Immune Activation Research Articles

First person – Alexandria Borges

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping researchers promote themselves alongside their papers. Alexandria Borges is first author on ‘ Maternal immune activation does not affect maternal microchimeric cells’, published in BiO. Alexandria conducted the research described in this article while a master's student in Naoki Irie's lab at The University of Tokyo, Tokyo, Japan. She is now a research technician in the lab of Keigo Machida/Linda Sher at USC Keck School of Medicine, Los Angeles, CA, USA, exploring cellular interactions in the context of development and cancer.

Innate and putative adaptive immunological responses of schistosome-parasitized snails.

Schistosomiasis is a neglected tropical disease caused by digenetic trematode from Schistosoma genus, as an etiological agent that uses snails as an intermediate host. In mollusc-trematode relationships, the miracidia attract in the aquatic media to a specific snail as an intermediate hosts, then penetrate its integument in the sporocyst form thereafter, the invasive sporocysts produce secreted/excreted products in order to survive and avoid the snails' immune system. The next larval stage is the cercariae that developed by sporocysts. Subsequently, the snail intermediate host suffers from biological, physiological, biochemical and immunological changes during the development of these parasite larval stages within their tissues. Snails and their parasites engage in an interactive innate and putative adaptive immune response that involves many immune mechanisms, such as the production of nitric oxide, lysozymes, phagocytosis, lectin formation and phenol oxidase activity. Schistosomes have developed a variety of strategies to evade and counteract these deliberate host reactions. These strategies include the secretion of many strong proteases, the use of an immune-resistant outer tegument, the molecular mimicry of host antigens, and the controlled release of certain immunomodulatory substances that influence immune cell activities. This review aims to characterize these important immune evasion mechanisms in order to comprehend the many immunological molecular determinants in the snail/schistosome interaction and to develop alternate management measures for schistosomiasis control.

MRNA vaccines as cancer therapies.

Cancer remains a major global health challenge, with conventional treatments like chemotherapy and radiotherapy often hindered by significant side effects, lack of specificity, and limited efficacy in advanced cases. Among emerging therapeutic strategies, mRNA vaccines have shown remarkable potential due to their adaptability, rapid production, and capability for personalized cancer treatment. This review provides an in-depth analysis of messenger RNA (mRNA) vaccines as a therapeutic approach for cancer immunotherapy, focusing on their molecular biology, classification, mechanisms, and clinical studies. Derived from reported literature and data on clinicaltrials.gov, it examines studies on mRNA vaccines encoding tumor-specific antigens (TSAs), tumor-associated antigens (TAAs), immunomodulators, and chimeric antigen receptors (CARs) across various cancer types. The review highlights the ability of mRNA vaccines to encode TSAs and TAAs, enabling personalized cancer treatments, and classifies these vaccines into non-replicating and self-amplifying types. It further explores their mechanisms of action, including antigen presentation and immune activation, while emphasizing findings from clinical studies that demonstrate the potential of mRNA vaccines in cancer therapy. Despite their promise, challenges remain in enhancing delivery systems, improving immunogenicity, and addressing tumor heterogeneity. Overcoming these obstacles will require further investigation to fully harness the potential of mRNA vaccines in personalized cancer treatment.

Breaking Down Bone Disease in People Living with HIV: Pathophysiology, Diagnosis, and Treatment.

Bone health in people living with HIV (PLWH) has emerged as a significant concern in the era of effective antiretroviral therapy (ART). While ART has transformed HIV infection into a chronic condition, it has also unmasked long-term health complications, including an increased risk of osteoporosis and fractures. This review aims to elucidate the multifactorial mechanisms contributing to bone health deterioration in PLWH, such as direct viral effects, immune activation, and ART-induced bone metabolism changes. We examine the current evidence on bone mineral density (BMD) reductions and the heightened fracture risk in this population. Furthermore, we evaluate diagnostic and management strategies, including radiological and non-radiological evaluations, vitamin D optimization, bisphosphonates, and other emerging treatments, to provide a comprehensive overview of effective interventions. By synthesizing the latest research, this review seeks to enhance the understanding of bone health issues in PLWH and guide clinicians in implementing strategies to mitigate these risks, ultimately improving patient outcomes.

Therapeutic potential of dopamine and serotonin in inflammation and cancer: Insights into immune regulation.

This review explores the significant roles of neurotransmitters, focusing on dopamine and serotonin, in inflammation and cancer. These neurotransmitters are vital for neural signaling and play crucial roles in various physiological and pathological processes. We conducted an extensive literature review, focusing on studies published between 2013 and 2024, using databases such as PubMed, Google Scholar, and Scopus. Studies were selected based on relevance to neurotransmitter synthesis, receptor function, and their involvement in diseases like cancer and neurodegenerative disorders. The key search terms included "dopamine", "serotonin", "inflammation", and "cancer". Dopamine and serotonin are synthesized intracellularly and function as pivotal signaling molecules within the central nervous system (CNS) and peripheral systems. Through their respective receptors, dopamine and serotonin influence immune responses and the functionality of various bodily systems. Dysregulation in their signaling pathways is associated with a range of cancers and imbalances within the immune system. The interplay between dopamine and serotonin systems extends beyond neural communication, significantly affecting immune responses and inflammation. Dopamine's role in modulating immune cell activity highlights its potential in treating inflammatory conditions and cancer. Similarly, serotonin's extensive physiological impact underscores the importance of targeting 5-HT pathways in various disorders. Future research should focus on developing therapeutic strategies that leverage these neurotransmitters' regulatory functions in both the CNS and peripheral systems.

Immunological effects of CD19.CAR-T cell therapy in systemic sclerosis: an extended case study

ObjectiveThe high potential of CD19.CAR-T cells to treat autoimmune diseases such as Systemic Sclerosis (SSc) supposedly relies on the disappearance of autoantibodies. Here we investigated effects of CAR-T cells on the innate immune system which is an important contributor to pathology in SSc.MethodsLongitudinal analysis of peripheral blood mononuclear cells from an Scl70 + SSc patient treated with CAR-T cells sampled over 18 months by 29-color spectral flow cytometry, in vitro experiments using sera from patient cohorts.ResultsIn the patient treated with CAR-T cells, the substantial clinical improvement was paralleled by dynamic changes in innate lymphoid cells, namely Fcγ-receptor IIIA-expressing natural killer (NK) cells. NK cells adopted a more juvenile, less activated, and less differentiated phenotype. In parallel, the potency of serum to form Scl70-containing immune complexes that activate Fcγ-receptor IIIA decreased over time. These observations suggested a mechanistic link between reversal of adaptive autoimmunity and recovering Fcγ-receptor IIIA-expressing innate immune cells after CAR-T cell therapy via regressing immune complex activity. Experiments with sera from the non-CAR-T-treated SSc cohort confirmed that Scl70-containing immune complexes activate Fcγ-receptor IIIA-expressing NK cells in a dose-dependent manner, substantiating the relevance of this link between adaptive and innate immunity in SSc.ConclusionThis report describes for the first time the phenotypic recovery of innate Fcγ-receptor-expressing cells in an SSc patient treated with CAR-T cells. Decreasing autoantibody levels associated with a reduced ability to form functional immune complexes, the latter appearing to contribute to pathology in SSc via activation of Fcγ receptor IIIA + cells such as NK cells.Graphical Proposed mechanism of involvement of NK cells and soluble Immune Complexes (sICs) in disease progression during active autoimmunity in SSc (left) and resolution of fibrosis after deep B cell depletion by CD19.CAR-T cells and disappearance of autoantibodies (right).

Individualizing Antiretroviral Therapy in the Older Patient.

Owing to widespread availability of potent and tolerable antiretroviral therapy, life expectancy of people with human immunodeficiency virus (HIV) has significantly increased. Consequently, the population of people with HIV are ageing, with over 50% over the age of 50 years, and it is expected that 25% will be over the age of 65 years by 2030. People diagnosed with HIV at older age tend to have more advanced disease, and may already be experiencing comorbidities that will influence the choice of initial antiretroviral treatment. Despite the well described changes in pharmacokinetics associated with ageing, there are a paucity of pharmacokinetics studies of contemporary antiretroviral drugs to help guide treatment for HIV. Irrespective of this, integrase inhibitor-based regimens have been shown to have similar treatment outcomes in older and young adults and are the preferred regimens for initiation and switching therapy in older adults. Non-acquired immunodeficiency syndrome (AIDS) comorbidities are more common in people with HIV owing to chronic immune activation and inflammation even in the presence of virological suppression on antiretroviral treatment. Screening and risk assessment of comorbidities is crucial as the presence of geriatric syndrome, frailty or neurocognitive impairment may impact medication adherence. Simplification of complex regimens, both antiretroviral and comorbidity treatments, is recommended to improve adherence. Regular medication reviews under the guidance of an experienced HIV pharmacist are recommended to identify adverse drug-drug interactions and inappropriate prescribing of drugs with potential adverse effects, such as falls risk. Antiretroviral stewardship has been shown to improve patient outcomes and quality of life for ageing people with HIV.

SARS-CoV-2 Nsp14 binds Tollip and activates pro-inflammatory pathways while downregulating interferon-α and interferon-γ receptors.

SARS-CoV-2 protein Nsp14 both activates NF-κB, which promotes virus replication and inflammation, and downregulates IFNAR1, which can render infected cells resistant to the antiviral effects of IFN-α/β. Our study demonstrates that Nsp14 also activates MAPK signaling and downregulates IFNGR1, causing broader impacts than previously recognized. Data from a panel of Nsp14 mutants suggests a common underlying effect of Nsp14 may be responsible for its multiple innate immune activities. We further describe a novel interaction between Nsp14 and Tollip, a selective autophagy receptor. We show that Tollip expression downregulates Nsp14 activation of NF-κB and that Tollip knockdown reverses IFNAR1 and IFNGR1 downregulation in SARS-CoV-2 infection, suggesting that Tollip functions as a regulator of Nsp14 innate immune modulation.

MRNA-LNPs induce immune activation and cytokine release in human whole blood assays across diverse health conditions.

RNA medicines have become a promising platform for therapeutic use in recent years. Understanding the immunomodulatory effects of novel mRNA-LNPs is crucial for future therapeutic development. An in vitro whole blood assay was developed to assess the impact of mRNA-LNPs on immune cell function, cytokine release, and complement activation. mRNA-LNPs significantly increased CD69 expression on T cells and natural killer (NK) cells, and CD80/CD86 on myeloid subsets, in a dose-dependent fashion. Furthermore, mRNA-LNPs elicited a robust release of pro-inflammatory cytokines, including TNF-α, IL-1β, MCP-1, IL-6, and IP-10, indicating a potent immune response. Notably, mRNA-LNPs stimulate early cytokine production prior to triggering immune cell activation, suggesting a temporal and biological relationship. Moreover, mRNA-LNPs induce complement activation via the alternative pathway, as evidenced by increased serum sC5b-9, C3a, and Bb which can amplify the inflammatory response and potentially impact safety. In vitro effects of mRNA-LNPs in whole blood of healthy human donors were compared to those from disease cohorts including systemic lupus erythematosus (SLE), type 2 diabetes mellitus (T2DM), and cancer donors. The differences in mRNA-LNPs effects on samples from healthy and diseased populations may impact therapeutic efficacy or toxicity, indicating a need for tailoring LNPs for specific target populations.

Cytokine Profiling of Erythroderma Biopsies Reveals Types 2 and 17 Immune Activation Status.

Erythroderma is a dermatologic condition characterized by widespread red and scaly skin. The causes include, but are not limited to, psoriasis, eczema, drug eruptions, pityriasis rubra pilaris (PRP), and cutaneous T-cell lymphoma. Most of these are typified by Type 2 (e.g., eczema) or Type 17 (e.g., psoriasis) immune activation. However, since the clinicopathologic features of erythroderma can be nonspecific, assays that determine the underlying immune activation status are desirable. IL-13 RNA insitu hybridization and IL-36 immunohistochemistry were performed on 30 specimens of erythroderma, to ascertain Type 2 and Type 17 immune signatures, respectively. Specimens of erythrodermic psoriasis and PRP showed strong expression of IL-36 and less than one IL-13-positive cell per millimeter. Conversely, those of spongiotic dermatitis showed low expression of IL-36 and greater than one IL-13-positive cell per millimeter. Most specimens of spongiotic, psoriasiform dermatitis demonstrated low IL-36 expression and greater than one IL-13-positive cell per millimeter, but a subset showed high IL-36 expression and greater than one IL-13-positive cell per millimeter. We developed a Type 2/17 immune signature classifier based on cytokine profiling, which showed that cases of erythroderma fall within distinct categories of immune activation. This categorization may have utility in guiding clinical decisions.

Immune Privilege in the Central Nervous System: Implications for Neuroinflammatory Diseases

The central nervous system (CNS) has long been considered an immune-privileged site, where immune responses are tightly regulated to protect neural tissue from inflammation-induced damage. Immune privilege in the CNS is maintained through various mechanisms, including the blood-brain barrier (BBB), the absence of conventional lymphatic drainage, the specialized function of CNS-resident immune cells, and the expression of immunosuppressive molecules like TGF-β and IL-10. These protective systems are essential for preserving CNS homeostasis, as uncontrolled immune activity in the CNS can lead to irreversible damage to neurons and glial cells. However, immune privilege is not absolute. In neuroinflammatory diseases such as multiple sclerosis (MS), neuromyelitis optica (NMO), and Alzheimer’s disease, immune privilege is breached, resulting in the infiltration of immune cells, chronic inflammation, and progressive neural damage. The breakdown of the BBB, immune cell activation, and dysregulated inflammation contribute to the pathophysiology of these diseases. This review examines the mechanisms that underlie immune privilege in the CNS, how these systems are compromised in neuroinflammatory conditions, and the therapeutic implications for modulating immune responses in the CNS. Targeted therapies aimed at restoring immune regulation and preserving CNS function offer promising prospects for treating neuroinflammatory diseases and maintaining CNS health. Keywords: Immune Privilege, Central Nervous System, Neuroinflammatory Diseases, Blood-Brain Barrier, Multiple Sclerosis, Immunosuppressive Mechanisms

Pathway Thermodynamic Analysis Postulates Change in Glutamate Metabolism as a Key Factor in Modulating Immune Responses.

Temperature, as seen during fever, plays a pivotal role in modulating immune responses and maintaining cellular homeostasis. Shifts in temperature influence the thermodynamic feasibility of metabolic reactions, with Gibbs free energy (ΔG) serving as a key indicator of the spontaneity of reactions under specific conditions. By altering ΔG in response to temperature changes across various metabolite concentrations and cell types, we can gain insights into the thermodynamic properties of metabolic pathways and identify critical factors involved in metabolism and immune function. Using Max-Min Driving Force (MDF) analysis, we can assess changes in ΔG by varying temperature and metabolite concentrations, allowing for a detailed examination of thermodynamic feasibility at both the pathway and individual reaction levels. In this study, MDF analysis is applied to measure the changes in the driving force of pathways and the ΔG of each reaction at normal human core temperature (310.15 K) and elevated temperatures (up to 315.15 K). Additionally, we explore how shifts in the thermodynamic feasibility of reactions under immune activation, compared to normal physiological conditions, highlight key metabolic intermediates-such as fructose-1,6-bisphosphate, glucose-6-phosphate, and several steps in glutamate metabolism-as important regulators of metabolic processes and immune responses. The goal of this study is to underscore the value of thermodynamic parameters such as ΔG, concentration, and temperature in identifying potential therapeutic targets, with the aim of mitigating the detrimental effects of fever while preserving its beneficial aspects.

Progress Toward Poliomyelitis Eradication - Afghanistan, January 2023-September 2024.

Since the Global Polio Eradication Initiative began in 1988, wild poliovirus (WPV) types 2 and 3 have been eradicated, and annual polio case numbers have decreased by >99.9%. WPV type 1 (WPV1) transmission remains endemic in Afghanistan and Pakistan, two countries that share a 1,600-mile (2,600-km) border. This report describes immunization and surveillance activities and progress toward polio eradication in Afghanistan during January 2023-September 2024. As of November 1, Afghanistan reported 23 WPV1 cases in 2024, with onset during January-September 30, 2024. During the 3 previous years, 12 WPV1 cases were reported, including six during 2023. In August 2021, the Taliban took control nationwide and allowed increased geographic access for poliovirus vaccination campaigns. Multiple challenges have affected polio eradication activities in Afghanistan, including mandated repatriation of approximately 1 million Afghans by Pakistan beginning in late 2023, the ongoing humanitarian crisis that limits international agency effectiveness, polio program constraints imposed by authorities, and increased restrictions on female participation in vaccination activities. House-to-house vaccination coverage reached 90%-98% of children during June-July 2024. Beginning in 2021, authorities had progressively lifted restrictions on house-to-house campaigns, but abruptly reverted to national restrictions in September 2024. Both nationwide house-to-house activities and strengthening of the routine childhood immunization program would help ensure that every vulnerable child is vaccinated and provide a pathway to polio eradication in Afghanistan.

Biomarkers of success of anti-PD-(L)1 immunotherapy for non-small cell lung cancer derived from RNA- and whole-exome sequencing: results of a prospective observational study on a cohort of 85 patients.

Immune checkpoint inhibitors (ICIs) treatment have shown high efficacy for about 15 cancer types. However, this therapy is only effective in 20-30% of cancer patients. Thus, the precise biomarkers of ICI response are an urgent need. We conducted a prospective observational study of the prognostic potential ofseveral existing and putative biomarkers of response to immunotherapy in acohort of 85 patients with lung cancer (LC) receiving PD-1 or PD-L1 targeted ICIs. Tumor biosamples were obtained prior to ICI treatment and profiled by whole exome and RNA sequencing. The entire 403 putative biomarkers were screened, including tumor mutation burden (TMB) and number of cancer neoantigens, 131 specific HLA alleles, homozygous state of 11 HLA alleles and their superfamilies; four gene mutation biomarkers, expression of 45 immune checkpoint genes and closely related genes, and three previously published diagnostic gene signatures; for the first time, activation levels of 188 molecular pathways containing immune checkpoint genes and activation levels of 19 pathways algorithmically generated using a human interactome model centered around immune checkpoint genes. Treatment outcomes and/or progression-free survival (PFS) times were available for 61 of 85 patients with LC, including 24 patients with adenocarcinoma and 27 patients with squamous cell LC, whose samples were further analyzed. For the rest 24 patients, both treatment outcomes and PFS data could not be collected. Of these, 54 patients were treated with PD1-specific and 7 patients with PD-L1-specific ICIs. We evaluated the potential of biomarkers based on PFS and RECIST treatment response data. In our sample, 45 biomarkers were statistically significantly associated with PFS and 44 with response to treatment, of which eight were shared. Five of these (CD3G and NCAM1 gene expression levels, and levels of activation of Adrenergic signaling in cardiomyocytes, Growth hormone signaling, and Endothelin molecular pathways) were used in our signature that showed an AUC of 0.73 and HR of 0.27 (p=0.00034) on the experimental dataset. This signature was also reliable (AUC 0.76, 0.87) for the independent publicly available LC datasets GSE207422, GSE126044 annotated with ICI response data and demonstrated same survival trends on independent dataset GSE135222 annotated with PFS data. In both experimental and one independent datasets annotated with samples' histotypes, the signature worked better for lung adenocarcinoma than for squamous cell LC. The high reliability of our signature to predict response and PFS after ICI treatment was demonstrated using experimental and 3 independent datasets. Additionally, annotated molecular profiles obtained in this study were made publicly accessible.

Structure Elucidation and Immunostimulatory Activity Evaluation of a Galactoglucan from Alpinia officinarum Hance.

Alpinia officinarum Hance has a medicinal history of thousands of years in treating cough, diabetes, and gastrointestinal system diseases, and it is also a medicine food homology (MFH) plant in China. To evaluate the pharmacological activities of polysaccharides from the rhizomes of A. officinarum, polysaccharides were initially obtained by hot-water extraction and the ethanol precipitation method. A homogenous polysaccharide designated as AOP-w was isolated by a DE-52 column. The proposed structure was elucidated and the immunoregulatory effects on RAW 264.7 macrophage cells were evaluated. The results showed that AOP-w had a molecular weight of 5.26 kDa, and mainly consisted of galactose and glucose (molar ratio of 0.12:0.88). Its backbone comprised α-(1→4)-Glcp, α-(1→4,6)-Glcp and β-(1→3,4)-Galp residues, terminated by α-(1→6)-Glcp and T-Glcp residues. AOP-w was nontoxic to RAW 264.7 cells, but demonstrated promotion in cell proliferation within a 100 μg/mL concentration. The immunostimulatory effects of AOP-w were confirmed by the elevated NO production of AOP-w-treated cells. Moreover, the RNAseq was conducted and the results showed that AOP-w may activate the TNF and NF-κB signaling pathways by binding to Toll-like receptors, thereby affecting the immune modulatory activity of RAW264.7 cells. These results suggest a high potential of AOP-w from A. officinarum for immunotherapeutic applications.

Modulatory effects of in ovo delivery of galactooligosaccharide and Lactiplantibacillus plantarum on antioxidant capacity, gene expression, and selected plasma metabolite parameters of broiler chickens.

A stable gut microbiota promotes a healthy gut and enhances immune function, antioxidant status, and metabolic activities in chickens. The present research work aimed to investigate the modulatory impacts of in ovo delivery of prebiotic and probiotic on oxidative stress, the intestinal transcriptome, and various plasma metabolites in chickens. Fertilized Ross 308 eggs were administered in ovo either with galactooligosaccharide (GOS) (3.5mg/egg or Lactiplantibacillus plantarum (LP) 1 × 106/egg on the 12th day of egg incubation. Three hundred viable Ross 308 broiler hatching eggs in total were randomly assigned to four groups, namely, the negative control not injected group, the group receiving physiological saline injections as the positive control, GOS, and LP. The analysis of genes associated with immune functions, antioxidants, barrier functions, and free fatty acid receptors were determined via qPCR. The analysis of the selected plasma blood metabolites was performed automatically with Pentra C 400. The antioxidant capacity of the chickens' liver, breast muscle, and spleen was enhanced by the in ovo injection of GOS and LP. The immune-related gene expression levels were upregulated after in ovo stimulation with either GOS or LP which improved the gut health of broiler chickens. In addition, several genes related to gut barrier functions were upregulated, thus ensuring epithelial integrity. As for blood plasma metabolites, no adverse effects were observed. In summary, we report that in ovo stimulation with either GOS or LP stimulates the immune system and improves the antioxidant status and gut health of chickens with no negative impact on plasma blood metabolite indices.

Challenges of HIV Management in an Aging Population.

Potent, well tolerated and simple to administer antiretroviral therapy (ART) has resulted in significant improvement in life expectancy for people with HIV. The increased lifespan does not necessarily equate to improved healthspan with increased rates of comorbidities, frailty and geriatric syndrome experienced by older people with HIV. This review explores the challenges in prevention and management of multimorbidity and geriatric syndrome with the ultimate goal of improving health and quality of life through holistic care. Recent studies have drawn attention to the multifactorial nature of most comorbidities experienced by people with HIV. Adverse effects of contemporary ART, combined with lifestyle factors of smoking, excess alcohol and other substance use, chronic immune activation and inflammation associated with chronic HIV infection and other co-infections, all impact multimorbidity and geriatric syndromes. The complex healthcare needs of the aging population of people with HIV will require comprehensive, multidisciplinary integrated models of care.

Prognostic Impact of Aetiology in Adult Hemophagocytic Lymphohistiocytosis: Insights from an Intensive Care Unit Experience.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome marked by excessive immune activation. It can be triggered by various factors, including infections, malignancies, and autoimmune diseases, making the diagnosis challenging due to its overlap with other severe conditions. We discuss two intensive care unit (ICU) cases illustrating the diverse manifestations of HLH and the critical importance of early recognition and treatment. The first case involves natural killer-cell leukaemia, and the second, a suspected viral trigger. Both highlight the necessity of a multidisciplinary approach in diagnosis and management, emphasizing the complexity of HLH in ICU settings. High mortality rates, particularly in malignancy-associated HLH, underscore the importance of tailored treatment strategies based on the underlying aetiology. Hemophagocytic lymphohistiocytosis (HLH) in adults can arise from a variety of triggers, including infections and malignancies, each influencing disease progression and prognosis differently. Recognizing these underlying aetiologies is crucial for tailoring management strategies and anticipating clinical outcomes.Due to its life-threatening nature, HLH requires prompt diagnosis and a coordinated, multidisciplinary approach. Early intervention, incorporating immunosuppressive therapies and supportive care, is essential to improve patient outcomes, particularly in intensive care unit settings where disease severity is often pronounced.Utilizing diagnostic tools such as the HScore and HLH-2004 criteria can facilitate early identification of HLH in critically ill patients with unexplained inflammatory symptoms. These tools, along with a high index of suspicion, help distinguish HLH from other hyperinflammatory conditions, enabling timely and appropriate therapeutic interventions.

Preparation, Characterization, and Immune Activity of Viola philippica Polysaccharide PLGA Nanoparticles.

Recent pharmacological studies have demonstrated that Viola philippica polysaccharide (VPP) exhibits a modulating effect on immune activity. However, its utilization has been hampered by its large particle size and complex spatial structure. Polylactic-co-glycolic acid (PLGA) copolymer is recognized as an effective drug delivery carrier, exhibiting excellent biochemical properties. In this experiment, VPP was encapsulated with PLGA to form VPP PLGA nanoparticles (VPP-PLGA NPs). The morphological structure and immunomodulatory effects of VPP-PLGA NPs were evaluated. The particle size of VPP-PLGA NPs was reduced compared to VPP, and the optimal preparation conditions were as follows: The ratio of the organic phase to the internal aqueous phase was 8:1, the ratio of the external aqueous phase to the primary emulsion was 7:1, and the concentration of PLGA was 20mg/mL. Additionally, VPP-PLGA NPs significantly increased the nitric oxide (NO) content, IL-4, and IFN-γ levels in RAW264.7 cells, as well as enhanced their phagocytic activity. Furthermore, VPP-PLGA NPs were found to increase NO content and IFN-γ secretion in bone marrow-derived dendritic cells (BMDCs). These findings suggest that VPP-PLGA NPs could enhance the immune activity and may be utilized as a VPP delivery system for inducing strong immune responses.

Sequential Release HydroLipo System for STING Gene Epigenetic Reprogramming and Immune Activation in Glioblastoma.

Glioblastoma (GBM) remains a daunting oncological challenge because of its aggressive nature and resistance to conventional therapies. Inhibition of the intrinsic STING pathway in GBM hampers the effectiveness of immunotherapies. To overcome this clinical limitation, a Sequential Release HydroLipo System (SRHLS) is developed, in which hydrogels and nanoparticles are combined for controlled drug release. The SRHLS sequentially released decitabine and STING agonists, thereby correcting STING signaling dysfunction through epigenetic reprogramming and enhancing antitumor immunity. According to in vitro and in vivo experiments, the SRHLS reshaped the tumor microenvironment and markedly inhibited tumor growth, recurrence, and metastasis. These findings underscore the potential of the SRHLS as a promising therapeutic strategy for GBM.