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The immunoregulatory cytokine TGF-β is pleiotropic due to the near-ubiquitous expression of the TGF-β receptors TβRI and TβRII on diverse cell types. The helminth parasite Heligmosomoides polygyrus has convergently evolved a family of TGF-β mimics (TGMs) that bind both these receptors through domains 1-3 of a 5-domain protein. One member of this family, TGM4, differs from TGF-β in acting in a cell-specific manner, failing to stimulate fibroblasts, but activating SMAD phosphorylation in macrophages. Primarily through domains 4 and 5, TGM4 interacts with multiple co-receptors, including CD44, CD49d (integrin α4) and CD206, and can up- and downmodulate macrophage responses to IL-4 and lipopolysaccharide (LPS), respectively. The dependence of TGM4 on combinatorial interactions with co-receptors is due to a moderated affinity for TβRII that is more than 100-fold lower than for TGF-β. Thus the parasite has elaborated TGF-β receptor interactions to establish cell specificity through combinatorial cis-signalling, an innovation absent from the mammalian cytokine., Competing Interests: Disclosure and competing interests statement. The authors declare no competing interests., (© 2024. The Author(s).)

Liebold et al. recently revealed how the identity of dying cells drives distinct changes to the macrophages which engulf and clear them, a process known as efferocytosis. During infection with the helminth Schistosoma mansoni, liver macrophages recapitulate these phenotypes, mediated by Axl/MerTK receptors and regulating egg burdens., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Demyelination in the central nervous system (CNS) resulting from injury or disease can cause loss of nerve function and paralysis. Cell therapies intended to promote remyelination of axons are a promising avenue of treatment, with mesenchymal stromal cells (MSCs) a prominent candidate. We have previously demonstrated that MSCs derived from human olfactory mucosa (hOM-MSCs) promote myelination to a greater extent than bone marrow-derived MSCs (hBM-MSCs). However, hOM-MSCs were developed using methods and materials that were not good manufacturing practice (GMP)-compliant. Before considering these cells for clinical use, it is necessary to develop a method for their isolation and expansion that is readily adaptable to a GMP-compliant environment. We demonstrate here that hOM-MSCs can be derived without enzymatic tissue digestion or cell sorting and without culture antibiotics. They grow readily in GMP-compliant media and express typical MSC surface markers. They robustly produce CXCL12 (a key secretory factor in promoting myelination) and are pro-myelinating in in vitro rodent CNS cultures. GMP-compliant hOM-MSCs are comparable in this respect to those grown in non-GMP conditions. However, when assessed in an in vivo model of demyelinating disease (experimental autoimmune encephalitis, EAE), they do not significantly improve disease scores compared with controls, indicating further pre-clinical evaluation is necessary before their advancement to clinical trials.

During inflammation, haematopoietic stem cells (HSCs) in the bone marrow (BM) and periphery rapidly expand and preferentially differentiate into myeloid cells that mediate innate immune responses. HSCs can be directed into quiescence or differentiation by sensing alterations to the haematopoietic niche, including cytokines, chemokines, and pathogen-derived products. Most studies attempting to identify the mechanisms of haematopoiesis have focused on bacterial and viral infections. From intracellular protozoan infections to large multicellular worms, parasites are a global health burden and represent major immunological challenges that remain poorly defined in the context of haematopoiesis. Immune responses to parasites vary drastically, and parasites have developed sophisticated immunomodulatory mechanisms that allow development of chronic infections. Recent advances in imaging, genomic sequencing, and mouse models have shed new light on how parasites induce unique forms of emergency haematopoiesis. In addition, parasites can modify the haematopoiesis in the BM and periphery to improve their survival in the host. Parasites can also induce long-lasting modifications to HSCs, altering future immune responses to infection, inflammation or transplantation, a term sometimes referred to as central trained immunity. In this review, we highlight the current understanding of parasite-induced haematopoiesis and how parasites target this process to promote chronic infections., (© 2023 The Authors. Parasite Immunology published by John Wiley & Sons Ltd.)

Long-lived parasites evade host immunity through highly evolved molecular strategies. The murine intestinal helminth, Heligmosomoides polygyrus , down-modulates the host immune system through release of an immunosuppressive TGF-β mimic, TGM1, which is a divergent member of the CCP (Sushi) protein family. TGM1 comprises 5 domains, of which domains 1-3 (D1/2/3) bind mammalian TGF-β receptors, acting on T cells to induce Foxp3 + regulatory T cells; however, the roles of domains 4 and 5 (D4/5) remain unknown. We noted that truncated TGM1, lacking D4/5, showed reduced potency. Combination of D1/2/3 and D4/5 as separate proteins did not alter potency, suggesting that a physical linkage is required and that these domains do not deliver an independent signal. Coprecipitation from cells treated with biotinylated D4/5, followed by mass spectrometry, identified the cell surface protein CD44 as a coreceptor for TGM1. Both full-length and D4/5 bound strongly to a range of primary cells and cell lines, to a greater degree than D1/2/3 alone, although some cell lines did not respond to TGM1. Ectopic expression of CD44 in nonresponding cells conferred responsiveness, while genetic depletion of CD44 abolished enhancement by D4/5 and ablated the ability of full-length TGM1 to bind to cell surfaces. Moreover, CD44-deficient T cells showed attenuated induction of Foxp3 by full-length TGM1, to levels similar to those induced by D1/2/3. Hence, a parasite protein known to bind two host cytokine receptor subunits has evolved a third receptor specificity, which serves to raise the avidity and cell type-specific potency of TGF-β signaling in mammalian cells.

Although significant progress has been made to improve short-term survival of transplant patients, long-term acceptance of allografts in solid organ and hematopoietic stem cell (HSC) transplantation is still a significant challenge. Current therapeutics for preventing or treating allograft rejection rely on potent immunosuppressive drugs that primarily target T cells of the adaptive immune response. Promising advances in transplant immunology have highlighted the importance of innate immune responses in allograft acceptance and rejection. Recent studies have demonstrated that innate immune cells are capable of mediating memory-like responses during inflammation, a term known as trained innate immunity. In this process, innate immune cells, such as macrophages and monocytes, undergo metabolic and epigenetic changes in response to a primary stimulus with a pathogen or their products that result in faster and more robust responses to a secondary stimulus. There is also some evidence to suggest that innate immune cells or their progenitors may be more anti-inflammatory after initial stimulation with appropriate agents, such as helminth products. Although this phenomenon has primarily been studied in the context of infection, there is emerging evidence to suggest that it could play a vital role in transplantation rejection and tolerance. Mechanisms of training innate immune cells and their progenitors in the bone marrow are therefore attractive targets for mediating long-term solid organ and HSC transplant tolerance. In this review, we highlight the potential role of proinflammatory and anti-inflammatory mechanisms of trained innate immunity in solid organ and HSC transplantation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Certain proinflammatory stimuli can metabolically and epigenetically modify monocytes/macrophages or NK cells to be more responsive to secondary stimuli, a process known as trained innate immunity. However, the longevity of trained innate immunity is unclear. In this study, we report that Fasciola hepatica excretory-secretory products (FHES) can imprint an anti-inflammatory phenotype on long-term hematopoietic stem cells (HSCs) and monocyte precursor populations, enhancing their proliferation and differentiation into anti-inflammatory Ly6C low monocytes. These monocytes expand and populate multiple compartments within mice, conferring hyporesponsiveness to proinflammatory stimuli and reduced susceptibility to induction of experimental autoimmune encephalomyelitis. Mice treated with FHES had enhanced alternatively activated macrophages, reduced Th1 and Th17 responses, and attenuating effects on autoimmunity that persisted for 8 mo. Furthermore, transplantation of HSCs from FHES-treated mice transferred the anti-inflammatory phenotype to naive mice. Our findings demonstrate that helminth products can modulate HSCs to promote development of anti-inflammatory myeloid cells that attenuate T cell-mediated autoimmune disease., (Copyright © 2021 by The American Association of Immunologists, Inc.)

Purpose Of the three currently recognized variants of primary progressive aphasia, behavioral differentiation between the nonfluent/agrammatic (nfvPPA) and logopenic (lvPPA) variants is particularly difficult. The challenge includes uncertainty regarding diagnosis of apraxia of speech, which is subsumed within criteria for variant classification. The purpose of this study was to determine the extent to which a variety of speech articulation and prosody metrics for apraxia of speech differentiate between nfvPPA and lvPPA across diverse speech samples. Method The study involved 25 participants with progressive aphasia (10 with nfvPPA, 10 with lvPPA, and five with the semantic variant). Speech samples included a word repetition task, a picture description task, and a story narrative task. We completed acoustic analyses of temporal prosody and quantitative perceptual analyses based on narrow phonetic transcription and then evaluated the degree of differentiation between nfvPPA and lvPPA participants (with the semantic variant serving as a reference point for minimal speech production impairment). Results Most, but not all, articulatory and prosodic metrics differentiated statistically between the nfvPPA and lvPPA groups. Measures of distortion frequency, syllable duration, syllable scanning, and-to a limited extent-syllable stress and phonemic accuracy showed greater impairment in the nfvPPA group. Contrary to expectations, classification was most accurate in connected speech samples. A customized connected speech metric-the narrative syllable duration-yielded excellent to perfect classification accuracy. Discussion Measures of average syllable duration in multisyllabic utterances are useful diagnostic tools for differentiating between nfvPPA and lvPPA, particularly when based on connected speech samples. As such, they are suitable candidates for automatization, large-scale study, and application to clinical practice. The observation that both speech rate and distortion frequency differentiated more effectively in connected speech than on a motor speech examination suggests that it will be important to evaluate interactions between speech and discourse production in future research.

Purpose: There is persistent uncertainty about whether sound error consistency is a valid criterion for differentiating between apraxia of speech (AOS) and aphasia with phonemic paraphasia. The purpose of this study was to determine whether speakers with a profile of aphasia and AOS differ in error consistency from speakers with aphasia who do not have AOS. By accounting for differences in overall severity and using a sample size well over three times that of the largest study on the topic to date, our ambition was to resolve the existing controversy., Method: We analyzed speech samples from 171 speakers with aphasia and completed error consistency analysis for 137 of them. The experimental task was to repeat four multisyllabic words five times successively. Phonetic transcriptions were coded for four consistency indices (two at the sound-level and two at the word-level). We then used quantitative metrics to assign participants to four diagnostic groups (one aphasia plus AOS group, one aphasia only group, and two groups with intermediate speech profiles). Potential consistency differences were examined with ANCOVA, with error frequency as a continuous covariate., Results: Error frequency was a strong predictor for three of the four consistency metrics. The magnitude of consistency for participants with AOS was either similar or lower compared to that of participants with aphasia only. Despite excellent transcription reliability and moderate to excellent coding reliability, three of the four consistency indices showed limited measurement reliability., Discussion: People with AOS and people with aphasia often produce inconsistent variants of errors when they are asked to repeat challenging words several times sequentially. The finding that error consistency is similar or lower in aphasia with AOS than in aphasia without AOS is incompatible with recommendations that high error consistency be used as a diagnostic criterion for AOS. At the same time, group differences in the opposite direction are not sufficiently systematic to warrant use for differential diagnosis between aphasia with AOS and aphasia with phonemic paraphasia. Greater attention should be given to error propagation when estimating reliability of derived measurements.

IL-33 is known to promote type 2 immune responses through ST2, a component of the IL-33R complex, expressed primarily on mast cells, Th2 cells, group 2 innate lymphoid cells and regulatory T cells, and to a lesser extent, on NK cells and Th1 cells. Consistent with previous studies, we found that IL-33 polarized alternatively activated macrophages (AAMΦ) in vivo. However, in vitro stimulation of murine bone marrow-derived or peritoneal macrophages with IL-33 failed to promote arginase activity or expression of YM-1 or Retnla , markers of AAMΦ. Furthermore, macrophages have low/no basal expression of ST2. This suggested that alternative activation of macrophages may involve an IL-33-responsive third-party cell. Because mast cells have the highest expression of ST2 relative to other leukocytes, we focused on this cell type. Coculture experiments showed that IL-33-stimulated mast cells polarized AAMΦ through production of soluble factors. IL-33-stimulated mast cells produced a range of cytokines, including IL-6 and IL-13. Mast cell-derived IL-13 was required for induction of AAMΦ, whereas mast cell-derived IL-6 enhanced macrophage responsiveness to IL-13 via upregulation of the IL-4Rα receptor. Furthermore, we found that AAMΦ polarized by IL-33-stimulated mast cells could suppress proliferation and IL-17 and IFN-γ production by T cells. Finally, we show that AAMΦ polarized by IL-33-stimulated mast cells attenuated the encephalitogenic function of T cells in the experimental autoimmune encephalomyelitis model. Our findings reveal that IL-33 can promote immunosuppressive responses by polarizing AAMΦ via mast cell-derived IL-6 and IL-13., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Engineering a pro-regenerative immune response following scaffold implantation is integral to functional tissue regeneration. The immune response to implanted biomaterials is determined by multiple factors, including biophysical cues such as material stiffness, topography and particle size. In this study we developed an immune modulating scaffold for bone defect healing containing bone mimetic nano hydroxyapatite particles (BMnP). We first demonstrate that, in contrast to commercially available micron-sized hydroxyapatite particles, in-house generated BMnP preferentially polarize human macrophages towards an M2 phenotype, activate the transcription factor cMaf and specifically enhance production of the anti-inflammatory cytokine, IL-10. Furthermore, nano-particle treated macrophages enhance mesenchymal stem cell (MSC) osteogenesis in vitro and this occurs in an IL-10 dependent manner, demonstrating a direct pro-osteogenic role for this cytokine. BMnPs were also capable of driving pro-angiogenic responses in human macrophages and HUVECs. Characterization of immune cell subsets following incorporation of functionalized scaffolds into a rat femoral defect model revealed a similar profile, with micron-sized hydroxyapatite functionalized scaffolds eliciting pro-inflammatory responses characterized by infiltrating T cells and elevated expression of M1 macrophages markers compared to BMnP functionalized scaffolds which promoted M2 macrophage polarization, tissue vascularization and increased bone volume. Taken together these results demonstrate that nano-sized Hydroxyapatite has immunomodulatory potential and is capable of directing anti-inflammatory innate immune-mediated responses that are associated with tissue repair and regeneration., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose The purpose of this study was to compare the utility of two automated indices of lexical diversity, the Moving-Average Type-Token Ratio (MATTR) and the Word Information Measure (WIM), in predicting aphasia diagnosis and responding to differences in severity and aphasia subtype. Method Transcripts of a single discourse task were analyzed for 478 speakers, 225 of whom had aphasia per an aphasia battery. We calculated the MATTR and the WIM for each participant. We compared the group means among speakers with aphasia, neurotypical controls, and left-hemisphere stroke survivors with mild aphasia not detected by an aphasia battery. We examined whether each measure distinguished levels of aphasia severity and subtypes of aphasia. We used each measure to classify aphasia versus neurotypical control and compared the areas under the curve. Results The WIM and the MATTR differentiated among people with aphasia, neurotypical controls, and people with mild aphasia. Both measures demonstrated moderately high predictive accuracy in classifying aphasia. The WIM demonstrated greater sensitivity to aphasia severity and subtype compared to the MATTR. Conclusions The WIM and the MATTR are promising measures that quantify lexical diversity in different and complementary ways. The WIM may be more useful for quantifying the effect of treatment or disease progression, whereas the MATTR may be more useful for discriminating discourse produced by people with very mild aphasia from discourse produced by neurotypical controls. Further validation is required.

Purpose Many communication disorders result in speech sound errors that listeners perceive as phonemic errors. Unfortunately, manual methods for calculating phonemic error frequency are prohibitively time consuming to use in large-scale research and busy clinical settings. The purpose of this study was to validate an automated analysis based on a string metric-the unweighted Levenshtein edit distance-to express phonemic error frequency after left hemisphere stroke. Method Audio-recorded speech samples from 65 speakers who repeated single words after a clinician were transcribed phonetically. By comparing these transcriptions to the target, we calculated the percent segments with a combination of phonemic substitutions, additions, and omissions and derived the phonemic edit distance ratio, which theoretically corresponds to percent segments with these phonemic errors. Results Convergent validity between the manually calculated error frequency and the automated edit distance ratio was excellent, as demonstrated by nearly perfect correlations and negligible mean differences. The results were replicated across 2 speech samples and 2 computation applications. Conclusions The phonemic edit distance ratio is well suited to estimate phonemic error rate and proves itself for immediate application to research and clinical practice. It can be calculated from any paired strings of transcription symbols and requires no additional steps, algorithms, or judgment concerning alignment between target and production. We recommend it as a valid, simple, and efficient substitute for manual calculation of error frequency.

Purpose Collaborative goal setting is at the heart of person-centered rehabilitation but can be challenging, particularly in the area of aphasia. The purpose of this clinical focus article is to present a step-by-step model for forming a collaborative partnership with clients to develop an intervention plan that follows the client's lead, addresses communicative participation, and integrates multiple treatment strategies. Method We introduce the rationale and core features of a 4-step and 4-pronged process (the FOURC model) and illustrate its application through 3 cases of people with aphasia who were treated in outpatient rehabilitation. Conclusions The model invites client initiative in a clinically feasible manner while supporting the clinician's role in guiding the intervention based on professional expertise and growing familiarity with the case. Outcomes observed in case studies include strengthened motivation and improved real-life communication.

Purpose: Diagnostic recommendations for acquired apraxia of speech (AOS) have been contradictory concerning whether speech sound errors are consistent or variable. Studies have reported divergent findings that, on face value, could argue either for or against error consistency as a diagnostic criterion. The purpose of this study was to explain discrepancies in error consistency results based on the unit of analysis (segment, syllable, or word) to help determine which diagnostic recommendation is most appropriate., Method: We analyzed speech samples from 14 left-hemisphere stroke survivors with clinical diagnoses of AOS and aphasia. Each participant produced 3 multisyllabic words 5 times in succession. Broad phonetic transcriptions of these productions were coded for consistency of error location and type using the word and its constituent syllables and sound segments as units of analysis., Results: Consistency of error type varied systematically with the unit of analysis, showing progressively greater consistency as the analysis unit changed from the word to the syllable and then to the sound segment. Consistency of error location varied considerably across participants and correlated positively with error frequency., Conclusions: Low to moderate consistency of error type at the word level confirms original diagnostic accounts of speech output and sound errors in AOS as variable in form. Moderate to high error type consistency at the syllable and sound levels indicate that phonetic error patterns are present. The results are complementary and logically compatible with each other and with the literature.

Purpose: This study was conducted to evaluate the clinical utility of error variability for differentiating between apraxia of speech (AOS) and aphasia with phonemic paraphasia., Method: Participants were 32 individuals with aphasia after left cerebral injury. Diagnostic groups were formed on the basis of operationalized measures of recognized articulatory and prosodic characteristics of AOS and phonemic paraphasia. Sequential repetitions of multisyllabic words were elicited as part of a motor speech evaluation and transcribed phonetically. Four metrics of variability at the syllable and word levels were derived from these transcripts., Results: The measures yielded different magnitudes of variability. There were no group differences between participants who displayed speech profiles consistent with AOS and participants who displayed speech profiles indicative of aphasia with phonemic paraphasia. Rather, correlation coefficients and analyses of covariance showed that the variability metrics were significantly mediated by overall error rate. Additionally, variability scores for individuals with salient diagnoses of AOS and conduction aphasia were inconsistent with current diagnostic guidelines., Conclusions: The results do not support diagnostic validity of error variability for differentiating between AOS and aphasia with phonemic paraphasia. Future research using error variability metrics should account for overall error rate in the analysis and matching of participant groups.

German pathologist Otto Aichel suggested, a century ago, that the cancer cell acquired its metastatic property from a leukocyte via cell-cell fusion. Since then, several revised versions of this theory have been proposed. Most of the proposals attribute the generation of the metastatic cancer cell to the fusion between a primary cancer cell and a macrophage. However, these theories have not addressed several issues, such as dormancy and stem cell-like self-renewal, of the metastatic cancer cell. On the other hand, recent studies have found that, like T- and B-/plasma cells, macrophages can also be categorized into naïve, effector, and memory/trained macrophages. As a memory/trained macrophage can enter dormancy/quiescence, be awakened from the dormancy/quiescence by acquainted primers, and re-populate via stem cell-like self-renewal, we, therefore, further specify that the macrophage fusing with the cancer cell and contributing to metastasis, belongs with the memory/trained macrophage, not other subtypes of macrophages. The current theory can explain many puzzling clinical features of cancer, including the paradoxal effects (recurrence vs. regression) of microbes on tumors, "spontaneous" and Coley's toxin-induced tumor regression, anticancer activities of b-blockers and anti-inflammatory/antiimmune/antibiotic drugs, oncotaxis, surgery- and trauma-promoted metastasis, and impact of microbiota on tumors. Potential therapeutic strategies, such as Coley's toxin-like preparations, are proposed. This is the last article of our trilogy on carcinogenesis theories. [ABSTRACT FROM AUTHOR]

5-HT3 receptor antagonists, ondansetron, granisetron and tropisetron are highly specific for the 5-HT3 receptor and have a selectivity ratio of approximately 1000:1 compared with affinities for other receptors. Other 5-HT3 receptor antagonists, largely those having a benzamide structure, are non-selective. These include metoclopramide, renzapride and zacopride which stimulate gastric motility via activation of 5-HT4 receptors; metoclopramide is also a potent dopamine receptor antagonist. Selective 5-HT3 receptor antagonists are a major advance in the treatment of chemotherapy- and radiotherapy-induced emesis in cancer patients. These agents inhibit emesis by blocking 5-HT3 receptors on vagal afferent nerve terminals in the gastrointestinal mucosa and on terminals on the same vagal nerves in the vomiting system. Inhibition of acute emesis appears to be produced by blocking the initiation of the emetic reflex induced via 5-HT3 receptors and by 5-HT released from enterochromaffin cells in the small intestine, as well as by blocking 5-HT3 receptors in the hindbrain vomiting system.

Leukemia relapse following stem cell transplantation remains a significant barrier to long-term remission. Timely and balanced immune recovery after transplantation is crucial for preventing leukemia relapse. After an extensive literature search of PubMed and Web of Science through October 2023, we provide an overview of the dynamics of immune reconstitution and its role in controlling leukemia relapse. We also discuss strategies to promote immune reconstitution and reduce disease recurrence following allogeneic hematopoietic stem cell transplantation. Immune reconstitution after transplantation has substantial potential to prevent relapse and might predict disease recurrence and prognosis. High dimensional cytometry, multi-omics, and T cell repertoire analysis allow for a more comprehensive and detailed understanding of the immune system's dynamics post-transplantation, and contribute to the identification of rare immune cell subsets or potential biomarkers associated with successful immune reconstitution or increased risk of complications. Strategies to enhance the immune system, such as adoptive immunotherapy and cytokine-based therapy, have great potential for reducing leukemia relapse after transplantation. Future research directions should focus on refining patient selection for these therapies, implementing appropriate and timely treatment, investigating combination approaches to maximize therapeutic outcomes, and achieving a robust graft-versus-leukemia (GVL) effect while minimizing graft-versus-host disease (GVHD) for optimal results. [ABSTRACT FROM AUTHOR]

Gastrointestinal nematode (GIN) infection has applied significant evolutionary pressure to the mammalian immune system and remains a global economic and human health burden. Upon infection, type 2 immune sentinels activate a common antihelminth response that mobilizes and remodels the intestinal tissue for effector function; however, there is growing appreciation of the impact GIN infection also has on the distal tissue immune state. Indeed, this effect is observed even in tissues through which GINs never transit. This review highlights how GIN infection modulates systemic immunity through (a) induction of host resistance and tolerance responses, (b) secretion of immunomodulatory products, and (c) interaction with the intestinal microbiome. It also discusses the direct consequences that changes to distal tissue immunity can have for concurrent and subsequent infection, chronic noncommunicable diseases, and vaccination efficacy. [ABSTRACT FROM AUTHOR]

Objectives: This scoping review aims to map the literature on goal-setting tools in adult rehabilitation, exploring their characteristics, target users and supporting evidence to inform practice and future research in this area. Methods: We completed a comprehensive search of four databases to identify relevant articles on tools for goal setting in rehabilitation. We followed Arkey and O'Malley's scoping review process to guide article selection, data extraction and data analysis. Results: We identified a total of 165 studies that reported on 55 different goal-setting tools, including tools for goal selection and goal documentation (n = 31), goal setting and intervention planning (n = 15), and for measuring the quality of the goal-setting process (n = 9). Over half of the tools were primarily designed for use in rehabilitation of physical disabilities (n = 32). Some tools fell under multiple sub-categories based on their characteristics as follows: 22 framework tools, 12 interview tools, 9 outcome measurement tools for goal achievement, 6 outcome measurement tools for goal quality and 25 documentation tools. The majority of goal-setting instruments targeted goals at the level of activity and participation (n = 51) and aimed to facilitate a client-centred or shared decision-making approach to rehabilitation planning (n = 46). Conclusions: This study provides a comprehensive overview of existing goal-setting tools, highlighting their characteristics, target users and identified needs. These findings can enhance practitioners' awareness of the range of goal-setting tools available and can enable more effective utilization of these tools in clinical practice. Further research should investigate how clinicians can combine multiple tools to deliver goal setting. [ABSTRACT FROM AUTHOR]

The osteoimmune microenvironment induced by implants plays a significant role in bone regeneration. It is essential to efficiently and timely switch the macrophage phenotype from M1 to M2 for optimal bone healing. This study examined the impact of a calcium phosphate (CaP) coating on the physiochemical properties of highly ordered polycaprolactone (PCL) scaffolds fabricated using melt electrowritten (MEW). Additionally, it investigated the influence of these scaffolds on macrophage polarization and their immunomodulation on osteogenesis. The results revealed that the CaP coated PCL scaffold exhibited a rougher surface topography and higher hydrophilicity in comparison to the PCL scaffold without coating. Besides, the surface morphology of the coating and the release of Ca2+ from the CaP coating were crucial in regulating the transition of macrophages from M1 to M2 phenotypes. They might activate the PI3K/AKT and cAMP-PKA pathways, respectively, to facilitate M2 polarization. In addition, the osteoimmune microenvironment induced by CaP coated PCL could not only enhance the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro but also promote the bone regeneration in vivo. Taken together, the CaP coating can be employed to control the phenotypic switching of macrophages, thereby creating a beneficial immunomodulatory microenvironment that promotes bone regeneration. [ABSTRACT FROM AUTHOR]

A high‐salt diet (HSD) elicits sustained sterile inflammation and worsens tissue injury. However, how this occurs after stroke, a leading cause of morbidity and mortality, remains unknown. Here, we report that HSD impairs long‐term brain recovery after intracerebral hemorrhage, a severe form of stroke, despite salt withdrawal prior to the injury. Mechanistically, HSD induces innate immune priming and training in hematopoietic stem and progenitor cells (HSPCs) by downregulation of NR4a family and mitochondrial oxidative phosphorylation. This training compromises alternative activation of monocyte‐derived macrophages (MDMs) without altering the initial inflammatory responses of the stroke brain. Healthy mice transplanted with bone marrow from HSD‐fed mice retain signatures of reduced MDM reparative functions, further confirming a persistent form of innate immune memory that originates in the bone marrow. Loss of NR4a1 in macrophages recapitulates HSD‐induced negative impacts on stroke outcomes while gain of NR4a1 enables stroke recovery in HSD animals. Together, we provide the first evidence that links HSD‐induced innate immune memory to the acquisition of persistent dysregulated inflammatory responses and unveils NR4a1 as a potential therapeutic target. Synopsis: High‐salt intake induces trained immunity through metabolic reprogramming and downregulation of NR4a nuclear receptors. Trained monocyte‐derived macrophages reduce reparative activities in the stroke brain, and consequently, hematoma clearance, brain repair, and functional recovery are impaired.Excessive dietary salt intake impedes long‐term stroke recovery even after high‐salt withdrawal prior to injury.High‐salt intake triggers immunological priming and training of bone marrow progenitor cells.The trained property is retained, which leads to diminished reparative macrophage polarization in the stroke brain.Pharmacological activation of NR4a1 by celastrol treatment rescues the adverse effects induced by high‐salt diet. [ABSTRACT FROM AUTHOR]

The preventive situation of parasitosis, a global public health burden especially for developing countries, is not looking that good. Similar to other infections, vaccines would be the best choice for preventing and controlling parasitic infection. However, ideal antigenic molecules for vaccine development have not been identified so far, resulting from the complicated life history and enormous genomes of the parasites. Furthermore, the suppression or down-regulation of anti-infectious immunity mediated by the parasites or their derived molecules can compromise the effect of parasitic vaccines. Comparing the early immune profiles of several parasites in the permissive and non-permissive hosts, a robust innate immune response is proposed to be a critical event to eliminate the parasites. Therefore, enhancing innate immunity may be essential for designing novel and effective parasitic vaccines. The newly emerging trained immunity (also termed innate immune memory) has been increasingly recognized to provide a novel perspective for vaccine development targeting innate immunity. This article reviews the current status of parasitic vaccines and anti-infectious immunity, as well as the conception, characteristics, and mechanisms of trained immunity and its research progress in Parasitology, highlighting the possible consideration of trained immunity in designing novel vaccines against parasitic diseases. [ABSTRACT FROM AUTHOR]

Pests are one of the most concerning biotic problems in agriculture and food. Humans are constantly in search of new strategies to control them. Traditional strategies like integrated pest management used in agriculture are insufficient, and applying chemical pesticides has adverse effects on animals and human beings in addition to declining soil fertility, pest resistance, elimination of natural enemies, environmental pollution, loss of biodiversity, and human health hazards. Using nanotechnology in pest management as an alternative strategy can be one of the most promising ways to overcome the problems of using conventional chemical pesticides. Although they still face many obstacles and uncertainties and More research is needed to improve their development, evaluation, and regulation, The advantage of nanotechnology as an alternative for the management of insect pests is increasing efficiency against target organisms and low toxicity of nanocides to non-target organisms, highlighting the insufficient collateral environmental damage were reported in this work. It also provides selective, targeted, and long-term-controlled release of formulated nanomaterial, which is ecologically more viable. So, using nanotechnology for insect pest management is considered environmentally sustainable and an excellent insect control strategy in green agriculture. [ABSTRACT FROM AUTHOR]

Phonemic paraphasia, a common characteristic of conduction aphasia, has traditionally been attributed to phonological representation dysfunction. An alternative hypothesis posits that phonemic paraphasia arises from difficulty converting phonemes into their corresponding articulatory maneuvers. However, detailed case studies supporting this theory have been lacking. In this report, we present the case of a 61-year-old right-handed man with right temporo-parietal infarction who exhibited crossed aphasia characterized by typical conduction aphasia symptoms (eg, relatively fluent speech with intact comprehension, frequent phonemic paraphasia, and pronounced difficulties in oral repetition) in the absence of distorted articulation, syllable segmentation, and prosody impairment. Despite the frequent occurrence of phonemic paraphasia and articulatory challenges, our patient's phonological representations remained relatively intact. His phonemic paraphasia was often self-corrected to produce correct responses, a feature known as conduit d'approche. During the oral repetition of individual mora (ie, the smallest unit of speech in Japanese), we observed that the patient consistently traced the corresponding Hiragana phonetic symbol accurately, despite his difficulties in articulation. We substantiated this phenomenon through objective assessment and posit that it resulted from an unusual separation of language functions in crossed aphasia-specifically, a disconnection between phonological representations in the right temporo-parietal cortex and speech articulation engrams in the left hemisphere. In this case of conduction aphasia, articulatory-based phonemic paraphasia may be viewed as an inability to convert phonemes into the appropriate articulatory maneuvers rather than as phonological representation dysfunction or apraxia of speech., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Through the effective targeting of the adaptive immune system, solid organ transplantation became a life-saving therapy for organ failure. However, beyond 1 y of transplantation, there is little improvement in transplant outcomes. The adaptive immune response requires the activation of the innate immune system. There are no modalities for the specific targeting of the innate immune system involvement in transplant rejection. However, the recent discovery of innate allorecognition and innate immune memory presents novel targets in transplantation that will increase our understanding of organ rejection and might aid in improving transplant outcomes. In this review, we look at the latest developments in the study of innate allorecognition and innate immune memory in transplantation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Hydatidosis is a disease caused by the larval stage of Echinococcus granulosus, which involves several organs of intermediate hosts. Evidence suggests a communication between hydatid cyst (HC) and hosts via extracellular vesicles. However, a little is known about the communication between EVs derived from HC fluid (HCF) and host cells. In the current study, EVs were isolated using differential centrifugation from sheep HCF and characterized by western blot, electron microscope and size distribution analysis. The uptake of EVs by human monocyte cell line (THP‐1) was evaluated. The effects of EVs on the expression levels of pro‐ and anti‐inflammatory cytokines were investigated using quantitative real‐time PCR (RT‐PCR), 3 and 24 h after incubation. Moreover, the cytokine level of IL‐10 was evaluated in supernatant of THP‐1 cell line at 3 and 24 h. EVs were successfully isolated and showed spherical shape with size distribution at 130.6 nm. After 3 h, the expression levels of pro‐inflammatory cytokine genes (IL1Β, IL15 and IL8) were upregulated, while after 24 h, the expression levels of pro‐inflammatory cytokines were decreased and IL13 gene expression showed upregulation. A statistically significant increase was seen in the levels of IL‐10 after 24 h. The main mechanism of the communication between EVs derived from HCF and their host remains unclear; however, time‐dependent anti‐inflammatory effects in our study suggest that HC may modulate the immune responses via EVs. [ABSTRACT FROM AUTHOR]

7864 infants were examined within 48 h of birth by junior medical staff; 5 with dislocation, 16 with dislocatable hip, and 25 with joint laxity were referred for abduction splinting. 622 of the infants (7.9%) had minor signs (clicking or grating hip). When these 622 infants underwent clinical and radiological examination at 4 months of age, 34 had serious hip pathology (5 dislocation, 5 dislocatable hip, and 24 radiological abnormalities). Of the 7196 infants considered normal in the newborn period, 7 were referred for orthopaedic opinion (3 with dislocation and 4 with subluxation) at age 2-9 months by general practitioners and community health physicians. Thus, dislocated or dislocatable hips were 39 times more frequent in infants who had minor signs on examination within 48 h of birth than in infants considered normal. The implication of these findings is that clicking and grating of the hip are important signs which require systematic follow-up, with radiological examination at 4-6 months.

Soil-transmitted helminths affect approximately 1.5 billion people worldwide. However, as no vaccine is currently available for humans, the current strategy for elimination as a public health problem relies on preventive chemotherapy. Despite more than 20 years of intense research effort, the development of human helminth vaccines (HHVs) has not yet come to fruition. Current vaccine development focuses on peptide antigens that trigger strong humoral immunity, with the goal of generating neutralizing antibodies against key parasite molecules. Notably, this approach aims to reduce the pathology of infection, not worm burden, with only partial protection observed in laboratory models. In addition to the typical translational hurdles that vaccines struggle to overcome, HHVs face several challenges (1): helminth infections have been associated with poor vaccine responses in endemic countries, probably due to the strong immunomodulation caused by these parasites, and (2) the target population displays pre-existing type 2 immune responses to helminth products, increasing the likelihood of adverse events such as allergy or anaphylaxis. We argue that such traditional vaccines are unlikely to be successful on their own and that, based on laboratory models, mucosal and cellular-based vaccines could be a way to move forward in the fight against helminth infection. Here, we review the evidence for the role of innate immune cells, specifically the myeloid compartment, in controlling helminth infections. We explore how the parasite may reprogram myeloid cells to avoid killing, notably using excretory/secretory (ES) proteins and extracellular vesicles (EVs). Finally, learning from the field of tuberculosis, we will discuss how anti-helminth innate memory could be harnessed in a mucosal-trained immunity-based vaccine. [ABSTRACT FROM AUTHOR]

Cytokines and receptors of the IL-1 family are key mediators in innate immune and inflammatory reactions in physiological defensive conditions, but are also significantly involved in immune-mediated inflammatory diseases. Here, we will address the role of cytokines of the IL-1 superfamily and their receptors in neuroinflammatory and neurodegenerative diseases, in particular Multiple Sclerosis and Alzheimer's disease. Notably, several members of the IL-1 family are present in the brain as tissue-specific splice variants. Attention will be devoted to understanding whether these molecules are involved in the disease onset or are effectors of the downstream degenerative events. We will focus on the balance between the inflammatory cytokines IL-1b and IL-18 and inhibitory cytokines and receptors, in view of future therapeutic approaches. [ABSTRACT FROM AUTHOR]

Osteoradionecrosis of the jaws (ORNJ) is a severe complication that occurs after radiotherapy of head and neck malignancies. Clinically, conservative treatments and surgeries for ORNJ exhibited certain therapeutic effects, whereas the regenerative disorder of the post-radiation jaw remains a pending problem to be solved. In recent years, the recognition of the role of the immune microenvironment has led to a shift from an osteoblasts (OBs) or bone marrow mesenchymal stromal cells (BMSCs)-centered view of bone regeneration to the concept of a complicated microecosystem that supports bone regeneration. Current advances in osteoimmunology have uncovered novel targets within the immune microenvironment to help improve various regeneration therapies, notably therapies potentiating the interaction between BMSCs and immune cells. However, these researches lack a thorough understanding of the immune microenvironment and the interaction network of immune cells in the course of bone regeneration, especially for the post-operative defect of ORNJ. This review summarized the composition of the immune microenvironment during bone regeneration, how the immune microenvironment interacts with the skeletal system, and discussed existing and potential strategies aimed at targeting cellular and molecular immune microenvironment components. [ABSTRACT FROM AUTHOR]

Type 2 immunity mediates protective responses to helminths and pathological responses to allergens, but it also has broad roles in the maintenance of tissue integrity, including wound repair. Type 2 cytokines are known to promote fibrosis, an overzealous repair response, but their contribution to healthy wound repair is less well understood. This review discusses the evidence that the canonical type 2 cytokines, IL-4 and IL-13, are integral to the tissue repair process through two main pathways. First, essential for the progression of effective tissue repair, IL-4 and IL-13 suppress the initial inflammatory response to injury. Second, these cytokines regulate how the extracellular matrix is modified, broken down, and rebuilt for effective repair. IL-4 and/or IL-13 amplifies multiple aspects of the tissue repair response, but many of these pathways are highly redundant and can be induced by other signals. Therefore, the exact contribution of IL-4Rα signaling remains difficult to unravel. [ABSTRACT FROM AUTHOR]

Pathogen infection causes a stereotyped state of sickness that involves neuronally orchestrated behavioural and physiological changes1,2. On infection, immune cells release a ‘storm’ of cytokines and other mediators, many of which are detected by neurons3,4; yet, the responding neural circuits and neuro–immune interaction mechanisms that evoke sickness behaviour during naturalistic infections remain unclear. Over-the-counter medications such as aspirin and ibuprofen are widely used to alleviate sickness and act by blocking prostaglandin E2 (PGE2) synthesis5. A leading model is that PGE2 crosses the blood–brain barrier and directly engages hypothalamic neurons2. Here, using genetic tools that broadly cover a peripheral sensory neuron atlas, we instead identified a small population of PGE2-detecting glossopharyngeal sensory neurons (petrosal GABRA1 neurons) that are essential for influenza-induced sickness behaviour in mice. Ablating petrosal GABRA1 neurons or targeted knockout of PGE2 receptor 3 (EP3) in these neurons eliminates influenza-induced decreases in food intake, water intake and mobility during early-stage infection and improves survival. Genetically guided anatomical mapping revealed that petrosal GABRA1 neurons project to mucosal regions of the nasopharynx with increased expression of cyclooxygenase-2 after infection, and also display a specific axonal targeting pattern in the brainstem. Together, these findings reveal a primary airway-to-brain sensory pathway that detects locally produced prostaglandins and mediates systemic sickness responses to respiratory virus infection.A small population of prostaglandin E2-responsive glossopharyngeal sensory neurons provides a sensory pathway between airway and brainstem that mediates sickness responses to early-phase influenza virus infection. [ABSTRACT FROM AUTHOR]

Innate immune cells can potentiate the response to reinfection through an innate form of immunological memory known as trained immunity. The potential of this fast-acting, nonspecific memory compared to traditional adaptive immunological memory in prophylaxis and therapy has been a topic of great interest in many fields, including infectious diseases. Amidst the rise of antimicrobial resistance and climate change--two major threats to global health--, harnessing the advantages of trained immunity compared to traditional forms of prophylaxis and therapy could be game-changing. Here, we present recent works bridging trained immunity and infectious disease that raise important discoveries, questions, concerns, and novel avenues for the modulation of trained immunity in practice. By exploring the progress in bacterial, viral, fungal, and parasitic diseases, we equally highlight future directions with a focus on particularly problematic and/or understudied pathogens. [ABSTRACT FROM AUTHOR]

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Inflammation is an essential host defense mechanism in response to microbial infection and tissue injury. In addition to its well-established role in infection, inflammation is actively involved in the repair of damaged tissues and restoration of homeostatic conditions after tissue injury. The intensity of the inflammatory response and types of cells involved in inflammation have a significant impact on the quality of tissue repair. Numerous immune cell subtypes participate in tissue repair and regeneration. In particular, immune cell-derived secretants, including cytokines and growth factors, can actively modulate the proliferation of resident stem cells or progenitor cells to facilitate tissue regeneration. These findings highlight the importance of inflammation during tissue repair and regeneration; however, the precise role of immune cells in tissue regeneration remains unclear. In this review, we summarize the current knowledge on the contribution of specific immune cell types to tissue repair and regeneration. We also discuss how inflammation affects the final outcome of tissue regeneration. [ABSTRACT FROM AUTHOR]

We have previously identified an immune modulating peptide, termed FhHDM-1, within the secretions of the liver fluke, Fasciola hepatica, which is sufficiently potent to prevent the progression of type 1 diabetes and multiple sclerosis in murine models of disease. Here, we have determined that the FhHDM-1 peptide regulates inflammation by reprogramming macrophage metabolism. Specifically, FhHDM-1 switched macrophage metabolism to a dependence on oxidative phosphorylation fuelled by fatty acids and supported by the induction of glutaminolysis. The catabolism of glutamine also resulted in an accumulation of alpha ketoglutarate (a-KG). These changes in metabolic activity were associated with a concomitant reduction in glycolytic flux, and the subsequent decrease in TNF and IL-6 production at the protein level. Interestingly, FhHDM-1 treated macrophages did not express the characteristic genes of an M2 phenotype, thereby indicating the specific regulation of inflammation, as opposed to the induction of an anti-inflammatory phenotype per se. Use of an inactive derivative of FhHDM-1, which did not modulate macrophage responses, revealed that the regulation of immune responses was dependent on the ability of FhHDM-1 to modulate lysosomal pH. These results identify a novel functional association between the lysosome and mitochondrial metabolism in macrophages, and further highlight the significant therapeutic potential of FhHDM-1 to prevent inflammation. [ABSTRACT FROM AUTHOR]

Immune response is an important factor in determining the fate of bone replacement materials, in which macrophages play an important role. It is a new idea to design biomaterials with immunomodulatory function to reduce inflammation and promote bone integration by regulating macrophages polarization. In this work, the immunomodulatory properties of CaP Zn-Mn-Li alloys and the specific mechanism of action were investigated. We found that the CaP Zn0.8Mn0.1Li alloy promoted the polarization of macrophages toward M2 and reduced inflammation, which could effectively upregulate osteogenesis-related factors and promote new bone formation, indicating the important role of macrophages polarization in biomaterial induction of osteogenesis. In vivo studies further demonstrated that CaP Zn0.8Mn0.1Li alloy could stimulate osteogenesis better than other Zn-Mn-Li alloys implantations by regulating macrophages polarization and reducing inflammation. In addition, transcriptome results showed that CaP Zn0.8Mn0.1Li played an important regulatory role in the life process of macrophages, activating Toll-like receptor signaling pathway, which participated in the activation and attenuation of inflammation, and accelerated bone integration. Thus, by preparing CaP coatings on the surface of Zn-Mn-Li alloys and combining the bioactive ingredient with controlled release, the biomaterial will be imbibed with beneficial immunomodulatory properties that promote bone integration. [ABSTRACT FROM AUTHOR]

Repairing osteoporotic bone defects is still a major clinical challenge. Recent studies have revealed that immune response is also essential in osteogenesis. The intrinsic inflammatory response of the host, especially the M1/M2 polarization status and inflammatory secretory function of macrophages, can directly affect osteogenic differentiation. Therefore, in this study, an electrospun naringin-loaded microspheres/sucrose acetate isobutyrate (Ng-m-SAIB) system was constructed to investigate its effect on the polarization of macrophage and osteoporotic bone defects. The results of both in vitro and in vivo experiments showed that Ng-m-SAIB had good biocompatibility and could promote the polarization of macrophage toward M2, thereby forming a favorable microenvironment for osteogenesis. The animal experiments also showed that Ng-m-SAIB could promote the osteogenesis of critical size defects in the skull of the osteoporotic model mouse (the senescence-accelerated mouse-strain P6). Together, these results collectively suggested that Ng-m-SAIB might be a promising biomaterial to treat osteoporotic bone defects with favorable osteo-immunomodulatory effects. [ABSTRACT FROM AUTHOR]

Addressing the repair and regeneration of large bone defects poses significant challenges in bone tissue engineering. Despite the abundant evidence demonstrating the positive role of MSCs in osteogenesis, their limited osteogenic differentiation ability still needs to be improved. The present study used lipopolysaccharide (LPS) to enhance the osteogenic properties of ecto-mesenchymal stem cells (EMSCs). Human nasal respiratory mucosa-derived EMSCs were cultured on plates and stimulated with LPS for 5 days prior to undergoing osteogenic differentiation. The findings revealed that LPS effectively stimulated the osteogenic differentiation capacity of EMSCs, as evidenced by heightened alkaline phosphatase activity, elevated expression levels of osteogenic-related proteins and enhanced mineralization of EMSCs. The present study also demonstrated that the augmentation occurred due to increased IL-10 levels, although it was not solely attributable to this factor. Together, the findings illustrated that the LPS-mediated adaptation of EMSCs is an active process driving osteogenic differentiation and could be a novel strategy for bone regeneration. [ABSTRACT FROM AUTHOR]

Aphasia is an impairment of language caused by acquired brain damage such as stroke or traumatic brain injury, that affects a person's ability to communicate effectively. The aim of rehabilitation in aphasia is to improve everyday communication, improving an individual's ability to function in their day-to-day life. For that reason, a thorough understanding of naturalistic communication and its underlying mechanisms is imperative. The field of aphasiology currently lacks an agreed, comprehensive, theoretically founded definition of communication. Instead, multiple disparate interpretations of functional communication are used. We argue that this makes it nearly impossible to validly and reliably assess a person's communicative performance, to target this behaviour through therapy, and to measure improvements post-therapy. In this article we propose a structured, theoretical approach to defining the concept of functional communication. We argue for a view of communication as "situated language use", borrowed from empirical psycholinguistic studies with non-brain damaged adults. This framework defines language use as: (1) interactive, (2) multimodal, and (3) contextual. Existing research on each component of the framework from non-brain damaged adults and people with aphasia is reviewed. The consequences of adopting this approach to assessment and therapy for aphasia rehabilitation are discussed. The aim of this article is to encourage a more systematic, comprehensive approach to the study and treatment of situated language use in aphasia. [ABSTRACT FROM AUTHOR]

Context: Asthma is a common respiratory system disease. Louki Zupa decoction (LKZP), a traditional Chinese medicine, presents a promising efficacy against lung diseases. Objective: To investigate the pathogenic mechanism of asthma and reveal the intervention mechanism of LKZP. Materials and methods: Forty-eight female Balb/c mice were randomly divided into 6 groups: normal control group (NC), ovalbumin (OVA)/saline asthma model group, OVA/LL group, OVA/LM group, OVA/LH group and OVA/DEX group (n = 8 per group). The asthmatic mice were modelled through intraperitoneal injecting and neutralizing OVA. LKZP decoction was administrated by gavage at the challenge stage for seven consecutive days (2.1, 4.2 and 8.4 g/kg/day). We investigated the change in lung function, airway inflammation, mucus secretion and TH-1/TH-2-related cytokines. We further verify the activated status of the IL-33/ST2/NF-κB/GSK3β/mTOR signalling pathway. Results: LKZP was proved to improve asthmatic symptoms, as evidenced by the down-regulated airway resistance by 36%, 58% and 53% (p < 0.01, p < 0.001 vs. OVA/saline group), up-regulated lung compliance by 102%, 114% and 111%, decreased airway inflammation and mucus secretion by 33%, 40% and 33% (p < 0.001 vs. OVA/saline group). Moreover, the content of cytokines in BALF related to airway allergy (such as IgE) and T helper 1/T helper 2 cells (like IL-2, IL-4, IL-5, IL-13, TNF-α and IFN-γ), were also markedly reduced by 13-65% on LKZP intervention groups compared with model group. Mechanistic research revealed that the IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway was activated in the OVA/saline group and LKZP significantly down-regulated this pathway. Discussion and conclusion: LKZP improves lung function, airway inflammation, mucus secretion and correct immune imbalance by intervening with the IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway, presenting a promising therapeutic choice for asthma. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) are immune cells widely distributed in the body, accompanied by diverse phenotypes and functions. Committed mast cell precursors (MCPs) leave the bone marrow and enter the blood circulation, homing to peripheral sites under the control of various molecules from different microenvironments, where they eventually differentiate and mature. Partly attributable to the unique maturation mechanism, MCs display high functional heterogeneity and potentially plastic phenotypes. High plasticity also means that MCs can exhibit different subtypes to cope with different microenvironments, which we call "the peripheral immune education system". Under the peripheral immune education system, MCs showed a new character from previous cognition in some cases, namely regulation of allergy and inflammation. In this review, we focus on the mucosal tissues, such as the gastrointestinal tract, to gain insights into the mechanism underlying the migration of MCs to the gut or other organs and their heterogeneity, which is driven by different microenvironments. In particular, the immunosuppressive properties of MCs let us consider that positively utilizing MCs may be a new way to overcome inflammatory and allergic disorders. [ABSTRACT FROM AUTHOR]