Malaria remains a major global health challenge, profoundly influencing host nutritional and immune status. Essential trace elements such as iron, zinc, copper and magnesium play pivotal roles in immune regulation, antioxidant defence, and pathogen control. However, their alterations during malaria infection and implications for disease outcome have been inconsistently reported. This systematic review aimed to synthesise current evidence on serum and plasma concentrations of key trace elements in malaria-infected individuals and experimental models, and to evaluate their relationship with immune responses, disease severity, and treatment outcomes. A systematic search was conducted in various academic databases, including PubMed, Web of Science, Scopus, and Google Scholar for studies published from January 2010 to November 2025. The quality assessment of the studies was done using the Critical Appraisal Skills Programme (CASP) tool. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to ensure a comprehensive and transparent process. Across human and experimental studies, malaria infection was consistently associated with reduced serum concentrations of iron, zinc, and magnesium, while copper levels showed variable trends, often elevated in acute infection, reflecting an inflammatory response. These alterations were linked to dysregulated cytokine production, particularly increased TNF-α and IL-10, higher parasitemia, and worsened clinical outcomes. Zinc supplementation improved micronutrient status but showed limited impact on malaria incidence. Emerging spectrometric approaches demonstrated utility in trace element profiling for malaria diagnosis and prognosis. Malaria-induced disturbances in trace element homeostasis, notably reduced iron, zinc, and magnesium, and altered copper levels, contribute to immune dysfunction and oxidative stress, aggravating disease severity. Integrating targeted micronutrient interventions with antimalarial therapy may enhance host immune competence and improve treatment outcomes.

Potential contribution of oxysterols and cholestanol in the vascular inflammatory process occurring in patients with Behcet's disease.

The objective of this study is to conduct network toxicology analysis based on smoking habits and develop a simpler and more effective toxicology product ingestion control system. Smoking behavior can affect the pathogenesis and prognosis of neuroimmune gastrointestinal diseases. The purpose of developing tools to assist clinical practice is to avoid the harm of cigarettes to the human body. Molecular dynamics method was used to elucidate the biophysical mechanism of TP53 gene mutation caused by harmful ingredients, and the signaling pathway of midbrain edge excitation was determined by molecular dynamics of nicotine and dopamine receptor D3. The possible involvement of nicotine in neuronal damage was determined through the molecular interaction between nicotine and ACHE. Molecular pathways were analyzed based on the aforementioned biological principles, developed artificial intelligence systems and brain computer interface systems. Several signaling pathways were elucidated, and effective AI algorithms were developed. The accuracy of artificial intelligence systems is over 70%. This study provides clinical doctors with a new precision medicine strategy and tool to regulate patient behavior and reduce disease risk. Other: This project was approved by the Ethics Committee of Chifeng Cancer Hospital and reported to the WHO.

Essential oil of Saposhnikovia divaricata mitigates Cutibacterium acnes-induced inflammatory acne via Nrf2 pathway activation and NF-κB pathway inhibition.

Effect of papaya leaf extract on growth performance, skin mucosal immune responses, liver enzymes, disease resistance, and tight junctions of Cyprinus carpio.

Fluorescent light-up probes for legumain imaging in macrophages: Minimal disturbance to macrophage cytoskeleton.

Nanosized natural products for immune dysregulation: A systematic review of mechanisms, therapeutic applications, and translational challenges.

Celebrating the 40-year milestone: NF-ĸB in oncoimmunity.

Mastitis represents one of the main challenges in dairy buffalo farming, with significant implications for animal health, milk quality, and farm profitability. Among its different forms, subclinical mastitis is difficult to detect due to the absence of standardised diagnostic tools. Epigenetic mechanisms, such as DNA methylation, have been associated with immune response and disease susceptibility in cattle, but remain unexplored in buffaloes. This study explores genome-wide DNA methylation profiles in Mediterranean Italian River Buffaloes, using nanopore sequencing technology, to identify potential epigenetic signatures associated with mastitis resistance. CpG sites showed a unimodal distribution, with most sites exhibiting high methylation levels. A total of 22 differentially methylated cytosines (DMCs) were identified, with 68% showing hypomethylation in the control group and 32% showing hypermethylation. Genomic annotation revealed that hypermethylated DMCs were predominantly located in intronic regions, while hypomethylated DMCs were largely enriched in distal intergenic regions. This study is the first to investigate DNA methylation changes associated with mastitis in Mediterranean Italian River Buffalo using nanopore sequencing. Distinct epigenetic patterns were identified between healthy and mastitic animals. This study provides a first epigenetic overview of mastitis in buffaloes and lays the groundwork for future investigations with larger cohorts to validate and extend these observations. Given the small sample size, these findings should be considered exploratory, but offer insights into the molecular basis of mastitis and may support the development of new diagnostic tools based on validated epigenetic signatures.

Lupus nephritis (LN), a severe renal complication of systemic lupus erythematosus (SLE), results from immune abnormalities. Qingre Kasen granules (QS), which have chicory as the main ingredient, play a significant role in treating various inflammatory and immune system diseases. This study aimed to identify LN biomarkers and mechanisms via systems biology approach, and multi-omics integration, and to screen potential active ingredients of QS for the treatment of LN. First, bioinformatics and machine learning were used to screen five genes, namely CHI3L1, CX3CR1, GBP2, CCND1, and PKP4, as well as the NF-kappaB signaling pathway. An external dataset was then employed to confirm that GBP2 plays a crucial role in the pathogenesis of LN. Immune infiltration analysis revealed significant changes in the proportion of CD4+ T cells. Subsequently, an LN mouse model was established to evaluate QS’s therapeutic effects. Results showed that QS treatment significantly improved symptoms and alleviated renal damage in these mice. Metabolomics and Western blot analyses further demonstrated that abnormal elevations of proteins related to purine metabolism and the NF-kappaB pathway were closely associated with LN’s pathogenesis. Finally, molecular docking and MMGBSA binding energy calculations identified cichoriin as a key component. Molecular dynamics simulations further predicted a strong binding affinity between cichoriin and GBP2, along with favorable ADMET properties. In summary, GBP2 is a key druggable gene in LN. This study verifies QS’s efficacy and positions cichoriin as a novel immunomodulator acting on the GBP2/NF-kappaB axis.

CCDC86 modulates immune cell infiltration and disease progression in head and neck squamous cell carcinoma.

BackgroundPeripheral inflammation is a known contributor to Alzheimer's disease (AD) risk and progression. As aging is associated with increasing inflammation that may precede AD onset, individuals with a parental history of AD, a risk factor that increases lifetime AD risk, may have inflammatory profiles that reflect their risk. This study examines whether having a parent with AD is associated with increased peripheral inflammation in middle‐aged adults. We hypothesize that individuals with parental history of AD will have higher levels of pro‐inflammatory cytokines compared with those without a parental history of AD across racial and ethnic groups.MethodParticipants comprised 1,043 non‐Hispanic White, non‐Hispanic Black, and Hispanic men and women from the Offspring Study who are the adult children of participants in the Washington Heights Inwood Columbia Aging Project. Parental AD status was determined by a diagnostic consensus conference. Plasma chemokine and cytokine concentrations were assayed with Luminex technology. were used for the associations between parental AD status and inflammatory cytokines, adjusting for age and sex, and interaction models were used to determine if associations differed by age, sex at birth, race and ethnicity, or APOE genotype.ResultParticipants with a parental history of AD (n = 660, mean age=54, 65% women) had higher levels of Eotaxin (log‐diff: 0.09, 95% CI: 0.01,.0.15) and lower levels of G‐CSF (‐0.2, 95% CI: ‐0.35,‐0.04), VEGF‐A (‐0.16, 95% CI: ‐0.3,‐0.01), and IL‐27 (‐0.07, 95% CI: ‐0.15,0.0) compared with those without a parental history of AD (n = 383, mean age=60, 71% women). IL‐18 levels were significantly higher in Black individuals with a parental history of AD compared to Black individuals without, while White individuals with a parental history of AD had higher levels of EGF compared to White individuals without. Women with a parent history of AD had higher levels of IFna2, IL‐12p70, sCD40L, and IL‐18 compared to women without parental AD history.ConclusionParental history of AD is associated with elevated markers of peripheral inflammation. These associations vary across sex and race and ethnicity.

Background Long-term follow-up for inborn errors of immunity (IEIs) after hematopoietic cell transplantation (HCT) remains poorly described. We report ≥5 years post-HCT. Methods Retrospective data collection from 16 clinical records. Results 12 males (75%) and 4 females (25%) with diagnosis of IEIs (1 severe combined immunodeficiency [SCID], 6 CID, 4 phagocyte defect, 3 immune dysregulation disease, and 2 bone marrow failure). Median follow-up 5.3 years [0-14] and median age at transplant 6.5 years [0-17]. Patients received bone marrow (n = 15) or peripheral blood stem cells (n = 1), from matched family (n = 1), matched (n = 11), or mismatched (n = 4) unrelated donors using (10, 62.5%) busulfan–fludarabine, (2, 12.5%) busulfan–cyclophosphamide, (2, 12.5%) melphalan–fludarabine, and (1, 6.3%) fludarabine–cyclophosphamide conditioning. 93.8% received serotherapy (antithymoglobulin). Tacrolimus and methotrexate as graft versus host disease (GvHD) prophylaxis in 10 patients (62.5%). 8 patients (50%) developed acute and 3 (18.8%) chronic GVHD. 4 (25%) had CMV, 3 (18.8%) EBV, and 1 (6.3%) adenovirus viremia. 1 patient (6.3%) developed severe veno-oclusive disease and died on day +30, and 1 (6.3%) had secondary graft failure. Post-HCT analysis was made in the 14 remaining patients. 7 (50%) improved growth, 4 (28.6%) had significant infections, and 4 (28.6%) improved or stabilized lung disease. 5 (35.7%) developed autoimmunity, most (4, 80%) were hematological (neutropenia, thrombocytopenia, or hemolytic anemia). 11 (78.6%) required immunoglobulin replacement after HCT, 8 (57.1%) suspended it with a median of 698 days [423-4,397]. 8 (57.1%) achieved GvHD prophylaxis suspension at 488 days [360-723]. 12 patients had whole blood chimerism performed >50% [50-100]. At last follow-up, 14 patients were alive and with good chimerism, resulting in a 16-year overall survival of 93%. Conclusions HCT for IEIs resulted in high long-term survival in our cohort. Most patients achieved good chimerism and showed improvement in clinical outcomes, despite significant posttransplant complications (infections, autoimmunity, GvHD). These findings highlight the effectiveness of HCT while underscoring the need for long-term follow-up.

The alarming trend in modern epidemiology of atopic dermatitis is omnipresent steady increase in its prevalence making the problem relevant. The purpose of the study is to shed light on historical aspects of development of ideas about atopic dermatitis and differences in classification approach. The search of publications was carried out in such Internet databases as Scopus, MedLine, еLibrary, Google Scholar according keywords atopic dermatitis, pathophysiology, history, classification. The study of etiology and pathogenesis of atopic dermatitis at different levels took thousands years. The theories and concepts of atopy and allergy were developed. The IgE and its key role in development of immune mediated diseases was discovered. The term atopic dermatitis was introduced. including its diagnostic criteria and classification. The concomitant and unrelated diseases were identified. The definition of dermatitis and eczema as synonyms that can be used to describe picture of inflammatory reaction in skin, histologically characterized by spongiosis with different degrees of acanthosis and presence of superficial perivascular lymphohistiocytic infiltrate. The clinical signs (itching, redness, peeling and papulovesicles of the skin) are developed under influence of combination of endogenous and exogenous factors, characterized by recurrent course and worsen quality of life of patients. The dermatitis and eczema requires identical approaches to treatment and prevention. Over the millennia, many scientists, physicians and dermatological schools contributed into description of pathophysiology and clinic of this disease that is important to be studied in order to understand modern concept and classification.

Ficolin-1 (FCN1, M-FCN), the key pattern recognition molecule of the innate immune system, possesses a collagen-like domain and a fibrinogen-like domain, exhibiting bidirectional immunomodulatory functions that influence immune homeostasis and disease progression. Recent studies reveal that beyond its well-established roles in pathogen recognition and complement activation, FCN1 orchestrates the balance between pro-inflammatory and anti-inflammatory responses, facilitating crosstalk between innate and adaptive immunity. This review synthesises cutting-edge research to systematically elucidate the multifaceted roles of FCN1 in human diseases, including autoimmune disorders, infectious diseases, tumour, cardiovascular and cerebrovascular disease. We highlight how FCN1 exerts its regulatory effects through diverse mechanisms ranging from pathogen binding and clearance to cytokine secretion modulation and immune cell fate determination, ultimately shaping disease susceptibility, progression and prognosis. By compiling these groundbreaking findings, we propose FCN1 as a pivotal orchestrator of immune responses, providing a theoretical foundation for its translation into diagnostic biomarkers and novel therapeutic targets in precision medicine. This review advocates for the establishment of standardised FCN1 assays and large-scale clinical validation to accelerate its transformation from bench to bedside.

Abstract Necroptosis is a highly inflammatory form of regulated cell death driven by Receptor-Interacting Protein Kinase 3 (RIPK3), which plays a crucial role in immune responses, inflammatory diseases, and tumor microenvironment modulation. Beyond driving cell death via MLKL phosphorylation, RIPK3 also activates NF-κB signaling, promoting cytokine production and immunogenic responses. However, the regulatory mechanisms governing RIPK3-dependent NF-κB activation remain largely unclear. Here, we identify Growth Arrest and DNA Damage-inducible β (GADD45β) as a novel regulator of RIPK3 activities. We show that GADD45β directly binds RIPK3 in a RHIM-independent manner, interfering with NEMO-RIPK1-RIPK3 complex formation and limiting RIPK3-mediated NF-κB activation. Furthermore, inducible expression of GADD45β selectively suppresses RIPK3-induced proinflammatory signaling without promoting caspase-dependent apoptosis and markedly reduces CXCL8 (IL-8) production during necroptotic stimulation. GADD45β also improves long-term cellular survival under sustained inflammatory stress. Our findings reveal GADD45β as a critical modulator of RIPK3-driven immune responses and suggest a potential therapeutic strategy for fine-tuning immunogenic cell death.

Since the COVID-19 pandemic, a growing number of reports suggest an association between severe acute respiratory syndrome coronavirus 2 and autoimmune diseases, including large-vessel vasculitis (LVV). However, the mechanism remains unclear. This report describes three cases of COVID-19-associated LVV with elevated anti-angiotensin-converting enzyme 2 (ACE2) antibodies. The first case was a 59-year-old man who developed a persistent headache and fever 2weeks after SARS-CoV-2 infection. FDG-PET/CT revealed diffuse vascular inflammation extending from the carotid arteries to the abdominal aorta. The second case was a 71-year-old man who presented with prolonged fever after SARS-CoV-2 infection. Imaging demonstrated vascular wall enhancement and FDG uptake from the thoracic aorta to the iliac aorta. The third case was a 67-year-old man who had persistent fever 10days after COVID-19, with FDG-PET/CT showing uptake from the ascending aorta to the aortic arch. In all cases, workups for immune and infectious diseases were negative. Symptoms and inflammatory markers resolved spontaneously or with nonsteroidal anti-inflammatory drugs. Serum anti-ACE2 IgG was positive during the active phase in all three patients and became negative during remission. We have encountered three cases of COVID-19-associated LVV with elevated anti-ACE2 antibodies that normalized after clinical remission. There have been multiple reports of LVV following SARS-CoV-2 infection, with onset typically within weeks of infection, and of elevated anti-ACE2 antibody levels in patients with COVID-19-related neurological complications. Further studies are warranted to determine if anti-ACE2 antibodies are associated with the pathogenesis of post-COVID-19 vasculitis.

Pharmacists provide pharmacological management prior to a physician visit, which is effective for the smooth introduction of biologics and the avoidance of serious side effects. However, pharmacists face challenges in implementing pharmacological management through dispensing alone. Furthermore, reports on the high risk of side effects associated with biologics remain limited. In this study, we investigated the cost-effectiveness and clinical impact of pharmaceutical management in outpatient pharmaceutical clinics for inflammatory immune diseases, from before the introduction of biologics until 52 weeks after introduction. The number of pharmacological management cases and their associated cost-effectiveness were compared between dispensing and outpatient pharmaceutical clinic groups. Patients aged ≥18 years with an autoimmune disease who were instructed to self-inject biologics between April 2018 and March 2023 were included. The primary outcome was the number of pharmacological management cases performed at the time of biologic introduction. A total of 264 eligible patients were identified, of whom 54 were excluded. After propensity score matching, patients were assigned to 2 groups (n = 67 each). Pharmacological management was significantly more common in the outpatient pharmaceutical clinic group (p < 0.05) than in the dispensing group. In the outpatient clinic group, 10 patients (14.9%) avoided severe adverse events, whereas avoidance was not observed in the dispensing group. The financial benefits of pharmacological management were 915000 and 26091000 yen in the dispensing and outpatient pharmaceutical clinic groups, respectively. Overall, this study demonstrated that pharmacist-led outpatient clinics targeting inflammatory autoimmune diseases can help prevent serious adverse drug reactions and are significantly cost-effective.

Abstract Introduction Murine ocular autoimmunity develops through 3 stages; prodrome, primary peak and secondary regulation. During the prodromal phase, leukocytes accumulate within the retina and vitreous. Methods Using the adoptive transfer of ocular antigen reactive T cells to induce experimental autoimmune uveitis, we can analyse the disease course and track the transferred cells being recruited to the ocular environment from prodrome through peak of disease to secondary regulation. Results During initiation (the prodrome) of disease ‘pathogenic’ transferred CD4+ T cells can be detected within the retina as well as an endogenous CD4+ infiltrate and as disease reaches peak, both transferred and endogenous CD4+ T cells can be found in large numbers in the retina. Active clinical disease resolves by day 21 but transferred CD4+ T cells persist within the retina when disease is in a clinically quiescent state. Concurrent transfer of RBP3 (also known as IRBP) specific and OVA specific activated cells induces a similar clinical disease phenotype and time course. Both RBP3 and OVA specific cells are recruited during active clinical disease in equal measure showing that autoantigen specific CD4+ T cells induce susceptibility for recruitment of other activated CD4+ T cells. When analysing the endogenous and transferred CD4+ T cells by RNA sequencing, differences between the two sets of gene signatures highlight genes that are also found in pathogenic T cells in other models, including upregulation of markers associated with cytokine interactions and NK cell mediated cytotoxicity. Conclusion Due to the persistence of the original transferred population throughout clinical disease, in depth analysis of this population could suggest pathways contributing to persistent ocular autoimmunity.

Risk of developing autoimmune and immune mediated disease following a diagnosis of myocarditis - a Danish nationwide register-based cohort study.