搜索结果：International reviews of immunology

Depression and anxiety disorders are common, and treatment often includes psychological interventions. Digital health interventions, delivered through technologies such as web-based programs and mobile apps, are increasingly used in mental health treatment. Acceptability, the extent to which an intervention is viewed positively, has been identified as contributing to patient adherence and engagement with digital health interventions. Acceptability, therefore, impacts the benefit derived from using digital health interventions in treatment. Understanding the acceptability of digital mental health interventions among patients with depression or anxiety disorders is essential to maximize the effectiveness of their treatment. This review investigated the acceptability of technology-based interventions among patients with depression or anxiety disorders. A systematic review was performed based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and PROSPERO (International Prospective Register of Systematic Reviews) guidelines. We searched PubMed, Web of Science, and Ovid in May 2022. Studies were included if they evaluated digital interventions for the treatment of depression or anxiety disorders and investigated their acceptability among adult patients. Studies were excluded if they targeted only specific populations (eg, those with specific physical health conditions), investigated acceptability in healthy individuals or patients under the age of 18 years, involved no direct interaction between patients and technologies, used technology only as a platform for traditional care (eg, videoconferencing), had patients using technologies only in clinical or laboratory settings, or involved virtual reality technologies. Acceptability outcome data were narratively synthesized by the direction of acceptability using vote counting. Included studies were evaluated using levels of evidence from the Oxford Centre for Evidence-Based Medicine. The risk of bias was assessed using a tool designed for this review and GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). A total of 143 articles met the inclusion criteria, comprising 67 (47%) articles on interventions for depression, 65 (45%) articles on interventions for anxiety disorders, and 11 (8%) articles on interventions for both. Overall, 90 (63%) were randomized controlled trials, 50 (35%) were other quantitative studies, and 3 (2%) were qualitative studies. Interventions used web-based programs, mobile apps, and computer programs. Cognitive behavioral therapy was the basis of 71% (102/143) of the interventions. Digital mental health interventions were generally acceptable among patients with depression or anxiety disorders, with 88% (126/143) indicating positive acceptability, 8% (11/143) mixed results, and 4% (6/143) insufficient information to categorize the direction of acceptability. The available research evidence was of moderate quality. Digital mental health interventions seem to be acceptable to patients with depression or anxiety disorders. Consistent use of validated measures for acceptability would enhance the quality of evidence. Careful design of acceptability as an evaluation outcome can further improve the quality of evidence and reduce the risk of bias. Open Science Framework Y7MJ4; https://doi.org/10.17605/OSF.IO/SPR8M.

Using cytotoxic CD8+ T cell-mediated cellular immunity has shown considerable efficacy in cancer treatment. However, the effectiveness of these cells against solid tumors is limited by the presence of an immunosuppressive tumor microenvironment (TME), which constitutes complex networks of regulatory pathways and resistance mechanisms. Given its critical role in TME deterioration through shedding of immunosuppressive molecules from tumor and immune cell surfaces, the upregulation of A Disintegrin and Metalloproteinase 10 (ADAM10) expression can reinforce CD8+ T cells into a state of exhaustion. This paper highlights the influence of ADAM10 and its proteolytic products on the primary pathways of CD8+ T cell exhaustion, including the expression of immune checkpoint molecules and modification across CD8+ T cell transcriptional, metabolic, and nutritional states. We remain optimistic about the critical role of ADAM10 in cytokine-induced T cell exhaustion, recruitment of immunosuppressive cells into the TME, and CD8+ T cell death/survival. Gaining significant insights into these processes may offer new strategies to advance CD8+ T cell-mediated cancer therapy. In solid tumors, the presence of an immunosuppressive tumor microenvironment (TME) inhibits the effectiveness of cytotoxic CD8+ T cell therapy.The TME upregulates ADAM10 expression, which may impair CD8+ T cell cytotoxic functions and lead to a state of exhaustion by shedding numerous soluble immunosuppressive molecules.This paper explores the influence of ADAM10 and its proteolytic products on the primary pathways of CD8+ T cell exhaustion, including the expression of immune checkpoint molecules and alterations in CD8+ T cell transcriptional, metabolic, and nutritional states. Furthermore, it considers the critical role of ADAM10 in cytokine-induced T cell exhaustion, immunosuppressive cell recruitment, and CD8+ T cell death/survival.Understanding the mechanism of ADAM10-mediated shedding may offer new strategies to advance CD8+ T cell-mediated cancer therapy and mitigate exhaustion in the TME.

Atheroma formation is initiated by the activation of endothelial and smooth muscle cells, as well as immune cells, including neutrophils, lymphocytes, monocytes, macrophages, and dendritic cells. Monocytes, macrophages, and neutrophils are the innate immune cells that provide a rapid initial line of defence against vascular disease. These cells have a short lifespan and cannot retain memories, making them potential therapeutic targets for the inflammatory process associated with atherosclerosis. In addition, macrophages comprise the majority of vessel wall infiltrates and are, therefore, implicated in all stages of atherosclerosis progression. Neutrophils are the most common type of leukocyte found in circulation, and their high levels of matrix-degrading protease explain their significance in fibrous cap destabilization. However, the activation of immune cells becomes more complex by various microenvironmental stimuli and cytokines, which ultimately transform immune cells into their pro-inflammatory state. Different types of macrophage subsets with distinct functions in inflammation, such as M1 macrophages, cause an increase in pro-inflammatory cytokines and produce reactive oxygen species and nitric oxide, further worsening the disease. This review aims to shed light on immune-mediated inflammation in cardiovascular disease by focusing on the role of macrophage subsets in vascular inflammation and plaque stability, as well as the interaction between neutrophils and monocyte-macrophages. Cardiovascular disease is a leading cause of global mortality. The onset of this condition frequently occurs due to vascular inflammation, which can be initiated at an early age. The body’s immune system, specifically phagocytic cells such as monocytes, macrophages, and neutrophils, significantly contributes to this process. These cells typically aid in combating infections, but they can also cause complications in our blood vessels, ultimately resulting in heart disease.Our review examines the role of these immune cells in the formation of plaques in our arteries, a condition called atherosclerosis that can result in heart attacks and strokes. Macrophages are a cellular type that engulfs and digests harmful cholesterol in our blood vessels. However, they can become overwhelmed and transform into foam cells, which play a significant role in the formation of these hazardous plaques. Neutrophils, a different category of immune cells, might exacerbate the condition by increasing the likelihood of plaque rupture, leading to a heart attack. Additionally, we discuss the varying behaviours of these cells in response to signals from their environment, which can either exacerbate or alleviate inflammation, alongside the existing anti-inflammatory strategies aimed at reducing inflammation associated with immune responses. A more profound understanding of these mechanisms may pave the way for identifying innovative treatment or prevention strategies for heart disease, specifically targeting these cells and their functions.Essentially, our bodies’ protective mechanisms can occasionally malfunction and result in the development of cardiac disease. Gaining further knowledge about this issue can facilitate the development of novel therapies to maintain the optimal functioning of our cardiovascular system.

Cancer is a leading cause of death globally. Accurate cancer burden information is crucial for policy planning, but many countries do not have up-to-date cancer surveillance data. To inform global cancer-control efforts, we used the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework to generate and analyse estimates of cancer burden for 47 cancer types or groupings by age, sex, and 204 countries and territories from 1990 to 2023, cancer burden attributable to selected risk factors from 1990 to 2023, and forecasted cancer burden up to 2050. Cancer estimation in GBD 2023 used data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Cancer mortality was estimated using ensemble models, with incidence informed by mortality estimates and mortality-to-incidence ratios (MIRs). Prevalence estimates were generated from modelled survival estimates, then multiplied by disability weights to estimate years lived with disability (YLDs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the GBD standard life expectancy at the age of death. Disability-adjusted life-years (DALYs) were calculated as the sum of YLLs and YLDs. We used the GBD 2023 comparative risk assessment framework to estimate cancer burden attributable to 44 behavioural, environmental and occupational, and metabolic risk factors. To forecast cancer burden from 2024 to 2050, we used the GBD 2023 forecasting framework, which included forecasts of relevant risk factor exposures and used Socio-demographic Index as a covariate for forecasting the proportion of each cancer not affected by these risk factors. Progress towards the UN Sustainable Development Goal (SDG) target 3.4 aim to reduce non-communicable disease mortality by a third between 2015 and 2030 was estimated for cancer. In 2023, excluding non-melanoma skin cancers, there were 18·5 million (95% uncertainty interval 16·4 to 20·7) incident cases of cancer and 10·4 million (9·65 to 10·9) deaths, contributing to 271 million (255 to 285) DALYs globally. Of these, 57·9% (56·1 to 59·8) of incident cases and 65·8% (64·3 to 67·6) of cancer deaths occurred in low-income to upper-middle-income countries based on World Bank income group classifications. Cancer was the second leading cause of deaths globally in 2023 after cardiovascular diseases. There were 4·33 million (3·85 to 4·78) risk-attributable cancer deaths globally in 2023, comprising 41·7% (37·8 to 45·4) of all cancer deaths. Risk-attributable cancer deaths increased by 72·3% (57·1 to 86·8) from 1990 to 2023, whereas overall global cancer deaths increased by 74·3% (62·2 to 86·2) over the same period. The reference forecasts (the most likely future) estimate that in 2050 there will be 30·5 million (22·9 to 38·9) cases and 18·6 million (15·6 to 21·5) deaths from cancer globally, 60·7% (41·9 to 80·6) and 74·5% (50·1 to 104·2) increases from 2024, respectively. These forecasted increases in deaths are greater in low-income and middle-income countries (90·6% [61·0 to 127·0]) compared with high-income countries (42·8% [28·3 to 58·6]). Most of these increases are likely due to demographic changes, as age-standardised death rates are forecast to change by -5·6% (-12·8 to 4·6) between 2024 and 2050 globally. Between 2015 and 2030, the probability of dying due to cancer between the ages of 30 years and 70 years was forecasted to have a relative decrease of 6·5% (3·2 to 10·3). Cancer is a major contributor to global disease burden, with increasing numbers of cases and deaths forecasted up to 2050 and a disproportionate growth in burden in countries with scarce resources. The decline in age-standardised mortality rates from cancer is encouraging but insufficient to meet the SDG target set for 2030. Effectively and sustainably addressing cancer burden globally will require comprehensive national and international efforts that consider health systems and context in the development and implementation of cancer-control strategies across the continuum of prevention, diagnosis, and treatment. Gates Foundation, St Jude Children's Research Hospital, and St Baldrick's Foundation.

Before the availability of biologic therapies, the main treatment for patients with severe asthma in Asia, Latin America, and the Middle East was oral corticosteroids (OCS), despite long-term use causing serious adverse effects. This post hoc analysis of the NUCALA Effectiveness Study (NEST) evaluated the effectiveness of mepolizumab, an anti-interleukin-5 monoclonal antibody, in patients with severe asthma and OCS dependence from regions with limited representation in real-world studies. NEST was a multicountry, observational cohort study in adults with severe asthma from Colombia, Chile, India, Türkiye, Saudi Arabia, United Arab Emirates, Kuwait, Oman, and Qatar. Patients received ≥ 1 dose of 100 mg mepolizumab. OCS dependence was defined as receiving maintenance OCS at mepolizumab initiation or for ≥ 26 weeks during the 12 months prior. Data were collected 12 months pre- and post-initiation. Outcomes included OCS use, rate of clinically significant exacerbations (CSEs), and level of asthma symptom control. Of 524 patients with OCS use data, 58.4% (n = 306) had OCS dependence pre-initiation. Mean (standard deviation) age was 49.2 (13.4) years; 73.9% (n = 226) were women. Of 251 patients with available data, 87.6% (n = 220) received lower OCS doses post-initiation and 68.9% (n = 173) stopped OCS use altogether. CSEs were reduced by 76.9% post-initiation. Of 222 patients with available data, 72.5% (n = 161) had improvements in Asthma Control Test scores post-initiation. In patients with severe asthma and OCS dependence from the countries studied, mepolizumab reduced OCS use and dose, asthma exacerbations, and improved symptom control. Severe asthma is a long-term disorder of the lungs. Symptoms can be difficult to control, despite treatment. Asthma treatment can differ depending on the healthcare services and treatments available, with some countries having more extensive research and access to asthma medications than others. People with severe asthma often receive high doses of oral corticosteroids (OCSs) over prolonged time periods which can cause side effects and affect quality of life. Mepolizumab is a medication used to treat severe asthma. Studies show that mepolizumab treatment can reduce the use of OCS, as well as the risk of major asthma attacks, and improve control of symptoms. The NUCALA Effectiveness Study was carried out to see how well mepolizumab works in real-life clinical practice for treatment of severe asthma in patients living in Colombia, Chile, India, Türkiye, Saudi Arabia, United Arab Emirates, Kuwait, Oman, and Qatar. Here, we looked at how effective mepolizumab was at reducing OCS use for people who required OCS consistently before they started taking mepolizumab (OCS dependence). We found that fewer people relied on OCS following mepolizumab treatment, with nearly 90% receiving a lower dose following treatment with mepolizumab. Almost 70% of these people had their dose reduced entirely so they no longer needed OCS. Additionally, mepolizumab treatment significantly reduced the number of major asthma attacks people experienced and led to better asthma symptom management. These results suggest that mepolizumab could be beneficial for people with severe asthma, in regions where asthma symptoms and the use of OCS are high.

Despite advancements in breast cancer treatment, therapeutic resistance, and tumor recurrence continue to pose formidable challenges. Therefore, a deep knowledge of the intricate interplay between the tumor and the immune system is necessary. In the pursuit of combating breast cancer, the awakening of antitumor immunity has been proposed as a compelling avenue. Tumor stroma in breast cancers contains multiple stromal and immune cells that impact the resistance to therapy and also the expansion of malignant cells. Activating or repressing these stromal and immune cells, as well as their secretions can be proposed for exhausting resistance mechanisms and repressing tumor growth. NK cells and T lymphocytes are the prominent components of breast tumor immunity that can be triggered by adjuvants for eradicating malignant cells. However, stromal cells like endothelial and fibroblast cells, as well as some immune suppressive cells, consisting of premature myeloid cells, and some subsets of macrophages and CD4+ T lymphocytes, can dampen antitumor immunity in favor of breast tumor growth and therapy resistance. This review article aims to research the prospect of harnessing the power of drugs, adjuvants, and nanoparticles in awakening the immune reactions against breast malignant cells. By investigating the immunomodulatory properties of pharmacological agents and the synergistic effects of adjuvants, this review seeks to uncover the mechanisms through which antitumor immunity can be triggered. Moreover, the current review delineates the challenges and opportunities in the translational journey from bench to bedside. Breast cancer is a formidable opponent, partly because it can create a protective environment that shields itself from the body’s immune system. To counter this, scientists have been developing various strategies to enhance the immune system’s ability to fight back. In this comprehensive review article, researchers have outlined several innovative approaches to boost antitumor immunity within the breast tumor microenvironment. One of the primary methods discussed is the use of immune checkpoint blockers. These are drugs that help immune cells recognize and attack cancer cells more effectively. The review also looks at other substances, including drugs, natural products, and also designed nanoparticles, that can help restore the strength and function of immune cells like CD8+ T lymphocytes and Natural Killer cells. These cells are crucial in the body’s defense against tumors, and by enhancing their activity, they can better locate and destroy cancer cells. It also considers the importance of reducing the number of immunosuppressive cells, such as Regulatory T cells, Myeloid-Derived Suppressor Cells, Tumor-Associated Macrophages, and Cancer-Associated Fibroblasts. These cells typically work to protect the tumor by weakening the immune response, so finding ways to deplete them could tip the scales in favor of the immune system. Additionally, the review addresses the challenging conditions within the tumor itself, such as low-oxygen levels and changes in metabolism that result in increased acidity. These factors can create a hostile environment for immune cells, so altering these conditions could make the tumor more vulnerable to an immune attack. In essence, the review provides a detailed examination of the current landscape and future possibilities for empowering the immune system in its battle against breast cancer.

Cerebral malaria (CM) is a life-threatening neurological complication of Plasmodium falciparum infection characterized by excessive inflammation, blood-brain barrier (BBB) disruption, and immune dysregulation. Macrophage-mediated inflammatory responses play a central role in CM pathogenesis, where imbalanced activation contributes to disease progression and tissue damage. However, integrated analyses combining macrophage surface phenotyping with transcriptional profiling remain limited, restricting comprehensive understanding of immune modulation during CM. To investigate the prophylactic immunomodulatory effects of MSCs administration in experimental CM and evaluate its impact on splenic macrophage responses. C57BL/6 mice infected with Pb.ANKA received intravenous MSC administration on the day of infection and were monitored for parasitemia and survival. BBB integrity was assessed using Evans blue extravasation, and brain pathology was evaluated histologically. MSC biodistribution was analyzed using near-infrared labeling. Macrophage polarization in F4/80+CD11b+ splenic cells was assessed by flow cytometry using M1 markers (CD86, CD38) and M2 markers (CD163, CD206, EGR-2). Gene expression of macrophage-associated markers (iNOS-2, Arginase-1, FPR-1, GPR-18, PTGES-2, EGR-2) was analyzed by quantitative real-time PCR. MSC administration reduced parasitemia, improved survival, preserved BBB integrity, and attenuated brain pathology. MSCs showed systemic distribution, suggesting peripheral immune modulation. Flow cytometry revealed reduced M1 markers with maintained or enhanced M2 markers. Gene expression showed downregulation of iNOS-2 and upregulation of Arginase-1, EGR-2, GPR-18, FPR-1, and PTGES-2, indicating macrophage reprogramming toward a balanced M1/M2 continuum. MSC administration mitigates disease severity in experimental CM by modulating macrophage polarization, promoting a balanced M1/M2 response, attenuating inflammatory pathways, and preserving BBB integrity. Malaria is a serious infectious disease that can cause severe complications, including harmful inflammation in the brain, known as cerebral malaria. Among innate immune cells, macrophages are the first line of defense of the immune system, are key players during inflammation. Macrophages can adopt different “states”: the M1 state is highly inflammatory and can cause tissue damage, while the M2 state is more protective and helps in healing. In severe malaria, the balance between these states is disrupted, leading to excessive inflammation. In this study, we explored whether mesenchymal stem cells (MSCs), a type of stem cell known for their immune-regulating properties, could help restore this balance. Using an experimental malaria mouse model infected with Plasmodium berghei ANKA, we examined macrophage behavior at both the surface marker protein and gene expression levels. We found that MSCs actively reprogram macrophages toward more balancing M1/M2 phenotypic continumm by reducing the expression of M1 markers such as CD86, CD38, and iNOS-2, while increasing M2-associated markers including CD163, Arginase-1 along with macrophage associated gene marker EGR-2, and PTGES-2, with a notable exception of FPR-1. This reprogramming led to tangible benefits: mice treated with MSCs showed lower levels of parasites in their blood (reduced parasitemia), improved survival, and reduced inflammatory responses. In addition, MSCS administration helped to protect the brain by preserving the blood–brain barrier integrity and reducing central nervous system (CNS) pathology associated with cerebral malaria. Overall, our findings highlight the potential of MSCs as an immunomodulatory strategy for severe malaria. By reshaping macrophage activity and controlling excessive inflammation, MSCS administration may offer a promising strategy to improve disease outcomes in malaria and other inflammatory diseases.

Macrophages are the primary targets of mycobacterial infection, which plays crucial roles both in nonspecific defence (innate immunity) as well as specific defence mechanisms (adaptive immunity) by secreting various cytokines, antimicrobial mediators and presenting antigens to T-cells. Sequencing of the mycobacterial genome revealed that 10% of its coding ability is devoted to the Pro-Glu motif-containing (PE) and Pro-Pro-Glu motif-containing (PPE) family proteins. While the function of most of the genes belonging to the PE-PPE family initially remained unannotated, recent studies have shown that many proteins of this family play critical roles in bacterial growth and cell functions, and manipulation of host immune responses, indicating their potential roles in mycobacterial virulence. In this review, we have focussed on describing the immunological importance of particularly the PE group of proteins in the context of 'virulence' determinants and outcome of tuberculosis disease. Additionally, we have discussed about the roles of these proteins on host-pathogen-interaction and how some of these genes can be targeted which may help us in designing effective anti-TB therapeutics. Macrophages are key players in the body’s defence against tuberculosis (TB), acting as both the initial line of defence and a communicator to initiate the adaptive immune responses. These cells act like security guards, gobbling up germs and sounding alarms to bring in backup. They also help train other immune cells to recognize and fight the specific germs causing health trouble. Macrophages help to fight against infection either by phago-lysosomal killing or by releasing various substances that kill the bacteria. They also present fragments of the bacteria to T-cells. The TB bacteria, known as Mycobacterium tuberculosis, has evolved clever ways to survive and thrive inside the body for many months to decades. A large part of its survival kit involves a group of proteins called PE and PPE. These proteins help the bacteria to grow, function, and trick innate as well as adaptive immune system. This review highlights how PE/PE-PPE proteins, modulate/manipulate different immune functions of macrophages and play a crucial role in bacterial pathogenesis which is important to develop therapeutic strategies to control the TB pandemic in a more effective manner.

Hospital discharge codes can be used to identify possible Adverse Events of Special Interest (AESI) following COVID-19 vaccinations. We sought to estimate the positive predictive value (PPV) and level of certainty of ICD-10-AM and SNOMED coding for meeting Brighton Collaboration case definitions of AESIs in Aotearoa, New Zealand. Our expert panel identified 24 ICD-10-AM codes and 2 SNOMED codes expected to identify 9 AESIs. We sought codes likely to be specific rather than sensitive. Medical record reviews were conducted by an experienced coder, adjudicated by medical specialists, for the level of certainty that each case met the target case definition. Admissions coded to an explicit alternative diagnosis were classified as Not a Case. Our data covered over 3 million people. Reviews were conducted on 761 medical records, randomly selected from admissions principally in calendar years 2016 to 2019. We report the PPV of each code with respect to its level of certainty of meeting the case definition. Only Guillain-Barré had a single code specific to a single AESI. Several neurological conditions had overlapping codes, conditions and case definitions. PPVs for individual codes to meet case definitions ranged from 11% to 100%. Level of certainty of each code and PPV are specified. PPVs of codes for each AESI need to be assessed on a case-by-case basis. Many codes are arguably insufficiently 'accurate' to identify a target AESI. We did not assess PPVs for combinations of codes. Our method did not allow us to estimate the number of cases missed by the coding.

Osteoporosis is a skeletal disease that affects the microarchitecture and mineralization of the bone, reduces bone strength, and lowers bone mineral density (BMD). Post-menopausal osteoporosis (PMO), caused by estrogen deficiency, is the most common type of osteoporosis. Given the chronic nature of PMO, sustained prevention or treatment with targeted bone-specific therapies and comprehensive medical management is crucial. Long-term usage of bone-specific pharmaceutical treatment therapies that include osteoanabolic and anti-resorptive drugs has sparked questions about side effects and possible rebound occurrences following treatment termination. Therefore, new therapy approaches with fewer side effects are needed. Studies in the past decade have demonstrated that immunological factors are crucial in the onset and progression of PMO. Treg and Th17 cells have long been recognized as critical factors in maintaining bone homeostasis, mainly via regulating osteoclast differentiation. However, astonishing data from our recent studies have highlighted the significant role of Breg and Th9 cells in bone homeostasis regulation. Breg and Th9 cells directly influence the development of bone cells and also regulate the Treg-Th17 cell balance to maintain skeletal integrity. We propose that although the Treg-Th17 cell axis is undeniably important in the pathophysiology of osteoporosis, the dynamic interplay between Breg-Treg and Th9-Th17 cells may play an even more pivotal role. This broader immune network likely exerts a greater influence on bone homeostasis and the progression of osteoporosis. However, the interplay between Breg-Treg vs Th9-Th17 cell axis in PMO remains limited. This review summarizes the most recent developments regarding the Breg-Treg vs Th9-Th17 cell axis in PMO and discusses the potential novel therapeutic strategies to address this issue. Novel pathophysiological insights into the Breg-Treg-Th9-Th17 cell axis in bone metabolism may pave the way for improved diagnosis and transformative treatments for PMO. Postmenopausal osteoporosis (PMO) is the most common bone condition, affecting more than 500 million people globally. The immune system plays a pivotal role in the pathogenesis of PMO, with Tregs and Th17 cells being the most extensively studied. However, emerging research has highlighted the involvement of Bregs and Th9 cells in modulating the Treg–Th17 axis to maintain bone homeostasis. This suggests the existence of a broader immunoregulatory network, comprising Bregs, Tregs, Th9, and Th17 cells in the regulation and maintenance of bone health. Despite its relevance, the Breg-Treg-Th9-Th17 axis is still poorly known. In this review, we have provided thorough information about this crucial axis in the PMO. Further, we have discussed the role of currently available therapeutics in mitigating bone loss by maintaining this critical axis, along with several novel immunotherapeutic targets that could be leveraged for the prevention and management of PMO.

Aluminum salt-based adjuvants like alum, alhydrogel and Adju-Phos are by far the most favored clinically approved vaccine adjuvants. They have demonstrated excellent safety profile and currently used in vaccines against diphtheria, tetanus, pertussis, hepatitis B, anthrax etc. These vaccinations cause minimal side effects like local inflammation at the injection site. Aluminum salt-based adjuvants primarily stimulate CD4+ T cells and B cell mediated Th2 immune response leading to generate a robust antibody response. In this review article, we have compiled the role of physio-chemical role of the two commonly used aluminum salt-based adjuvants alhydrogel and Adju-Phos, and the effect of surface properties, buffer composition, and adjuvant dosage on the immune response. After being studied for almost a century, researchers have come up with various mechanism by which these aluminum adjuvants activate the immune system. Firstly, we have covered the initial works of Glenny and his "repository effect" which paved the work for his successors to explore the involvement of cytokines, chemokines, recruitment of innate immune cells, enhanced antigen uptake by antigen presenting cells, and formation of NLRP3 inflammasome complex in mediating the immune response. It has been reported that aluminum adjuvants activate multiple immunological pathways which synergistically activates the immune system. We later discuss the recent developments in nanotechnology-based preparations of next generation aluminum based adjuvants which has enabled precise size control and morphology of the traditional aluminum adjuvants thereby manipulating the immune response as per our desire. Aluminum salt adjuvants like alum, aluminum hydroxide gel, and aluminum phosphate have been regularly used in vaccine formulations to potentiate the immune response. Despite being discovered nearly a century ago by Alexander Glenny, the cellular and molecular mechanism behind the working of these adjuvants is still elusive. In this article, we review the advances made in understanding the mechanism of action of these adjuvants. Firstly, we cover the “repository theory” put forward by Glenny, and gradually review the role of innate and adaptive immune cells, immune complexes, and different immunological pathways in aluminum adjuvant orchestrated immune response. We also take a dig into the role of physio-chemical parameters like surface properties, buffer composition and adjuvant dosage of aluminum adjuvants in eliciting an immune response. Finally, we discuss the advances made by nano-preparations of aluminum adjuvants and their diverse physio-chemical properties as well as hypothesize their probable mechanism of action.

Studies in murine experimental models have made significant contributions to the understanding of asthma pathophysiology and the discovery of innovative therapeutic approaches. Nonetheless, there is a plethora of options available for selecting mouse strains, sensitization methods, challenge routes and doses, as well as approaches to evaluating host response in murine asthma model protocols. Due to the diversity of models employed, comparing results across different studies proves exceedingly challenging. The study conducted a search of pertinent PubMed articles from 2022 to April 15th, 2024. After relevant publications had been selected, the characteristics of each study were extracted, including animal strains, animal sex, sensitization methods, challenge methods, and reported outcome measures. The modeling parameters of Ovalbumin (OVA)-induced asthma model, and House Dust Mite-induced asthma model were analyzed. Additionally, we extracted data on the dose of OVA sensitization, alum administration, challenge OVA dose, and alum/sensitization OVA ratio from seven included studies. Subsequently, we conducted an analysis to determine the correlation between each of these factors and the lung resistance index (RI). This study presents an overview of the current mouse asthma models, offering valuable methodological guidance for researchers. Furthermore, this study highlights that certain parameters like sensitization dose, challenge dose, and so on, exert specific effects on the asthma lung resistance. However, there is a lack of standardized criteria and guidelines in this regard. The effects and underlying mechanisms of parameters on asthma responses remain unclear, necessitating further investigation into model parameters. Researchers have gained a wealth of knowledge about asthma through mouse studies, but the various methods used to establish asthma models make it difficult to compare results. We examined researches from 2022 to 2024 and reviewed different mouse asthma models in order to understand how factors such as the type of mouse, allergen exposure method, and dosage can impact study outcomes. Common models were analyzed, including those using egg protein (OVA) or house dust mite (HDM) as triggers for asthma. The study revealed that details like allergen dosage and exposure method can significantly influence results, making comparisons between studies challenging. This highlights the need for greater standardization in these models to improve our understanding of asthma and test new treatments.

Because of numerous stress signals, intracellular protein complexes are called inflammasomes. They function as catalysts for the proteolytic transformation of pro-interleukin into the active form of interleukin. Inflammasomes can promote a type of cell death process known as pyroptosis. The NLRP3 inflammasome, comprised of the NLRP3 protein, procaspase-1, and ASC, tightly regulates inflammation. The NLRP3 inflammasome is activated by a variety of stimuli, and several molecular and cellular events, such as ion influx, mitochondrial dysfunction, reactive oxygen species production, and lysosomal damage have been shown to trigger its activation. Inflammation plays a major role in almost all types of human diseases. The NLRP3 inflammasome has been the most widely studied and plays an important pathogenic role in various inflammatory pathologies. This review briefly presents the basic features of NLRP3 inflammasome and their mechanisms of activation and regulation. In addition, recent studies report the role of NLRP3 inflammasome in several diseases have been summarized. Because of numerous stress signals, intracellular protein complexes are called inflammasomes. They function as catalysts for the proteolytic transformation of pro-interleukin into the active form of interleukin. Inflammasomes can promote a type of cell death process known as pyroptosis. The NLRP3 inflammasome, comprised of the NLRP3 protein, procaspase-1, and ASC, tightly regulates inflammation. The NLRP3 inflammasome is activated by a variety of stimuli, and several molecular and cellular events, such as ion influx, mitochondrial dysfunction, reactive oxygen species production, and lysosomal damage, have been shown to trigger its activation. Also, NLRP3 inflammasome plays a role in several different diseases.

Analyses of the association between circulating inflammatory cytokine levels and polymyositis (PM) remains challenging because of the limitations of traditional observational studies. Therefore, we used Mendelian randomization (MR) to assess the causal relationship between the levels of 41 circulating inflammatory cytokines and the risk of PM. Using pooled data from genome-wide association studies (GWASs), we performed two-way MR analyses on two individual samples containing data for circulating inflammatory modulators (n = 8,186) and PM (n = 213,264) in patients of European ancestry. We used a random-effects inverse variance-weighted (IVW) method for our primary analysis and performed sensitivity and multiplicity analyses using MR-Egger, weighted-median, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran's Q tests. The results showed that decreased circulating levels of granulocyte colony stimulating factor (GCSF) were associated with an increased risk of PM with an odds ratio (OR) of 0.31 (95% confidence interval [CI]: 0.13-0.74, p = 0.009). PM was also associated with increased circulating levels of interleukin (IL)-13 and IL-7, with OR values of 1.03 (95% CI = 1.01-1.06, p = 0.012) and 1.03 (95% CI = 1.01-1.06, p = 0.018), respectively, and decreased circulating levels of IL-1RA (OR, 0.97; 95% CI: 0.94-0.99, p = 0.040). These findings suggest that GCSF plays an important role in the pathogenesis of PM and that PM also affects the expression of the cytokines IL-13, IL-7, and IL-1RA. Further studies are required to determine whether these biomarkers can be used to prevent or treat PM.

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by excessive production of type I interferons (IFNs) and autoantibodies with limited effective clinical treatments. Solute carrier family 15 member 4 (SLC15A4), a proton-coupled oligopeptide transporter, facilitates the transmembrane transport of L-histidine and some di- and tripeptides from the lysosome to the cytosol. A growing body of evidence has elucidated the critical role of SLC15A4 in pathogenesis and disease progression of SLE. Genome-wide association studies have identified SLC15A4 as a new susceptibility locus of SLE. Further mechanistical studies have demonstrated that SLC15A4 involves in the production of type I IFNs in plasmacytoid dendritic cells (pDCs) and its necessity in B cells for autoantibody production in lupus models. These studies strongly support the potential of SLC15A4 as a promising therapeutic target for SLE. This review aims to summarize recent advances in understanding the role of SLC15A4 in disease progression of SLE and the development of SLC15A4-targeted inhibitors as well as discuss its potential as a target for SLE treatment. Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by excessive production of type I interferons (IFNs) in the body and the presence of self-targeting antibodies. Current treatments for SLE are not very effective, highlighting the need for novel therapeutic approaches. Solute carrier family 15 member 4 (SLC15A4) is a lysosomal protein that helps transport of L-histidine and some di- and tripeptides from the lysosome to the cytosol. Recent research has investigated the role of SLC15A4 in the development and progression of SLE, identifying it as a key player in disease mechanisms. Genetic studies have also identified SLC15A4 as a gene that may contribute to susceptibility to SLE. Further research has shown that SLC15A4 is involved in the production of specific substances in certain cells and is necessary for the production of self-targeting antibodies in mouse models of lupus. These findings suggest that targeting SLC15A4 could be a potential approach for developing new therapies for SLE. This review article aims to summarize recent findings regarding the role of SLC15A4 in the development and progression of SLE and discuss the potential of developing drugs that specifically target SLC15A4 as a treatment for this challenging autoimmune disease.

Innate lymphoid cells (ILCs) have emerged as pivotal players in the field of immunology, expanding our understanding of innate immunity beyond conventional paradigms. This comprehensive review delves into the multifaceted world of ILCs, beginning with their serendipitous discovery and traversing their ontogeny and heterogeneity. We explore the distinct subsets of ILCs unraveling their intriguing plasticity, which adds a layer of complexity to their functional repertoire. As we journey through the functional activities of ILCs, we address their role in immune responses against various infections, categorizing their interactions with helminthic parasites, bacterial pathogens, fungal infections, and viral invaders. Notably, this review offers a detailed examination of ILCs in the context of specific infections, such as Mycobacterium tuberculosis, Citrobacter rodentium, Clostridium difficile, Salmonella typhimurium, Helicobacter pylori, Listeria monocytogenes, Staphylococcus aureus, Pseudomonas aeruginosa, Influenza virus, Cytomegalovirus, Herpes simplex virus, and severe acute respiratory syndrome coronavirus 2. This selection aimed for a comprehensive exploration of ILCs in various infectious contexts, opting for microorganisms based on extensive research findings rather than considerations of virulence or emergence. Furthermore, we raise intriguing questions about the potential immune functional resemblances between ILCs and epithelial cells, shedding light on their interconnectedness within the mucosal microenvironment. The review culminates in a critical assessment of the therapeutic prospects of targeting ILCs during infection, emphasizing their promise as novel immunotherapeutic targets. Nevertheless, due to their recent discovery and evolving understanding, effectively manipulating ILCs is challenging. Ensuring specificity and safety while evaluating long-term effects in clinical settings will be crucial. Innate lymphoid cells (ILCs) are fascinating components of our immune system, akin to superheroes unveiling the body’s defense mysteries. This comprehensive review delves into their journey, from a chance discovery to unraveling the intricate tapestry of their development and diversity. Exploring various ILC types, the narrative highlights their remarkable adaptability, adding a layer of complexity to their functions.As we navigate the terrain of ILCs’ contributions, the focus extends to their pivotal roles in immune responses against diverse infections. The review sheds light on their role in specific infections. Notably, attention is drawn to their potential cooperation with epithelial cells in safeguarding the body, unveiling interconnected dynamics within the mucosal environment.Concluding the exploration, the review critically examines the therapeutic potential of targeting ILCs during infections. Despite promising avenues, the intricate nature of ILCs poses challenges in their manipulation, necessitating a careful balance between specificity, safety, and consideration of long-term effects in clinical applications.

Advanced schistosomiasis, the most severe stage of Schistosoma japonicum infection, profoundly impairs patients' quality of life (QoL) and increases vulnerability to anxiety and depression. Since 2004, China has launched a medical assistance program for the patients with access to medical and/or surgical treatment, in which health workers have incorporated nursing interventions to address these challenges. This meta-analysis evaluated the effects of nursing interventions on QoL, anxiety, depression, and complications in advanced schistosomiasis patients. Seven databases [PubMed, Web of Science, the Cochrane Library, China Biology Medicine, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang] were systematically searched for randomized controlled trials up to August 1, 2024. Data were analyzed using Review Manager 5.4 (Cochrane Collaboration) and R 4.2.3 (R Project, a free, open-source language and environment primarily used for statistical computing and graphics). Outcomes included QoL (World Health Organization Quality of Life Brief scale and Karnofsky performance status), anxiety (Self-rating Anxiety Scale), depression (Self-rating Depression Scale), and complications. The protocol was previously registered with the International Prospective Register of Systematic Reviews (CRD42023406707). A total of 23 studies with 2232 patients were included. Nursing interventions improved QoL with greater benefits observed in longer intervention periods. Anxiety (standardized mean difference: -1.52, 95% confidence interval (CI): -2.10 to -0.94) and depression (standardized mean difference: -1.13, 95% CI: -1.43 to -0.84) scores were markedly reduced. The risk of complications decreased by 64% (relative risk: 0.36, 95% CI: 0.27 to 0.48). Subgroup analyses highlighted age as a key modifier of intervention efficacy. Nursing interventions effectively enhance QoL, alleviate psychological distress, and reduce complications in advanced schistosomiasis patients. These findings advocate for integrating structured nursing protocols into China's national healthcare programs and global schistosomiasis management strategies.

Regulatory T cells (Tregs) represent a distinct T cell subpopulation crucial for preserving immune homeostasis. Their primary function is to facilitate self-tolerance and suppress other immune responses, achieved through multifaceted mechanisms, including the secretion of extracellular vesicles (EVs) such as exosomes, which effectively modulate the activity of other innate and adaptive immune cells. Treg-derived extracellular vesicles (Treg-EVs) are minute, membrane-bound vesicles containing specific biological molecules, comprising proteins, nucleic acids, and lipids. Upon transfer to target cells, these molecules exert diverse effects on immune responses. The Treg-mediated immune suppression process encompasses several contact-dependent and contact-independent mechanisms. These encompass the expression of various inhibitory receptors, such as CTLA-4, PD-1, CD39, and CD73, which serve to regulate the immune response. Furthermore, Tregs exhibit the capacity to directly eliminate target cells through the expression of perforin and granzyme B. Additionally, Tregs produce immunosuppressive cytokines that play a pivotal role in maintaining immune system equilibrium. Studying the impact of Treg-derived exosomes on the immune system in cancer is crucial for advancing cancer research and treatment. Understanding these interactions is vital for unraveling the potential implications for cancer development and progression. Regulatory T cells, commonly called Tregs, represent a subset of white blood cells that play a pivotal role in modulating the immune system. Often termed suppressor T cells, Tregs are implicated in various immune system disorders when their function is compromised. Extracellular vesicles (EVs) released from these cells are minute particles, containing molecular components that mirror those of their originating cells and fulfill comparable physiological functions. Recent research has increasingly focused on small EVs derived from Tregs, which are instrumental in regulating immune responses. These vesicles exhibit immunosuppressive properties and are associated with the progression and development of multiple cancer types. This review aims to provide an in-depth examination of the latest findings concerning the classifications and suppressive functions of Treg-derived exosomes, with particular emphasis on their relevance to cancer.

Allergic rhinitis (AR) impacts quality of life, work and school productivity. Over the last years, an important body of evidence resulting from mHealth data has led to a better understanding of AR. Such advances have motivated an EAACI-endorsed update of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines (ARIA 2024-2025). This manuscript presents the ARIA 2024-2025 recommendations for intranasal treatments, one of the mainstays for AR management. The ARIA 2024-2025 guideline panel issued recommendations following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework. Several sources of evidence were used to inform panel judgments and recommendations, including systematic reviews, evaluation of mHealth and pharmacovigilance data, as well as a survey of experts on costs. Eleven guideline questions concerning intranasal treatments for AR were prioritized, leading to recommendations. Overall, these questions concern the choice between different classes of intranasal medications-most notably, intranasal corticosteroids (INCS), antihistamines (INAH), fixed combinations of INAH+INCS and decongestants-or between different individual medications within each class. Four questions had not been evaluated in previous ARIA guidelines, while for the other three there was a change in the strength or directionality of recommendations. Overall, recommendations point to the suggested use of INAH+INCS over INAH or INCS and INCS over INAH. This ARIA 2024-2025 article supports patients, their caregivers, and healthcare professionals in choosing an intranasal treatment. However, decisions on AR treatment should consider the clinical variability of the disease, patients' values, and the affordability of medications.