' quality papers were included. MAIN RESULTS AND THE ROLE OF CHANCE Twenty-seven studies met the selection criteria and were included in this review: 10 cross-sectional studies investigated B cells in the normal endometrium; and 17 case–control studies compared the characteristics of endometrial B cells in control and benign female reproductive pathologies including endometritis, endometriosis, infertility, abnormal uterine bleeding, endometrial polyps and uterine fibroids. In all studies, B cells were present in the endometrium, scattered or in the form of LAs. CD20+ B cells were more abundant in patients with endometritis, but the data were inconsistent as to whether B-cell numbers were increased in endometriosis and patients with reproductive pathologies. LIMITATIONS, REASONS FOR CAUTION Although only 'good' quality papers were included in this systematic review, there were variations in patients' age, diagnostic criteria for different diseases and sample collection time among included studies. Additionally, a large number of the included studies only used immunohistochemistry as the identification method for endometrial B cells, which may fail to provide an accurate representation of the numbers of endometrial B cells. WIDER IMPLICATIONS OF THE FINDINGS Histological studies found that endometrial B cells are either scattered or surrounded by T cells in LAs: the latter structure seems to be under hormonal control throughout the menstrual cycle and resembles TLSs that have been observed in other tissues. Further characterization of endometrial B cells and LAs could offer insights to endometrial B-cell function, particularly in the context of autoimmune-associated pathologies, such as endometriosis. Additionally, clinicians should be aware of the limited value of diagnosing plasma cell infiltration using only CD138. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Finox Biotech. The authors have no conflicts of interest to declare. PROSPERO REGISTRATION NUMBER This systematic review was registered in PROSPERO in January 2020 (PROSPERO ID: CRD42020152915). [ABSTRACT FROM AUTHOR]

The article offers update on bone fracture prevention and treatments for conditions such as osteoporosis. It discusses findings of several research including fracture repair via bone remodeling using osteoclasts, potential of high frequency sound waves to convert bone marrow derived mesenchymal stem cells into bone cells, and a demineralised bone paper biomaterial used to advanced the understanding of bone biology, model disease progression and screen drug responses.

Purpose: The purpose of this review is to discuss the significance of IL-17 in SLE and the potential of IL-17-targeted therapy. Background: Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many organs and tissues throughout the body. It is characterized by overactive B and T cells and loss of immune tolerance to autoantigens. Interleukin-17 (IL-17) is a cytokine that promotes inflammation and has been implicated in the pathogenesis of several autoimmune diseases as well as inflammatory diseases. In in vitro cellular experiments in lupus susceptible mice or SLE patients, there is substantial evidence that IL-17 is a highly promising therapeutic target. Methods: We searched papers from PubMed database using the search terms, such as interleukin-17, systemic lupus erythematosus, treatment targets, T cells, lupus nephritis, and other relevant terms. Results: We discuss in this paper the molecular mechanisms of IL-17 expression, Th17 cell proliferation, and the relationship between IL-17 and Th17. The significance of IL-17 in SLE and the potential of IL-17-targeted therapy are further discussed in detail. Conclusion: IL-17 has a very high potential for the development as a star target in SLE. [ABSTRACT FROM AUTHOR]

Human B cell immortalization that maintains the constant growth characteristics and antibody expression of B cells in vitro is very critical for the development of antibody drugs and products for the diagnosis and bio-therapeutics of human diseases. Human B cell immortalization methods include Epstein-Barr virus (EBV) transformation, Simian virus 40 (SV40) virus infection, in vitro genetic modification, and activating CD40, etc. Immortalized human B cells produce monoclonal antibodies (mAbs) very efficiently, and the antibodies produced in this way can overcome the immune rejection caused by heterologous antibodies. It is an effective way to prepare mAbs and an important method for developing therapeutic monoclonal antibodies. Currently, the US FDA has approved more than 100 mAbs against a wide range of illnesses such as cancer, autoimmune diseases, infectious diseases, and neurological disorders. This paper reviews the research progress of human B cell immortalization, its methods, and future directions as it is a powerful tool for the development of monoclonal antibody preparation technology. [ABSTRACT FROM AUTHOR]

Simple Summary: This article addresses the topic of primary immunodeficiencies, with particular emphasis on antibody deficiencies with near-normal immunoglobulin levels or hyperimmunoglobulinemia. This paper goes beyond genetics and emphasizes the importance of the immune system and particularly immune checkpoints and Epstein–Barr virus (EBV) reactivation in the context of these disorders. The article delves into the immune dysregulations occurring in the course of this type of disease and the potential role of EBV reactivation, which affects the clinical picture of patients and, in the future, may contribute to the development of cancer, especially those related to hematological malignancies. Disturbances observed in the immunopathogenesis of the presented diseases go beyond the accepted scheme, with the development of PID largely associated only with genetic disorders, and the article emphasizes that the regulation of immunity and virus reactivation also contributes to the progression of PID. This study delves into the intricate landscape of primary immunodeficiencies, with a particular focus on antibody deficiencies characterized by near-normal immunoglobulin levels or hyperimmunoglobulinemia. Contrary to the conventional focus on genetic dysregulation, these studies investigate the key roles of immune checkpoints, such as PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200, on selected subpopulations of T and B lymphocytes and their serum concentrations of soluble forms in patients recruited for the studies in healthy volunteers. In addition, the studies also show the role of Epstein–Barr virus (EBV) reactivation and interactions with tested pathways of immune checkpoints involved in the immunopathogenesis of this disease. By examining the context of antibody deficiencies, this study sheds light on the nuanced interplay of factors beyond genetics, particularly the immune dysregulations that occur in the course of this type of disease and the potential role of EBV reactivation, which affects the clinical presentation of patients and may contribute to the development of cancer in the future, especially related to hematological malignancies. [ABSTRACT FROM AUTHOR]

This paper formulates and analyzes two mathematical models that describe the within-host dynamics of human immunodeficiency virus type 1 (HIV-1) with impairment of both cytotoxic T lymphocytes (CTLs) and B cells. Both viral transmission (VT) and cellular infection (CT) mechanisms are considered. The second model is a generalization of the first model that includes distributed time delays. For the two models, we establish the non-negativity and boundedness of the solutions, find the basic reproductive numbers, determine all possible steady states and establish the global asymptotic stability properties of all steady states by means of the Lyapunov method. We confirm the theoretical results by conducting numerical simulations. We conduct a sensitivity analysis to show the effect of the values of the parameters on the basic reproductive number. We discuss the results, showing that impaired B cells and CTLs, time delay and latent CT have significant effects on the HIV-1 dynamics. [ABSTRACT FROM AUTHOR]

This work investigates the existence and asymptotic behavior of solutions to a nonlocal dispersal in‐host viral model with humoral immunity. The model features both spatial movement of virus and humoral immunity response to the virus. This paper gives the principal eigenvalue (H0$\mathcal {H}_0$) of the nonlocal dispersal problem, and it is verified to be a critical value that determines the infection dynamics. The uninfected equilibrium is unique and stable for H0≤0$\mathcal {H}_0\le 0$. For H0>0$\mathcal {H}_0>0$, the equilibrium is not stable, and infected with/without B cells response equilibrium emerges. This paper also establishes the dynamics of infected equilibria. Numerical simulations are carried out to demonstrate the analytical results of this study. [ABSTRACT FROM AUTHOR]

The clonal selection theory (CST) is the centrepiece of the current paradigm used to explain immune recognition and memory. Throughout the past decades, the original CST had been expanded and modified to explain new experimental evidences since its original publication by Burnet. This gave origin to new paradigms that govern experimental immunology nowadays, such as the associative recognition of antigen model and the stranger/danger signal model. However, these new theories also do not fully explain experimental findings such as natural autoimmune immunoglobulins, idiotypic networks, low and high dose tolerance, and dual‐receptor T and B cells. To make sense of these empirical data, some authors have been trying to change the paradigm of immune cognition using a systemic approach, analogies with brain processing and concepts from second‐order cybernetics. In the present paper, we review the CST and some of the theories/hypotheses derived from it, focusing on immune recognition. We point out their main weaknesses and highlight arguments made by their opponents and believers. We conclude that, until now, none of the proposed theories can fully explain the totality of immune phenomena and that a theory of everything is needed in immunology. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common tumor among women throughout the world. Diagnosis and treatment of breast cancer are associated with stress and depression. Self-efficacy is one of the most important personal characteristics, studied in cancer, and is correlated with depression and immunity. The aim of the study is as follows: 1. Examining the correlation between coping self-efficacy with depression, DHEA levels, and immunity 2. Examining the correlation between depression and DHEA levels 3. Studying the effect of depression and DHEA levels on immunity 4. Examining the intermediate effect of DHEA levels on the correlation between coping self-efficacy and immunity Methods: Thirty newly diagnosed breast cancer patients recruited from the Oncology Department, Kasr EL-Aini, Cairo University (ages 51.40 + 8.24 years) responded to two questionnaires: Coping Self-Efficacy Scale (CSES) and Patient Health Questionnaire-9 (PHQ-9); blood samples were collected to measure the phenotype of patients' cellular immunity and DHEA levels by flowcytometry and ELISA technique. Results: There was a significant negative correlation between CSES and PHQ-9, a significant positive correlation between PHQ-9 and B-cell count, and there is a significant negative correlation between CSES and B-cell count. The presence of DHEA has no mediatory role on correlation between CSES and B-cell count. Conclusion: This paper presents a new model of psychoneuroimmunology by suggesting an effect of coping self-efficacy on immunity against breast cancer patients. [ABSTRACT FROM AUTHOR]

Linear-B cell epitopes (LBCE) play a vital role in vaccine design; thus, efficiently detecting them from protein sequences is of primary importance. These epitopes consist of amino acids arranged in continuous or discontinuous patterns. Vaccines employ attenuated viruses and purified antigens. LBCE stimulate humoral immunity in the body, where B and T cells target circulating infections. To predict LBCE, the underlying protein sequences undergo a process of feature extraction, feature selection, and classification. Various system models have been proposed for this purpose, but their classification accuracy is only moderate. In order to enhance the accuracy of LBCE classification, this paper presents a novel 2-step metaheuristic variant-feature selection method that combines a linear support vector classifier (LSVC) with a Modified Genetic Algorithm (MGA). The feature selection model employs mono-peptide, dipeptide, and tripeptide features, focusing on the most diverse ones. These selected features are fed into a machine learning (ML)-based parallel ensemble classifier. The ensemble classifier combines correctly classified instances from various classifiers, including k-Nearest Neighbor (kNN), random forest (RF), logistic regression (LR), and support vector machine (SVM). The ensemble classifier came up with an impressively high accuracy of 99.3% as a result of its work. This accuracy is superior to the most recent models that are considered to be state-of-the-art for linear B-cell classification. As a direct consequence of this, the entire system model can now be utilised effectively in real-time clinical settings. [ABSTRACT FROM AUTHOR]

Introduction: Lymphoma is a diverse group of malignant proliferations that arise as discrete tissue masses. The 5th edition of the World Health Organization classification of Tumours of Haematopoietic and Lymphoid Tissues was released on 22nd June 2022. The WHO-HAEM5 classification of Mature T and NK neoplasms is further subclassified into various categories which are detailed in this review. Methods: A search was conducted using bibliographic databases, various repositories, and the Clinical Research Centre website retrieving journal articles, conference proceedings, book Chapters, guidelines, and thesis. The search terms used were Malaysia AND lymphoma. Results: The search earmarked a total of 561 papers. There were nine case series retrieved from 1967 to 2022. The site, age distribution, prognostic markers, and the various subclassification of NK/T cell lymphomas were studied. The gastrointestinal tract was the commonest site for extranodal lymphomas. Prognostic markers associated were EBV, C-MYC protein and staining for CD2, CD3, CD20, CD56, and CD57 antigens. For anaplastic large cell lymphoma (ALCL), CD30 (Ki-1) and ALK antigens were noted as important. The use of 18F-Fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PETCT) has emerged as an important investigation. Various chemotherapeutic regimens, surgical interventions where necessary and autologous peripheral blood stem cell transplantation when indicated are the mainstay of treatment. Conclusion: Research on NK/T cell lymphoma, including ALCL, has been ongoing in recent years. This review adds on to the existing literature on lymphoma in Malaysia that can lead to further research, into the diagnosis and treatment of lymphoma in Malaysia and around the world. [ABSTRACT FROM AUTHOR]

Since the pioneering works of Berg and Purcell, discriminating between diffusion followed by binding has played a central role in understanding cell signaling. B cell receptors (BCR) and antibodies (Ab) challenge that simplified view as binding to the antigen follows after a chain of diffusion and rotations, including whole molecule rotation and independent tilts and twists of their Fab arms due to their Yshaped structure and flexibility. In this paper, we combine analytical calculations with Brownian simulations to derive the first-passage times due to these three rotations positioning the Fab paratopes at a proper distance and orientation required for antigen binding. Our results indicate that when measuring Ab--Ag effective kinetic binding rates, using experimental methods in which the analyte is in solution only gives values proportional to the intrinsic binding rates, k+, and k-, for values of k+ up to 109 s-1. Beyond that, a plateau of the effective 3D on rate between 108 M-1s-1 and 109 M-1s-1 is attained. Additionally, for BCR--Ag interactions, the effective 2D on and off binding rates can only be inferred from the corresponding effective 3D on and off rates for values of effective 3D on rates lower than 106 M-1s-1. This is highly relevant when trying to relate BCR--antigen-binding strength and B cell response, especially during germinal center reactions. Therefore, there is a pressing need to reexamine our current understanding of the BCR--antigen kinetic rates in germinal centers using the latest experimental assays for BCR--Ag interactions. [ABSTRACT FROM AUTHOR]

Astragaloside IV (AS-IV) is one of the main active components extracted from the Chinese medicinal herb Astragali and serves as a marker for assessing the herb's quality. AS-IV is a tetracyclic triterpenoid saponin in the form of lanolin ester alcohol and exhibits various biological activities. This review article summarizes the chemical structure of AS-IV, its pharmacological effects, mechanism of action, applications, future prospects, potential weaknesses, and other unexplored biological activities, aiming at an overall analysis. Papers were retrieved from online electronic databases, such as PubMed, Web of Science, and CNKI, and data from studies conducted over the last 10 years on the pharmacological effects of AS—IV as well as its impact were collated. This review focuses on the pharmacological action of AS-IV, such as its anti-inflammatory effect, including suppressing inflammatory factors, increasing T and B lymphocyte proliferation, and inhibiting neutrophil adhesion-associated molecules; antioxidative stress, including scavenging reactive oxygen species, cellular scorching, and regulating mitochondrial gene mutations; neuroprotective effects, antifibrotic effects, and antitumor effects. [ABSTRACT FROM AUTHOR]

Prediction of conformational B-cell epitopes (CBCE) is an essential phase for vaccine design, drug invention, and accurate disease diagnosis. Many laboratorial and computational approaches have been developed to predict CBCE. However, laboratorial experiments are costly and time consuming, leading to the popularity of Machine Learning (ML)-based computational methods. Although ML methods have succeeded in many domains, achieving higher accuracy in CBCE prediction remains a challenge. To overcome this drawback and consider the limitations of ML methods, this paper proposes a novel DL-based framework for CBCE prediction, leveraging the capabilities of deep learning in the medical domain. The proposed model is named Deep Learning-based Temporal Convolutional Neural Network (DL-TCNN), which hybridizes empirical hyper-tuned 1D-CNN and TCN. TCN is an architecture that employs causal convolutions and dilations, adapting well to sequential input with extensive receptive fields. To train the proposed model, physicochemical features are firstly extracted from antigen sequences. Next, the Synthetic Minority Oversampling Technique (SMOTE) is applied to address the class imbalance problem. Finally, the proposed DL-TCNN is employed for the prediction of CBCE. The model's performance is evaluated and validated on a benchmark antigen–antibody dataset. The DL-TCNN achieves 94.44% accuracy, and 0.989 AUC score for the training dataset, 78.53% accuracy, and 0.661 AUC score for the validation dataset; and 85.10% accuracy, 0.855 AUC score for the testing dataset. The proposed model outperforms all the existing CBCE methods. [ABSTRACT FROM AUTHOR]

Epigallocatechin‐3‐gallate (EGCG) is a major bioactive compound in tea polyphenol extract. After ingestion, EGCG reaches the intestine and may commence anti‐inflammation in the intestinal organ. Thus, in this paper, the anti‐inflammatory effect of EGCG was studied using lipopolysaccharide (LPS)‐induced inflammation in RAW 264.7 cells. LPS induction instigated morphological deformation extensively which was normalized by EGCG. In LPS‐induced macrophage cells, EGCG was found to lower cellular nitric oxide (32% of LPS group) and intercellular ROS level (45.4% of LPS group). It also suppressed the expression of IL‐1β (LPS 132.6 ± 14.6, EGCG 10.67 ± 3.65), IL‐6 (LPS 2994.44 ± 178.5, EGCG 408.33 ± 52.34), TNF‐α (LPS 27.11 ± 2.84, EGCG 1.22 ± 0.03), and iNOS (LPS 40.45 ± 11.17, EGCG 10.24 ± 0.89). The GO function analysis identified that these differential genes involved 24 biological processes, 18 molecular functions, and 19 cellular component‐related processes. KEGG pathway enrichment analysis revealed that LPS significantly affects NF‐κB, TNF, and TLR signaling pathways. Western blotting revealed that EGCG diminished P‐IκB/IκB ratio by 75% and p‐p65/p65 by 50% compared to the LPS group. Finally, Arg‐1 and CD‐206 mRNA expression were determined by RT‐PCR, which was consistent with the RNA‐Seq result. These findings indicate that EGCG exerts an anti‐inflammatory effect by reducing NO and ROS production, suppressing TLR4 protein expression, and inhibiting IκB and p65 phosphorylation. [ABSTRACT FROM AUTHOR]

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune systemic disease with a wide range of clinical symptoms, complex development processes, and uncertain prognosis. The clinical treatment of SLE is mainly based on hormones and immunosuppressants. Research on novel therapy strategies for SLE has flourished in recent years, especially the emergence of new targeted drugs and natural products that can modulate related symptoms. This review discusses the current experience including B-cell targeted drugs (belimumab, tabalumab, blisibimod, atacicept, rituximab, ofatumumab, ocrelizumab, obexelimab, and epratuzumab), T-cell targeted drugs (abatacept, dapirolizumab, and inhibitor of syk and CaMKIV), cytokines targeted drugs (anifrolumab and sifalimumab), and natural products (curcumin, oleuropein, punicalagin, sulforaphane, icariin, apigenin, and resveratrol). The aim of this paper is to combine the existing in vitro and in vivo models and clinical research results to summarize the efficacy and mechanism of natural drugs and targeted drugs in SLE for the reference and consideration of researchers. [ABSTRACT FROM AUTHOR]

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This document is a letter written by Hasta Handayani Idrus, Fitriana, and Setyo Adiningsih in response to a paper by Kang Peng Li et al on the detection of HIV-1 DNA/RNA in patients with osteonecrosis of the femoral head. The authors commend the study for providing new information on the profile of viral infection in the bone marrow and femur of people living with HIV. They highlight the importance of investigating impaired immune responses in osteonecrosis and the potential role of excessive corticosteroid therapy in inducing the condition. The authors also suggest further research on the bone marrow of chronically HIV-infected individuals who are not receiving antiretroviral therapy. [Extracted from the article]

This article explores the role of T helper cells in autoimmune diseases and the need for more effective treatment strategies. The authors specifically focus on autoreactive CD4+ T helper cells, particularly the T follicular helper subset, which promote the production of autoantibodies. They also discuss the imbalance between pathogenic peripheral T helper cells and tissue-resident Tregs in autoimmune diseases. The article highlights the importance of further research to develop targeted therapies for controlling autoimmune diseases. Additionally, the document provides a summary of various studies and reviews on the role of T helper cells in specific autoimmune diseases, aiming to contribute to the understanding of T cell involvement and potential therapeutic targets. [Extracted from the article]

The polymorphic membrane proteins (Pmps) are a family of autotransporters that play an important role in infection, adhesion and immunity in Chlamydia trachomatis. Here we show that the characteristic GGA(I,L,V) and FxxN tetrapeptide repeats fit into a larger repeat sequence, which correspond to the coils of a large beta-helical domain in high quality structure predictions. Analysis of the protein using structure prediction algorithms provided novel insight to the chlamydial Pmp family of proteins. While the tetrapeptide motifs themselves are predicted to play a structural role in folding and close stacking of the beta-helical backbone of the passenger domain, we found many of the interesting features of Pmps are localized to the side loops jutting out from the beta helix including protease cleavage, host cell adhesion, and B-cell epitopes; while T-cell epitopes are predominantly found in the beta-helix itself. This analysis more accurately defines the Pmp family of Chlamydia and may better inform rational vaccine design and functional studies. [ABSTRACT FROM AUTHOR]

B-cell Acute Lymphoblastic Leukemia (B-ALL) is a deadly cancer within the bone marrow. Despite modern cancer fighting approaches such as chemotherapy, radiation therapy, and stem cell transplants, this disease still has high recurrence rates and is unable to be cured in many patients. With the recent emergence of Chimeric Antigen Receptor T-cell therapy (CAR-T therapy), B-ALL can be treated using new and improved strategies. CAR-T therapy relies on engineered T-cells to target specific cancer cells that the body normally is unable to detect. In order to further improve CAR-T therapy and increase its effectiveness in fighting B-ALL, the breakthrough genome editing tool CRISPR/Cas9 has been used to genetically modify these cells. In this paper, we consider how CRISPR/Cas9 can be used to generate an off-the-shelf CAR-T resource, improve CAR-T cell persistence, and reduce CAR-T associated toxicities. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis with nasal polyps (CRSwNP) has long been considered a benign, chronic inflammatory, and hyperplastic disease. Recent studies have shown that autoimmune-related mechanisms are involved in the pathology of nasal polyps. Activated plasma cells, eosinophils, basophils, innate type 2 lymphocytes, mast cells, and proinflammatory cytokine in polyp tissue indicate the mobilization of innate and adaptive immune pathways during polyp formation. The discovery of a series of autoantibodies further supports the autoimmune nature of nasal polyps. Local homeostasis dysregulation, infection, and chronic inflammation may trigger autoimmunity through several mechanisms, including autoantigens overproduction, microbial translocation, molecular mimicry, superantigens, activation or inhibition of receptors, bystander activation, dysregulation of Toll-Like Receptors (TLRs), epitope spreading, autoantigens complementarity. In this paper, we elaborated on the microbiome-mediated mechanism, abnormal host immunity, and genetic changes to update the role of autoimmunity in the pathogenesis of chronic rhinosinusitis with nasal polyps. [ABSTRACT FROM AUTHOR]

The purpose of this paper was to assess the value of ultrasonography in the prognosis of diffuse large b-cell lymphoma (DLBCL) by developing a new prognostic model. One hundred and eleven DLBCL patients with complete clinical information and ultrasound findings were enrolled in our study. Univariate and multivariate regression analyses were used to identify independent risk factors for progression-free survival (PFS) and overall survival (OS). Receiver operator characteristic (ROC) curves were plotted and the corresponding area under the curve (AUC) was calculated to assess the accuracy of the international prognostic index (IPI) and new model in DLBCL risk stratification. The results suggested that hilum loss and ineffective treatment were independent risk variables for both PFS and OS in DLBCL patients. Additionally, the new model that added hilum loss and ineffective treatment to IPI had a better AUC for PFS and OS than IPI alone (AUC: 0.90, 0.88, and 0.82 vs. 0.71, 0.74, and 0.68 for 1-, 3-, and 5-year PFS, respectively; AUC: 0.92, 0.85 and 0.86 vs. 0.71, 0.75 and 0.76, for 1-, 3-, and 5-year OS, respectively). The model based on ultrasound images could better suggest PFS and OS of DLBCL, allowing for better risk stratification. [ABSTRACT FROM AUTHOR]

Simple Summary: B cells are increasingly appreciated as important contributors to the tumor microenvironment in a myriad of cancer histologies, including sarcoma. In sarcoma, recent investigations have revealed associations between B cell expression signatures, the presence of tertiary lymphoid structures, and responses to immunotherapy. In this paper, we aim to provide a comprehensive review of the multiple putative roles of B cells in sarcoma, including a historical overview, an assessment of B cells within the sarcoma microenvironment, the role of tertiary lymphoid structures, the relationship between immunotherapy efficacy and B cell signatures, sarcoma antigens and anti-tumor antibodies, pro-tumor B cell relationships, and future research directions. Despite being one of the first types of cancers studied that hinted at a major role of the immune system in pro- and anti-tumor biology, little is known about the immune microenvironment in sarcoma. Few types of sarcoma have shown major responses to immunotherapy, and its rarity and heterogeneity makes it challenging to study. With limited systemic treatment options, further understanding of the underlying mechanisms in sarcoma immunity may prove crucial in advancing sarcoma care. While great strides have been made in the field of immunotherapy over the last few decades, most of these efforts have focused on harnessing the T cell response, with little attention on the role B cells may play in the tumor microenvironment. A growing body of evidence suggests that B cells have both pro- and anti-tumoral effects in a large variety of cancers, and in the age of bioinformatics and multi-omic analysis, the complexity of the humoral response is just being appreciated. This review explores what is currently known about the role of B cells in sarcoma, including understanding the various B cell populations associated with sarcoma, the organization of intra-tumoral B cells in tertiary lymphoid structures, recent trials in immunotherapy in sarcoma, intra-tumoral immunoglobulin, the pro-tumor effects of B cells, and exciting future areas for research. [ABSTRACT FROM AUTHOR]

Introduction: The potential mechanisms governing drug induced osteonecrosis of the jaw (ONJ) is not well understood, and is one of the objectives of this study. Thus, we tested the release of IFN-g within different immune compartments including bone marrow and gingivae upon treatment with zoledronic acid (ZOL) and denosumab which are known to induce ONJ in susceptible individuals. Methods: We used humanized-BLT mouse model for the in-vivo studies reported in this paper. To determine the effects of zoledronic acid and denosumab on IFN-g secretion and NK cell-mediated cytotoxicity; peripheral blood, bone marrow, spleen and gingiva were obtained after the injection of ZOL and denosumab in mice. Results: Percentages of B cells are much higher in wild-type mice whereas the proportions of immune subsets in humans and reconstituted hu-BLT peripheralblood are similar. Therefore, hu-BLT mice are preferable model to study human disease, in particular, immune-pathologies induced by ZOL and denosumab. Both agents resulted in a severe suppression of IFN-g in the gingiva, whereas they heightened the release of IFN-g and NK cell-mediated cytotoxicity by the BMderived immune cells. ZOL increased the IFN-g secretion by the spleen and peripheral blood immune cells, whereas denosumab decreased the release IFNg by these cells significantly. Discussion: ZOL and denosumab may likely suppress IFN-g secretion in gingiva through different mechanisms. In addition, to the suppression of IFN-g secretion, denosumab mediated effect could in part be due to the decrease in the bone resorptive function of osteoclasts due to the induction of antibody dependent cellular cytotoxicity and lysis of osteoclasts, whereas ZOL is able to mediate cell death of osteoclasts directly. Suppression of IFN-gamma in gingiva is largely responsible for the inhibition of immune cell function, leading to dysregulated osteoblastic and osteoclastic activities. Restoration of IFN-gamma in the local microenvironment may result in establishment of homeostatic balance in the gingiva and prevention of osteonecrosis of jaw. [ABSTRACT FROM AUTHOR]

Background: The specific etiopathogenesis of inflammatory bowel disease (IBD) is still unknown. Although the conventional anti-inflammatory or immunomodulatory drugs relatively nonspecific to pathogenesis have been quite useful in many cases, elucidating the pathogenesis has gradually facilitated developments of disease-specific therapies for refractory cases in the last 2 decades. Summary: With a greater understanding of the multiple overactive signaling pathways of the gut mucosal immune response and enhanced leukocyte trafficking, several biological agents or small molecule drugs following the first novel biologic, anti-tumor necrosis factor α (anti-TNFα), have been developed against several modes of action including adhesion molecules, sphingosine-1-phospate receptors, cytokines (IL-12/23, TL1A, and IL-36), Janus kinase (JAK), and phosphodiesterase. Although preceding biological agents have dramatically changed the IBD treatment strategy, many patients still require alternative therapies due to failure or side effects. Newer treatments are now expected to be provided for better efficacy with an improved adverse event profile. In addition, translational studies have highlighted the new therapeutic concepts' potential, including modulation of host-microbiome interactions, stem therapy for perianal fistula, regulation of fibrosis, regulation of the gut-brain axis, and control of previously less targeted immune cells (B cells and innate lymphoid cells). This paper comprehensively reviewed not only the latest already or shortly available therapies but also emerging promising treatments that will be hopefully established in the future for IBD. Key Messages: Many kinds of new treatments are available, and promising treatments with new perspectives are expected to emerge for refractory IBD in the future. [ABSTRACT FROM AUTHOR]

This paper studies a mechanical metamaterial with tetrachiral topology by mathematical modeling. Chirality is the property of an object that makes the object distinguishable from its mirror image; chirality can be left- or right-handed. The mechanical response of two metamaterial unit cells with different configurations (patterns A and B) is investigated. It is found that the cubic cell with a regular pattern A exhibits orthotropic mechanical behavior under loading along three coordinate axes. An irregular pattern B differs from pattern A in that the upper face of the unit cell has an opposite chirality. This architectural transformation is considered as a topological defect, which enhances the twisting effect in the loaded metamaterial. Analysis of displacements and stresses shows that the mechanical behavior of the pattern B cell is described by the model of a transversely isotropic material. The orthotropic and transversely isotropic behavior of the cells of given configurations is also confirmed by the values of the effective elastic constants. Microstructural geometry and mechanical deformation of metamaterials are shown to be closely related. It is shown that a topological defect in a unit cell of a tetrachiral metamaterial strongly determines its twisting behavior. [ABSTRACT FROM AUTHOR]

This article, titled "Editorial: Pathogenic roles of T cells in autoimmunity," explores the role of T cells in autoimmune diseases. The immune system has mechanisms in place to prevent self-reactive T and B lymphocytes from causing autoimmune diseases, but these mechanisms are imperfect. Helper T cells, specifically CD4 T cells, play a crucial role in the development of autoimmune diseases. The article discusses the different subsets of helper T cells and their functions, as well as the potential for targeting pathogenic T cells in the treatment and prevention of autoimmune diseases. The research topic also includes papers on the pathogenic roles of T cells in specific autoimmune diseases such as vitiligo, idiopathic inflammatory myopathies, and primary Sjogren Syndrome. [Extracted from the article]

In recent years, due to advancements in medical conditions and the development of scientific research, the fundamental research of TCM antitumor treatments has progressed from the cellular level to the molecular and genetic levels. Previous studies have demonstrated the significant role of traditional Chinese medicine (TCM) in antitumor therapy through various mechanisms and pathways. Its mechanism of action is closely associated with cancer biology across different stages. This includes inhibiting tumor cell proliferation, blocking invasion and metastasis to surrounding tissues, inducing tumor cell apoptosis, inhibiting tumor angiogenesis, regulating immune function, maintaining genome stability, preventing mutation, and regulating cell energy metabolism. The use of TCM for eliciting antitumor effects not only has a good therapeutic effect and low side effects, it also provides a solid theoretical basis for clinical treatment and medication. This paper reviews the mechanism of the antitumor effects of TCM based on tumor characteristics. Through our review, we found that TCM not only directly inhibits tumors, but also enhances the body's immunity, thereby indirectly inducing an antitumor effect. This function aligns with the TCM theory of "strengthening the body's resistance to eliminate pathogenic factors". Furthermore, TCM will play a significant role in tumor treatment in clinical settings. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease that affects nearly 3.41 million people globally, with 90% of the cases affecting women of childbearing age. SLE is a complex disease due to the interplay of various immunological pathways and mechanisms. This scoping review aims to highlight the latest research findings on the therapeutic mechanisms of action of EVs in SLE. Relevant research articles were identified using the PRISMA framework from databases such as PubMed/MEDLINE (National Library of Medicine), Scopus (Elsevier), and Web of Science: Core Collection (Clarivate Analytics) from July 2023 to October 2023. Eleven studies met the inclusion criteria and thus were included in this scoping review. The findings showed that EVs have therapeutic effects on ameliorating the disease progression of SLE. EVs can reduce the pro-inflammatory cytokines and increase the anti-inflammatory cytokines. Moreover, EVs can increase the levels of regulatory T cells, thus reducing inflammation. EVs also have the potential to regulate B cells to alleviate SLE and reduce its adverse effects. The scoping review has successfully analysed the therapeutic potential in ameliorating the disease progression of SLE. The review also includes prospects to improve the effects of EVs further to increase the therapeutic effects on SLE. [ABSTRACT FROM AUTHOR]

It is very important to understand the communication and interaction mechanisms between the host and its resident microorganisms on host physiology and for precise diagnosis and treatment. Although intestinal fungi and bacteria dysbiosis is increasingly linked to ankylosing spondylitis (AS), their mechanisms of action have been rarely illustrated. In this paper, fecal samples from 10 AS monkeys and 10 healthy controls were collected to systematically characterize the gut mycobiota and microbiota in AS monkeys by 16S rRNA and ITS2 DNA sequencing. Our results showed the gut fungi of Kazachstania pintolopesii, Saccharomycetaceae, Kazachstania, and Saccharomyceteles. Saccharomycetes were specially enriched in AS, and the microbiota of AS monkeys was characterized by an increased abundance of Clostridia, Clostridiales, Ruminococcaceae, and Prevotella 2, using Line Discriminant Analysis Effect Size. Compared to healthy controls, decreased ITS2/16S biodiversity ratios and altered bacterial--fungal interkingdom networks were observed in AS monkeys. Oral administration of K. pintolopesii activates IL-17RA pathway and induce inflammatory reaction in the colonic tissue of C57BL/6 mice, as well as multiple AS phenotypes, including fungal and bacterial dysbiosis, immune responses of NK cells, platelets, T cells, leukocytes, B-cell activation, rheumatoid arthritis, and inflammatory bowel disease. We also found the secreted products of K. pintolopesii could activate the IL-17RA pathway, which induces PANoptosis in macrophage RAW264.7 cells. Much worse, the PANoptosis products could promote the proliferation and morphological changes of K. pintolopesii, which resulted in much more K. pintolopesii and a severe inflammatory reaction. Interestingly, the inflammatory factor TNF-α can promote the morphological transformation of Candida albicans and K. pintolopesii, which is worthy of further study. The characteristic fungi in all these findings implied that fungal and bacterial dysbiosis have a close link to AS and that their communication and interaction indeed play an important role in autoimmune responses, and K. pintolopesii could be a potential marker microorganism in AS, although its specific mechanism is not fully elucidated. [ABSTRACT FROM AUTHOR]

The bursa of Fabricius, the acknowledged humoral immune organ unique to birds, plays a vital role in B cell development. Bursopentin (BP5) derived from the bursa is reported to induce the development and formation of B cells. However, the mechanism of BP5 on B cell differentiation is still unclear. In this paper, total B lymphocytes from mice immunized with H9N2 subtype AIV vaccine were stimulated with BP5. The results show that BP5 at the experimental dosages promoted B cell differentiation, including the total B cells, activated B cells, differentiated B cells, mature B cells and plasma cells. Then, the in vivo immune experiment proved that the percentages of activated and differentiated B cells from mice immunized with AIV vaccine and 0.25 mg/mL BP5 were increased. To investigate the molecular mechanism of BP5 on B cell differentiation, the gene expression profiles of B cells purified from the spleen cells of mice immunized with AIV vaccine and BP5 were detected following RNA sequencing technology. The results show that BP5 at 0.05 and 0.25 mg/mL induced the enrichment of various biological functions, and stimulated five common significant enrichment pathways in B cells from the immunized mice. Additionally, 120 and 59 differentially expressed genes (DEG) represented transcriptional factors in B cells following 0.05 and 0.25 mg/mL BP5 immunization, respectively. In summary, these results suggest that BP5 regulates various gene expression involved in regulation of B cell development, which provides the knowledge required for additional studies on B cell differentiation in response to bursal-derived peptides and also provides an important experimental basis for improving vaccine immunity. [ABSTRACT FROM AUTHOR]

Simple Summary: Colic, a condition affecting the digestive tract of horses, manifests itself in severe pain and may be life-threatening. Recurrent colic is usually caused by ongoing, chronic inflammatory process (and may be defied as: ≥3 episodes of colic within a 6-month period, with at least 48 h between colic episodes), associated with a chronic process, often of an inflammatory nature. Multiple causes of recurrent colic may exist, including, for an improper diet, management changes, stress, or parasites infestation. During the diagnostic process, a noninvasive test in the form of taking a biopsy of the duodenal or rectal mucosa proves to be useful, but its usefulness is limited only to diffuse processes. The study presented here depicts a retrospective analysis of the histopathological findings of samples taken from 77 horses with recurrent colic, focusing on cellular infiltration, fibrosis, and erosions. All samples from the duodenum showed the presence of leukocytes infiltrates in the mucosal lamina propria, of which almost 70% were diffuse infiltrates. The most frequently observed cellular infiltration was a moderate infiltration consisting of lymphocytes and plasma cells. More than one-fourth of the horses were also found to have shortened intestinal villi. Similarly, in biopsies from the rectum, cellular infiltration was observed in all horses in this section, which consisted of a mixed population of plasma cells, lymphocytes, and eosinophilia. Analysis of the inflammatory lesions present may help in understanding the pathogenesis of chronic colic in horses. Colic, a condition affecting the gastrointestinal tract of horses, manifests as severe pain and may be a life-threatening condition. It is possible to distinguish between an acute, disposable process, as well as recurrent colic symptoms (abdominal pain) caused by an ongoing chronic inflammatory process. This paper presents a retrospective analysis of the histopathological findings of duodenal and rectal samples taken from horses with recurrent colic, with the aim to determine the frequency and extent of inflammation. The samples, i.e., duodenal biopsy (60 samples) and rectal biopsy (17 samples), were taken from 77 horses showing recurrent colic symptoms. Histopathological examination included staining with hematoxylin and eosin. The examination included evaluation of the superficial epithelium, mucosal lamina propria, and submucosa. All samples from the duodenum and rectum showed the presence of leukocyte infiltration in the mucosal lamina propria. The most frequently observed cellular infiltration was a moderate infiltration consisting of lymphocytes and plasma cells in duodenum and mixed populations of plasma cells, lymphocytes, and eosinophilia in the rectum. Mott cells were also noted among the inflammatory infiltrates. More than one-fourth of the horses were found to have shortened intestinal villi. The results presented here showed the involvement of inflammation in the course of recurrent colic, which can be both its cause (by impairing motility and absorption) and its effect (as a result of obstruction or ischemia). [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the efficacy of rituximab in the treatment of recurrent primary Sjögren syndrome (pSS) associated dry eye, so as to provide reference for clinical treatment. METHODS: Totally 81 patients with recurrent pSS associated xerophthalmia admitted into this hospital from Jan. 2015 to Aug. 2021 were selected and divided into two groups by random number table. The control group (41 cases, 82 eyes) was given prednisone acetate, hydroxychloroquine sulfate and cyclophosphamide for systemic administration and topical eye drops for 8 weeks; while the observation group (40 cases, 80 eyes) were given rituximab 375 mg/m² for intravenous drip based on the control group, once a week for 8 weeks. Scores of the standard patient evaluation of eye dryness (SPEED) questionnaire, rupture time of tear film, scores of Schirmer Ⅰ tear secretion test and corneal fluorescein staining of the two groups were observed, incidence of adverse drug reactions and recurrence during follow-up were recorded. RESULTS: After treatment, the SPEED scores of eye dryness, foreign body sensation, pain, burning sensation or tearing and total score, and scores of corneal fluorescein staining of both groups were significantly lower than before treatment, the rupture time of tear film was longer than before treatment, and the length of Schirmer I tear secretionsoaked filter paper was increased compared with before treatment in both groups, with statistically significant differences (P<0. 01). The SPEED scores of eye dryness [(2. 15±0. 36) points vs. (3. 26±0. 47) points], foreign body sensation [(2. 11±0. 28) points vs. (3. 02±0. 40) points], pain [(2. 03±0. 28) points vs. (2. 95±0. 36) points], burning sensation or tearing [(1. 26±0. 24 ) points vs. (2. 15±0. 39) points] and total score [(7. 55± 1. 46) points vs. (11. 38±2. 74) points], and scores of corneal fluorescein staining [(3. 11±0. 53) points vs. (4. 02± 0. 69) points] of the observation group were lower than those of the control group after treatment, and the rupture time of tear film [(9. 57±2. 03) s vs. (7. 35±1. 95 ) s] of the observation group was longer than that of the control group, the length of Schirmer Ⅰ tear secretion-soaked filter paper [(8. 97 ±2. 17) mm vs. (6. 95 ±1. 72) mm] of the observation group was greater than that of the control group, with statistically significant differences (P<0. 01). The recurrence rate of the observation group [5. 00% (2/40) vs. 24. 39% (10/41)] was lower than that of the control group, with statistically significant difference (P<0. 05). The difference in the incidences of adverse drug reactions between two groups was not statistically significant ( P > 0. 05). CONCLUSIONS: Compared with conventional treatment, the application of rituximab for recurrent pSS associated dry eye can significantly induced lacrimal secretion, improved dry eye symptoms and reduced the risk of recurrence. [ABSTRACT FROM AUTHOR]

Next generation sequencing of B cell receptor (BCR) repertoires has become a ubiquitous tool for understanding the antibody-mediated immune response: it is now common to have large volumes of sequence data coding for both the heavy and light chain subunits of the BCR. However, until the recent development of high throughput methods of preserving heavy/light chain pairing information, these samples contained no explicit information on which heavy chain sequence pairs with which light chain sequence. One of the first steps in analyzing such BCR repertoire samples is grouping sequences into clonally related families, where each stems from a single rearrangement event. Many methods of accomplishing this have been developed, however, none so far has taken full advantage of the newly-available pairing information. This information can dramatically improve clustering performance, especially for the light chain. The light chain has traditionally been challenging for clonal family inference because of its low diversity and consequent abundance of non-clonal families with indistinguishable naive rearrangements. Here we present a method of incorporating this pairing information into the clustering process in order to arrive at a more accurate partition of the data into clonally related families. We also demonstrate two methods of fixing imperfect pairing information, which may allow for simplified sample preparation and increased sequencing depth. Finally, we describe several other improvements to the partis software package. Author summary: Antibodies form part of the adaptive immune response, and are critical to immunity acquired by both vaccination and infection. Next generation sequencing of the B cell receptor (BCR) repertoire provides a broad and highly informative view of the DNA sequences from which antibodies arise. Until recently, however, this sequencing data was not able to pair together the two domains (from separate chromosomes) that make up a functional antibody. In this paper we present several methods to improve analysis of the new paired data that does pair together sequence data for complete antibodies. We first show a method that better groups together sequences stemming from the same ancestral cell, solving a problem called "clonal family inference." We then show two methods that can correct for various imperfections in the data's identification of which sequences pair together to form complete antibodies, which together may allow for significantly simplified experimental methods. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a global health problem with increasing prevalence and association with an enormous medical and socioeconomic burden. New recognition of immune cells such as type 2 innate lymphocytes (ILC2s), T helper (Th2) 2 cells, follicular helper T cells, follicular regulatory T cells, regulatory T cells, B cells, dendritic cells, and epithelial cells in AR pathogenesis has been updated in this review paper. An in‐depth understanding of the mechanisms underlying AR will aid the identification of biomarkers associated with disease and ultimately provide valuable parameters critical to guide personalized targeted therapy. As the only etiological treatment option for AR, allergen‐specific immunotherapy (AIT) has attracted increasing attention, with evidence for effectiveness of AIT recently demonstrated in several randomized controlled trials and long‐term real‐life studies. The exploration of biologics as therapeutic options has only involved anti‐IgE and anti‐type 2 inflammatory agents; however, the cost‐effectiveness of these agents remains to be elucidated precisely. In the midst of the currently on‐going COVID‐19 pandemic, a global life‐threatening disease, although some studies have indicated that AR is not a risk factor for severity and mortality of COVID‐19, this needs to be confirmed in multi‐centre, real‐life studies of AR patients from different parts of the world. [ABSTRACT FROM AUTHOR]