Proton Therapy Reduces the Effective Dose to Immune Cells in Mediastinal Hodgkin Lymphoma Patients.

Purpose: Effective dose to circulating immune cells (EDIC) is associated with survival in lung and esophageal cancer patients. This study aimed to evaluate the benefit of intensity-modulated proton therapy (IMPT) for EDIC reduction compared with volumetric modulated arc therapy (VMAT) in mediastinal Hodgkin lymphoma (mHL) patients. Materials and Methods: Ten consecutive mHL patients treated with involved-site IMPT after frontline chemotherapy were included. The mean dose to the heart, lung, and liver and the integral dose to the body were obtained, and we calculated EDIC based on these variables. The effective dose to circulating immune cells was compared between IMPT and VMAT schedules. Results: The median EDIC was reduced from 1.93 Gy (range: 1.31-3.87) with VMAT to 1.08 Gy (0.53-2.09) with IMPT (P < .01). Integral dose reduction was the main driver of EDIC reduction with IMPT, followed by lung sparing. Conclusion: Intensity-modulated proton therapy significantly reduced EDIC in mHL patients undergoing consolidation involved-site radiation therapy. Integral dose reduction combined with improved lung sparing was the main driver of EDIC reduction with IMPT.

Microbiome-host interactions in the pathogenesis of acute exacerbation of chronic obstructive pulmonary disease.

Objective: To explore the underlying mechanisms the airway microbiome contributes to Acute Exacerbation of Chronic Obstructive Pulmonary Disease(AECOPD). Methods: We enrolled 31 AECOPD patients and 26 stable COPD patients, their sputum samples were collected for metagenomic and RNA sequencing, and then subjected to bioinformatic analyses. The expression of host genes was validated by Quantitative Real-time PCR(qPCR) using the same batch of specimens. Results: Our results indicated a higher expression of Rothia mucilaginosa(p=0.015) in the AECOPD group and Haemophilus influenzae(p=0.005) in the COPD group. The Different expressed genes(DEGs) detected were significantly enriched in "type I interferon signaling pathway"(p<0.001, q=0.001) in gene function annotation, and "Cytosolic DNA-sensing pathway"(p=0.002, q=0.024), "Toll-like receptor signaling pathway"(p=0.006, q=0.045), and "TNF signaling pathway"(p=0.006, q=0.045) in KEGG enrichment analysis. qPCR amplification experiment verified that the expression of OASL and IL6 increased significantly in the AECOPD group. Conclusion: Pulmonary bacteria dysbiosis may regulate the pathogenesis of AECOPD through innate immune system pathways like type I interferon signaling pathway and Toll-like receptor signaling pathway.

Low Absolute Lymphocyte Count Correlates with Lymph Node Metastases and Worse Survival of Patients with Gastric Cancer.

BACKGROUND: Several studies have found that the absolute lymphocyte (ALC) or neutrophil count predicts the survival of patients with solid tumors, and that the neutrophil-to-lymphocyte ratio and the prognostic nutritional index are useful markers of gastric cancer prognosis. However, it remains unclear whether the ALC is prognostic of lymph node (LN) metastasis in patients with gastric cancer. In this study, we aimed to explore the impact of ALC on prognosis and distinctive clinical characteristics in patients with gastric cancer. PATIENTS AND METHODS: The medical records of patients with gastric adenocarcinomas who underwent radical gastrectomy with curative intent at Seoul St. Mary's Hospital and Yeouido St. Mary's Hospital between January 2010 and December 2017 were reviewed. Of these, 4149 patients for whom preoperative white blood cell, neutrophil, and lymphocyte counts were available were enrolled. RESULTS: In all 4149 patients, ALC gradually decreased as the pN stage increased. Those with an ALC of less than 1360 cells/µL were defined as a low-ALC group, and advanced cT and cN stages were the strongest risk factors for LN metastasis in both univariate and multivariate analyses; undifferentiated tumor histology and a low ALC were also significant risk factors. Patients of all stages in the ALC-low group exhibited poorer prognoses. The ALC-low group also exhibited a higher recurrence rate in a greater proportion of LNs. CONCLUSIONS: In patients with gastric cancer, as the preoperative ALC decreases, the incidence of LN metastasis increases. A low ALC is associated with a high recurrence rate, particularly in LNs.

Analysis of the expression of cytokines and chemokines, platelet-leukocyte aggregates, sCD40L and sCD62P in cutaneous melanoma.

BACKGROUND: Cutaneous melanoma (CM) is a malignancy with a variable incidence worldwide and a poor advanced-stage prognosis. Melanoma growth is closely associated with the immune system. METHODS: A cross-sectional study was performed on CM patients admitted at the Hospital de Cancer de Pernambuco (HCP) between 2015 and 2018. Fifty-one CM patients were included, and 30 healthy individuals. The study aimed to evaluate the association of platelet activation mechanisms and inflammatory response in patients with cutaneous melanoma. RESULTS: Elevated serum IL10 and low serum TNF levels in CM patients compared to controls (p < 0.05). High IL6 levels in patients with negative lymph nodes LN (-) compared to positive lymph nodes group (LN +, p = 0.0005). Low RANTES levels in patients compared to controls (p < 0.05). Elevated levels of platelet-lymphocyte (PLA), platelet-monocytes (PMA), and platelet-neutrophils (PNA) aggregates were observed in patients compared to controls (p < 0.05). CM patients with stage II had lower PMA levels than stages I and III (p < 0.05). High PMA levels were observed in patients with LN (+) compared to the LN (-) group (p < 0.0001). Patients with SSM had high levels of sCD40L and sCD62P compared to controls (p < 0.05)). High sCD40L levels in stage II compared to the stage III group, and sCD62P in stages I and II compared to the stage III group (p < 0.05). High sCD62P levels in patients with LN (-) compared to the group LN (+) (p < 0.05). CONCLUSION: It was observed the immunosuppressive profile in CM may favor tumor progression. High levels of platelet-leukocyte aggregates, sCD40L, and sCD62P may be associated with the worst prognosis.

Exploring beneficial effects of phytobiotics in marine shrimp farming: A review.

Marine shrimp farming, mainly Penaeus monodon and Litopenaeus vannamei, is an important component of the aquaculture industry. Marine shrimp farming helps produce a protein source for humans, provides job opportunities, and generates lucrative profits for investors. Intensification farming practices can lead to poor water quality, stress, and malnutrition among the farmed marine shrimp, resulting in disease outbreaks and poor production, impeding the development of marine shrimp farming. Antibiotics are the common short-term solution to treat diseases in marine shrimp farming. Moreover, the negative impacts of using antibiotics on public health and the environment erode consumer confidence in aquaculture products. Recently, research on using phytobiotics as a prophylactic agent in aquaculture has become a hot topic. Various phytobiotics have been explored to reveal their beneficial effects on aquaculture species. In this review paper, the sources and modes of action of phytobiotics are presented. The roles of phytobiotics in improving growth performance, increasing antioxidant capacity, enhancing the immune system, stimulating disease resistance, and mitigating stress due to abiotic factors in marine shrimp culture are recapitulated and discussed.

Pharmaceutical-mediated neuroimmune modulation in psychiatric/psychological adverse events.

The therapeutic use of many pharmaceuticals, including small molecules and biological therapies, has been associated with the onset of psychiatric and psychological adverse events (PPAEs), posing substantial concerns to patients' health and safety. These events, which encompass mood (e.g., depression, schizophrenia, suicidal ideation) and cognitive changes (e.g., learning and memory impairment, dementia) often remain undetected until advanced stages of clinical trials or pharmacovigilance, mostly because the mechanisms underlying the onset of PPAEs remain poorly understood. In recent years, the role of neuroimmune modulation (comprising an intricate interplay between various cell types and signaling pathways) in PPAEs has garnered substantial interest. Indeed, understanding these complex interactions would substantially contribute to increase the ability to predict the potential onset of PPAEs during preclinical stages of a new drug's R&D. This review provides a comprehensive summary of the most recent advances in neuroimmune modulation-related mechanisms contributing to the onset of PPAEs and their association with specific pharmaceuticals. Reported data strongly support an association between neuroimmune modulation and the onset of PPAEs. Pharmaceuticals may target specific molecular pathways and pathway elements (e.g., cholinergic and serotonergic systems), which in turn may directly or indirectly impact the inflammatory status and the homeostasis of the brain, regulating inflammation and neuronal function. Also, modulation of the peripheral immune system by pharmaceuticals that do not permeate the blood-brain barrier (e.g., monoclonal antibodies) may alter the neuroimmunomodulatory status of the brain, leading to PPAEs. In summary, this review underscores the diverse pathways through which drugs can influence brain inflammation, shedding light on potential targeted interventions.

From Tumor Macroenvironment to Tumor Microenvironment: The Prognostic Role of the Immune System in Oral and Lung Squamous Cell Carcinoma.

BACKGROUND: The interplay between cancer cells and the immune system is crucial in cancer progression and treatment. In this regard, the tumor immune microenvironment and macroenvironment, marked by systemic inflammation markers and TILs, could be considered key prognostic factors in tumors, including oral and lung squamous cell carcinoma. METHODS: We conducted a retrospective clinical study on patients with Oral Squamous Cell Carcinoma (OSCC) and Lung Squamous Cell Carcinoma (LUSCC), examining stages, comorbidities, treatments, and outcomes. We evaluated the prognostic significance of pre-surgical systemic inflammation markers and tumor microenvironment composition. RESULTS: Associations were found between systemic inflammation markers-NLR, MLR, and PLR-and tumor microenvironment factors, such as TILs and CD8+ cell prevalence-elevated inflammation markers correlated with advanced stages. Specifically, NLR was prognostic in OSCC, whereas PLR was prognostic in LUSCC. Using a cutoff value, we divided our tumor samples into two prognostic groups. Moreover, TILs levels >15% of tumor stroma correlated with prolonged overall survival in both OSCC and LUSCC, while increased CD8+ expression was linked to extended disease-free survival in LUSCC. DISCUSSION: Systemic inflammation markers and TILs can be valuable prognostic factors of survival, highlighting the immune response's role in OSCC and LUSCC. Despite limited clinical integration of the presented cohorts due to a lack of standardization, we concluded that analyzing tumor immune profiles may offer novel prognostic insights. CONCLUSIONS: Future integration into cancer classification could improve risk stratification and treatment guidance.

Balancing immune responses: regulatory cells in eosinophilic gastrointestinal disorders.

Eosinophilic gastrointestinal disorders (EGIDs) are a group of conditions characterized by an abnormal accumulation of eosinophils in the gastrointestinal tract, leading to inflammation and tissue damage. Regulatory cells are a subset of immune cells that are crucial in maintaining the balance of the immune system and preventing the occurrence of autoimmune diseases. In EGIDs, regulatory cells are believed to play a key role in controlling the immune response and overseeing the growth and activation of eosinophils in the gastrointestinal tract. There is evidence indicating that regulatory T cells (Tregs) and regulatory eosinophils may play a role in suppressing the inflammatory response in EGIDs. Regulatory eosinophils are a subgroup of eosinophils that possess an anti-inflammatory role. Recent studies have shown that enhancing the number or effectiveness of regulatory eosinophils can reduce the severity of EGIDs. Regulatory eosinophils dampen inflammation through their regulatory mediators, such as galectin-10 and growth factor beta (TGF-ß), which promote Treg expansion and inhibit effector T cell function. Further research on regulatory cells in EGIDs may have significant implications for the advancement of novel therapies for these uncommon and intricate disorders. The aim of this review is to provide complete view of the immune responses connected to EGIDs, examine the regulatory cells that control these responses, and evaluate their potential as therapeutic targets for EGID treatment.

Genetic diversity and signatures of selection in Icelandic horses and Exmoor ponies.

BACKGROUND: The Icelandic horse and Exmoor pony are ancient, native breeds, adapted to harsh environmental conditions and they have both undergone severe historic bottlenecks. However, in modern days, the selection pressures on these breeds differ substantially. The aim of this study was to assess genetic diversity in both breeds through expected (HE) and observed heterozygosity (HO) and effective population size (Ne). Furthermore, we aimed to identify runs of homozygosity (ROH) to estimate and compare genomic inbreeding and signatures of selection in the breeds. RESULTS: HO was estimated at 0.34 and 0.33 in the Icelandic horse and Exmoor pony, respectively, aligning closely with HE of 0.34 for both breeds. Based on genomic data, the Ne for the last generation was calculated to be 125 individuals for Icelandic horses and 42 for Exmoor ponies. Genomic inbreeding coefficient (FROH) ranged from 0.08 to 0.20 for the Icelandic horse and 0.12 to 0.27 for the Exmoor pony, with the majority of inbreeding attributed to short ROHs in both breeds. Several ROH islands associated with performance were identified in the Icelandic horse, featuring target genes such as DMRT3, DOCK8, EDNRB, SLAIN1, and NEURL1. Shared ROH islands between both breeds were linked to metabolic processes (FOXO1), body size, and the immune system (CYRIB), while private ROH islands in Exmoor ponies were associated with coat colours (ASIP, TBX3, OCA2), immune system (LYG1, LYG2), and fertility (TEX14, SPO11, ADAM20). CONCLUSIONS: Evaluations of genetic diversity and inbreeding reveal insights into the evolutionary trajectories of both breeds, highlighting the consequences of population bottlenecks. While the genetic diversity in the Icelandic horse is acceptable, a critically low genetic diversity was estimated for the Exmoor pony, which requires further validation. Identified signatures of selection highlight the differences in the use of the two breeds as well as their adaptive trait similarities. The results provide insight into genomic regions under selection pressure in a gaited performance horse breed and various adaptive traits in small-sized native horse breeds. This understanding contributes to preserving genetic diversity and population health in these equine populations.

Moderate physical activity during neoadjuvant chemotherapy in breast cancer patients: effect on cancer-related inflammation and pathological complete response-the Neo-Runner study.

BACKGROUND: Physical activity (PA) reduces the risk of developing breast cancer (BC) and mortality rate in BC patients starting PA after diagnosis. Immunomodulation is considered responsible for these effects. However, limited data exist on the immunomodulation induced by moderate PA (mPA) during neoadjuvant chemotherapy (NACT). We have investigated the longitudinal change of cytokines during NACT alone or combined with mPA. MATERIALS AND METHODS: Twenty-three cytokines were analyzed in BC patients at consecutive timepoints: at baseline (T0), before starting mPA (T1), before surgery (T2), and after surgery (T3). mPA consisted of 3-weekly brisk-walking sessions for 9-10 consecutive weeks. RESULTS: Ninety-two patients were assessed: 21 patients refused mPA (untrained) and 71 agreed (trained). At T1, NACT induced significant up-regulation of interleukin (IL)-5, IL-6, IL-15, chemokine ligand (CCL)-2, interferon-γ, and C-X-C motif ligand (CXCL)-10 and reduction of expression of IL-13 and CCL-22. At T2, NACT and mPA induced up-regulation of IL-21, CCL-2, and tumor necrosis factor-α and reduction of expression of IL-8, IL-15, vascular endothelial growth factor, and soluble interleukin 6 receptor. Only CXCL-10 increased in untrained patients. A cytokine score (CS) was created to analyze, all together, the changes between T1 and T2. At T2 the CS decreased in trained and increased in untrained patients. We clustered the patients using cytokines and predictive factors and identified two clusters. The cluster A, encompassing 90% of trained patients, showed more pathological complete response (pCR) compared to the cluster B: 78% versus 22%, respectively. CONCLUSIONS: mPA interacts with NACT inducing CS reduction in trained patients not observed in untrained patients, suggesting a reduction of inflammation, notwithstanding chemotherapy. This effect may contribute to the higher rate of pCR observed in the cluster A, including most trained patients.

Stress-sensitive neural circuits change the gut microbiome via duodenal glands.

Negative psychological states impact immunity by altering the gut microbiome. However, the relationship between brain states and microbiome composition remains unclear. We show that Brunner's glands in the duodenum couple stress-sensitive brain circuits to bacterial homeostasis. Brunner's glands mediated the enrichment of gut Lactobacillus species in response to vagus nerve stimulation. Cell-specific ablation of the glands markedly suppressed Lactobacilli counts and heightened vulnerability to infection. In the forebrain, we mapped a vagally mediated, polysynaptic circuit connecting the central nucleus of the amygdala to Brunner's glands. Chronic stress suppressed central amygdala activity and phenocopied the effects of gland lesions. Conversely, excitation of either the central amygdala or parasympathetic vagal neurons activated Brunner's glands and reversed the effects of stress on the gut microbiome and immunity. The findings revealed a tractable brain-body mechanism linking psychological states to host defense.

Expression of C/EBP and Kr-h1 transcription factors under immune stimulation in the noble crayfish.

Transcription factors (TFs) have an important role in the regulation of the gene expression network. The role of TFs in the immune response of freshwater crayfish is poorly understood, but leveraging the regulatory mechanisms of immune response could augment the resistance against the invasive oomycete pathogen, Aphanomyces astaci. Previous studies indicated that the TFs CCAAT/enhancer-binding protein (C/EBP) and putative Krüppel homolog-1 protein (Kr-h1) might play a role in immune and stress response of the noble crayfish (Astacus astacus). Here, we aimed to further characterise these two gene products to gain a better understanding of their evolutionary origin, domain organisation and expression patterns across different crayfish tissues. Furthermore, we conducted an immune stimulation experiment to observe the potential changes in the gene expression of C/EBP and Kr-h1 under immune challenge in different crayfish tissues. Our results showed that both C/EBP and Kr-h1 are closely related to other C/EBPs and Kr-h1s in Malacostraca. Gene expression analysis revealed that both TFs are present in all analysed tissues, with higher expression of C/EBP in the gills and Kr-h1 in the abdominal muscle. Immune stimulation with laminarin (mimicking ß-1-3-glucan in the oomycete cell wall) showed an activation of the crayfish immune system, with an overall increase in the total haemocyte count (THC) compared to untreated control and crayfish buffered saline (CBS) treatment. On the gene expression level, an up-regulation of the C/EBP gene was detected in the laminarin treated group in hepatopancreas and heart, while no changes were observed for the Kr-h1 gene. Our results indicate an early change in C/EBP expression in multiple tissues during immune stimulation and suggest its involvement in the immune response of the noble crayfish.

Lysosomal Activation Mediated by Endocytosis in J774 Cell Culture Treated with N-Trimethyl Chitosan Nanoparticles.

Safety and effectiveness are the cornerstone objectives of nanomedicine in developing nanotherapies. It is crucial to understand the biological interactions between nanoparticles and immune cells. This study focuses on the manufacture by the microfluidic technique of N-trimethyl chitosan/protein nanocarriers and their interaction with J774 cells to elucidate the cellular processes involved in absorption and their impact on the immune system, mainly through endocytosis, activation of lysosomes and intracellular degradation. TEM of the manufactured nanoparticles showed spherical morphology with an average diameter ranging from 36 ± 16 nm to 179 ± 92 nm, depending on the concentration of the cargo protein (0, 12, 55 µg/mL). FTIR showed the crosslinking between N-trimethyl chitosan and the sodium tripolyphosphate and the α-helix binding loss of BSA. TGA revealed an increase in the thermal stability of N-trimethyl chitosan/protein nanoparticles compared with the powder. The encapsulation of the cargo protein used was demonstrated using XPS. Their potential to improve cell permeability and use as nanocarriers in future vaccine formulations was demonstrated. The toxicity of the nanoparticles in HaCaT and J774 cells was studied, as well as the importance of evaluating the differentiation status of J774 cells. Thus, possible endocytosis pathways and their impact on the immune response were discussed. This allowed us to conclude that N-trimethyl chitosan nanoparticles show potential as carriers for the immune system. Still, more studies are required to understand their effectiveness and possible use in therapies.

The Role of the Gut and Airway Microbiota in Chronic Rhinosinusitis with Nasal Polyps: A Systematic Review.

In recent years, there has been growing interest in understanding the potential role of microbiota dysbiosis or alterations in the composition and function of human microbiota in the development of chronic rhinosinusitis with nasal polyposis (CRSwNP). This systematic review evaluated the literature on CRSwNP and host microbiota for the last ten years, including mainly nasal bacteria, viruses, and fungi, following the PRISMA guidelines and using the major scientific publication databases. Seventy original papers, mainly from Asia and Europe, met the inclusion criteria, providing a comprehensive overview of the microbiota composition in CRSwNP patients and its implications for inflammatory processes in nasal polyps. This review also explores the potential impact of microbiota-modulating therapies for the CRSwNP treatment. Despite variability in study populations and methodologies, findings suggest that fluctuations in specific taxa abundance and reduced bacterial diversity can be accepted as critical factors influencing the onset or severity of CRSwNP. These microbiota alterations appear to be implicated in triggering cell-mediated immune responses, cytokine cascade changes, and defects in the epithelial barrier. Although further human studies are required, microbiota-modulating strategies could become integral to future combined CRSwNP treatments, complementing current therapies that mainly target inflammatory mediators and potentially improving patient outcomes.

Role of tight junction proteins in shaping the immune milieu of malignancies.

INTRODUCTION: Tight junctions (TJs) and their constituent proteins play pivotal roles in cellular physiology and anatomy by establishing functional boundaries within and between neighboring cells. While the involvement of TJ proteins, such as claudins, in cancer is extensively studied, studies highlighting their interaction with immune system are still meager. Studies indicate that alterations in cytokines and immune cell populations can affect TJ proteins, compromising TJ barrier function and exacerbating pro-inflammatory conditions, potentially leading to epithelial cell malignancy. Disrupted TJs in established tumors may foster a pro-tumor immune microenvironment, facilitating tumor progression, invasion, epithelial-to-mesenchymal transition and metastasis. Although previous literature contains many studies describing the involvement of TJs in pathogenesis of malignancies their role in modulating the immune microenvironment of tumors is just beginning to be unleashed. AREAS COVERED: This article for the first time attempts to discern the importance of interaction between TJs and immune microenvironment in malignancies. To achieve the above aim a thorough search of databases like PubMed and Google Scholar was conducted to identify the recent and relevant articles on the topic. EXPERT OPINION: Breaking the vicious cycle of dysbiosis/infections/chemical/carcinogen-induced inflammation-TJ remodeling-malignancy-TJ dysregulation-more inflammation can be used as a strategy to complement the effect of immunotherapies in various malignancies.

Biological Clock Perspective in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic polyarticular pain, and its main pathological features include inflammatory cell infiltration, synovial fibroblast proliferation, and cartilage erosion. Immune cells, synovial cells and neuroendocrine factors play pivotal roles in the pathophysiological mechanism underlying rheumatoid arthritis. Biological clock genes regulate immune cell functions, which is linked to rhythmic changes in arthritis pathology. Additionally, the interaction between biological clock genes and neuroendocrine factors is also involved in rhythmic changes in rheumatoid arthritis. This review provides an overview of the contributions of circadian rhythm genes to RA pathology, including their interaction with the immune system and their involvement in regulating the secretion and function of neuroendocrine factors. A molecular understanding of the role of the circadian rhythm in RA may offer insights for effective disease management.

Exploring genetic associations in systemic lupus erythematosus through Mendelian randomization: implications for novel biomarkers and therapeutic targets.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a significant health burden. There is an essential need for novel biomarkers and therapeutic targets to improve diagnosis and management. Mendelian randomization (MR) was applied to explore causal links between SLE and various biomarkers like immune cells, metabolites, and inflammatory cytokines using multiple databases. Initially, biomarkers significantly associated with SLE were identified. Bidirectional MR helped clarify these relationships, and a two-step mediation MR examined their effects on SLE risk. Intersection analysis was used to identify biomarkers with consistent effects across datasets. Four biomarkers were identified as having significant associations with SLE risk: 1-palmitoyl-2-arachidonoyl-GPI levels [odds ratio (OR), 1.379; 95% confidence interval (CI), 1.180 to 1.613; FDR, 0.046], IL-17A levels (OR, 2.197; 95% CI, 1.412 to 3.418; FDR, 0.044), N-acetyl-aspartyl-glutamate (NAAG) levels (OR, 0.882; 95% CI, 0.831 to 0.936; FDR, 0.030), and ribitol levels (OR, 0.743; 95% CI, 0.644 to 0.857; FDR, 0.012). Bidirectional MR showed an inverse effect of NAAG on IL-17A levels (OR, 0.978; 95% CI, 0.962 to 0.994; p = 0.006). Mediation analysis indicated that NAAG influenced SLE risk both directly (beta = - 0.108) and indirectly through IL-17A (beta = - 0.018), highlighting the potential mediating role of IL-17A. After expanding the significance criteria to p < 0.05, intersection analysis across multiple datasets revealed 29 biomarkers with consistent beta directions, including 19 potential risk factors (beta > 0) and 10 protective factors (beta < 0) for SLE. This research has revealed significant genetic associations with SLE and demonstrated that IL-17A mediates the relationship between NAAG levels and SLE risk, highlighting potential new targets for personalized therapeutic interventions. Key Points • This study employs MR to identify significant genetic associations between various biomarkers and SLE, providing novel insights into potential biomarkers and therapeutic targets. • Four key biomarkers were identified as significantly associated with SLE risk: 1-palmitoyl-2-arachidonoyl-GPI, IL-17A, N-acetyl-aspartyl-glutamate (NAAG), and ribitol. • The findings suggest that NAAG levels have a protective effect against SLE, partly mediated through IL-17A, indicating a complex interplay between these biomarkers in the pathogenesis of SLE. • Intersectional analysis across multiple datasets revealed 29 biomarkers with consistent effects on SLE risk, highlighting new directions for future research and potential personalized therapeutic strategies.

Association between cardiovascular inflammation and alterations in immune system induced by HIV infection detected on [18F]FDG PET/MRI.

OBJECTIVE: To assess by [18F]FDG PET/MR the biomarkers of HIV-induced inflammation at baseline and 1 year post-antiretroviral therapy (ART). METHODS: Prospective study, 14 patients, newly diagnosed HIV-positive, asymptomatic. [18F]FDG PET/MRI (PET/MR-3.0 T, Signa.GE) whole body and heart was performed, baseline and 1 year post-ART. Qualitative vascular assessment (hepatic reference). Quantitative assessment (SUVmax) of the whole body. T1 and T2 value estimation in 16 myocardial segments. RESULTS: Baseline CMR showed in 3 (21.4%) a decreased LVEF, normalising post-TAR. Fibrosis was ruled out (T1), with no signs of myocardial oedema (T2) at baseline or post-TAR. Four (28.6%) showed baseline vascular [18F]FDG uptake, two in ascending thoracic aorta and two in ascending and descending thoracic aorta, normalising post-TAR. All (100%) showed basal lymph-nodes activity; supra (n:14) and infradiaphragmatic (n:13), laterocervical (n:14) and inguinal (n:13), with variable number of territories (9 patients >6;64.3%). Post-ART, 7 patients (50%) showed resolution and the other 7 reduction in extension (0 patients >5): 7 supra (100%) and 2 infradiaphragmatic (28.6%), 5 in the axilla and 2 in the groin. All (100%) had persistent basal adenoid uptake post-ART, 9 (64.3%) splenic all resolved post-ART and 7 (50.5%) gastric, persistent 3 post-ART. CONCLUSIONS: Cardiovascular biomarkers by [18F]FDG PET/MR have shown baseline 28.6% of patients with large vessel activity and 21.4% with low LVEF, normalising post-ART. Inflammatory/immune biomarkers showed baseline activity in 100% of lymph-nodes, 100% adenoids, 64.3% splenic and 50.5% gastric. Post-TAR the reduction was 50% lymph-nodes, 0% adenoid, 100% splenic and 57.1% gastric.

Recurrent herpes infection showing a new facial phenotype: A case report.

BACKGROUND: Facial herpes is a common form of the herpes simplex virus-1 infection and usually presents as vesicles near the mouth, nose, and periocular sites. In contrast, we observed a new facial symptom of herpes on the entire face without vesicles. CASE SUMMARY: A 33-year-old woman with a history of varicella infection and shingles since an early age presented with sarcoidosis of the entire face and neuralgia without oral lesions. The patient was prescribed antiviral treatment with valacyclovir and acyclovir cream. One day after drug administration, facial skin lesions and neurological pain improved. Herpes simplex without oral blisters can easily be misdiagnosed as pimples upon visual examination in an outpatient clinic. CONCLUSION: As acute herpes simplex is accompanied by neuralgia, prompt diagnosis and prescription are necessary, considering the pathological history and health conditions.