Immune Mechanisms Research Articles

Broadly potent spike-specific human monoclonal antibodies inhibit SARS-CoV-2 Omicron sub-lineages

The continuous emergence of SARS-CoV-2 variants of concern has rendered many therapeutic monoclonal antibodies (mAbs) ineffective. To date, there are no clinically authorized therapeutic antibodies effective against the recently circulating Omicron sub-lineages BA.2.86 and JN.1. Here, we report the isolation of broad and potent neutralizing human mAbs (HuMabs) from a healthcare worker infected with SARS-CoV-2 early in the pandemic. These include a genetically unique HuMab, named K501SP6, which can neutralize different Omicron sub-lineages, including BQ.1, XBB.1, BA.2.86 and JN.1, by targeting a highly conserved epitope on the N terminal domain, as well as an RBD-specific HuMab (K501SP3) with high potency towards earlier circulating variants that was escaped by the more recent Omicron sub-lineages through spike F486 and E484 substitutions. Characterizing SARS-CoV-2 spike-specific HuMabs, including broadly reactive non-RBD-specific HuMabs, can give insight into the immune mechanisms involved in neutralization and immune evasion, which can be a valuable addition to already existing SARS-CoV-2 therapies.

SY11-2 The mechanism of gut microbiome-mediated immunity on the clinical efficacy of anti-PD-1 immunotherapy in solid tumors

SY11-2 The mechanism of gut microbiome-mediated immunity on the clinical efficacy of anti-PD-1 immunotherapy in solid tumors

Activating Invasion and Metastasis in Small Cell Lung Cancer: Role of the Tumour Immune Microenvironmentand Mechanisms of Vasculogenesis, Epithelial-Mesenchymal Transition, Cell Migration, and Organ Tropism.

Small cell lung cancer (SCLC) harbours the most aggressive phenotype of all lung cancers to correlate with its bleak prognosis. The aggression of SCLC is partially attributable to its strong metastatic tendencies. The biological processes facilitating the metastasis in SCLC are still poorly understood and garnering a deeper understanding of these processes may enable the exploration of additional targets against this cancer hallmark in the treatment of SCLC. This narrative review will discuss the proposed molecular mechanisms by which the cancer hallmark of activating invasion and metastasis is featured in SCLC through important steps of the metastatic pathway, and address the various molecular targets that may be considered for therapeutic intervention. The tumour immune microenvironment plays an important role in facilitating immunotherapy resistance, whilst the poor infiltration of natural killer cells in particular fosters a pro-metastatic environment in SCLC. SCLC vasculogenesis is achieved through VEGF expression and vascular mimicry, and epithelial-mesenchymal transition is facilitated by the expression of the transcriptional repressors of E-cadherin, the suppression of the Notch signalling pathway and tumour heterogeneity. Nuclear factor I/B, selectin and B1 integrin hold important roles in SCLC migration, whilst various molecular markers are expressed by SCLC to assist organ-specific homing during metastasis. The review will also discuss a recent article observing miR-1 mRNA upregulation as a potential therapeutic option in targeting the metastatic activity of SCLC. Treatment of SCLC remains a clinical challenge due to its recalcitrant and aggressive nature. Amongst the many hallmarks used by SCLC to enable its aggressive behaviour, that of its ability to invade surrounding tissue and metastasise is particularly notable and understanding the molecular mechanisms in SCLC metastasis can identify therapeutic targets to attenuate SCLC aggression and improve mortality.

Tumor-Activated Neutrophils Promote Lung Cancer Progression through the IL-8/PD-L1 Pathway.

Lung cancer remains a major global health threat due to its complex microenvironment, particularly the role of neutrophils, which are crucial for tumor development and immune evasion mechanisms. This study aimed to delve into the impact of lung cancer cell-conditioned media on neutrophil functions and their potential implications for lung cancer progression. Employing in vitro experimental models, this study has analyzed the effects of lung cancer cell-conditioned media on neutrophil IL-8 and IFN-γ secretion, apoptosis, PD-L1 expression, and T-cell proliferation by using techniques, such as ELISA, flow cytometry, immunofluorescence, and CFSE proliferation assay. The roles of IL-8/PD-L1 in regulating neutrophil functions were further explored using inhibitors for IL-8 and PD-L1. Lung cancer cell lines were found to secrete higher levels of IL-8 compared to normal lung epithelial cells. The conditioned media from lung cancer cells significantly reduced apoptosis in neutrophils, increased PD-L1 expression, and suppressed T-cell proliferation and IFN-γ secretion. These effects were partially reversed in the presence of IL-8 inhibitors in Tumor Tissue Culture Supernatants (TTCS), while being further enhanced by IL-8. Both apoptosis and PD-L1 expression in neutrophils demonstrated dose-dependency to TTCS. Additionally, CFSE proliferation assay results further confirmed the inhibitory effect of lung cancer cell-conditioned media on T-cell proliferation. This study has revealed lung cancer cell-conditioned media to modulate neutrophil functions through regulating factors, such as IL-8, thereby affecting immune regulation and tumor progression in the lung cancer microenvironment.

Dissecting the Mechanisms of Intestinal Immune Homeostasis by Analyzing T-Cell Immune Response in Crohn's Disease and Colorectal Cancer.

Crohn's disease (CD) and colorectal cancer (CRC) represent a group of intestinal disorders characterized by intricate pathogenic mechanisms linked to the disruption of intestinal immune homeostasis. Therefore, comprehending the immune response mechanisms in both categories of intestinal disorders is of paramount significance in the prevention and treatment of these debilitating intestinal ailments. IIn this study, we conducted single-cell analysis on paired samples obtained from primary colorectal tumors and individuals with Crohn's disease, which was aimed at deciphering the factors influencing the composition of the intestinal immune microenvironment. By aligning T cells across different tissues, we identified various T cell subtypes, such as γδ T cell, NK T cell, and regulatory T (Treg) cell, which maintained immune system homeostasis and were confirmed in enrichment analyses. Subsequently, we generated pseudo-time trajectories for subclusters of T cells in both syndromes to delineate their differentiation patterns and identify key driver genes Result: Furthermore, cellular communication and transcription factor regulatory networks are all essential components of the intricate web of mechanisms that regulate intestinal immune homeostasis. The identified complex cellular interaction suggested potential T-lineage immunotherapeutic targets against epithelial cells with high copy number variation (CNV) levels in CD and CRC. Finally, the analysis of regulon networks revealed several promising candidates for cell-specific transcription factors (TFs). This study focused on the immune molecular mechanism under intestinal diseases. It contributed to the novel insight of depicting a detailed immune landscape and revealing T-cell responding mechanisms in CD and CRC.

Palmitoleate protects against Lipopolysaccharide-induced Inflammation and Inflammasome Activity

Inflammation is part of natural immune defense mechanism against any form of infection or injury. However, prolonged inflammation could perturb cell homeostasis and contribute to the development of metabolic and inflammatory diseases including maternal obesity, diabetes, cardiovascular diseases, and metabolic dysfunction-associated steatotic liver diseases. Polyunsaturated fatty acids have been shown to mitigate inflammatory response by generating specialized pro-resolving lipid mediators which take part in resolution of inflammation. Here, we show that palmitoleate, an omega-7 monounsaturated fatty acid exerts anti-inflammatory properties in response to lipopolysaccharide (LPS)-mediated inflammation. Exposure of bone-marrow derived macrophages (BMDMs) to LPS or TNFα induces robust increase in the expression of pro-inflammatory cytokines and supplementation of palmitoleate inhibited LPS-mediated upregulation of pro-inflammatory cytokines. We also observed that palmitoleate was able to block LPS+ATP-induced inflammasome activation mediated cleavage of pro-caspase 1 and pro-interleukin (IL)-1β. Further, treatment of palmitoleate protects against LPS-induced inflammation in human THP-1 derived macrophages and trophoblasts. Co-exposure of LPS and palmitate (saturated free fatty acid) induces inflammasome and cell death in BMDMs, however, treatment of palmitoleate blocked LPS and palmitate-induced cell death in BMDMs. Further, LPS and palmitate together results in the activation of mitogen activated protein kinases (MAPK) and pretreatment of palmitoleate inhibited the activation of MAPKs and nuclear translocation of nuclear factor kappa B (NF-kB) in BMDMs. In conclusion, palmitoleate shows anti-inflammatory properties against LPS-induced inflammation and LPS+palmitate/ATP-induced inflammasome activity and cell death.

The role of calcium homeostasis in modulating the immune response in cancer and infectious diseases

Calcium homeostasis is a pivotal determinant of physiological processes, particularly in cellular signaling and immune system regulation. This balance is crucial for modulating immune responses in the context of both infectious and oncological diseases. Disruptions in calcium homeostasis have been shown to influence disease progression, immune efficacy, and treatment outcomes. Our study investigates the critical role of calcium homeostasis in shaping the immune response to cancer and infectious diseases through a comprehensive literature review. The electronic databases Scopus, Google Scholar, and PubMed were utilized to gather relevant studies, identified using key terms such as "calcium homeostasis," "immune response," "cancer," and "infectious diseases." Emerging evidence underscores that calcium levels directly impact immune cell function, including the activation of immune effector cells, cytokine production, and the orchestration of the overall immune response. These processes are critical to the body's ability to combat infections and malignancies. Aberrant calcium signaling may lead to compromised immune defense mechanisms, negatively affecting the outcomes of therapeutic interventions. In cancer, for example, altered calcium homeostasis can suppress immune surveillance, while in infectious diseases, it can hinder the immune system's capacity to clear pathogens. Our review highlights that the pathophysiology of both cancer and infectious diseases is tightly interwoven with calcium regulation, suggesting a promising avenue for therapeutic targeting. Modulating calcium homeostasis may enhance immune functionality, thereby improving treatment efficacy. By restoring calcium balance, novel therapeutic approaches could be developed to optimize immune responses and bolster clinical outcomes across a range of diseases. Further research is warranted to elucidate the precise molecular mechanisms linking calcium homeostasis and immune regulation, with the goal of refining future therapeutic strategies. Maintaining calcium equilibrium is thus essential for the advancement of effective treatments in both cancer and infectious disease contexts.

ADVANCING INFORMATION TECHNOLOGY WITH IMMUNOLOGICAL COMPUTING – SOFT COMPUTING TECHNIQUES FOR ADAPTIVE AND ROBUST SYSTEMS

The field of Information Technology (IT) is evolving rapidly, and with this growth comes the need for systems that are both adaptive and robust. Biological systems, especially the human immune system, demonstrate remarkable adaptability and resilience, inspiring the development of Immunological Computing (IC). This paper explores the application of immunological principles in Soft Computing techniques to create systems capable of responding to dynamic environments. Current IT systems often face challenges such as handling unpredictable changes, scalability, and security threats. Traditional computing approaches struggle to address these issues efficiently due to their rigid structures and limited adaptability. Immunological Computing, inspired by the immune system’s ability to learn, remember, and adapt, offers a promising solution. The proposed method integrates immune system mechanisms like clonal selection, immune memory, and self/non-self-recognition into computational models. These models are coupled with soft computing techniques such as fuzzy logic, genetic algorithms, and neural networks, enhancing the system’s ability to adapt to changing environments and uncertainties. In simulated tests, this approach demonstrated a significant improvement in robustness and adaptability compared to traditional IT systems. For instance, in a cybersecurity application, the immunological-based system detected and neutralized 94.6% of threats, a notable improvement over the 82.3% detected by conventional systems. Similarly, in a resource optimization scenario, the system adapted to dynamic workloads with an efficiency increase of 15% compared to static systems.

Emerging druggable targets for immune checkpoint modulation in cancer immunotherapy: the iceberg lies beneath the surface.

The immune system serves as a fundamental defender against the initiation and progression of cancer. Failure of the immune system augments immunosuppressive action that leading to cancer manifestation. This immunosuppressive effect causes from significant alterations in immune checkpoint expression associated with tumoral progression. The tumor microenvironment promotes immune escape mechanisms that further amplifying immunosuppressive actions. Notably, substantial targeting of immune checkpoints has been pragmatic in the advancement of cancer research. This study highlights a comprehensive review of emerging druggable targets aimed at modulating immune checkpoint co-inhibitory as well as co-stimulatory molecules in response to immune system activation. This modulation has prompted to the development of newer therapeutic insights, eventually inducing immunogenic cell death through immunomodulatory actions. The study emphasizes the role of immune checkpoints in immunogenic regulation of cancer pathogenesis and explores potential therapeutic avenues in cancer immunotherapy.Modulation of Immunosuppressive and Immunostimulatory pathways of immune checkpoints in cancer immunotherapy.

The intrauterine device: how to deploy this strategy in the molecular world?

Progestin-based therapy can safely be offered to a subset of patients with atypical endometrial hyperplasia or Grade 1 endometrioid endometrial cancer who desire fertility preservation. A recent study shows that levonorgestrel intrauterine device confers durable clinical benefit and identifies possible immune mechanisms of relapse and resistance.

Glucocorticoids Suppress NF-κB-Mediated Neutrophil Control of Aspergillus fumigatus Hyphal Growth.

Glucocorticoids are a major class of therapeutic anti-inflammatory and immunosuppressive drugs prescribed to patients with inflammatory diseases, to avoid transplant rejection, and as part of cancer chemotherapy. However, exposure to these drugs increases the risk of opportunistic infections such as with the fungus Aspergillus fumigatus, which causes mortality in >50% of infected patients. The mechanisms by which glucocorticoids increase susceptibility to A. fumigatus are poorly understood. In this article, we used a zebrafish larva Aspergillus infection model to identify innate immune mechanisms altered by glucocorticoid treatment. Infected larvae exposed to dexamethasone succumb to infection at a significantly higher rate than control larvae. However, both macrophages and neutrophils are still recruited to the site of infection, and dexamethasone treatment does not significantly affect fungal spore killing. Instead, the primary effect of dexamethasone manifests later in infection with treated larvae exhibiting increased invasive hyphal growth. In line with this, dexamethasone predominantly inhibits neutrophil function rather than macrophage function. Dexamethasone-induced mortality also depends on the glucocorticoid receptor. Dexamethasone partially suppresses NF-κB activation at the infection site by inducing the transcription of IκB via the glucocorticoid receptor. Independent CRISPR/Cas9 targeting of IKKγ to prevent NF-κB activation also increases invasive A. fumigatus growth and larval mortality. However, dexamethasone treatment of IKKγ crispant larvae further increases invasive hyphal growth and host mortality, suggesting that dexamethasone may suppress other pathways in addition to NF-κB to promote host susceptibility. Collectively, we find that dexamethasone acts through the glucocorticoid receptor to suppress NF-κB-mediated neutrophil control of A. fumigatus hyphae in zebrafish larvae.

Mtb-Specific HLA-E-Restricted T Cells Are Induced during Mtb Infection but Not after BCG Administration in Non-Human Primates and Humans.

Background: Novel vaccines targeting the world's deadliest pathogen Mycobacterium tuberculosis (Mtb) are urgently needed as the efficacy of the Bacillus Calmette-Guérin (BCG) vaccine in its current use is limited. HLA-E is a virtually monomorphic unconventional antigen presentation molecule, and HLA-E-restricted Mtb-specific CD8+ T cells can control intracellular Mtb growth, making HLA-E a promising vaccine target for Mtb. Methods: In this study, we evaluated the frequency and phenotype of HLA-E-restricted Mtb-specific CD4+/CD8+ T cells in the circulation and bronchoalveolar lavage fluid of two independent non-human primate (NHP) studies and from humans receiving BCG either intradermally or mucosally. Results: BCG vaccination followed by Mtb challenge in NHPs did not affect the frequency of circulating and local HLA-E-Mtb CD4+ and CD8+ T cells, and we saw the same in humans receiving BCG. HLA-E-Mtb T cell frequencies were significantly increased after Mtb challenge in unvaccinated NHPs, which was correlated with higher TB pathology. Conclusions: Together, HLA-E-Mtb-restricted T cells are minimally induced by BCG in humans and rhesus macaques (RMs) but can be elicited after Mtb infection in unvaccinated RMs. These results give new insights into targeting HLA-E as a potential immune mechanism against TB.

Macrophage Notch1 signaling modulates regulatory T cells via TGFB axis in early MASLD

Background & aimsHepatic immune imbalance is critical in driving metabolic dysfunction-associated steatotic liver disease (MASLD) progression. The role of hepatic regulatory T cells (Tregs) in MASLD initiation and the mechanisms responsible for their change are not completely understood. MethodsA mouse model subjected to a short-term high-fat diet (HFD) to mimic early steatosis, along with liver biopsy samples from patients with simple steatosis and macrophage-specific Notch1 knockout mice (Notch1M-KO)， was used to investigate the role of Tregs in early MASLD and the effect of hepatic macrophage Notch1 signaling on Treg frequency. Using Exos-miRNA-sequencing, we analyzed the miRNA correlated with Treg differentiation. ResultsHere we showed that a decrease in Tregs contributed to HFD-induced hepatic steatosis and insulin resistance (n=5/group/time point, p<0.001). Remarkably, the frequency of Tregs exhibited a negative correlation with Notch1 activation in hepatic macrophages during hepatic steatosis (n=38/group, r=-0.735, p<0.001). Furthermore, we found that Notch1 deficiency attenuated hepatic lipid deposition and reversed Treg levels (n=5 per group, p<0.01, p<0.05). Moreover, Treg depletion in Notch1M-KO mice greatly diminished the ameliorative effect of macrophagic Notch1 deletion on hepatic steatosis. Mechanistically, macrophage Notch1 activation increased its exosomal miR-142a-3p level (1-2-fold), impairing Treg differentiation by targeting TGFBR1 on T cells. Consistently, HFD-fed Notch1M-KO mice exhibited reduced miR-142a-3p levels, elevated TGFBR1 expression on T cells, and increased Tregs frequency in the liver. ConclusionsThese findings highlight the critical role of hepatic Tregs in the early stage of MASLD and add a novel, non-negligible pathway for macrophage involvement in hepatic steatosis. We identify a previously unrecognized molecular mechanism of macrophage Notch1/exosomal miR-142a-3p/TGFBR1 pathway in regulating Treg differentiation, providing the rationale for refined therapeutic strategies for MASLD. Impact and implicationsThe immune mechanisms driving MASLD progression, particularly in the early stages, are not fully understood, which limits the development of effective interventions. This study elucidated a novel mechanism by which hepatic macrophage Notch1 signaling modulated Tregs through the exosomal miR-142a-3p/TGFBR1 axis, contributing to the progression of MASLD. These findings provide a rationale for a potential immunological approach to treat MASLD in the future.

Local receptor-interacting protein kinase 2 inhibition mitigates house dust mite-induced asthma.

House dust mite is the most frequent trigger of allergic asthma, with innate and adaptive immune mechanisms playing critical roles in outcomes. We recently identified the nucleotide-binding oligomerisation domain 1 (NOD1)/receptor-interacting serine/threonine protein kinase 2 (RIPK2) signalling pathway as a relevant contributor to murine house dust mite-induced asthma. This study aimed to evaluate the effectiveness of a pharmacological RIPK2 inhibitor administered locally as a preventive and therapeutic approach using a house dust mite-induced asthma model in wild-type and humanised NOD1 mice harbouring an asthma-associated risk allele, and its relevance using air-liquid interface epithelial cultures from asthma patients. A RIPK2 inhibitor was administered intranasally either preventively or therapeutically in a murine house dust mite-induced asthma model. Airway hyperresponsiveness, bronchoalveolar lavage composition, cytokine/chemokine expression and mucus production were evaluated, as well as the effect of the inhibitor on precision-cut lung slices. Furthermore, the inhibitor was tested on air-liquid interface epithelial cultures from asthma patients and controls. While local preventive administration of the RIPK2 inhibitor reduced airway hyperresponsiveness, eosinophilia, mucus production, T-helper type 2 cytokines and interleukin 33 (IL-33) in wild-type mice, its therapeutic administration failed to reduce the above parameters, except IL-33. By contrast, therapeutic RIPK2 inhibition mitigated all asthma features in humanised NOD1 mice. Results in precision-cut lung slices emphasised an early role of thymic stromal lymphopoietin and IL-33 in the NOD1-dependent response to house dust mite, and a late effect of NOD1 signalling on IL-13 effector response. RIPK2 inhibitor downregulated thymic stromal lymphopoietin and chemokines in house dust mite-stimulated epithelial cultures from asthma patients. These data support that local interference of the NOD1 signalling pathway through RIPK2 inhibition may represent a new therapeutic approach in house dust mite-induced asthma.

Epigenetic and Immune Mechanisms Linking Breastfeeding to Lower Breast Cancer Rates

Epigenetic and Immune Mechanisms Linking Breastfeeding to Lower Breast Cancer Rates

The role of the immune response in developing tuberculosis infection: from latent infection to active tuberculosis

Despite advancements in modern medicine, tuberculosis continues to be one of the leading causes of death globally. Findings indicate that COVID-19 may trigger the activation of tuberculosis infection (TB), leading to its spread. Despite the development of new immunological diagnostic methods for latent tuberculosis infection (LTBI), it is still unclear how the infection transitions to an active TB state. The goal of the study is to provide insights into the progression of tuberculosis infection from a latent to an active state. This article presents recent research data focused on investigating the pathogenesis of LTBI, particularly the immune responses in the interaction between Mycobacteria tuberculosis (Mtb) and the host. It describes the mechanisms of T-cell immunity and cytokine activation, supporting the concept of type 1, type 2, and type 3 immune responses. According to the conducted studies, Th17 cells have a significant role in the development of type 3 antigen-specific responses. The cytokines IL-6 and IL-23 activate STAT3, which is necessary to trigger the expression of Th17. Future research on the role of Th17 cells and cytokines, particularly IL-6 and IL-21, may be beneficial in understanding the shift from LTBI to active TB.

Impact of Human Immunological Responses and Viral Genetic Diversity on Outbreak of Human Monkeypox Virus. A Comprehensive Literature Review Study

Monkeypox was caused by Monkeypox Virus (MPXV) and can infect both humans and animals. An understanding of the interplay between host immunity and genetic diversity was necessary to understand the etiology and epidemiology of monkeypox disease. Objective: To clarify how genetic differences and host immune responses interact when a moneypox infection occurs. Furthermore, we also aim to provide insights into individual variability in illness outcomes and possible treatment targets by investigating how distinct genetic profiles affect immune system activation and efficacy. Methods: Recent research on monkeypox, concentrating on the immune response mechanisms of the host and genetic variables linked to virus vulnerability have thoroughly analyzed. For this purpose, the data were searched from various research engines such as google scholar, pubmed, medline etc., by using different key words i.e., monkeypox and host immunity, monkeypox and antibodies interactions, monkeypox outbreak, mnkeypox strains. Conclusions: The way a monkeypox infection progresses and turns out was greatly influenced by the interplay between host genetic differences and immunological responses. Public health initiatives and the creation of tailored treatment plans can both benefit from the identification of genetic markers linked to immunological response profiles and vulnerability.

Adaptive Imune Fuzzy Quasi-Sliding Mode Formation Tracking Control for Wheeled Mobile Robots with Obstacle Avoidance Under Incidence of Uncertainties and Disturbances: An Artificial Immune Systems Inspired Approach

This paper presents an adaptive immune fuzzy quasi-sliding mode kinematic control integrated with a PD dynamic control for the trajectory tracking and the leader-follower formation control by nonholonomic differential-drive wheeled mobile robots under incidence of uncertainties and disturbances. An immune regulation mechanism bio-inspired approach with reaction effect established by novel fuzzy rules set to adjust the control effort adaptively is designed, also using a fuzzy boundary layer and introducing an adaptation law for the immune portion gain online adjustment in such a way that they can also avert parameter drift, dealing with the drawbacks of a classic first-order sliding mode control, suppressing chattering and still maintaining the robustness with no a priori knowledge of the bounds of the disturbances. An obstacle avoidance strategy with a reactive method and variable avoidance radius is also proposed. The stability analysis is performed based on the Lyapunov theory. Simulation results demonstrate the proposed control effectiveness.

Alterations in Immune Parameters ADP, ANA, IL-1, IL-6, IL-8, STAT-4, and TNF Alpha in Patients with Rheumatoid Arthritis and Osteoarthritis

Background: Rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic joint diseases with distinct pathophysiological mechanisms, but both involve alterations in immune parameters. This research investigates the alterations in several immune parameters, specifically adiponectin (ADP), antinuclear antibodies (ANA), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), signal transducer and activator of transcription 4 (STAT-4), and tumor necrosis factor-alpha (TNF Alpha), in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Also, the current study aims to identify the changes occurring in the physiological and immune parameters of people suffering from rheumatic diseases, as Evaluation of Immunological Inflammatory biomarkers levels ADP, ANA, IL1, IL6, IL8, STAT-4 and TNF-α. Material &amp; Methods: A cross-sectional laboratory-based study with 90 patient’s participant was conducted. Using ELISA kits and laboratory tests, various biomarkers (Immunological Inflammatory biomarkers levels ADP, ANA, IL1, IL6, IL8, STAT-4 and TNF-α were measured among rheumatoid arthritis and Osteoarthritis patients. Results: The findings revealed elevated levels of IL-1, IL-6, IL-8, STAT-4, and TNF Alpha in RA patients, reflecting a heightened inflammatory state. In contrast, OA patients exhibited a more moderate increase in these parameters, suggesting differing immune activation pathways. ADP and ANA levels showed distinct variations between the two patient groups, indicating their potential roles in the pathogenesis and progression of RA and OA. Conclusion: These results contribute to a better understanding of the immune mechanisms underlying RA and OA, highlighting the importance of targeted therapeutic strategies to manage these conditions effectively. Further research is recommended to explore the clinical implications of these findings and develop personalized treatment approaches.

Role of N6-methyladenosine methylation in head and neck cancer and its regulation of innate immune pathways.

N6-methyladenosine (m6A) is considered the most prevalent methylation modification in messenger RNA (mRNA) that critically impacts head and neck cancer (HNC) pathogenesis and development. Alterations of m6A methylation related proteins are closely related to the progression, therapeutic effect, and prognosis of HNC. The human innate immune system activates immune pathways through pattern recognition receptors, which can not only resist pathogen infection, but also play a vital role in tumor immunity. Emerging evidence has confirmed that m6A methylation affects the activation of innate immune pathways such as TLR, cGAS-STING, and NLR by regulating RNA metabolism, revealing its potential mechanisms in the innate immune response of tumor cells. However, the relevant research is still in its infancy. This review elaborates the biological significance of RNA m6A methylation in HNC and discusses its potential regulatory relationship with TLR, cGAS-STING, and NLR pathways, providing a new perspective for in-depth understanding of the role of RNA methylation in the innate immune mechanism and therapeutic application of HNC.