Immunological Response Research Articles

The Effect of Metformin Therapy on Serum IL-33 and ST-2 Receptor Levels in Patients With Type 2 Diabetes Mellitus

Introduction: Patients with type 2 had elevated levels of inflammatory biomarkers, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF-α). Significant elevations in serum levels of TNF-α and C-reactive protein were seen in individuals with type 2 diabetes mellitus (T2DM). The IL-1 superfamily (IL-1β, IL-18, and IL-33) plays a crucial role in the development of diabetes mellitus by modifying immunological and inflammatory immune responses. Objectives: Little is known about the role of metformin in type 2 diabetes mellitus with respect to serum levels of IL-33 and ST-2 receptors. Therefore, in the present study, we sought toexplore such role. Patients and Methods: This single arm study included 45 type 2 diabetes patients with an age range of 30 to less than 60 years. Patients were given metformin (500 mg orally; for two months then, serum level of interleukin- 33 (IL-33) and ST-2 receptors were evaluated. Results: Treatment resulted in significant reduction of serum the suppression of tumorigenicity suppressor 2 (ST2) from 0.71 ±0.157 µg/mlto 0.59 ±0.11 µg/ml (p<0.001), across with significant increase in serum IL-33 from 0.60 ±0.18 pg/ml to 0.75 ±0.13 pg/ml (p < 0.001). Conclusion: Treatment of type 2 diabetes mellitus using metformin revealed a crucial role for IL-33 and ST-2 receptors in glycemic control since increment in IL-33 and reduction in ST-2 receptors were associated with good glycemic control suggesting an inflammatory role in disease pathogenesis and response to treatment.

A rare case of hemophagocytic lymphohistiocytosis (HLH) secondary to Salmonella infection

HLH (Hemophagocytic lymphohistiocytosis) is a severe hyperinflammatory disease which could be caused by a range of pathogenic organisms, involving Salmonella. This unique case of bacterial-induced HLH tells the story of a 24y/o male who has been admitted to the hospital and is experiencing the severe symptoms of HLH that developed after an enteric fever caused by Salmonella. Despite earlier hospitalization and intravenous antibiotic treatment, he presented with a high temperature, excessive sweating, yellowish staining of urine and eyes, shortness of breath, and significant systemic inflammation. Laboratory studies revealed severe anemia, bicytopenia, and increased markers such as hyperferritinemia and hypertriglyceridemia, resulting in the diagnosis of HLH. The treatment method includes intensive care with intravenous immunoglobulins (IVIG), corticosteroids, and broad-spectrum antibiotics to address both the underlying infection and the inflammatory condition. Despite intense care, his condition was complex and created substantial complications. This instance emphasizes the significance of early detection as well as treatment of HLH, especially when accompanied by bacterial infections, which are not generally thought to produce this strong immunological response. The example emphasizes the requirement to include HLH in the individuals differential diagnosis with severe illness and systemic inflammatory reactions that do not respond to standard treatment. It also emphasizes the necessity of a comprehensive therapeutic approach, customized to the underlying cause and specific clinical presentations of the disease, in improving outcomes in critically sick patients.

Evaluation The Role Of Some Immunological Markers In Coronavirus-19 Infection In A Sample Of Iraqi Patients

Background: cells produce proinflammatory cytokines like il-8, which activates neutrophils and stimulates immunological responses. Il-6 is produced quickly and transiently in response to infections and stimulates hematopoiesis and acute phase responses, aiding host defense. Dysregulated il-6 production can lead to chronic inflammation and autoimmunity despite its transcriptional and posttranscriptional regulation. Objective: the study aims to identify immunological markers that could serve as diagnostic factors for covid-19 infections, using rt-pcr for diagnosis and estimation of interleukin-6 and interleukin-8 levels and evaluating their association with infection progression, given the importance of covid-19 in various medical fields. Methods: blood samples collected from al-zafaraniyah general hospital, fatima-alzahra hospital, and al-yarmook teaching hospital in baghdad city identified 40 patients with coronavirus. The study used the enzyme-linked immune sorbent assay (elisa) approach to detect interleukin-6 and interleukin-8 antibodies in the patients ' serum. Results: the study reveals a strong correlation between immunological markers and corona virus-19 infection, with 40 patients showing higher levels of interleukin-6 and interleukin-8 antibodies, indicating a significant association between these markers. Conclusions: the study found a significant association between coronavirus-19 infection patients and immunological markers, with high levels of interleukin-6 and interleukin-8 antibodies in serum highly associated with coronavirus -19 incidence.

The Role of MicroRNAs and Stem cells in Rheumatoid Arthritis: A Therapeutic and Diagnostic Approach.

In autoimmune illnesses like Rheumatoid Arthritis (RA), the synovium is constantly inflamed, and joints are ruptured. It is becoming increasingly clear that stem cells, especially notably mesenchymal stem cells (MSCs) and microRNAs (miRNAs), play important roles in the onset and amelioration of RA. There is mounting evidence from both animal and human studies that suggests a potentially safe and effective method to treat RA and other intractable diseases by reducing chronic inflammation and spurring tissue regeneration through the transplantation of multipotent adult stem cells, such as mesenchymal stromal/stem cells. To control gene expression, which impacts immune cell differentiation and inflammatory pathways, microRNAs (miRNAs) are crucial, even though MSCs can self-renew and modify inflammatory reactions. The pathophysiology of RA is marked by the dysregulation of immunological responses and the proliferation of fibroblast-like synoviocytes, which are linked to the aberrant expression of specific microRNAs (miRNAs). This study mainly aims to examine the therapeutic implications of these microRNAs (miRNAs) in relation to RA, as they can function as diagnostic and prognostic indicators. This study explores the functions of microRNAs (miRNAs) and stem cells in rheumatoid arthritis (RA), drawing attention to the relevance of these biological processes and the potential for creating novel therapeutic strategies to improve patient outcomes.

The Microbiota in Children and Adolescents with Asthma.

The role of the respiratory microbiome has been deeply explored for at least two decades. Its characterization using modern methods is now well-defined, and the impacts of many microorganisms on health and diseases have been elucidated. Moreover, the acquired knowledge in related fields enables patient stratification based on their risk for disease onset, and the microbiome can play a role in defining possible phenotypes. The interplay between the lung and gut microbiomes is crucial in determining the microbial composition and immuno-inflammatory reaction. Asthma is still not a well-defined condition, where hyperreactivity and the immune system play important roles. In this disease, the microbiome is mostly represented by Proteobacteria, Streptococcus, and Veillonella, while Cytomegalovirus and Epstein-Barr viruses are the most prevalent viruses. A mycobiome may also be present. The passage from infancy to adolescence is examined by evaluating both the clinical picture and its relationship with possible variations of the microbiome and its effects on asthma. Otherwise, asthma is considered a heterogeneous disease that often starts in childhood and follows a particular personalized track, where adolescence plays a pivotal role in future prognosis. Under this point of view, the microbiota, with its possible variations due to many factors, both internal and external, can modify its composition; consequently, its inflammatory action and role in the immunological response has obvious consequences on the clinical conditions.

Granzyme K provides protection for Nile tilapia (Oreochromis niloticus) from acute bacterial infection.

Granzyme K (GzmK) is a trypsin-like serine protease that functions as a pro-apoptotic protease, has non-cytotoxic functions, and is involved in various physiopathological processes. However, the impact of GzmK on the immunological response of Nile tilapia against bacterial challenge is still poorly explored. In this study, we identified the GzmK gene from Nile tilapia (On-GzmK) and investigated its immunologic roles through in vivo experiments. On-GzmK has an open reading frame of 786 bp and encodes 255 amino acids. On-GzmK has over 60 % genetic similarity with other fish and over 30 % similarity with mammals. Its transcript levels were highest in the liver and vastly increased after being challenged with Streptococcus agalactiae and Aeromonas hydrophila. In vivo experiments implied that On-GzmK might promote inflammatory responses and regulate apoptosis and pyroptosis by participating in the activation of multiple signaling pathways, such as JAK-STAT, MAPK, and NF-κB. The present observations offer additional theoretical support for investigating the processes by which GzmK shields fish against bacterial infections.

How increasing temperature affects the innate immune system of sea urchin Paracentrotus lividus (Lamarck, 1816) reared in a RAS system

The purple sea urchin, Paracentrotus lividus, is the most exploited and economically important in Southern Europe due to the high value of its gonads. Temperature generally affects several physiological functions of marine invertebrates and the ocean warming has been linked to increasing frequency and severity of disease outbreaks in several echinoderms. Sea urchins have an innate immune system consisting of coelomocytes, the cellular components responsible for the immune response, supported by proteases and lysozymes. The present study aimed to investigate the effect of increasing seawater temperature on the immunological response of P. lividus. In this experiment, the animals were exposed to an increase in temperature up to 24 °C for 36 days, after which cellular and humoral immunity parameters were measured. The number of coelomocytes in the animals increased with the temperature rise, mainly the phagocytes and the colourless granulocytes. In the humoral response of the animals, only the concentration of lysozyme responded to the increase in temperature.

Innate and adaptive immunity gene expression profiles induced by virulent Aeromonas hydrophila infection in the immune-related organs of channel catfish

Aeromonas hydrophila causes motile Aeromonas septicemia (MAS) in freshwater fish. In recent years, MAS outbreaks due to virulent Aeromonas hydrophila (vAh) have been responsible for large-scale losses within commercial catfish farms in Mississippi and Alabama. The aim of this study was to evaluate immune gene expression in catfish immune-competent tissues during infection with vAh strain ML09-119. Specific pathogen-free catfish fingerlings were intraperitoneally infected with vAh strain ML09-119, and relative expression of thirteen immune-related genes was evaluated from head kidney, spleen, and liver. Our results revealed that vAh was detected 2 h post-infection (hpi) in the head kidney, liver, and spleen. The highest concentration of vAh was detected at 12 hpi, from which point concentrations decreased until clearance at 5 days post-infection (dpi). Gene expression analysis revealed upregulation of pro-inflammatory cytokines and innate immune response (TLR 4 and 5) in the first 24 hpi. Adaptive immune-related genes were upregulated at 7 dpi in the spleen and 14 dpi in the head kidney. Furthermore, immunoglobulin M showed significant upregulation at 14 dpi in the head kidney and 21 dpi in the spleen. In summary, vAh ML09-119 infection induced a strong inflammatory response involving multiple innate immunity genes, proinflammatory cytokines, and chemokines. Surviving catfish were able to clear the infection and produce antibodies and memory cells. Assessment of the immunological response to vAh infection is critical for understanding the pathogen's mechanisms of pathogenesis and developing means for MAS control, including vaccine development and improved treatments.

High Seroprevalence to Aedes-borne arboviruses in Ethiopia: a Cross-sectional Survey in 2024.

Aedes-borne diseases infect millions of people each year. In the last decade several arbovirus outbreaks have been reported in Ethiopia. Arbovirus diagnosis and surveillance is lacking and the true burden is unknown. In this study we conducted a seroprevalence survey using a commercially available test kit that that tests for immunological responses to IgM and IgG for dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) viruses in Dire Dawa city, eastern Ethiopia. We found a high IgG seroprevalence for DENV (76%), CHIKV (44%), and ZIKV (38%), and <20% IgM seropositivity across all viruses. As a comparison, we conducted serosurveillance in Addis Ababa, the national capital with no reported history of arbovirus outbreaks. The highest seropositivity we found was to IgM for DENGV at approximately 3%. Our results suggest both past and recent widespread exposure to these arboviruses, underscoring the need for improved surveillance and public health interventions in Ethiopia.

Asthma and pregnancy: Understanding the dynamic relationship - A comprehensive review

The health of pregnant women and their developing fetuses can be greatly impacted by asthma, a prevalent chronic respiratory disease. Pregnancy-related asthma is a serious health risk. A potentially fatal condition that makes many pregnancies more difficult is asthma. The prevalence of asthma has increased within the past few decades. This comprehensive review explored the complex connection between asthma and pregnancy. Analyzing physiological alterations during pregnancy revealed dynamic interactions between immunological responses and respiratory function. These Important discoveries highlight the susceptibility to exacerbations of asthma. This discussion focuses on the links between poorly managed asthma and unfavourable - perinatal outcomes, with particular attention given to maternal and fetal outcomes, tracking and tailored treatment to provide the best possible management of asthma. This review emphasizes how important it is to manage asthma throughout pregnancy because it can have a positive impact on both the mothers and fetuses long-term health. Consequences for clinical practice emphasize the value of preconception care, ongoing surveillance, and joint obstetrician-pulmonologist efforts. This review also sheds light on how common asthma is in expectant mothers, and this field's future directions require further investigation. Low birth weights and small for gestational age are associated with a greater risk, especially in women who have moderate-to-severe asthma and have episodes of the condition during pregnancy. Additionally, there was a slight but statistically significant increase in the chance of congenital deformities. By preventing exacerbations, active management may lessen these risks. Ensuring optimal management of asthma during pregnancy is crucial for the welfare of the expectant mother and the unborn child. While poorly managed and undertreated asthma is linked to a number of dangers for both mothers and fetuses, well-controlled asthma reduces the risk of complications for both mothers and fetuses.

Long-Lasting, Fine-Tuned Anti-Tumor Activity of Recombinant Listeria monocytogenes Vaccine Is Controlled by Pyroptosis and Necroptosis Regulatory and Effector Molecules.

One of the main objectives of developing new anti-cancer vaccine strategies is to effectively induce CD8+ T cell-mediated anti-tumor immunity. Live recombinant vectors, notably Listeria monocytogenes, have been shown to elicit a robust in vivo CD8+ T-cell response in preclinical settings. Significantly, it has been demonstrated that Listeria induces inflammatory/immunogenic cell death mechanisms such as pyroptosis and necroptosis in immune cells that favorably control immunological responses. Therefore, we postulated that the host's response to Listeria-based vectors and the subsequent induction of CD8+ T cell-mediated immunity would be compromised by the lack of regulatory or effector molecules involved in pyroptosis or necroptosis. To test our hypothesis, we used recombinant L. monocytogenes carrying the ovalbumin gene (LM.OVA) to vaccinate wild-type (WT), caspase-1/11-/-, gsdmd-/-, ripk3-/-, and mlkl-/- C57Bl/6 mice. We performed an in vivo cytotoxicity assay to assess the efficacy of OVA-specific CD8+ T lymphocytes in eliminating target cells in wild-type and genetically deficient backgrounds. Furthermore, we evaluated the specific anti-tumor immune response in mice inoculated with the B16F0 and B16F0.OVA melanoma cell lines. Our findings demonstrated that while caspase-1/11 and GSDMD deficiencies interfere with the rapid control of LM.OVA infection, neither of the KOs seems to contribute to the early activation of OVA-specific CTL responses. In contrast, the individual deficiency of each one of these proteins positively impacts the generation of long-lasting effector CD8+ T cells.

Insights into renal and urological complications of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic condition characterized by immune-mediated inflammation in the gastrointestinal tract, which follows a relapsing and remitting course. Apart from affecting the gastrointestinal tract, IBD also has extra-intestinal manifestations (EIMs). While the etiology of extraintestinal manifestation remains unclear, it is theorized to be based on immunological responses influenced by genetic factors. Renal involvement is one of the EIMs observed in ulcerative colitis and Crohn's disease. The renal manifestations in IBD patients encompass a range of conditions including nephrolithiasis, amyloidosis, tubulointerstitial nephritis, glomerulonephritis (GN), obstructive pathologies, and chronic kidney disease (CKD). The incidence of CKD in IBD patients varies from 5%-15%. The decline in renal function can stem from various factors such as direct inflammatory damage to the kidneys leading to glomerular or tubular injury, or from complications like recurrent stones, amyloidosis, or GN. Additionally, nephrotoxic medications used in treating IBD, such as TNF-α inhibitors, calcineurin inhibitors, and aminosalicylates, can exacerbate the decline in renal function. Currently, there is a lack of consensus regarding these patients' screening and renal function monitoring. This review aims to assess the existing literature on the different renal complications among individuals with IBD, shedding light on their pathophysiology and management.

The Antifungal Activity of Chitosan Nanoparticle-Incorporated Probiotics Against Oral Candidiasis.

Candida species, especially Candida albicans, cause oral candidiasis, also known as oral thrush. It affects the elderly, newborns, patients under antibiotics, chemotherapeutic agents, and patients with weaker immune systems. Although successful, traditional antifungal medications are available, they may have negative effects and do not prevent recurrence. Conventional antifungal medications have a restricted range of effectiveness; hence, the need for a novel antifungal agent arises. Chitosan, a natural polymer made from chitin found in crustaceans, kills fungal cells by damaging membranes. Excellent biocompatibility and biodegradability make it a promising medical material. Probiotics, live bacteria, compete with pathogenic microbes for adhesion sites and nutrients, produce antimicrobials such as lactic acid, hydrogen peroxide, and bacteriocins, and modulate the host's immunological response. Adding probiotics to chitosan nanoparticles (CSNPs) boosts their antifungal activity against Candida species and increases their stability and transport to the infection site. The antifungal activity was evaluated through in vitro experiments utilizing Candida strains that are significant to oral candidiasis. Different concentrations of CSNPs and formulations loaded with probiotics were examined to assess their effectiveness. The antifungal properties were assessed using microbiological assays, specifically agar diffusion and minimum inhibitory concentration (MIC). The study demonstrated a notable fungicidal impact of CSNPs combined with probiotics against oral candidiasis. Furthermore, the MICvalues were lower for the probiotic-loaded CSNPs than for chitosan alone or probiotics alone. The combination of CSNPs and probiotics shows potential in effectively combating oral candidiasis by inhibiting fungal growth. This novel method offers a promising strategy for creating therapeutic treatments for oral candidiasis by utilizing the combined benefits of chitosan and probiotics to combat fungal infections effectively.

Quantification and evaluation of plasma free amino acid concentrations by LC-MS/MS after total gastrectomy

The effect of total gastrectomy (TG) on plasma free amino acid (PFAA) concentrations in patients with stage II gastric cancer was investigated in the study. Nineteen patients' plasma samples were collected before and three months post-gastrectomy, and PFAA levels were quantified using LC-MS/MS. For gradient elution of amino acids, the mobile phases (A: 3% formic acid-5% methanol-30 mM ammonium formate, B: acetonitrile) and a Hypersil C18 column (100 mm x 2.1 m, 1.9 µm) were used. The findings revealed substantial modifications in the profile of PFAA after TG. In particular, the concentrations of twenty amino acids increased significantly, including branched-chain amino acids, L-glutamate, L-alanine, L-methionine, glycine, L-cystine, and L-histidine. Conversely, L-arginine was also reduced statistically. These alterations in the PFAA profile indicate the favorable effects of TG on various physiological processes, such as enhanced immune function, improved tissue healing, and increased energy production. Investigating the effects of various surgical techniques on PFAA profiles is a promising approach for optimizing surgical procedures, improving metabolic function, increasing immunological responses, and improving overall quality of life. These findings highlight the significance of evaluating amino acid metabolism as an important part of treatment, given its potential to improve clinical outcomes and general well-being.

Seroprevalence of SARS-CoV-2 infection in pediatric patients in a tertiary care hospital setting.

Globally, cases of children's coronavirus disease 2019 (COVID-19) have been reported since the pandemic started. Most children have an asymptomatic or mild infection. Therefore, the incidence rate of COVID-19 in children might have been underestimated. This study aimed to determine (1) the seroprevalence (and seroconversion rates) of COVID-19, including associated risk factors, in pediatric patients visiting hospitals; and (2) the immunological responses to COVID-19. This was a prospective, cross-sectional study. Patients aged 0-18 years who visited the hospital from September 2020 to February 2022 were included. Demographic, clinical, and laboratory data were reviewed. A total of 1,443 pediatric patients were enrolled. Of these, 323 (22.6%) had a history of COVID-19. In the pre-Delta period, the seroprevalence increased from 4.1% to 70.6% in all included patients and from 0.5% to 10% in patients without a known history of COVID-19 compared with the Delta-Omicron period. The seroconversion rate was 6.8% (19 per 100 person-years) in pediatric patients with COVID-19. Risk factors for COVID-19 seropositivity were respiratory symptoms, being in an outpatient department setting, and infection during the Delta-Omicron period. Exposure to household members with confirmed COVID-19 was a risk factor for seropositivity and seroconversion. Infection during the Delta-Omicron period and testing conducted >2 weeks after the onset of symptoms was associated with spike immunoglobulin (Ig) M and spike and nucleocapsid IgG, respectively. High nucleocapsid IgG levels were associated with pneumonia in pediatric patients with COVID-19. Pediatric patients exposed to household members with COVID-19 and respiratory symptoms should be tested for COVID-19. Nucleocapsid IgG can be used as a surrogate marker to identify patients who may have experienced pneumonia from COVID-19 and as a screening tool for the COVID-19 outbreak, regardless of COVID-19 vaccination status.

Role of Salivary Protease Enzymatic Activity in Saliva of Children with and without Early Childhood Caries: A Randomized Clinical Trial.

Early childhood caries (ECC) is one of the most prevalent diseases in children worldwide. Early childhood caries is driven by a dysbiotic state of oral microorganisms, mainly caused by a sugar-rich diet. Additionally, poor oral hygiene or insufficient dental plaque removal leads to the rapid progression of ECC. Early childhood caries leads not only to dental destruction and pain in children but also affects the quality of life of the caregivers.Additionally, upon neutrophil activation at inflammatory locations, these proteases are externalized in an active state, aiding in the control of inflammatory and immunological responses. Any enzyme that catalyzes proteolysis reactions is known as a protease. Proteases are produced by human glands or derived from microbes in the oral cavity. Additionally, the oropharyngeal mucosae and crevicular fluids are sources of protease. This study is aimed at the estimation and correlation of salivary protease enzymatic activity in the saliva of children with and without ECC. A total of 50 children were included in the study, which was divided into two groups: group I (caries-active) and group II (caries-free)-each consisting of 25 children. Unstimulated saliva samples were collected and subjected to a spectrophotometer for analysis. Salivary protease levels were estimated and correlated between caries-active and caries-free children. The correlation between caries score and salivary protease activity was statistically significant with a moderate correlation. The comparison of mean salivary protease activity between caries-active and caries-free groups was statistically significant. However, the comparison of salivary protease activity based on different age-groups was not statistically significant, whereas gender and caries scores in group A were statistically significant. In conclusion, there is a substantial correlation between salivary protease enzyme levels and the severity of dental caries, and an increase in salivary protease enzyme levels is linked to a considerable rise in caries severity. As a result, prevention may be possible with early detection. Thimmegowda U, Kuri PN, Dhamnekar P. Role of Salivary Protease Enzymatic Activity in Saliva of Children with and without Early Childhood Caries: A Randomized Clinical Trial. Int J Clin Pediatr Dent 2024;17(8):877-880.

Directed protein engineering identifies a human TIM-4 blocking antibody that enhances anti-tumor response to checkpoint inhibition in murine colon carcinoma

Abstract Background T-cell immunoglobulin and mucin domain containing molecule-4 (TIM-4) is a scavenger receptor best known for its role in recognizing dying cells. TIM-4 orchestrates phagocytosis allowing for cellular clearance of apoptotic cells, termed efferocytosis. It was previously shown that TIM-4 directly interacts with AMPKα1, activating the autophagy pathway, leading to degradation of ingested tumors, and effectively reducing antigen presentation. Methods This study sought to identify a novel human TIM-4 antibody that can prevent phagocytosis of tumor cells thereby allowing for more antigen presentation resulting in anti-tumor immunological response. Using phage display panning directed against human TIM-4, we engineered a novel human TIM-4 antibody (SKWX301). Combination of in vitro phagocytosis assays and cell viability assays were used to test functionality of SKWX301. To examine the effect of SKWX301 in mouse models, we employed a syngeneic mouse model. CT26 cells were subcutaneously injected into BALB/c mice and tumor growth and mouse survival were analyzed. Results SKWX301can prevent human macrophage phagocytosis of cancer cells in vitro. Combination of low dose SKWX301 and anti-PD1 antibody significantly inhibited tumor growth and increased overall survival in mice. This demonstrates that SKWX301 is effective in both human in vitro models and mouse in vivo models. Conclusion Our study has demonstrated a rapid antibody discovery approach and identified a novel human TIM-4 antibody that can serve as a therapeutic for antitumor immunity to improve cancer therapy.

Dietary biogenic selenium nanoparticles improve growth and immune-antioxidant indices without inducing inflammatory responses in Nile tilapia

The present study evaluated the use of green-synthesized selenium nanoparticles (SeNPs), using the microalgae Pediastrum boryanum as a diet additive in aquaculture to improve the growth performance, health, and immune response of Nile tilapia. Nile tilapia were fed different concentrations of green SeNPs (79.26 nm) as follows: 0, 0.75, and 1.5 mg/kg of SeNPs for 8 weeks. Following the trial, growth performance, biochemical indices, antioxidant and pro-inflammatory cytokine-related genes, and tissue histological examinations were performed. The study showed that SeNPs significantly improved (P < 0.05) growth performance and innate immune parameters (P < 0.001, IgM, and lysozyme) at both supplemented doses compared with the control. The protein profile and liver function enzymes were normal compared with those in the control group (P > 0.05). Serum malondialdehyde and superoxide dismutase levels were not significantly changed, while reduced glutathione and catalase were significantly enhanced (P < 0.01, P < 0.05) in the SeNPs 1.5 mg/kg compared to the control group. No inflammatory response was detected upon SeNP supplementation, as indicated by the absence of changes in the expression of pro-inflammatory cytokine genes. The earlier assays’ results were histopathologically evidenced, where hepatic and splenic tissue architectures in SeNPs groups did not reveal any deviation from the control group. Our findings indicate that green selenium nanoparticles can potentially improve the growth and immunological response of Nile tilapia, offering opportunities for incorporating health benefits into functional foods and nutraceuticals, which corresponds to the increasing consumer interest in eco-friendly, environmentally sustainable dietary supplements.

Nuclear factor kappa-B: The El Dorado of inflammatory immune response

For more than a decade, the nuclear factor kappa-B (NFκB) family and their signaling pathways have proved crucial to the immune system's functioning. According to research, this factor is implicated in almost every immune system event, including immune cell development and function, activation, and pathogen-activated cell death. A considerable body of evidence suggests the idea that, in addition to being a possible transcription factor, it plays a very significant role in the establishment of inflammation-associated immunological responses in host cells. Inflammation is a cascade of events that involve vasodilation and immune cell migration to the site of infection in order to defend the host. However, if dysregulation occurs, it may lead to the emergence of chronic inflammatory illnesses. When immune cells migrate to an inflamed area NFκB activation occurs, which causes release of pro-inflammatory cytokines and development of inflammatory response. Furthermore, this complex transcription factor activation takes part in several innate and adaptive immunity-related cellular processes, including immune cell proliferation and differentiation. Grasp the relationship between the immune system and inflammation requires a thorough understanding of NFκB's capabilities. This review explores the role of NFκB activity as a key inflammatory mediator in various malignancies and auto-inflammatory diseases. We have shed light on how NFκB regulates inflammatory responses by producing cytokines and chemokines and directing the transcription of inflammatory molecules involved in both innate as well as adaptive immunity.

Immunological responses to brain metastasis stereotactic radiosurgery in patient-matched longitudinal blood and tumour samples

BackgroundStereotactic radiosurgery (SRS) is highly effective as focal treatment for brain metastases (BrMs), but whether it can promote anti-tumour immune responses that synergise with immunotherapy remains unclear. We investigated this by examining blood samples from a clinical trial for HER2-amplified breast cancer (HER2-BC) BrMs, matched with longitudinal HER2-BC BrM samples resected from the same location in the same patient. MethodsBlood samples from 10 patients taken pre- and 7–14 days post-SRS were analysed by mass and flow cytometry. One patient received pre-operative SRS for a BrM that recurred 7 months after resection, followed by planned re-resection 8 days post-SRS. Pre- and post-SRS tumours from this patient were analysed by bulk RNAseq, multiplex immunohistochemistry (mIHC), and TCR sequencing. ResultsMonocytes, central memory CD8+ T and regulatory T cells were enriched in blood post-SRS, together with increased MHC-II expression on monocytes, conventional DCs, and monocytic MDSCs. In tumour, SRS upregulated antigen presentation, T cell proliferation and T cell co-stimulation signatures, alongside an influx of tumour-associated macrophages (TAMs) and CD4+ T cells. Specifically, TAMs and CD4+ T cells, but not CD8+ T cells, demonstrated spatial co-localisation post-SRS. These TAMs were lowly PD-L1 expressing, but CD4+ T cells showed increased PD-1 expression. A sizeable proportion of T cell clonotypes were retained post-SRS, and four clones demonstrated significant, non-stochastic expansion. ConclusionSystemic and local immunological changes in this homogenous patient cohort suggest that SRS may facilitate MHC-II-restricted T cell priming responses involving the monocyte-macrophage lineage and CD4+ T cells, which should be further explored.