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Despite ample experimental data indicating a role of inflammatory mediators in the behavioral and neurobiological manifestations elicited by exposure to physical and psychologic stressors, causative associations between systemic low-grade inflammation and central nervous system inflammatory processes in posttraumatic stress disorder (PTSD) patients remain largely conceptual. As in other stress-related disorders, pro-inflammatory activity may play an equivocal role in PTSD pathophysiology, one that renders indiscriminate employment of anti-inflammatory agents of questionable relevance. In fact, as several pieces of preclinical and clinical research convergingly suggest, timely and targeted potentiation rather than inhibition of inflammatory responses may actually be beneficial in patients who are characterized by suppressed microglia function in the face of systemic low-grade inflammation. The deleterious impact of chronic stress-associated inflammation on the systemic level may, thus, need to be held in context with the - often not readily apparent - adaptive payoffs of low-grade inflammation at the tissue level.

The biological mechanisms underlying the onset of major depressive disorder (MDD) have predominantly been studied in adult populations from high-income countries, despite the onset of depression typically occurring in adolescence and the majority of the world's adolescents living in low- and middle-income countries (LMIC). Taking advantage of a unique adolescent sample in an LMIC (Brazil), this study aimed to identify biological pathways characterizing the presence and increased risk of depression in adolescence, and sex-specific differences in such biological signatures. We collected blood samples from a risk-stratified cohort of 150 Brazilian adolescents (aged 14-16 years old) comprising 50 adolescents with MDD, 50 adolescents at high risk of developing MDD but without current MDD, and 50 adolescents at low risk of developing MDD and without MDD (25 females and 25 males in each group). We conducted RNA-Seq and pathway analysis on whole blood. Inflammatory-related biological pathways, such as role of hypercytokinemia/hyperchemokinemia in the pathogenesis of influenza (z-score = 3.464, p

Equine endometritis is one of the main causes of subfertility in the mare. Unraveling the molecular mechanisms involved in this condition and pinpointing proteins with biomarker potential could be crucial in both diagnosing and treating this condition. This study aimed to identify the endometritis-induced changes in the endometrial proteome in mares and to elucidate potential biological processes in which these proteins may be involved. Secondly, biomarkers related to bacterial endometritis (BE) in mares were identified. Uterine lavage fluid samples were collected from 28 mares (14 healthy: negative cytology and culture, and no clinical signs and 14 mares with endometritis: positive cytology and culture, in addition to clinical signs). Proteomic analysis was performed with a UHPLC-MS/MS system and bioinformatic analysis was carried out using Qlucore Omics Explorer. Gene Ontology enrichment and pathway analysis (PANTHER and KEGG) of the uterine proteome were performed to identify active biological pathways in enriched proteins from each group. Quantitative analysis revealed 38 proteins differentially abundant in endometritis mares when compared to healthy mares (fold changes >4.25, and q-value = 0.002). The proteins upregulated in the secretome of mares with BE were involved in biological processes related to the generation of energy and REDOX regulation and to the defense response to bacterium. A total of 24 biomarkers for BE were identified using the biomarker workbench algorithm. Some of the proteins identified were related to the innate immune system such as isoforms of histones H2A and H2B involvement in neutrophil extracellular trap (NET) formation, complement C3a, or gelsolin and profilin, two actin-binding proteins which are essential for dynamic remodeling of the actin cytoskeleton during cell migration. The other group of biomarkers were three known antimicrobial peptides (lysosome, equine cathelicidin 2 and myeloperoxidase (MPO)) and two uncharacterized proteins with a high homology with cathelicidin families. Findings in this study provide the first evidence that innate immune cells in the equine endometrium undergo reprogramming of metabolic pathways similar to the Warburg effect during activation. In addition, biomarkers of BE in uterine fluid of mares including the new proteins identified, as well as other antimicrobial peptides already known, offer future lines of research for alternative treatments to antibiotics. • Mares with bacterial endometritis exhibited a significantly higher relative abundance of endometrial proteins compared to clinically healthy mares. • The proteins upregulated in the secretome of mares with bacterial endometritis were involved in biological processes related to the generation of energy and REDOX regulation and to the defense response to bacterium (neutrophil extracellular trap (NET) formation pathway). • A total of 24 biomarkers for bacterial endometritis were identified. Some of the proteins identified were related to the innate immune system such as isoforms of histones H2A and H2B, complement C3a, or gelsolin and profilin. The other group of biomarkers were three known antimicrobial peptides (lysosome, equine cathelicidin 2 and MPO) and two uncharacterized proteins with a high homology with cathelicidin families. [ABSTRACT FROM AUTHOR]

Background and Purpose: This study analyses whether first‐line antihypertensive drugs ameliorate the dysbiosis state in hypertension, and to test if this modification contributes to their blood pressure (BP) lowering properties in a genetic model of neurogenic hypertension. Experimental Approach: Twenty‐week‐old male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were untreated or treated with captopril, amlodipine or hydrochlorothiazide. A faecal microbiota transplantation (FMT) experiment was also performed by gavage of faecal content from donor SHR‐treated groups to SHR recipients for 3 weeks. Key results: Faeces from SHR showed gut dysbiosis, characterized by lower acetate‐ and higher lactate‐producing bacteria and lower strict anaerobic bacteria. All three drugs increased the anaerobic bacteria proportion, captopril and amlodipine restored the proportion of acetate‐producing bacterial populations to WKY levels, whereas hydrochlorothiazide decreased butyrate‐producing bacteria. Captopril and amlodipine decreased gut pathology and permeability and attenuated sympathetic drive in the gut. Both drugs decreased neuroinflammation and oxidative stress in the hypothalamic paraventricular nuclei. Hydrochlorothiazide was unable to reduce neuroinflammation, gut sympathetic tone and gut integrity. FMT from SHR‐amlodipine to SHR decreased BP, ameliorated aortic endothelium‐dependent relaxation to acetylcholine, lowered NADPH oxidase activity, aortic Th17 infiltration and reduced neuroinflammation, whereas FMT from SHR‐hydrochlorothiazide did not have these effects. Conclusions and Implications: First‐line antihypertensive drugs induced different modifications of gut integrity and gut dysbiosis in SHR, which result in no contribution of microbiota in the BP lowering effects of hydrochlorothiazide, whereas the vasculo‐protective effect induced by amlodipine involves gut microbiota reshaping and gut‐immune system communication. [ABSTRACT FROM AUTHOR]

The immune system has a vital, albeit complex, relationship with the microbes residing within us, one that we are only beginning to understand. We asked investigators what they felt were the fundamental challenges we currently face in unraveling the impacts of microbes and their metabolites on host immunity and to discuss key opportunities toward achieving future insights and innovation. [ABSTRACT FROM AUTHOR]

Fish, first jawed vertebrate group appearing in evolution, have immune system similar to those of mammals. These early animals' innate and adaptive immune systems are completely developed, having head kidney and thymus as primary, spleen and mucosa associated lymphoid tissue as secondary immune organs. The adaptive immunity performs key role in defence against recurring infections and elimination of fish pathogens with the help of its memory cells, T‐cell‐receptors and immunoglobulins. Epidermal secretions including antibacterial peptides, lysozymes, lectins, complement and C‐reactive proteins which function in disruption of antigens, phagocytosis, inflammatory response and mending of tissue injury play a significant role as elements of fish immune system. Fish, however, have greater innate immunity than humans do. Estrogens play crucial role in immunomodulation through nuclear oestrogen receptors, which are found in majority of immune cells and lymphoid organs in fish. There is mounting proof that xenoestrogens, that can attach as agonists to oestrogen receptors, pose significant ecotoxicological risk by disrupting the defence mechanism in fish. Though less potent than natural oestrogen, they can bioaccumulate to finally reach a substantial dose. This review's objective is to give an overview of the fish defence system, its estrogenic regulation and estrogenic‐endocrine disruption. [ABSTRACT FROM AUTHOR]

The intricate interplay between Homeobox genes, long non-coding RNAs (lncRNAs), and the development of malignancies represents a rapidly expanding area of research. Specific discernible lncRNAs have been discovered to adeptly regulate HOX gene expression in the context of cancer, providing fresh insights into the molecular mechanisms that govern cancer development and progression. An in-depth comprehension of these intricate associations may pave the way for innovative therapeutic strategies in cancer treatment. The HOX gene family is garnering increasing attention due to its involvement in immune system regulation, interaction with long non-coding RNAs, and tumor progression. Although initially recognized for its crucial role in embryonic development, this comprehensive exploration of the world of HOX genes contributes to our understanding of their diverse functions, potentially leading to immunology, developmental biology, and cancer research discoveries. Thus, the primary objective of this review is to delve into these aspects of HOX gene biology in greater detail, shedding light on their complex functions and potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Background: Activation of innate immunity is a first line of host defense during acute critical illness (ACI) that aims to contain injury and avoid tissue damages. Aberrant activation of innate immunity may also participate in the occurrence of organ failures during critical illness. This review aims to provide a narrative overview of recent advances in the field of innate immunity in critical illness, and to consider future potential therapeutic strategies. Main text: Understanding the underlying biological concepts supporting therapeutic strategies modulating immune response is essential in decision-making. We will develop the multiple facets of innate immune response, especially its cellular aspects, and its interaction with other defense mechanisms. We will first describe the pathophysiological mechanisms of initiation of innate immune response and its implication during ACI. We will then develop the amplification of innate immunity mediated by multiple effectors. Our review will mainly focus on myeloid and lymphoid cellular effectors, the major actors involved in innate immune-mediated organ failure. We will third discuss the interaction and integration of innate immune response in a global view of host defense, thus considering interaction with non-immune cells through immunothrombosis, immunometabolism and long-term reprogramming via trained immunity. The last part of this review will focus on the specificities of the immune response in children and the older population. Conclusions: Recent understanding of the innate immune response integrates immunity in a highly dynamic global vision of host response. A better knowledge of the implicated mechanisms and their tissue-compartmentalization allows to characterize the individual immune profile, and one day eventually, to develop individualized bench-to-bedside immunomodulation approaches as an adjuvant resuscitation strategy. [ABSTRACT FROM AUTHOR]

Summary The study of antibodies in jawed vertebrates (gnathostomes) provides every immunologist with a bird's eye view of how human immunoglobulins (Igs) came into existence and subsequently evolved into their present forms. It is a fascinating Darwinian history of conservation on the one hand and flexibility on the other, exemplified by the Ig heavy chain (H) isotypes IgM and IgD/W, respectively. The cartilaginous fish (e.g., sharks) Igs provide a glimpse of “how everything got off the ground,” while the amphibians (e.g., the model Xenopus) reveal how the adaptive immune system made an about face with the emergence of Ig isotype switching and IgG‐like structure/function. The evolution of mucosal Igs is a captivating account of malleability, convergence, and conservation, and a call to arms for future study! In between there are spellbinding chronicles of antibody evolution in each class of vertebrates and rather incredible stories of how antibodies can adapt to occupy niches, for example, single‐domain variable regions, cold‐adapted Igs, convergent mechanisms to dampen antibody function, provision of mucosal defense, and many more. The purpose here is not to provide an encyclopedic examination of antibody evolution, but rather to hit the high points and entice readers to appreciate how things “came to be.” [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third most common cancer and the second most lethal cancer in the world. The main cause of the disease is due to dietary and behavioral factors. The treatment of this complex disease is mainly based on traditional treatments, including surgery, radiotherapy, and chemotherapy. Due to its high prevalence and high morbidity, more effective treatments with fewer side effects are urgently needed. In recent years, immunotherapy has become a potential therapeutic alternative and one of the fastest-developing treatments. Immunotherapy inhibits tumor growth by activating or enhancing the immune system to recognize and attack cancer cells. This review presents the latest immunotherapies for immune checkpoint inhibitors, cell therapy, tumorinfiltrating lymphocytes, and oncolytic viruses. Some of these have shown promising results in clinical trials and are used in clinical treatment. [ABSTRACT FROM AUTHOR]

Over the last decade, a new paradigm for cancer therapies has emerged which leverages the immune system to act against the tumor. The novel mechanism of action of these immunotherapies has also introduced new challenges to drug development. Biomarkers play a key role in several areas of early clinical development of immunotherapies including the demonstration of mechanism of action, dose finding and dose optimization, mitigation and prevention of adverse reactions, and patient enrichment and indication prioritization. We discuss statistical principles and methods for establishing the prognostic, predictive aspect of a (set of) biomarker and for linking the change in biomarkers to clinical efficacy in the context of early development studies. The methods discussed are meant to avoid bias and produce robust and reproducible conclusions. This review is targeted to drug developers and data scientists interested in the strategic usage and analysis of biomarkers in the context of immunotherapies. [ABSTRACT FROM AUTHOR]

This article explores the role of O-GlcNAcylation in regulating the immune system. O-GlcNAcylation is a post-translational modification that affects cell signaling, metabolism, and development. It has been linked to immune dysfunction and the development of autoimmune, inflammatory, and allergic diseases, as well as immune cell malignancies. The article includes original research articles and comprehensive reviews that cover various aspects of O-GlcNAcylation in the immune system, such as its impact on leukemia, immune cell infiltration, and inflammation. The collection of articles provides a comprehensive overview of O-GlcNAcylation's role in the immune system, highlighting the potential for therapeutic interventions and improved disease diagnoses. [Extracted from the article]

Background: Chronic spontaneous urticaria (CSU) is a highly prevalent and difficult to manage cutaneous disease characterized by the presence of recurrent urticaria, angioedema, or both, for a period of 6 weeks or longer. One of the biological treatments used for patients with CSU with an autoimmune background and bad control of the disease is omalizumab, an anti-IgE monoclonal antibody. The understanding of the mechanism of action of this biological drug in CSU along with the identification of potential biomarkers of clinical response can be helpful in the personalized management of the disease. Objective: The purpose of this study was to analyze the effect of omalizumab on peripheral blood lymphocyte subpopulations in patients with CSU in order to identify potential biomarkers of treatment response. Methods: We analyzed 71 patients with CSU [33 under omalizumab and 38 under non-immunomodulatory drugs (treated with antihistamines; NID)] and 50 healthy controls. An exhaustive immunophenotyping of whole blood T-cell subpopulations, including naïve, central memory, effector memory, effector cells, Th1, Th2, and Th17 was performed by multiparametric flow cytometry. Moreover, in CSU patients, we analyzed markers of inflammation (ESR, DD, CRP), atopy (prick test, IgE quantification), and autoimmunity (anti-thyroid antibodies and indirect basophil activation test).To evaluate the clinical activity, the Urticaria Activity Score 7 (UAS 7) test was used. Results: In patients with CSU under treatment with omalizumab, there was a significant decrease in the percentage of naïve and an increase in the percentage of central memory CD4 T cells as well as a decrease in the percentage of naïve and increase in the percentage of effector CD8 T-cell subsets. Moreover, patients under treatment with omalizumab had higher percentages of Th1 and Th2 cells than patients under treatment with NID. Conclusion: The immune monitoring of T-cell subpopulations in patients with CSU starting omalizumab, may be a useful strategy to analyze treatment response in the clinical practice. [ABSTRACT FROM AUTHOR]

To ensure good welfare of animals in human hands, it is essential to modify housing conditions according to the animals’ needs. Traditionally, the effects of such modifications are studied by means of group-level comparisons, thereby widely neglecting consistent inter-individual differences (i.e., so-called ‘animal personalities’). However, as animals with distinct personality types might differ in their environmental needs and hence react differently to the same environment, such systematic inter-individual differences might have important welfare consequences. This becomes particularly apparent under laboratory conditions, where animals are typically housed under highly standardized and barren environments. Against this background, we here aim to investigate personality-dependent welfare consequences in response to different housing conditions in laboratory mice. Female C57BL/6J mice were characterized for their personality type in exploration behavior and the most and the least explorative individuals were set up in either simple or in highly complex housing conditions that included constantly changing environmental enrichment items. We monitored individual welfare by studying behavioral, physiological, and immunological outcome measures. Besides personality dependent differences in immune parameters and overall improved welfare under complex housing conditions, we indeed found hints that individual mice were differently affected in their welfare depending on the specific combination of personality type and housing condition. Specifically, highly explorative mice appeared to be more adversely affected by simple housing, but also profited more from complex housing compared to low explorative mice. These findings indicate that welfare promoting adjustments do not necessarily benefit all individuals equally and therefore, call for a shift of perspectives in the evaluation of animal welfare. [ABSTRACT FROM AUTHOR]

Food incompatibility (Virudhaahar) is described elaborately in Ayurveda health science. Various types of food incompatibilities with the examples of combination are mentioned in the Ayurveda literatures like in Charaka Samhita and Susruta Samhita but these type of food combinations are not practiced in today's era. Today with the change in lifestyle, food processing methods and the combination of food articles are also modified. So, there is a need to review and identify new food incompatibilities, which are currently practiced as per Ayurvedic perspectives. Such food combinations can prove harmful, which may be imparting its untoward effects on the immune system, cellular metabolism, hormone secretions, and hence, the need to acknowledge this health issue arise. The unwanted effect of wrong combinations of food is not limited up to gastrointestinal tract only but may hamper the major systems of the body as well. Thereby, unwanted side effects can emerge inside the body when two or more types of foods are consumed together. This review article is an endeavour to compile and critically analyse the researches reporting the incompatible food effects with their probable pathogenesis and to identify new food incompatibilities, which are currently practiced. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a highly variable course that is dependent on the host immune system reaction. Lung tissue damage, endothelial dysfunction, and microthrombosis in severe COVID-19 is linked to neutrophilia and the production of neutrophil extracellular traps (NETs). Previous studies have shown that NETs are involved in the pathology of COVID-19 and that the virus itself induces NET formation, although the underlying mechanisms are not clear. In this study, we aimed to investigate the induction of NETs by SARS-CoV-2 in vitro. We have found that both, infectious and heat-inactivated virus induce NETs formation. Surprisingly, cell culture media derived from uninfected Vero cells exhibit similar potency. This suggests that NET inducers other than the virus might be involved. Mitochondria released from dying cells during SARS-CoV-2 infection acting as damage-associated molecular patterns (DAMPs) were identified as potential contributors to neutrophil activation and NET formation. Our findings point to an important source of bias when analyzing NETs induction by SARS-CoV-2 in vitro, but also the immune reaction to viruses in general. Further implications for the understanding of COVID-19 pathogenesis remain to be elucidated. [ABSTRACT FROM AUTHOR]

To examine the fetal thymic-thoracic ratio (TTR) in intrahepatic cholestasis of pregnancy (ICP). This prospective case-control study was conducted in a single tertiary center. The sample consisted of 86 pregnant women at 28–37 weeks of gestation, including 43 women with ICP and 43 healthy controls. TTR was calculated for each patient using the anterior-posterior measurements of the thymus and intrathoracic mediastinal measurements. The median TTR value was found to be smaller in the ICP group compared to the control group (0.32 vs. 0.36, p<0.001). The ICP group had a greater rate of admission to the neonatal intensive care unit (NICU) (p<0.001). Univariate regression analysis revealed that lower TTR values increased the possibility of NICU admission six times (95 % confidence interval: 0.26–0.39, p=0.01). A statistically significant negative correlation was detected between TTR and the NICU requirement (r: −0.435, p=0.004). As a result of the receiver operating characteristic analysis, in predicting NICU admission, the optimal cut-off value of TTR was determined to be 0.31 with 78 % sensitivity and 67 % specificity (area under the curve=0.819; p<0.001). We determined that the fetal TTR may be affected by the inflammatory process caused by the maternal-fetal immune system and increased serum bile acid levels in fetal organs in the presence of ICP. We consider that TTR can be used to predict adverse pregnancy outcomes in patients with ICP. [ABSTRACT FROM AUTHOR]

The immune system has a substantial impact on the growth and expansion of lung malignancies. Immune cells are encompassed by a stroma comprising an extracellular matrix (ECM) and different cells like stromal cells, which are known as the tumor immune microenvironment (TIME). TME is marked by the presence of immunosuppressive factors, which inhibit the function of immune cells and expand tumor growth. In recent years, numerous strategies and adjuvants have been developed to extend immune responses in the TIME, to improve the efficacy of immunotherapy. In this comprehensive review, we outline the present knowledge of immune evasion mechanisms in lung TIME, explain the biology of immune cells and diverse effectors on these components, and discuss various approaches for overcoming suppressive barriers. We highlight the potential of novel adjuvants, including toll-like receptor (TLR) agonists, cytokines, phytochemicals, nanocarriers, and oncolytic viruses, for enhancing immune responses in the TME. Ultimately, we provide a summary of ongoing clinical trials investigating these strategies and adjuvants in lung cancer patients. This review also provides a broad overview of the current state-of-the-art in boosting immune responses in the TIME and highlights the potential of these approaches for improving outcomes in lung cancer patients. PLAIN LANGUAGE SUMMARY: Lung cancer remains a significant global health concern, and researchers are actively exploring innovative approaches to boost the immune system's ability to recognize and destroy cancer cells. Boosting the immune system responses against the lung tumor microenvironment is one of promising approaches for lung cancer therapy. The lung tumor microenvironment refers to the complex network of cells, proteins, and molecules that surround and support the growth of lung tumors. Unfortunately, this environment often hinders the body's immune response, allowing cancer cells to evade detection and destruction. By comprehending the cellular and molecular factors at play, researchers can devise novel strategies to tip the balance in favor of the immune system. Cancer cells often employ various mechanisms to suppress the immune system within the lung tumor microenvironment. One approach to combating this suppression is the use of adjuvants, substances that enhance the immune response. Adjuvants can be administered alongside cancer vaccines or other immunotherapies to strengthen the immune system's ability to recognize and attack tumor cells. The recent progresses have shown the potential of some products, adjuvants, immunotherapy drugs, vaccines, and nanoparticles. This article aims to discuss recent advancements in the field of cancer immunotherapy, specifically focusing on strategies to strengthen the body's immune response against lung tumors. [ABSTRACT FROM AUTHOR]

Objectives Anti-IL-6 receptor antibodies are clinically efficacious in the management of RA with an associated increase in Tregs; however, the role of functional Treg subsets has yet to be clarified. This study aimed to evaluate how functional Treg subsets are altered by IL-6 receptor blockade and to analyse the relationship between these Treg subsets and the clinical outcome of RA. Methods We collected frozen peripheral blood mononuclear cells (PBMCs) from 40 patients with RA who started tocilizumab (TCZ) with or without MTX and 11 healthy controls (HCs). We fractionated Tregs with flow cytometry based on markers of phenotype and function and measured the proportions of detailed Treg subsets sequentially from baseline to week 52. Results The proportions of resting Tregs (rTregs) and rTregs+activated Tregs (aTregs) were significantly lower in RA patients at baseline than in HCs. The proportions of all those CD127low Tregs, rTregs, aTregs and rTregs+aTregs were significantly increased with TCZ treatment. In patients treated with TCZ without MTX, rTreg were increased. Patients with an increase in the proportion of rTregs at week 12 had significantly less arthritis flares during the observation period. Conclusions Blocking the IL-6 receptor with TCZ increased the proportion of rTregs, a functional Treg subpopulation. Patients with an early increase in rTregs showed a favourable treatment course and this increase in rTregs may reflect molecular remission induced by IL-6 signal inhibition. [ABSTRACT FROM AUTHOR]

Parkinson's disease displays clinical heterogeneity, presenting with motor and non-motor symptoms. Heterogeneous phenotypes, named brain-first and body-first, may reflect distinct α-synuclein pathology starting either in the central nervous system or in the periphery. The immune system plays a prominent role in the central and peripheral pathology, with misfolded α-synuclein being placed at the intersection between neurodegeneration and inflammation. Here, we characterized the inflammatory profile and immune-phenotype of peripheral blood mononuclear cells (PBMCs) from Parkinson's disease patients upon stimulation with α-synuclein monomer or oligomer, and investigated relationships of immune parameters with clinical scores of motor and non-motor symptoms. Freshly isolated PBMCs from 21 Parkinson's disease patients and 18 healthy subjects were exposed in vitro to α-synuclein species. Cytokine/chemokine release was measured in the culture supernatant by Multiplex Elisa. The immune-phenotype was studied by FACS-flow cytometry. Correlation analysis was computed between immune parameters and parkinsonian motor and non-motor scales. We found that Parkinson's disease patients exhibited a dysregulated PBMC-cytokine profile, which remained unaltered after exposure to α-synuclein species and correlated with both motor and non-motor severity, with a strong correlation observed with olfactory impairment. Exposure of PBMCs from healthy controls to α-synuclein monomer/oligomer increased the cytokine/chemokine release up to patient's values. Moreover, the PBMCs immune phenotype differed between patients and controls and revealed a prominent association of the Mos profile with olfactory impairment, and of NK profile with constipation. Results suggest that a deranged PBMC-immune profile may reflect distinct clinical subtypes and would fit with the recent classification of Parkinson's disease into peripheral-first versus brain-first phenotype. [ABSTRACT FROM AUTHOR]

Pathogen-inspired nanocarriers take lessons from microbes and ferry multiple innate immune agonists to the same target cell; together, they activate multiple innate immune sensing pathways and orchestrate robust and synergistic cytokine responses. Nanomaterials engineering design strategies must take into consideration the varying extra- and intracellular localizations of innate immune sensing receptors to optimize agonist delivery to specific cognate receptors. Different classes of lipids, polymers, metals, and hybrid combinations of materials have been and are being tested for multi-agonist delivery. This underscores the central importance of rational nanocarrier design to achieve therapeutic efficacy. Cytokine remodeling therapies that utilize innate immune agonists may offer a shift in or complementary treatment paradigms for cancer and other complex diseases. Rational nanocarrier engineering design considerations are strongly warranted, particularly from the materials perspective. These pathogen-inspired, multi-agonist delivery technologies emerge as a significant class of next-generation cancer therapeutic strategy. In complex diseases such as cancer, modulating cytokine signatures of disease using innate immune agonists holds therapeutic promise. Novel multi-agonist treatments offer tunable control of the immune system because they are uniquely pathogen inspired, eliciting robust antitumor responses by promoting synergistic cytokine responses. However, the chief strategic hurdle is ensuring multi-agonist delivery to the same target cells, highlighting the importance of using nanomaterial-based carriers. Here, we place nanocarriers in center stage and review the delivery hurdles related to the varying extra- and intracellular localizations of innate immune receptors. We discuss a range of nanomaterials used for multi-agonist delivery, highlighting their respective benefits and drawbacks. Our overarching stance is that rational nanocarrier design is crucial for developing pathogen-inspired multi-agonist immunotherapies. [ABSTRACT FROM AUTHOR]

Objective: The present study was performed to identify key biomarkers associated with immune cell infiltration in peri‐implantitis through bioinformatic analyses. Methods: Six peri‐implantitis soft tissue samples and six healthy gingiva samples were obtained from GSE106090, and were used to identify immune‐associated differentially expressed genes (DEGs) in peri‐implantitis. The candidate biomarkers associated with immune cell infiltration were examined by immunohistochemical staining. Results: We identified 2089 upregulated and 2173 downregulated genes. Upregulated DEGs were significantly associated with immune response. Ten key candidate biomarkers were identified in the PPI network, including IL1B, TLR2, TLR4, CCL4, CXCL8, IL10, IL6, CD4, CCL3, and PTPRC. The expression level of the 10 genes increased in peri‐implantitis soft tissue samples compared with healthy gingiva samples. The proportion of CD4+ T cells, iTreg, and Tfh in infiltration immune cells increased in peri‐implantitis soft tissue samples and were positively correlated with the expression level of candidate biomarkers TLR4, CCL3, CXCL8, and IL1B. Immunohistochemistry showed that there were more lymphocytes in peri‐implantitis soft tissue samples, with an increased expression level of TLR4, CCL3, CXCL8, and IL1B. Conclusion: Identification of four novel diagnostic biomarkers was helpful for revealing the molecular mechanisms and could serve as a risk predictor for the immune microenvironment in peri‐implantitis. [ABSTRACT FROM AUTHOR]

Purpose: This paper aims to propose a robust kinematic controller based on sliding mode theory designed to solve the trajectory tracking problem and also the formation control using the leader–follower strategy for nonholonomic differential-drive wheeled mobile robots with a PD dynamic controller. Design/methodology/approach: To deal with classical sliding mode control shortcomings, such as the chattering and the requirement of a priori knowledge of the limits of the effects of disturbances, an immune regulation mechanism-inspired approach is proposed to adjust the control effort magnitude adaptively. A simple fuzzy boundary layer method and an adaptation law for the immune portion gain online adjustment are also considered. An obstacle avoidance reactive strategy is proposed for the leader robot, given the importance of the leader in the formation control structure. Findings: To verify the adaptability of the controller, obstacles are distributed along the reference trajectory, and the simulation and experimental results show the effectiveness of the proposed controller, which was capable of generating control signals avoiding chattering, compensating for disturbances and avoiding the obstacles. Originality/value: The proposed design stands out for the ability to adapt in a case involving obstacle avoidance, trajectory tracking and leader–follower formation control by nonholonomic robots under the incidence of uncertainties and disturbances and also considering that the immune-based control provided chattering mitigation by adjusting the magnitude of the control effort, with adaptability improved by a simple integral-type adaptive law derived by Lyapunov stability analysis. [ABSTRACT FROM AUTHOR]

Background: SARS‐CoV‐2 has triggered a pandemic and contributes to long‐lasting morbidity. Several studies have investigated immediate cellular and humoral immune responses during acute infection. However, little is known about long‐term effects of COVID‐19 on the immune system. Methods: We performed a longitudinal investigation of cellular and humoral immune parameters in 106 non‐vaccinated subjects ten weeks (10 w) and ten months (10 m) after their first SARS‐CoV‐2 infection. Peripheral blood immune cells were analyzed by multiparametric flow cytometry, serum cytokines were examined by multiplex technology. Antibodies specific for the Spike protein (S), the receptor‐binding domain (RBD) and the nucleocapsid protein (NC) were determined. All parameters measured 10 w and 10 m after infection were compared with those of a matched, noninfected control group (n = 98). Results: Whole blood flow cytometric analyses revealed that 10 m after COVID‐19, convalescent patients compared to controls had reduced absolute granulocyte, monocyte, and lymphocyte counts, involving T, B, and NK cells, in particular CD3+CD45RA+CD62L+CD31+ recent thymic emigrant T cells and non‐class‐switched CD19+IgD+CD27+ memory B cells. Cellular changes were associated with a reversal from Th1‐ to Th2‐dominated serum cytokine patterns. Strong declines of NC‐ and S‐specific antibody levels were associated with younger age (by 10.3 years, p <.01) and fewer CD3−CD56+ NK and CD19+CD27+ B memory cells. Changes of T‐cell subsets at 10 m such as normalization of effector and Treg numbers, decline of RTE, and increase of central memory T cell numbers were independent of antibody decline pattern. Conclusions: COVID‐19 causes long‐term reduction of innate and adaptive immune cells which is associated with a Th2 serum cytokine profile. This may provide an immunological mechanism for long‐term sequelae after COVID‐19. [ABSTRACT FROM AUTHOR]

Maintaining immunoglobulin levels in the body is important to protect the body from exposure to pathogens. One effort can be made by consuming herbs containing immunomodulatory compounds, such as Cheral®, which includes a combination of herbs Phyllanthus niruri and Curcuma longa. This research aims to determine the expression of immunoglobulin M (IgM) and immunoglobulin G (IgG) following the administration of Cheral® to Wistar rats. The study was conducted in vivo, utilizing 24 healthy male Wistar rats for a 90-day treatment period. The research was divided into four treatment groups, including a control group and three dosage groups: Dose 1 (156.25 mg/kg BW), Dose 2 (312.5 mg/kg BW), and Dose 3 (468.75 mg/kg BW). IgM and IgG were isolated from the spleen and analyzed using flow cytometry. Flow cytometry data were analyzed using SPSS with a one-way ANOVA and post hoc test (p-value <0.05). The analysis showed that the relative number of IgM-producing cells in the control group was significantly higher than in the treatment groups, with a difference of 44.40%. In contrast, the relative number of IgG-producing cells in Dose 3 was significantly lower than all other treatment groups, showing a decrease of 29.21%. Overall, the expression of IgG and IgM did not differ substantially across all treatments. The lower IgG and IgM profiles compared to the control group indicate Cheral®'s ability to prevent infections and maintain the immune system of the rats throughout the treatment period. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has caused governments and individuals to face important but difficult trade‐offs between health and the economy. How do individuals choose between health and economic outcomes during the pandemic? Based on the behavioural immune system (BIS) theory and the life history (LH) theory, the present study examined the effects of individual differences in pathogen disgust sensitivity and life history strategy on people's health‐economic trade‐offs during the COVID‐19 pandemic. Results of an online study (N = 300) showed that people with higher pathogen disgust sensitivity felt less sense of control during the pandemic, and therefore chose health‐related options over economic‐related options. In addition, the association between pathogen disgust sensitivity and health outcome preference only existed in people with relatively faster life history strategies. Further, people's health‐economic trade‐offs were not influenced by their current economic status. Findings have important implications for policymakers and the public to understand people's health‐economic choices during the pandemic. [ABSTRACT FROM AUTHOR]

cGAS-STING Signaling Pathway-Mediated Cancer Immunotherapy: In this comprehensive review, the highlight advances of engineered biomaterials-mediated the cGAS-STING signaling pathway activation for antitumor immunotherapy are discussed and summarized in detail, and the critical challenges and future research direction are also discussed. [Display omitted] Immunotherapy that harnesses the specificity of the patients' immune system to heighten natural defenses against tumors has become one of the most attractive strategies in cancer therapy. Currently, the majority of immunotherapies mainly focused on encouraging the adaptive offshoot of the immune systems. Nevertheless, it is increasingly recognized that both the innate and adaptive immune offshoots need to be involved to motivate optimal antitumor immunity. Among them, the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway is vitally important for activating innate and adaptive antitumor immunity. Ongoing research related to the cGAS-STING signaling pathway mediated immunotherapies have testified their advantages in preventing cancer progression and achieving favorable clinical outcomes. In this review, we systematically elaborated the synopsis of the cGAS-STING signaling pathway as well as involved immunological effects in cancer immune cycle, and thoroughly overviewed the summary of chemical or engineering strategies to heighten the potential application of the cGAS-STING signaling pathway-related agonists. Meanwhile, the highlight advances of engineered biomaterials-mediated different strategies-guided the cGAS-STING signaling pathway activation for antitumor immunotherapy are summarized in detail. Moreover, the critical challenges and future research direction of the cGAS-STING signaling pathway-mediated cancer immunotherapeutic strategy are also discussed. [ABSTRACT FROM AUTHOR]

The Rab family of proteins is involved in organelle regulation, trafficking, signal transduction, mitosis, phagocytosis, growth differentiation, cytoskeleton protein depolymerization and other cellular functions and abnormal expression has been associated with many pathologies, including cancer. Previous work has focused on Rab function in higher animals but fish, crustaceans and other aquatic animals also express the Rab proteins. The current review summarizes research progress on Rab proteins, focusing on immune defense against pathogens in aquatic animals. Some differences in Rab protein function between aquatic and higher animals were found and greater involvement in the fish and crustacean immune system than that of higher animals. Novel insights into Rab protein in aquatic animals are offered with implications for the development of aquaculture strategies. [ABSTRACT FROM AUTHOR]

Introduction: Physical activity (PA) during pregnancy has numerous benefits, which may be mediated via effects on the immune system. However, supportive evidence is inconsistent and is mainly from studies in high‐risk groups. We estimated the effect of PA during pregnancy on systemic inflammatory markers and cytokines in mothers recruited in the Barwon infant study. Material and Methods: The Barwon infant study is a prebirth cohort of 1064 mothers recruited in the Barwon Region of Victoria, Australia. Participants reported their previous week's PA at their 28‐week antenatal appointment using the International PA Questionnaire. Women were grouped into low, moderate, and high PA categories based on daily duration and weekly frequency of walking, moderate‐ or vigorous‐intensity PA. Women reporting moderate levels of PA, consistent with current recommendations, served as the comparison group. Markers of systemic inflammation, high‐sensitivity C‐reactive protein (hsCRP), glycoprotein acetyls (GlycA), and 17 cytokines were measured at 28 weeks gestation and log transformed as appropriate. Regression analyses adjusted for maternal smoking, gestational diabetes mellitus, prepregnancy BMI, and household size were performed. Results: Compared to women in the moderate group (n = 371, 42%), women reporting low PA (n = 436, 50%) had 10.1% higher hsCRP (95% CI (3.7% to 16.6%), p < 0.01) while women in high PA (n = 76, 9%) had a 14% higher hsCRP (95% CI (3.1% to 24.8%), p = 0.01). Women in the high PA category had higher interleukin (IL)‐4 (q = 0.03) and IL‐9 (q = 0.03) levels compared to those in moderate category. Each vigorous MET minute/week was associated with lower GlycA (β = −0.004, 95% CI (−0.044 to 0.035); p = 0.03). Conclusions: Low and high PA are each associated with higher hsCRP than moderate PA, suggesting that undertaking the recommended moderate PA during pregnancy decreases systemic inflammation. High PA affects T cell‐associated cytokines during pregnancy. Evidence from our study suggests that PA can modulate the immune responses during pregnancy. Studies are now required to assess whether PA during pregnancy impacts maternal and infant clinical outcomes by modifying inflammatory responses. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease, which is characterized by the selective loss of the upper and lower motor neurons. The pathogenesis of ALS remains to be elucidated and has been connected to genetic, environmental and immune conditions. Evidence from clinical and experimental studies has suggested that the immune system played an important role in ALS pathophysiology. Autoantibodies are essential components of the immune system. Several autoantibodies directed at antigens associated with ALS pathogenesis have been identified in the serum and/or cerebrospinal fluid of ALS patients. The aim of this review is to summarize the presence and clinical significance of autoantibodies in ALS. [ABSTRACT FROM AUTHOR]

Background: Glycine is a conditional non-essential amino acid in human and other mammals. It is abundant in the liver and is known for a wide spectrum of characteristics including the antioxidant, antiinflammatory, immunomodulatory, and cryoprotective effects. The amino acid is a naturally occurring osmolyte compatible with protein surface interactions and has been reported in literature as a potent therapeutic immuno-nutrient for liver diseases such as alcoholic liver disease. Oral glycine administration protects ethanol-induced liver injury, improves serum and tissue lipid profile, and alleviates hepatic injury in various conditions. In recent years, sodium salt of boron (borax) has been reported for its beneficial effects on cellular stress, including the effects on cell survival, immunity, and tissue redox state. Incidentally both glycine and boron prevent apoptosis and promote cell survival under stress. Objective: This study investigates the beneficial effect of borax on liver protection by glycine. Methods: Briefly, liver toxicity was induced in rats by a single intraperitoneal injection of thioacetamide (400 mg/kg b. wt.). Results: Significant changes in oxidative stress and liver function test parameters, the molybdenum Fe-S flavin hydroxylase activity, nitric oxide and tissue histopathology were observed in thioacetamide treated positive control group. The changes were ameliorated both by glycine as well as borax, but the combinatorial treatment yielded a better response indicating the impact of boron supplementation on glycine mediated protection of liver injury in experimental animal model. Conclusions: The study has clinical implications as the hepatotoxicity caused by thioacetamide mimics features of hepatitis C infection in human. [ABSTRACT FROM AUTHOR]

The study of bacterial immune systems has recently gained momentum, revealing a fascinating trend: many systems form large supramolecular assemblies. Here, we examine the potential mechanisms underpinning the evolutionary success of these structures, draw parallels to eukaryotic immunity, and offer fresh perspectives to stimulate future research into bacterial immunity. [ABSTRACT FROM AUTHOR]

Postbiotics are recognized as the most innovative, multidisciplinary biotechnological approach. Each year, the quantity of research results and patents grows. According to PubMed, around 250 research papers in the field of postbiotics were cited in 2023, followed by approximately 74 publications in early 2024. Concurrently, the global postbiotic market has grown significantly, becoming one of the most formidable markets in the biotic sector. Yet, there is no thorough analysis of the current progress of the postbiotics market or how research studies and discoveries can impact the quantity and quality of postbiotics. This review provides an insightful perspective on current consumer brands and highlights the latest therapeutic and non- therapeutic applications in the postbiotics market. In comparison to other therapeutic agents such as antibiotics, probiotics, and growth boosters, this review suggests that postbiotics are an effective and eco-friendly alternative therapy. Furthermore, postbiotics, an industrially sustainable technology, are highlighted, shedding light on the development of biotic markets. [Display omitted] • Postbiotics are a promising trend in both therapeutic and non-therapeutic markets. • Postbiotics enhance the immune system and strengthen defensive mechanisms against various disorders. • Postbiotics are an eco-friendly alternative to antibiotics and growth promoter therapies. • Postbiotic research enriches biotic markets by developing new detergents, biofuels, and artificial intelligence-based research tools. [ABSTRACT FROM AUTHOR]

Protein deficiency is a major difficulty for human needs in the past few decades, while different types of aquatic species are rich in high quality protein. Therefore, aquaculture is considered as the main developing food production sector globally. Bacterial infections are the main problem for aquaculture, and their outbreaks have a great impact on productivity, and previously indiscriminate use of antibiotics to control them. However, the emergence of multidrug-resistant pathogens might lead to sudden infectious disease outbreaks resulting in serious economic loss. Immunostimulants application is an effective technique to protect and enhance the immune system of aquatic animals and therefore improve aquaculture production. Nutrient immunostimulants such as essential fatty acids, amino acids, vitamins, and minerals are the most important responsibility to improve aquaculture production, as well as the cost of this method, which is effective, non-toxic, and environment friendly. These nutrient immunostimulants are supportive to increase the immune system, antioxidant, antiinflammatory, and infection resistance of aquatic animals. In addition, nutritional feed additives improved feed palatability and the excellence of aquatic products and also enhance gut functions. Some information is available on nutrient immunostimulants in aquaculture applications, and this review provides information on different kinds of nutritional administration used in aquaculture to enhance positive impacts on aquatic animals' health as well as feed quality development. This review will provide theoretical references for the application of nutrient immunostimulants in aquatic feeds. [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests neuro‐immune mechanisms may link dietary patterns to chronic painful conditions (CPC). In the research field of oro‐facial pain (OFP), studies focuses primarily on dietary mechanical limitations due to pain and dysfunction. Objective: This narrative review aimed to overview the role of nutrition on CPC, with emphasis on temporomandibular disorder (TMD), enlightening OFP researcher on dietary assessment possibilities and providing directions for studies in the field of OFP and nutrition. Methods: A PubMed database search was performed using the MeSH and non‐MeSH descriptors: "temporomandibular joint disorder"; "orofacial pain"; "musculoskeletal pain"; "chronic pain disorders"; "nutrition"; "diet"; "dietary therapy"; "dietary intake" and "inflammation". No time restrictions were applied. Literature reviews, systematic reviews, meta‐analyses and clinical and pre‐clinical trials were included. Results: Exogenous oxidants from unhealthy dietary patterns may contribute to peripheral and central pro‐inflammatory immune signalling leading to peripheral and central sensitization. Furthermore, diets rich in bioactive compounds are suggested to contribute to pain management of CPC. High dietary intake of ultra‐processed foods impacts the quality of the diet and shows adverse health outcomes. In this context, the role of nutrition on TMD remains overlooked. Conclusion: Considering diet may influence CPC, allied with the scarcity of studies evaluating the role of nutrition on TMD, well‐designed clinical trials based on dietary assessments and measurements capable of evaluating food quality, UPF consumption and nutrient adequacy—added to serum nutrient levels evaluation—are suggested. [ABSTRACT FROM AUTHOR]

In the last decade, the thermostatted kinetic theory has been proposed as a general paradigm for the modeling of complex systems of the active matter and, in particular, in biology. Homogeneous and inhomogeneous frameworks of the thermostatted kinetic theory have been employed for modeling phenomena that are the result of interactions among the elements, called active particles, composing the system. Functional subsystems contain heterogeneous active particles that are able to perform the same task, called activity. Active matter living systems usually operate out-of-equilibrium; accordingly, a mathematical thermostat is introduced in order to regulate the fluctuations of the activity of particles. The time evolution of the functional subsystems is obtained by introducing the conservative and the nonconservative interactions which represent activity-transition, natural birth/death, induced proliferation/destruction, and mutation of the active particles. This review paper is divided in two parts: In the first part the review deals with the mathematical frameworks of the thermostatted kinetic theory that can be found in the literature of the last decade and a unified approach is proposed; the second part of the review is devoted to the specific mathematical models derived within the thermostatted kinetic theory presented in the last decade for complex biological systems, such as wound healing diseases, the recognition process and the learning dynamics of the human immune system, the hiding-learning dynamics and the immunoediting process occurring during the cancer-immune system competition. Future research perspectives are discussed from the theoretical and application viewpoints, which suggest the important interplay among the different scholars of the applied sciences and the desire of a multidisciplinary approach or rather a theory for the modeling of every active matter system. • Kinetic equations with Gaussian-type thermostat. • Nonlinear partial-integro differential equations. • Complex living systems. • Immune system modeling. • Fibrosis disease modeling. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is a major health problem. It is one of the most common types of stroke and results in mortality in approximately half of patients. More than half of the fatalities occur in the first 2 days. In addition to the mass effect after ICH hemorrhage, complex pathophysiological mechanisms such as intracranial vessel vasospasm, microthrombosis, and inflammatory immune reaction also increase brain damage. Both resident (including microglia and astrocytes) and circulating immune cells (including neutrophils, macrophages, and lymphocytes) involved in the inflammatory process. The inflammatory response is especially harmful in the acute phase due to harmful substances secreted by infiltrating immune cells. The inflammatory response also has beneficial effects, especially in the later stages. Their role in pathophysiology makes immune cells important therapeutic targets. General immunosuppressive approaches and depleting cell groups such as neutrophils or keeping them away from the lesion site may not be sufficient to prevent poor outcomes after ICH. This is most likely because they suppress anti-inflammatory activities and pro-inflammatory effects. Instead, directing immune cells to the beneficial subpopulation seems like a more rational solution. The pro-inflammatory N1 subpopulation of neutrophils damages the tissue surrounding ICH. In contrast, the N2 subpopulation is associated with anti-inflammatory reactions and tissue repair. Studies show that when neutrophils are polarized toward the N2 subpopulation, clinical outcomes improve and the volume of the infarct decreases. However, more research is still needed. This study aims to evaluate the role of neutrophils as immunotherapeutic targets in ICH in light of current knowledge. [ABSTRACT FROM AUTHOR]

The gut microbiota is a complex ecosystem including both beneficial and harmful microbes, which is essential for the metabolism, health and immunity of the host. Fecal microbiota transplantation (FMT) is an effective treatment for diseases of altered intestinal microbiota. Nosema ceranae, a parasitic fungus in intestinal epithelial cells, destroys the honey bee's gut integrity. This study provided the first report that the number of spores was significantly lower in the native host (Asian honey bee) compared with the novel host (European honey bee). The treatment effect of FMT was denoted by feeding the gut tissue solution from the original host to the new host. The results showed that FMT did not significantly decrease the spore load but enhanced the expression levels of immune genes in the Toll pathway. Our data confirmed that the native host inhibits N. ceranae proliferation. Our data suggest microbes of the native host could be an alternative approach to treat the parasite in the novel host. [ABSTRACT FROM AUTHOR]

Background and Hypothesis The gut-brain axis plays important roles in both gastrointestinal diseases (GI diseases) and schizophrenia (SCZ). Moreover, both GI diseases and SCZ exhibit notable abnormalities in brain subcortical volumes. However, the genetic mechanisms underlying the comorbidity of these diseases and the shared alterations in brain subcortical volumes remain unclear. Study Design Using the genome-wide association studies data of SCZ, 14 brain subcortical volumes, and 8 GI diseases, the global polygenic overlap and local genetic correlations were identified, as well as the shared genetic variants among those phenotypes. Furthermore, we conducted multi-trait colocalization analyses to bolster our findings. Functional annotations, cell-type enrichment, and protein-protein interaction (PPI) analyses were carried out to reveal the critical etiology and pathology mechanisms. Study Results The global polygenic overlap and local genetic correlations informed the close relationships between SCZ and both GI diseases and brain subcortical volumes. Moreover, 84 unique lead-shared variants were identified. The associated genes were linked to vital biological processes within the immune system. Additionally, significant correlations were observed with key immune cells and the PPI analysis identified several histone-associated hub genes. These findings highlighted the pivotal roles played by the immune system for both SCZ and GI diseases, along with the shared alterations in brain subcortical volumes. Conclusions These findings revealed the shared genetic architecture contributing to SCZ and GI diseases, as well as their shared alterations in brain subcortical volumes. These insights have substantial implications for the concurrent development of intervention and therapy targets for these diseases. [ABSTRACT FROM AUTHOR]

The prevalence of autoimmune diseases ranks as the third most common disease category globally, following cancer and heart disease. Numerous studies indicate that long non-coding RNA (lncRNA) plays a pivotal role in regulating human growth, development, and the pathogenesis of various diseases. It is more than 200 nucleotides in length and is mostly involve in the regulation of gene expression. Furthermore, lncRNAs are crucial in the development and activation of immune cells, with an expanding body of research exploring their association with autoimmune disorders in humans. LncRNA Ifng antisense RNA 1 (IFNG-AS1), a key regulatory factor in the immune system, also named NeST or TMEVPG1, is proximally located to IFNG and participates in the regulation of it. The dysregulation of IFNG-AS1 is implicated in the pathogenesis of several autoimmune diseases. This study examines the role and mechanism of IFNG-AS1 in various autoimmune diseases and considers its potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

The prevalence of fragrances in various hygiene products contributes to their sensorial allure. However, fragrances can induce sensitization in the skin or respiratory system, and the mechanisms involved in this process are incompletely understood. This study investigated the intricate mechanisms underlying the fragrance's effects on sensitization response, focusing on the interplay between CYP450 enzymes, a class of drug‐metabolizing enzymes, and the adaptive immune system. Specifically, we assessed the expression of CYP450 enzymes and cytokine profiles in culture of BEAS‐2B and mature dendritic cells (mDC) alone or in co‐culture stimulated with 2 mM of a common fragrance, cinnamyl alcohol (CA) for 20 h. CYP1A1, CYP1A2, CYP1B1, CYP2A6, and CYP2A13 were analyzed by RT‐PCR and IL‐10, IL‐12p70, IL‐18, IL‐33, and thymic stromal lymphopoietin (TSLP) by Cytometric Bead Array (CBA). Through RT–PCR analysis, we observed that CA increased CYP1A2 and CYP1B1 expression in BEAS‐2B, with a further increased in BEAS‐2B‐mDC co‐culture. Additionally, exposure to CA increased IL‐12p70 levels in mDC rather than in BEAS‐2B‐mDC co‐culture. In regards to IL‐18, level was higher in BEAS‐2B than in BEAS‐2B‐mDC co‐culture. A positive correlation between the levels of IL‐10 and CYP1B1 was found in mDC‐CA‐exposed and between IL‐12p70 and CYP1A1 was found in BEAS‐2B after CA exposure. However, IL‐12p70 and CYP1A2 as well as IL‐18, IL‐33, and CYP1A1 levels were negative, correlated mainly in co‐culture control. These correlations highlight potential immunomodulatory interactions and complex regulatory relationships. Overall, exposure to CA enhances CYP450 expression, suggesting that CA can influence immune responses by degrading ligands on xenosensitive transcription factors. This study investigated mechanisms underlying the fragrance's effects on sensitization response through CYP450 enzymes and immune system. We quantified CYP450 enzymes and cytokines in BEAS‐2B and mature dendritic cells (mDC) alone or in co‐culture stimulated with 2 mM of cinnamyl alcohol (CA) for 20 h. Positive correlations between IL‐10 and CYP1B1 in mDC‐CA‐exposed and IL‐12p70 and CYP1A1 in BEAS‐2B‐CA‐exposed were found. These correlations highlight potential immunomodulatory interactions and regulatory relationships, suggesting that CA could influence immune responses by degrading ligands on xenosensitive transcription factors. [ABSTRACT FROM AUTHOR]