Immune System Abnormalities Research Articles

Important role of relationship between brain and spleen in the mechanisms of chronic pain development and maintenance in fibromyalgia

Fibromyalgia (FM) is characterized by chronic generalized pain accompanied by various symptoms, such as extreme fatigue, insomnia and depression. Clinical studies have indicated the presence of psychological stress, sympathetic nervous system hyperexcitation and immune system abnormalities, as a trigger for the onset of the disease, but the contribution to the pathogenesis of the disease remains unclear. Here, we employed the repeated acid saline-induced generalized pain (AcGP) model, as an experimental mouse model of FM. In this model, the unilateral repeated acid injection into gastrocnemius muscle induced transient and long-lasting mechanical hypersensitivity. We focused on the spleen, a secondary lymphoid organ, and found that the intravenous treatments of splenocytes derived from AcGP mice caused mechanical hypersensitivity in naїve mice. Since the spleen is directly innervated by sympathetic nerve, we examined whether adrenergic receptors are necessary for pain development or maintenance. The administration of butoxamine, a selective β2-blocker, prevented the development but did not reverse the maintenance of pain-like behavior in AcGP mice. Furthermore, β2-blockade in donor AcGP mice eliminated pain reproduction in recipient mice injected with AcGP splenocytes. We currently employed another model of FM, the intermittent psychological stress-induced generalized pain (IPGP) model and found that as in AcGP model, the sympathetic nervous system and the spleen play important roles. These results suggest that sympathetic β2 signaling is enhanced by physical/psychological stress, and that immune system cells in the spleen activated in response play an important role in the formation and maintenance of chronic pain.

Pseudomonas aeruginosa-Mannose Sensitive Hemagglutinin-based Treatment Strategy for Liver Cancer

Background Although it does not represent a threat to healthy humans, Pseudomonas aeruginosa is a type of aerobic, gram-negative bacteria that can cause catastrophic infections in patients with immune system abnormalities and cystic fibrosis. Purpose The current study investigated the effect of Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA) on liver cancer cell viability, colony formation, and invasion potential, and explored the underlying mechanism. Methods Proliferation potential and clonogenic survival of the cells were studied using MTT and colony formation assays, respectively. Transwell and Western blotting assays were used for the assessment of invasive potential and protein expression, respectively. Results The results revealed that exposure to PA-MSHA led to a time-dependent suppression in HepG2 and HEP3B cell proliferation. Incubation with PA-MSHA decreased HepG2 cell proliferation to 92%, 75%, 50%, 35%, and 20%, respectively, after 12, 24, 36, 48, and 72 hours. Similarly, incubation for 12, 24, 36, 48, and 72 hours reduced the proliferation of HEP3B cells to 94%, 79%, 55%, 41%, and 26%, respectively. The rate of clonogenic survival was significantly lower in HepG2 and HEP3B cells on incubation with PA-MSHA. The cell invasion potential was also significantly reduced on incubation with PA-MSHA. In HepG2 cells, incubation with PA-MSHA significantly reduced the expression of Bcl-2 (26 kDa) protein and promoted Bax (21 kDa) level. Following incubation with PA-MSHA, HepG2 cells showed higher cleaved caspase-3 level compared to the control cells. Compared to control cells, the PA-MSHA incubation of HepG2 cells resulted in a prominent reduction in Notch3 protein expression. Conclusion In summary, PA-MSHA treatment prevents liver cancer cell proliferation and targets the survival of clonogenic cells. It reduces invasiveness, targets Notch3 protein expression in liver cancer cells, and increases the level of proapoptotic and suppresses antiapoptotic protein expression. Therefore, PA-MSHA shows encouraging anticancer effects on HepG2 and HEP3B cancer cells, suggesting that it could be developed as a viable treatment option for liver cancer.

7975 TLR4 Signaling Modulates Reproductive and Metabolic Outcomes in a Mouse Model of Polycystic Ovary Syndrome

Abstract Disclosure: K.D. Wiggins: None. Z. Del Mundo: None. J.A. Ayala Angulo: None. M. Lopez: None. C. Garcia: None. C. Nguyen: None. J. De La Torre: None. A. Saba: None. D. Trinh: None. D. Nicholas: None. Polycystic Ovarian Syndrome (PCOS), characterized by disruptions in both reproductive and metabolic functions, is associated with abnormal immune system activity and chronic inflammation. Although the precise mechanistic drivers of chronic inflammation in PCOS are not fully elucidated, elevated serum levels of lipopolysaccharide (LPS) have been observed. We propose that Toll-like receptor 4 (TLR4) signaling, influenced by dysregulated LPS levels, is a central driver of chronic inflammation affecting both reproductive and metabolic pathways. To investigate this hypothesis, we subcutaneously implanted a nonsteroidal aromatase inhibitor, Letrozole (LET), in pubertal TLR4 knockout mice (TLR4KO) and C57BL/6J (wild type) mice. Our five-week LET treatment revealed that TLR4KO mice successfully entered all phases of the estrous cycle, with normalized Luteinizing Hormone (LH) and increased Follicle Stimulating Hormone (FSH) levels. These findings highlight TLR4's role in shaping cycling patterns and regulating fundamental hormonal pathways vital for reproductive health. Despite the genetic manipulation of the inflammatory pathway leading to a reduction in overall body weight gain, it had no discernible impact on the overall body composition of fat and lean mass. Additionally, our study found that dysregulation of blood glucose levels over time was independent of reduced body weight. TLR4KO mice demonstrated inefficient glucose clearance compared to wild-type mice, hinting at potential increases in insulin resistance, imbalances in adipose tissue inflammation, or possible alterations in the gut microbiota. Our study underscores the significance of disrupting the pro-inflammatory TLR4 pathway in shaping the reproductive and metabolic phenotypes in Letrozole-induced PCOS. The investigation into TLR4 becomes pivotal for comprehending the role of chronic inflammation in PCOS development or progression, offering valuable insights into potential therapeutic targets. Presentation: 6/2/2024

Systemic lupus erythematosus and epilepsy: A Mendelian randomization study.

Numerous observational studies have found a relationship between systemic lupus erythematosus (SLE) and epilepsy; however, their causal relationship remains unclear. This study aimed to investigate the causal role of SLE in epilepsy or any of its subtypes using a two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms (SNPs) linked to SLE were utilized as instrumental variables in MR analysis to assess their causal impact on epilepsy. The primary MR findings were derived using the inverse variance weighted (IVW) method, which was further supported by the weighted median and MR-Egger regression techniques. Additionally, sensitivity analyses, including Cochran's Q test and pleiotropy tests, were conducted to evaluate the influence of these SNPs on epilepsy, particularly looking for signs of horizontal pleiotropy and heterogeneity. We selected 43 SNPs that reached genome-wide significance from genome-wide association studies (GWASs) on SLE to serve as instrumental variables in this study. The IVW method showed no evidence to support a causal association between SLE and epilepsy (all epilepsy: odds ratio (OR) = 1.006, 95% confidence interval (CI) = 0.994-1.018; focal epilepsy: OR = 1.006, 95% CI = 0.994-1.019; generalized epilepsy: OR = 1.015, 95% CI = 0.996-1.035). Other MR complementary methods revealed consistent results. Furthermore, there was no evidence indicating heterogeneity or horizontal pleiotropy. The findings of MR analysis did not support a genetically predicted causal relationship between SLE and epilepsy, but emphasized the need for further research on shared pathophysiological mechanisms, particularly the role of immune system abnormalities and potential influences such as chronic inflammation and therapeutic interventions. The etiology of epilepsy is complex and diverse, including immune factors. Through a Mendelian randomization analysis, we did not find evidence of a genetic causal relationship between systemic lupus erythematosus and epilepsy. However, this does not invalidate epidemiological evidence, and further exploration is needed to investigate factors influencing the relationship between the two.

Exploring Dietary Interventions in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) involves social communication difficulties and repetitive behaviors, and it has a growing prevalence worldwide. Symptoms include cognitive impairments, gastrointestinal (GI) issues, feeding difficulties, and psychological problems. A significant concern in ASD is food selectivity, leading to nutrient deficiencies. Common GI issues in ASD, such as constipation and irritable bowel syndrome, stem from abnormal gut flora and immune system dysregulation. Sensory sensitivities and behavioral challenges exacerbate these problems, correlating with neurological symptom severity. Children with ASD also exhibit higher oxidative stress due to low antioxidant levels like glutathione. Therapeutic diets, including ketogenic, high-antioxidant, gluten-free and casein-free, and probiotic-rich diets, show potential in managing ASD symptoms like behavior, communication, GI issues, and oxidative stress, though the evidence is limited. Various studies have focused on different populations, but there is increasing concern about the impact among children. This review aims to highlight the food preferences of the ASD population, analyze the effect of the physicochemical and nutritional properties of foods on the selectivity in its consumption, GI problems, and antioxidant deficiencies in individuals with ASD, and evaluate the effectiveness of therapeutic diets, including diets rich in antioxidants, gluten-free and casein-free, ketogenic and essential fatty acids, and probiotic-rich diets in managing these challenges.

A case report of Stevens-Johnson syndrome caused by omeprazole.

Stevens-Johnson syndrome (SJS) is a rare but severe skin-mucosal reaction with a high mortality rate. It is characterized by sudden, painful blistering lesions on the skin, often accompanied by high fever and systemic toxicity. Lesions typically appear on the dorsal surfaces of the hands, feet, forearms, legs, and soles of the feet. They can also affect the conjunctiva, oral mucosa, labial mucosa, and vaginal mucosa. Patients may experience complications such as pneumonia, severe comorbidities, and liver and renal failure. A 51-year-old female patient was admitted to the hospital due to "abdominal distention and skin yellowing for 20 days." After using omeprazole, she developed a rash all over her body, and her liver function further deteriorated, ultimately leading to chronic acute liver failure. The diagnosis included fever, rash suspected to be drug-induced, chronic and acute liver failure, and decompensation of post-Hepatitis B cirrhosis. During hospitalization, suspected adverse drug reactions were discontinued, and symptomatic supportive treatment with methylprednisolone and fluid replacement was promptly provided. The patient's symptoms and follow-up showed that the rash disappeared and liver and kidney function improved significantly after treatment. We explored how chronic acute liver failure can cause immune system abnormalities and immune paralysis in patients, manifested as susceptibility to infection. This case report describes a drug-induced allergic reaction - SJS - in patients with chronic acute liver failure, as well as subsequent treatment, including hormone dosage and treatment duration. I hope this report will help enrich the relevant literature on drug-induced SJS combined with chronic and acute liver failure, laying the foundation for improving the survival rate of patients with the disease.

Rosacea and autoimmune liver diseases: a two-sample Mendelian randomization study

Rosacea and autoimmune liver diseases (AILDs) are diseases closely associated with immune system abnormalities. AILDs primarily includes autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Currently, research on the association between these two conditions is limited. Therefore, this study employed the bidirectional Mendelian randomization (MR) method to investigate potential causal relationships between rosacea and AILDs based on genetic predictions. Summary data related to Rosacea, AIH, PSC, and PBC were obtained from public genome-wide association studies (GWAS). The inverse variance weighted (IVW) method was used as the primary analytical approach, supplemented by the MR-Egger, weighted mode method, weighted median, and simple mode. A series of sensitivity analyses were also conducted to identify heterogeneity and pleiotropy effects. The MR analysis results indicated a significant increase in the risk of rosacea being associated with PBC (OR = 1.09, 95% CI = 1.02–1.18, P = 0.014), but no such association was found with AIH or PSC. Furthermore, this study did not find a significant impact of rosacea on the risk of AILDs. This study represents the first in-depth exploration of the potential causal relationship between rosacea and AILDs using MR analysis. Thes findings suggest an increased risk of rosacea among PBC patients.

The plasma viral communities associate with clinical profiles in a large-scale haematological patients cohort

BackgroundHaematological patients exhibit immune system abnormalities that make them susceptible to viral infections. Understanding the relationship between the virome in the blood plasma of haematological patients and their clinical characteristic is crucial for disease management. We aimed to explore the presence of viral pathogens and identify close associations between viral infections and various clinical features.ResultsA total of 21 DNA viruses and 6 RNA viruses from 12 virus families were identified from 1383 patients. Patients with haematological diseases exhibited significantly higher diversity, prevalence, and co-detection rates of viral pathogens. During fever episodes, pathogen detection was notably higher, with Epstein-Barr virus (EBV) and Mucorales infections being the most probable culprits for fever symptoms in non-haematological patients. The detection rate of torque teno virus (TTV) significantly increases in haematological patients after transplantation and during primary lung infections. Additionally, TTV-positive patients demonstrate significantly higher absolute neutrophil counts, while C-reactive protein and procalcitonin levels are notably lower. Furthermore, TTV, cytomegalovirus, and parvovirus B19 (B19V) were found to be more prevalent in non-neutropenic patients, while non-viral pathogenic infections, such as Gram-negative bacteria and Mucorales, were more common in neutropenic patients. Pegivirus C (HPgV-C) infection often occurred post-transplantation, regardless of neutropenia. Additionally, some viruses such as TTV, B19V, EBV, and HPgV-C showed preferences for age and seasonal infections.ConclusionsAnalysis of the plasma virome revealed the susceptibility of haematological patients to plasma viral infections at specific disease stages, along with the occurrence of mixed infections with non-viral pathogens. Close associations were observed between the plasma virome and various clinical characteristics, as well as clinical detection parameters. Understanding plasma virome aids in auxiliary clinical diagnosis and treatment, enabling early prevention to reduce infection rates in patients and improve their quality of life.EnXnzQJ5tBc4iYM41USpCeVideo

Application of Cross-Validation Techniques to Handle Overfitting in a Case Study of Decision Tree Implementation for Lung Cancer Prediction

Lung cancer is a condition caused by cancer cells growing in the lungs. Lung cancer causes a weakened immune system, tumors, and other abnormalities that prevent the body from functioning properly. Lung cancer examination uses various technologies, namely CT Scan, X-ray, and others. However, the examination is relatively expensive and takes a long time. The use of machine learning makes it possible to support lung cancer diagnosis. With the large amount of medical data available today, machine learning can recognize patterns in the data so that it will help the process of diagnosing lung cancer more effectively. This study aims to correct overfitting in previous research which used the decision tree method to predict lung cancer with cross-validation techniques. In this research, we use a public dataset from Data World. This dataset consists of 25 data attributes and has 1000 data. The results of this research are rules obtained from decision trees which are then evaluated to produce 96.7% accuracy, 96.7% precision, 96.7% recall, and 96.7% f1-score. These results show that the decision tree method performs well in predicting lung cancer early and the cross-validation technique can overcome overfitting in decision trees with more general and stable results.

Neutrophil/lymphocyte ratio and cognitive performances in first-episode patients with schizophrenia and healthy controls

Abnormal immune and inflammatory responses are considered to contribute to schizophrenia (SZ). The neutrophil/lymphocyte ratio (NLR) is an inexpensive and reproducible marker of systemic inflammatory responses. Accumulating studies have demonstrated that NLR values are increased in SZ compared to healthy controls and closely related to clinical symptoms in antipsychotic-naïve first-episode SZ (ANFES) patients. However, to our knowledge, only one study has examined NLR in relation to neurocognition in 27 first-episode psychosis patients and 27 controls. This study aimed to examine the relationship of NLR values with cognitive performances in ANFES patients with a larger sample size. Whole blood cell counts were measured in ninety-seven ANFES patients and fifty-six control subjects. The neurocognitive functions of all subjects were measured by the repeatable battery for the assessment of neuropsychological status (RBANS). ANFES patients performed worse on cognition and had increased NLR values relative to healthy controls. In addition, increased NLR was negatively associated with cognitive functions in ANFES patients. Lymphocyte count was positively correlated with cognitive functions in patients. These findings suggest that the abnormal immune and inflammation system indicated by NLR may be involved in the cognitive functions in ANFES patients.

Parotid saliva and blood biomarkers in juvenile idiopathic arthritis in relation to temporomandibular joint magnetic resonance imaging findings.

Juvenile idiopathic arthritis (JIA) often affects the temporomandibular joint (TMJ) caused by an abnormal immune system that includes overactive inflammatory processes. Salivary biomarkers may be a powerful tool that can help establishing diagnosis, prognosis and monitor disease progress. The objective was to investigate biomarkers in parotid saliva and blood plasma in relation to temporomandibular joint (TMJ) magnetic resonance imaging (MRI) findings in patients with JIA and healthy individuals. Forty-five children aged 6 to 16 years with JIA and 16 healthy age- and sex-matched controls were included. Unstimulated parotid saliva samples and venous blood were collected. Biochemical analyses were performed for the cytokine biomarkers. The participants underwent MR imaging of the TMJs, where changes in the inflammatory and the damage domains were assessed. In the JIA patients, lower concentrations of IL-6R and gp130 were found in parotid saliva than in plasma. Higher concentrations of IL-6 were found in parotid saliva than in plasma. IL-6, IL-6R and gp130 in parotid saliva explained the presence of bone marrow oedema and effusion in the JIA patients. This study suggests that the IL-6 family in parotid saliva is associated with TMJ bone marrow oedema and effusion in patients with JIA, suggesting that IL-6 has promising properties as a parotid saliva biomarker for TMJ inflammatory activity.

Cardiovascular risk reduction in type 2 diabetes: What the non-specialist needs to know about current guidelines.

In the US, approximately 11% of the population have diagnosed diabetes and nearly 40% have prediabetes. In addition, chronic kidney disease (CKD) affects 14% of the US population including up to 40% of those with diabetes. Cardiovascular disease (CVD) remains the leading cause of death worldwide where it affects approximately half of adults. The presence of CKD or diabetes doubles the risk of cardiovascular events. When both CKD and diabetes occur in the same patient the risks are further increased. The clinical problems of hypertension, hyperglycemia, and hyperlipidemia are all closely related with obesity, metabolic syndrome, Type 2 diabetes, CKD, atherosclerotic cardiovascular disease, heart failure and non-alcoholic fatty liver disease and metabolic dysfunction-associated steatohepatitis. The increasing frequency of obesity has driven increases in all of these medical comorbidities. These conditions frequently cluster together in the same patient exacerbating the risk of morbidity and mortality. They are also associated with cognitive dysfunction/dementia, pulmonary diseases, cancers, gastrointestinal diseases, immune system abnormalities, and inflammatory disorders. Only 6.8% of adults in US meet all targets for cardiovascular risk management with significant disparities based on race and ethnicity. Given the complexity of these multisystem problems in people with diabetes and obesity, it would seem reasonable to attempt to diagnose and treat many of the comorbidities earlier in the course of disease rather than wait for substantial end organ dysfunction to occur. The American Diabetes Association (ADA) has recently published a consensus statement recommending early screening for the diagnosis of heart failure, CKD and diabetes, recognizing both the frequency and gravity of this combination. Likewise, there are recommendations in the guidelines to facilitate screening for microalbuminuria, blood pressure, glycemic control and lipids earlier in patients at risk rather than wait and treat as a secondary prevention program. Thus, the general principle is to facilitate earlier recognition and diagnosis and provide treatment before downstream target organ complications occur. This review will focus on CVD and risk management based on newest recommendations and standards of care in people with diabetes by the ADA. The main considerations in the treatment of people with diabetes are glycemic control, blood pressure, lipids, and the use of medications with proven cardiorenal disease progression capability to prevent or delay.

A comprehensive review on the association and prevention of long-term COVID-induced heart failure: A review.

The coronavirus disease 2019 (COVID-19) disease caused by the severe acute respiratory syndrome coronavirus 2 has had a widespread global impact. In addition to the main respiratory symptoms, research has found significant effects of this virus on the cardiovascular system. This article comprehensively explores the phenomenon of "long-term COVID-19" or postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection, wherein some recovered patients continue to experience long-term health issues after the resolution of acute illness. We delve into the potential reasons behind these symptoms, including increased risk of heart disease, myocardial injury, abnormal inflammatory responses, thrombosis formation, and immune system dysfunction, among others. Furthermore, this paper highlights the potential association between long-term COVID-19 and HF (heart failure), and proposes corresponding preventive strategies. To address this, we advocate for a collaborative approach involving interdisciplinary teams for treatment and management.

A sensitive CRISPR/Cas12a-assisted fluorescent aptasensor for rapid detection of food allergens

Food allergens elicit abnormal immune system responses among allergic individuals and sensitive detection for allergenic ingredient is greatly significant. To address this need, a novel fluorescent aptasensor, assisted by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), have been developed for food allergens. In this study, aptamer offers distinctive recognition capabilities in binding specific targets, while CRISPR-associated-12a protein (Cas12a) holds precise cis-cleavage for cutting fluorescent signal probes. Notably, the utilization of Cas12a cis-cleavage activity, rather than trans-cleavage, eliminates the necessity for additional fluorescent probes, thus reducing interference between substances and enhancing sensitivity. Throughout the process, complementary DNA (cDNA) plays a crucial dual role in target recognition conversion and signal presentation, representing a key challenge and innovative aspect of this study. To evaluate the performance of the aptasensor, lysozyme (LYS) is employed as a representative model target of food allergens. Under optimal conditions, the developed aptasensor could achieve an exceptional low limit of detection (LOD) of 6.10 pM with a dynamic detection range of 10 pM-320 pM. The aptasensor demonstrates high selectivity and great recovery rates. This strategy yields promising outcomes, holding the potential to serve as a valuable reference for various food allergens detection.

Therapeutic effect of an Ayurvedic drug in the management of Respiratory Allergic Disorders in children - A comprehensive review

Background: Respiratory allergic disorders (RAD) are the most common allergy symptom seen in children. Respiratory allergies are primarily caused by hyper responsiveness of the respiratory mucosa, which results in histamine release and mast cell activation. In Ayurvedic words, this could be viewed as an abnormality of the body's immune system or Ojus induced by disrupted Vata, Kapha, and Pitta. The prevalence of respiratory allergies in school-aged children in India varies widely, ranging from 5-20%. Methods: This study was completed by gathering the knowledge from classical Ayurvedic literature, research articles, guidelines and PubMed and MedLine databases. Results and Discussion: Dashmoola Katutrayadi drug is mentioned in Sahastra Yogam under Swasa Kasahara Kashaya have Shwas-Kasahar, anti-inflammatory, anti-histaminic and anti-asthmatic effects individually and in combinations. Conclusion: Present review reveals that these drugs have potential to alleviate the severity and frequency of RAD and can be used for the management of the same.

The Role of TLR7 and TLR9 in the Pathogenesis of Systemic Sclerosis.

The bleomycin-induced scleroderma model is a well-established and dependable method for creating a mouse model of SSc (systemic sclerosis). In the field of skin connective tissue diseases, increasing evidence from clinical and animal experiments suggests that TLRs (Toll-like receptors) play an important role in several diseases. This study aimed to determine the role of TLR7 (Toll-like receptor 7) and TLR9 (Toll-like receptor 9) in the mechanisms of immune abnormalities and fibrosis in SSc. This study used TLR7-KO mice (TLR7-knockout mice with a balb/c background) and TLR9-KO mice (TLR9-knockout mice with a balb/c background) as well as WT mice (wild-type balb/c mice). All three kinds of mice were induced by BLM (bleomycin) in a scleroderma model as the experimental group; meanwhile, WT mice treated with PBS (phosphate-buffered saline) were used as the control group. We analyzed the fibrotic phenotype and the immunological abnormality phenotype of TLR7-deficient and TLR9-deficient mice in the SSc disease model using flow cytometry, RT-PCR (reverse transcription-polymerase chain reaction), a histological examination, and IHC (immunohistochemical staining). In a mouse model of SSc disease, the deletion of TLR7 attenuated skin and lung fibrosis, while the deletion of TLR9 exacerbated skin and lung fibrosis. The deletion of TLR7 resulted in a relative decrease in the infiltration and expression of various pro-inflammatory and fibrotic cells and cytokines in the skin. On the other hand, the deletion of TLR9 resulted in a relative increase in the infiltration and expression of various pro-inflammatory and cytokine-inhibiting cells and cytokines in the skin. Under the influence of pDCs (plasmacytoid dendritic cells), the balances of Beff/Breg (IL-6 + CD19 + B cell/IL-10 + CD19 + B cell), Th17/Treg (IL-17A + CD4 + T cell/Foxp3 + CD25 + CD4 + T cell), M1/M2 (CD86 + macrophage/CD206 + macrophage), and Th1/Th2 (TNFα + CD3 + CD4 + T cell/IL-4 + CD3 + CD4 + T cell) were biased towards the suppression of inflammation and fibrosis as a result of the TLR7 deletion. Comparatively, the balance was biased towards promoting inflammation and fibrosis due to the TLR9 deletion. In the SSc model, TLR7 promoted inflammation and fibrosis progression, while TLR9 played a protective role. These results suggest that TLR7 and TLR9 play opposite roles in triggering SSc to produce immune system abnormalities and skin fibrosis.

Recent Advances in Phytochemical-Based Topical Applications for the Management of Eczema: A Review

Eczema (atopic dermatitis, AD) is a skin disease characterized by skin barrier dysfunction due to various factors, including genetics, immune system abnormalities, and environmental triggers. Application of emollients and topical drugs such as corticosteroids and calcineurin inhibitors form the mainstay of treatments for this challenging condition. This review aims to summarize the recent advances made in phytochemical-based topical applications to treat AD and the different carriers that are being used. In this review, the clinical efficacy of several plant extracts and bioactive phytochemical compounds in treating AD are discussed. The anti-atopic effects of the herbs are evident through improvements in the Scoring Atopic Dermatitis (SCORAD) index, reduced epidermal thickness, decreased transepidermal water loss, and alleviated itching and dryness in individuals affected by AD as well as in AD mouse models. Histopathological studies and serum analyses conducted in AD mouse models demonstrated a reduction in key inflammatory factors, including thymic stromal lymphopoietin (TSLP), serum immunoglobulin E (IgE), and interleukins (IL). Additionally, there was an observed upregulation of the filaggrin (FLG) gene, which regulates the proteins constituting the stratum corneum, the outermost layer of the epidermis. Carriers play a crucial role in topical drug applications, influencing dose delivery, retention, and bioavailability. This discussion delves into the efficacy of various nanocarriers, including liposomes, ethosomes, nanoemulsions, micelles, nanocrystals, solid-lipid nanoparticles, and polymeric nanoparticles. Consequently, the potential long-term side effects such as atrophy, eruptions, lymphoma, pain, and allergic reactions that are associated with current topical treatments, including emollients, topical corticosteroids, topical calcineurin inhibitors, and crisaborole, can potentially be mitigated through the use of phytochemical-based natural topical treatments.

Single-cell BCR and transcriptome analysis reveals peripheral immune signatures in patients with thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) is the most prevalent orbital disease in adults caused by an autoimmune disorder, which can lead to disfigurement and vision impairment. Developing effective treatments for this condition presents challenges due to our limited understanding of its underlying immune aberrations. In this study, we profiled the immune components in the peripheral blood of patients with TAO as well as healthy individuals, utilizing single-cell RNA sequencing and B-cell receptor repertoires (BCR) analysis. We observed a significant reduction in the proportions of regulatory B cells (Bregs) and type 2 conventional dendritic cells (DCs) in patients with TAO during the active phase. Conversely, there was a significant increase in the proportion of type 1 DCs. Further analysis of cell differentiation trajectory revealed potential impairment in the transition of B cells towards Breg phenotype during the active phase of TAO. Besides, the activation process of TAO appeared to involve inflammation and immune dysfunction, as indicated by the dynamic changes in the activities of key regulators. The abnormalities in the peripheral immune system, such as the reduced capacity of Bregs to suppress inflammation, were primarily driven by the enhanced interaction among Breg, DCs, and monocytes (i.e., CD22-PTPRC and BTLA-TNFRSF14). Collectively, our findings offer a comprehensive insight into the molecular regulation and cellular reconfiguration during the active phase of TAO at the single-cell level, in order to explore the pathogenesis of TAO and provide new ideas for the future treatment of TAO.

The role of the immune system in early-onset schizophrenia: identifying immune characteristic genes and cells from peripheral blood

BackgroundEarly-onset schizophrenia (EOS) is a type of schizophrenia (SCZ) with an age of onset of < 18 years. An abnormal inflammatory immune system may be involved in the occurrence and development of SCZ. We aimed to identify the immune characteristic genes and cells involved in EOS and to further explore the pathogenesis of EOS from the perspective of immunology.MethodsWe obtained microarray data from a whole-genome mRNA expression in peripheral blood mononuclear cells (PBMCs); 19 patients with EOS (age range: 14.79 ± 1.90) and 18 healthy controls (HC) (age range: 15.67 ± 2.40) were involved. We screened for differentially expressed genes (DEGs) using the Limma software package and modular genes using weighted gene co-expression network analysis (WGCNA). In addition, to identify immune characteristic genes and cells, we performed enrichment analysis, immune infiltration analysis, and receiver operating characteristic (ROC) curve analysis; we also used a random forest (RF), a support vector machine (SVM), and the LASSO-Cox algorithm.ResultsWe selected the following immune characteristic genes: CCL8, PSMD1, AVPR1B and SEMG1. We employed a RF, a SVM, and the LASSO-Cox algorithm. We identified the following immune characteristic cells: activated mast cells, CD4+ memory resting T cells, resting mast cells, neutrophils and CD4+ memory activated T cells. In addition, the AUC values of the immune characteristic genes and cells were all > 0.7.ConclusionOur results indicate that immune system function is altered in SCZ. In addition, CCL8, PSMD1, AVPR1B and SEMG1 may regulate peripheral immune cells in EOS. Further, immune characteristic genes and cells are expected to be diagnostic markers and therapeutic targets of SCZ.

Immune Dysregulation in Endometriomas: Implications for Inflammation.

The most common manifestation of endometriosis, a condition characterized by the presence of endometrial-like tissue outside of the uterus, is the endometrioma, a cystic ovarian lesion. It is a commonly occurring condition associated with chronic pelvic pain exacerbated prior to and during menstruation, as well as infertility. The exact pathomechanisms of the endometrioma are still not fully understood. Emerging evidence suggests a pivotal role of immune dysregulation in the pathogenesis of endometriomas, primarily influencing both local and systemic inflammatory processes. Among the factors implicated in the creation of the inflammatory milieu associated with endometriomas, alterations in both serum and local levels of several cytokines stand out, including IL-6, IL-8, and IL-1β, along with abnormalities in the innate immune system. While numerous signaling pathways have been suggested to play a role in the inflammatory process linked to endometriomas, only NF-κB has been conclusively demonstrated to be involved. Additionally, increased oxidative stress, both resulting from and contributing to endometriomas, has been identified as a primary driver of both systemic and local inflammation associated with the condition. This article reviews the current understanding of immune dysfunctions in the endometrioma and their implications for inflammation.