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Medulloblastoma (MB) is a highly malignant childhood brain tumor. Group 3 MB (Gr3 MB) is considered to have the most metastatic potential, and tailored therapies for Gr3 MB are currently lacking. Gr3 MB is driven by PRUNE-1 amplification or overexpression. In this paper, we found that PRUNE-1 was transcriptionally regulated by lysine demethylase LSD1/KDM1A. This study aimed to investigate the therapeutic potential of inhibiting both PRUNE-1 and LSD1/KDM1A with the selective inhibitors AA7.1 and SP-2577, respectively. We found that the pharmacological inhibition had a substantial efficacy on targeting the metastatic axis driven by PRUNE-1 (PRUNE-1-OTX2-TGFβ-PTEN) in Gr3 MB. Using RNA seq transcriptomic feature data in Gr3 MB primary cells, we provide evidence that the combination of AA7.1 and SP-2577 positively affects neuronal commitment, confirmed by glial fibrillary acidic protein (GFAP)-positive differentiation and the inhibition of the cytotoxic components of the tumor microenvironment and the epithelial–mesenchymal transition (EMT) by the down-regulation of N-Cadherin protein expression. We also identified an impairing action on the mitochondrial metabolism and, consequently, oxidative phosphorylation, thus depriving tumors cells of an important source of energy. Furthermore, by overlapping the genomic mutational signatures through WES sequence analyses with RNA seq transcriptomic feature data, we propose in this paper that the combination of these two small molecules can be used in a second-line treatment in advanced therapeutics against Gr3 MB. Our study demonstrates that the usage of PRUNE-1 and LSD1/KDM1A inhibitors in combination represents a novel therapeutic approach for these highly aggressive metastatic MB tumors. [ABSTRACT FROM AUTHOR]

Introduction: Looking into the literature, many articles accuse bacterial persister cells as important causes of infection relapse/recalcitrance. This opinion paper, highlights the knowledge gaps and scientific misconceptions in experimental procedures regarding the role of persisters in relapse/recalcitrance of infections and recommends a roadmap for investigations in this field. Conclusion: It is debated in this paper, that unless the queries and missing points are addressed clearly, persisters cannot be stigmatized as the culprit of infection relapse/recalcitrance. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune condition frequently found in rheumatological patients that sometimes raises diagnosis and management problems. The pathogenesis of the disease is complex and involves the activation of many cells and intracellular signaling pathways, ultimately leading to the activation of the innate and acquired immune system and producing extensive tissue damage. Along with joint involvement, RA can have numerous extra-articular manifestations (EAMs), among which lung damage, especially interstitial lung disease (ILD), negatively influences the evolution and survival of these patients. Although there are more and more RA-ILD cases, the pathogenesis is incompletely understood. In terms of genetic predisposition, external environmental factors act and subsequently determine the activation of immune system cells such as macrophages, neutrophils, B and T lymphocytes, fibroblasts, and dendritic cells. These, in turn, show the ability to secrete molecules with a proinflammatory role (cytokines, chemokines, growth factors) that will produce important visceral injuries, including pulmonary changes. Currently, there is new evidence that supports the initiation of the systemic immune response at the level of pulmonary mucosa where the citrullination process occurs, whereby the autoantibodies subsequently migrate from the lung to the synovial membrane. The aim of this paper is to provide current data regarding the pathogenesis of RA-associated ILD, starting from environmental triggers and reaching the cellular, humoral, and molecular changes involved in the onset of the disease. [ABSTRACT FROM AUTHOR]

Sepsis is a clinical syndrome caused by uncontrollable immune dysregulation triggered by pathogen infection, characterized by high incidence, mortality rates, and disease burden. Current treatments primarily focus on symptomatic relief, lacking specific therapeutic interventions. The core mechanism of sepsis is believed to be an imbalance in the host's immune response, characterized by early excessive inflammation followed by late immune suppression, triggered by pathogen invasion. This suggests that we can develop immunotherapeutic treatment strategies by targeting and modulating the components and immunological functions of the host's innate and adaptive immune systems. Therefore, this paper reviews the mechanisms of immune dysregulation in sepsis and, based on this foundation, discusses the current state of immunotherapy applications in sepsis animal models and clinical trials. [ABSTRACT FROM AUTHOR]

A severe condition of sepsis can be a complication of necrotizing enterocolitis (NEC), which can occur in premature infants and becomes a medical challenge in the neonatal intensive care unit (NICU). It is a multifactorial intestinal disease (can affect both the small and large intestine) that can lead to ischemia of the intestinal tissues that evolves into acute organ necrosis. One of these factors is that different types of nutrition can influence the onset or the progression of the disease. Cow-milk-based infant formulas have been shown to cause it in premature infants more frequently than human milk. Recently, nutrition has been shown to be beneficial after surgery. Several issues still under study, such as the pathogenesis and the insufficient and often difficult therapeutic approach, as well as the lack of a common and effective prevention strategy, make this disease an enigma in daily clinical practice. Recent studies outlined the emerging role of the host immune system and resident gut microbiota, showing their close connection in NEC pathophysiology. In its initial stages, broad-spectrum antibiotics, bowel rest, and breastfeeding are currently used, as well as probiotics to help the development of the intestinal microbiota and its eubiosis. This paper aims to present the current knowledge and potential fields of research in NEC pathophysiology and therapeutic assessment. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: The infectious bursal disease virus (IBDV) is a major pathogen in the poultry industry due to its profound impact on the immune systems of young chickens. Various genetic types with distinct biological characteristics have been described. In this study, we evaluated the expression of different cytokines in the bursa of Fabricius and thymus over a 28-day experimental infection with two strains from the G1a (Classical) and G6 (ITA) genogroups. The G6 strain appeared to induce a more immediate immunosuppression, and unlike the G1a strain, did not show signs of gene expression recovery by the end of the study. This finding aligns with the higher replication level previously reported for the G6 and with the clinical outcome, as this genotype, although subclinical, has often been considered more immunosuppressive. Unlike other studies that focused on shorter periods post-infection, the patterns observed in this study were highly variable and complex, depending on the strain, tissue, and time point. Therefore, this study not only confirms the effect of strain/genogroup on immune system modulation but also highlights the importance of extended monitoring post-infection to better understand the intricate patterns and interactions with the host response. Infectious bursal disease virus (IBDV) is a significant burden for poultry production and market due to both direct disease and induced immunosuppression. In the present study, the expression of different cytokines in the bursa of Fabricius and thymus was evaluated during a 28-day-long experimental infection with two strains classified in the G1a (Classical) and G6 (ITA) genogroups. Although both strains significantly affected and modulated the expression of different molecules, the G6 strain seemed to induce a delayed immune response or suppress it more promptly. A recovery in the expression of several mediators was observed in the G1a-infected group at the end of the study, but not in the G6 one, further supporting a more persistent immunosuppression. This evidence fits with the higher replication level previously reported for the G6 and with the clinical outcome, as this genotype, although subclinical, has often been considered more immunosuppressive. However, unlike other studies focused on shorter time periods after infection, the patterns observed in this paper were highly variable and complex, depending on the strain, tissue, and time point, and characterized by a non-negligible within-group variability. Besides confirming the strain/genogroup effect on immune system modulation, the present study suggests the usefulness of longer monitoring activities after experimental infection to better understand the complex patterns and interactions with the host response. [ABSTRACT FROM AUTHOR]

Tumor–immune system interactions are very complicated, being highly nonlinear and not well understood. A large number of tumors can potentially weaken the immune system through various mechanisms such as secreting cytokines that suppress the immune response. In this paper, we propose a tumor–immune system interaction model with a nonmonotonic immune response function and adoptive cellular immunotherapy (ACI). The model has a tumor-free equilibrium and at most three tumor-presence equilibria (low, moderate and high ones). The stability of all equilibria is studied by analyzing their characteristic equations. The consideration of nonmonotonic immune response results in a series of bifurcations such as the saddle-node bifurcation, transcritical bifurcation, Hopf bifurcation and Bogdanov–Takens bifurcation. In addition, numerical simulation results show the coexistence of periodic orbits and homoclinic orbits. Interestingly, along with various bifurcations, we also found two bistable scenarios: the coexistence of a stable tumor-free as well as a high-tumor-presence equilibrium and the coexistence of a stable-low as well as a high-tumor-presence equilibrium, which can show symmetric and antisymmetric properties in a range of model parameters and initial cell concentrations. The new findings indicate that under ACI, patients can possibly reach either a stable tumor-free state or a low-tumor-presence state in the presence of nonmonotonic immune response once the immune system is activated. [ABSTRACT FROM AUTHOR]

The composition of human breast milk is an ideal combination of substances necessary for the healthy development of an infant's body while protecting from pathogens and the balanced development of the microbiota. Its composition is dynamic and changes with the age of the child, meeting their current needs. The study provides a thorough overview of human milk components, such as immunological components, growth factors, hormones, carbohydrates, lipids, minerals, and vitamins. Authors focus on capturing the most important aspects of the effects of these substances on a newborn's body, while also looking for specific connections and describing the effects on given systems. Supplementation and the use of ingredients are also discussed. The purpose of this paper is to present the current state of knowledge about the bioactive components of human milk and their impact on the growth, development, and health of the young child. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer is the sixth most common cancer among women worldwide, with an increasing mortality rate. The standard treatment of patients with advanced or recurrent endometrial cancer has not changed significantly in recent decades. However, in recent years, immunotherapy has emerged as a promising strategy that harnesses the body's immune system against cancer, particularly in advanced or recurrent cases, offering patients the possibility of better results and longer survival. Our critical review analyses recent findings in the literature in this field, focusing on the role of immunotherapy in the treatment of this disease. In particular, it focuses on the importance of molecular biology and highlights how this can change the choice of treatment, providing insights for future therapeutic strategies. The Cancer Genome Atlas (TCGA) has radically changed the history of endometrial cancer by outlining a new classification, based on its molecular characteristics. In the field of oncology, we are approaching the new era of molecular biology, particularly regarding endometrial cancer, with the increasing importance of targeted therapy. This paper is a review of phase III randomized controlled trials published in English between January 2019 and December 2023, comparing drugs of interest with standard adjuvant treatment and molecular subtypes in endometrial cancer. The use of immunotherapy alone or in combination with chemotherapy as therapy in patients with recurrent or advanced primary or metastatic endometrial cancer significantly improves the prognosis of these patients. The results show greater efficacy of all proposed treatments for mismatch repair deficiency (dMMR/MSI-H) patients compared to mismatch repair proficiency (pMMR) patients. Progression-free survival (PFS) and overall survival (OS) are better in dMMR patients in all studies analysed. Immunotherapy has the potential to revolutionize the gynaecological cancer treatment landscape, offering a new pathway and new hope for endometrial cancer patients, improving their outcomes in the future. Given the exciting results obtained in dMMR/MSI-H patients, MMR status should be investigated in every patient with advanced endometrial cancer at the time of diagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: The microenvironment of hepatocellular carcinoma is a really complex milieu, containing a wide variety of cells with specific tasks, belonging to both the mesenchimal and immunitary systems, the extracellular matrix, growth factors, proinflammatory cytokines, and translocated bacterial products. This intricate environment represents a source of potential targets in order to establish a wide and multitask therapeutic strategy for hepatocellular carcinoma. Hepatocellular carcinoma is a malignant tumor that originates from hepatocytes in an inflammatory substrate due to different degrees of liver fibrosis up to cirrhosis. In recent years, there has been growing interest in the role played by the complex interrelationship between hepatocellular carcinoma and its microenvironment, capable of influencing tumourigenesis, neoplastic growth, and its progression or even inhibition. The microenvironment is made up of an intricate network of mesenchymal cells, immune system cells, extracellular matrix, and growth factors, as well as proinflammatory cytokines and translocated bacterial products coming from the intestinal microenvironment via the enterohepatic circulation. The aim of this paper is to review the role of the HCC microenvironment and describe the possible implications in the choice of the most appropriate therapeutic scheme in the prediction of tumor response or resistance to currently applied treatments and in the possible development of future therapeutic perspectives, in order to circumvent resistance and break down the tumor's defensive fort. [ABSTRACT FROM AUTHOR]

The alternative pathway of the complement system is implicated in the etiology of age-related macular degeneration (AMD). Complement depletion with pegcetacoplan and avacincaptad pegol are FDA-approved treatments for geographic atrophy in AMD that, while effective, have clinically observed risks of choroidal neovascular (CNV) conversion, optic neuritis, and retinal vasculitis, leaving room for other equally efficacious but safer therapeutics, including Poly Sialic acid (PSA) nanoparticle (PolySia-NP)-actuated complement factor H (CFH) alternative pathway inhibition. Our previous paper demonstrated that PolySia-NP inhibits pro-inflammatory polarization and cytokine release. Here, we extend these findings by investigating the therapeutic potential of PolySia-NP to attenuate the alternative complement pathway. First, we show that PolySia-NP binds CFH and enhances affinity to C3b. Next, we demonstrate that PolySia-NP treatment of human serum suppresses alternative pathway hemolytic activity and C3b deposition. Further, we show that treating human macrophages with PolySia-NP is non-toxic and reduces markers of complement activity. Finally, we describe PolySia-NP-treatment-induced decreases in neovascularization and inflammatory response in a laser-induced CNV mouse model of neovascular AMD. In conclusion, PolySia-NP suppresses alternative pathway complement activity in human serum, human macrophage, and mouse CNV without increasing neovascularization. [ABSTRACT FROM AUTHOR]

DNA oncoviruses represent an intriguing subject due to their involvement in oncogenesis. These viruses have evolved mechanisms to manipulate the host immune response, facilitating their persistence and actively contributing to carcinogenic processes. This paper describes the complex interactions between DNA oncoviruses and the innate immune system, with a particular emphasis on the cGAS-STING pathway. Exploring these interactions highlights that DNA oncoviruses strategically target and subvert this pathway, exploiting its vulnerabilities for their own survival and proliferation within the host. Understanding these interactions lays the foundation for identifying potential therapeutic interventions. Herein, we sought to contribute to the ongoing efforts in advancing our understanding of the innate immune system in oncoviral pathogenesis. [ABSTRACT FROM AUTHOR]

The purpose of this research is to examine whether Buddhist ethics can improve the health and well-being of Buddhist practitioners during pandemics like COVID-19. It is hypothesized that diseases are part of suffering, and Buddhist teachings aim to eliminate the suffering of all beings. Buddhism also offers ethical codes of conduct for its practitioners to improve their health and well-being. So, the Buddha's teaching or Buddhist ethics, when practiced seriously, should be able to improve one's health, physically and mentally, enhancing the well-being of all Buddhist practitioners during the spread of all pandemics including COVID-19. The present study found that Buddhist ethical practices like the chanting of Buddhist suttas and the development of mindfulness, concentration/meditation, and insight (vipassanā) can improve both physical and mental health, which are important for dealing with any pandemic, tremendously. If the cores of Buddhist ethics (morality, meditation, and wisdom) are perfectly practiced, not only will one live with good physical and mental health but one also will be able to eliminate all the mental defilements that are the root causes of all illnesses and thus enter nibbāna, the state of mind that is beyond all sources of suffering including pandemics/epidemics. More specifically, this paper highlights a set of Buddhist practices, called four bhāvanās (types of development), that can be used to improve health and well-being during any pandemic. [ABSTRACT FROM AUTHOR]

Since the approval for the treatment of melanoma in 2014, immune checkpoint inhibitors (ICIs) have revolutionized the therapy pattern across various malignancies. Coinciding with their frequent usage, their adverse effects, including fever, cannot be neglected. In the context of cancer diseases and cancer treatments, fever of unknown origin (FUO), which has long posed a challenge for clinicians in terms of diagnosis and management, brings forth new connotation and significance. In this paper review, we present the concept of ICIs-associated FUO, consider activated immune system and elevated cytokines as common mechanisms by which ICIs induce fever and various immune-related adverse events (irAEs), summarize and compare the primary etiologies of ICI-associated FUO, and compare it with conventional types of FUO. [ABSTRACT FROM AUTHOR]

The Global Polio Eradication Initiative made immense progress after its establishment in 1988 as a consequence of high coverage with various poliovirus vaccines in all populations of the world. Problems have arisen in recent years, however, related to security issues in some countries, to the circulation of vaccine-derived polioviruses, and to the recognition that individuals with certain immune deficiencies can remain infected and infectious for many months or years. As natural infection and different vaccines have different effects on the immune system, the patterns of humoral and mucosal immunity to polioviruses in the world today are complex but are crucial to the ultimate success of the eradication initiative. This paper describes the background of the current situation and current immunological patterns and discusses their implications for managing population immunity to polioviruses in the years ahead. [ABSTRACT FROM AUTHOR]

Background: Intraoperative radiation therapy (IORT), is a promising method which has been widely applied in breast cancer lumpectomy. Although its effect on destructing remaining cancer cells was approved, maintaining or draining post intraoperative radiation therapy wound fluids (PIWF) is challenging. Moreover, the roles of immune cells in interaction with PIWFs have not been studied before which is the main investigation of this paper. Methods: Surgical wound fluids were collected from 24 IDC patients one day after lumpectomy. The patients were divided into control and IORT groups. The collected wound fluids were centrifuged for 20 minutes at 2000 rpm. The concentration of tumor-associated cytokines and inflammasomes were recorded using the immunoassays. Results: PIWFs stimulate the residue of cancer cells in cavity sides causing disease progression. Here we have focused on the effect of PIWFs on the proactivation or deactivation of WBCs in the tumor bed environment. By sequential imaging in time-transient intervals from the interaction between WBCs and cancer cells, PIWFs have no additive proactivating effect on immune cells. Conclusion: PIWFs have significant roles in proliferation of cancer cells but did not show an observable role in pro-activating immune cells against cancer cells. The functions of immune cells did not show any independent proactivation in the presence of PIWFs with respect to their activation in the presence of blood serum. It seems that draining the PIWFs may be required. In future research, we will use tumor samples of the patients instead of cell lines to better investigate the personalized immune-tumor interactions of patients. [ABSTRACT FROM AUTHOR]

Background: Total hip arthroplasty is indubitably a dominant elective surgery in orthopaedics, contributing to prodigious improvement in the quality of life of patients with osteoarthritis. One of the most potentially devastating complications of this operation is periprosthetic joint infection. Immunocompromised patients might be afflicted by infrequent low-virulence organisms not typically detected with conventional procedures. Consequently, employing advanced identification methods, such as the circumstantial sonication of orthopaedic implants, could be crucial to managing such cases. Case Presentation: We present a peculiar case of a 72-year-old female patient suffering from a chronic periprosthetic hip infection due to Corynebacterium striatum. The pathogen was only identified after rigorous sonication of the extracted implants. The overall management of this case was immensely exacting, primarily because of the patient's impaired immune system, and was finally treated with two-stage revision in our Institution. Literature Review: Although copious literature exists concerning managing periprosthetic hip infections, no concrete guidelines are available for such infections in multimorbid or immunocompromised patients with rare low-virulence microorganisms. Hence, a diagnostic work-up, antibiotic treatment and appropriate revision timeline must be determined. Sonication of extracted implants could be a powerful tool in the diagnostic arsenal, as it can aid in identifying rare microbes, such as Corynebacterium spp. Pertinent antibiotic treatment based on antibiogram analysis and apposite final revision-surgery timing are the pillars for effective therapy of such infections. Clinical Relevance: Corynebacterium striatum has been increasingly recognized as an emerging cause of periprosthetic hip infection in the last decade. A conspicuous rise in such reports has been observed in multimorbid or immunocompromised patients after the COVID-19 pandemic. This case is the first report of Corynebacterium striatum periprosthetic hip infection diagnosed solely after the sonication of extracted implants. This paper aims to increase awareness surrounding Corynebacterium spp. prosthetic joint infections, while highlighting the fields for further apposite research. [ABSTRACT FROM AUTHOR]

Tattoo-associated cutaneous reactions have become quite frequent given the increasing percentage of tattooed subjects globally and also in Italy. On the other hand, the increasing use of target therapy is showing the ability of these drugs to affect the immune system and also cause adverse tattoo-related reactions. In this paper, we report a case of a 42-year-old patient with stage-IIID melanoma undergoing treatment with Dabrafenib and Trametinib. The patient reported erythema, oedema and scaling in areas of the body containing a black tattoo, and, conversely, no signs and/or symptoms in areas with tattoos of a different color. Histopathological and immunohistochemical features indicated a lympho-histiocytic reaction with a granulomatous morphology, mainly distributed around the vessels and hair adnexa. By discussing the cases reported in the literature prior to ours, we concluded and provided the possible indications of the pathogenesis. [ABSTRACT FROM AUTHOR]

Artificial immune systems (AIS), as nature-inspired algorithms, have been developed to solve various types of problems, ranging from machine learning to optimization. This paper proposes a novel hybrid model of AIS that incorporates cellular automata (CA), known as the cellular automata-based artificial immune system (CaAIS), specifically designed for dynamic optimization problems where the environment changes over time. In the proposed model, antibodies, representing nominal solutions, are distributed across a cellular grid that corresponds to the search space. These antibodies generate hyper-mutation clones at different times by interacting with neighboring cells in parallel, thereby producing different solutions. Through local interactions between neighboring cells, near-best parameters and near-optimal solutions are propagated throughout the search space. Iteratively, in each cell and in parallel, the most effective antibodies are retained as memory. In contrast, weak antibodies are removed and replaced with new antibodies until stopping criteria are met. The CaAIS combines cellular automata computational power with AIS optimization capability. To evaluate the CaAIS performance, several experiments have been conducted on the Moving Peaks Benchmark. These experiments consider different configurations such as neighborhood size and re-randomization of antibodies. The simulation results statistically demonstrate the superiority of the CaAIS over other artificial immune system algorithms in most cases, particularly in dynamic environments. [ABSTRACT FROM AUTHOR]

The recognition of smoking as an independent risk factor for lung cancer has become a widely accepted within the realm of respiratory medicine. The emergence of tumor immunotherapy has notably enhanced the prognosis for numerous late-stage cancer patients. Nevertheless, some studies have noted a tendency for lung cancer patients who smoke to derive greater benefit from immunotherapy. This observation has sparked increased interest in the interaction between smoking and the immune response to tumors in lung cancer. The concept of cancer immunoediting has shed light on the intricate and nuanced relationship between the immune system and tumors. Starting from the perspectives of immune surveillance, immune equilibrium, and immune evasion, this narrative review explores how smoking undermines the immune response against tumor cells and induces the generation of tumor neoantigens, and examines other behaviors that trigger tumor immune evasion. By elucidating these aspects, the review concludes that smoking is not conducive to tumor immunoediting. [ABSTRACT FROM AUTHOR]

Severe acute pancreatitis (SAP) begins with premature activation of enzymes, promoted by the immune system, triggering a potential systemic inflammatory response that leads to organ failure with increased mortality and a bleak prognosis. Interleukin-22 (IL-22) is a cytokine that may have a significant role in SAP. IL-22, a member of the IL-10 cytokine family, has garnered growing interest owing to its potential tissue-protective properties. Recently, emerging research has revealed its specific effects on pancreatic diseases, particularly SAP. This paper provides a review of the latest knowledge on the role of IL-22 and its viability as a therapeutic target in SAP. Highlights: 1. Interleukin-22 (IL-22) is a member of the IL-10 family of cytokines. 2. IL-22 is a potential indicator for monitoring organ dysfunction and severity of severe acute pancreatitis (SAP). 3. IL-22 acts as a protective factor against acinar cell damage by suppressing autophagy and reducing the infiltration of inflammatory cells. 4. IL-22 alleviate SAP-induced multiorgan injury. 5. IL-22 protect SAP-induced intestinal barrier damage. [ABSTRACT FROM AUTHOR]

Background: Anosmia and dysgeusia are symptoms associated with COVID-19 infection following the announcement of the disease as a pandemic. Moreover, there is no effective treatment for the disease. Garlic is a well-known herb with antimicrobial and antiviral properties. This study evaluates the potential therapeutic effect of garlic consumption on reducing the recovery time from anosmia and dysgeusia symptoms among participants with COVID-19. Methods: 388 Jordanian participants with COVID-19 infection were enrolled in an online computer-assisted web survey during the period from 20th September 2021 to 20th January 2022. The survey consisted of three constructs; socio-demographic profile, symptoms associated with COVID-19, and frequency of garlic and onion consumption used during the infection. Results: The results of this study showed that almost half of the participants were between 20-40 (193, 49.7%); most of them complained about fever, fatigue, anosmia, and dysgeusia and used onion (20, 93%) and garlic (29, 23%) to alleviate symptoms of the disease. In total, 40.7% of garlic-using participants recovered from anosmia within the first 11-15 days, whereas 35.3% recovered between 6-10 days. Results also revealed that there was no correlation between garlic consumption and recovery from dysgeusia. Hence, there was a weak inverse association between garlic consumption and recovery time from anosmia. Conclusion: The authors concluded that consumption of garlic will enhance immune system during the fight against COVID-19. There is need for further study to identify the proper amount of garlic consumption to relieve anosmia symptoms during COVID-19. [ABSTRACT FROM AUTHOR]

Allergies affect approximately 10–30% of people worldwide, with an increasing number of cases each year; however, the underlying mechanisms are still poorly understood. In recent years, extracellular vesicles (EVs) have been suggested to play a role in allergic sensitization and skew to a T helper type 2 (Th2) response. The aim of this review is to highlight the existing evidence of EV involvement in allergies. A total of 22 studies were reviewed; 12 studies showed EVs can influence a Th2 response, while 10 studies found EVs promoted a Th1 or Treg response. EVs can drive allergic sensitization through up-regulation of pro-Th2 cytokines, such as IL-4 and IL-13. In addition, EVs from MRSA can induce IgE hypersensitivity in mice towards MRSA. On the other hand, EVs can induce tolerance in the immune system; for example, pre-exposing OVA-loaded EVs prevented OVA sensitization in mice. The current literature thus suggests that EVs play an essential role in allergy. Further research utilizing human in vitro models and clinical studies is needed to give a reliable account of the role of EVs in allergy. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) are a key component of the immunosuppressive cell and cytokine network. They play a critical role in allowing tumors to evade the immune system. To successfully combat cancer through immunotherapy, it is essential to re-educate TAMs. This study introduces a TAM-targeting nanoreporter that can reshape the tumor immune microenvironment, enhancing cancer immunotherapy. Additionally, the nanoreporter allows for the monitoring of TAM immune activation through protease-responsive photoacoustic/fluorescent imaging. [Display omitted] • This paper described a non-invasive optical imaging technique for tracing the immune activation of tumor-associated macrophages. • This nanoreporter could target TAMs and achieve precise controlled release of TLR agonists. • This "all-in-one" nanoplatform shows promise in cancer diagnosis, treatment and prognosis assessment. Tumor-associated macrophages (TAMs) are vital in the tumor microenvironment, contributing to immunosuppression and therapy tolerance. Despite their importance, the precise re-education of TAMs in vivo continues to present a formidable challenge. Moreover, the lack of real-time and efficient methods to comprehend the spatiotemporal kinetics of TAMs repolarization remains a significant hurdle, severely hampering the accurate assessment of treatment efficacy and prognosis. Herein, we designed a metal–organic frameworks (MOFs) based Caspase-1 nanoreporter (MCNR) that can deliver a TLR7/8 agonist to the TAMs and track time-sensitive Caspase-1 activity as a direct method to monitor the initiation of immune reprogramming. This nanosystem exhibits excellent TAMs targeting ability, enhanced tumor accumulation, and stimuli-responsive behavior. By inducing the reprogramming of TAMs, they were able to enhance T -cell infiltration in tumor tissue, resulting in inhibited tumor growth and improved survival in mice model. Moreover, MCNR also serves as an activatable photoacoustic and fluorescent dual-mode imaging agent through Caspase-1-mediated specific enzyme digestion. This feature enables non-invasive and real-time antitumor immune activation monitoring. Overall, our findings indicate that MCNR has the potential to be a valuable tool for tumor immune microenvironment remodeling and noninvasive quantitative detection and real-time monitoring of TAMs repolarization to immunotherapy in the early stage. [ABSTRACT FROM AUTHOR]

INTRODUCTION Breastfeeding to strengthen the immune system suggests allergy prevention as a possible option. The connection between breastfeeding and the development of atopic-allergic diseases is being discussed. The primary aim of this work was to investigate an association of the first early skin-to-skin contact following cesarean section with the development of atopic diseases within the 1st year of life. METHODS The present study was conducted as a bicentric prospective cohort study in central Germany with a 15-month recruitment period. Data collection was by telephone interviews with a follow-up of 12 months. The statistical evaluation procedure was based on a hierarchical test of the association of early skin-to-skin contact between mother and child with the two main outcome measures. The primary outcome is the duration of breastfeeding. The second outcome is the onset of atopic-allergic disease within the 1st year of life. RESULTS Mothers breastfed longer if they had skin-to-skin contact within the first 30 minutes postpartum [χ²(df=5) = 19.020, p=0.002], if they breastfed their newborns early immediately after birth (p<0.001), and if the first skin-to-skin contact lasted more than one hour [χ²(df=4) = 19.617, p<0.001]. Regarding atopic-allergic diseases, no significant effects of skin-to-skin contact were found in relation to disease development. Regarding breastfeeding, no significant effects of atopic-allergic diseases could be detected either. CONCLUSIONS The results of this study reflect the benefits of skin-to-skin contact in the context of breastfeeding and atopic disease. The current scientific knowledge regarding skin contact and the development of atopic-allergic diseases should be extended and deepened. [ABSTRACT FROM AUTHOR]

Deep learning-based face recognition models are vulnerable to adversarial attacks. In contrast to general noises, the presence of imperceptible adversarial noises can lead to catastrophic errors in deep face recognition models. The primary difference between adversarial noise and general noise lies in its specificity. Adversarial attack methods give rise to noises tailored to the characteristics of the individual image and recognition model at hand. Diverse samples and recognition models can engender specific adversarial noise patterns, which pose significant challenges for adversarial defense. Addressing this challenge in the realm of face recognition presents a more formidable endeavor due to the inherent nature of face recognition as an open set task. In order to tackle this challenge, it is imperative to employ customized processing for each individual input sample. Drawing inspiration from the biological immune system, which can identify and respond to various threats, this paper aims to create an artificial immune system to provide adversarial defense for face recognition. The proposed defense model incorporates the principles of antibody cloning, mutation, selection, and memory mechanisms to generate a distinct “antibody” for each input sample, wherein the term “antibody” refers to a specialized noise removal manner. Furthermore, we introduce a self-supervised adversarial training mechanism that serves as a simulated rehearsal of immune system invasions. Extensive experimental results demonstrate the efficacy of the proposed method, surpassing state-of-the-art adversarial defense methods. The source code is available here, or you can visit this website: https://github.com/RenMin1991/SIDE [ABSTRACT FROM AUTHOR]

As one of the significant challenges to human health, cancer has long been a focal point in medical treatment. With ongoing advancements in the field of medicine, numerous methodologies for cancer therapy have emerged, among which oncolytic virus therapy has gained considerable attention. However, oncolytic viruses still exhibit limitations. Combining them with various therapies can further enhance the efficacy of cancer treatment, offering renewed hope for patients. In recent research, scientists have recognized the promising prospect of amalgamating oncolytic virus therapy with diverse treatments, potentially surmounting the restrictions of singular approaches. The central concept of this combined therapy revolves around leveraging oncolytic virus to incite localized tumor inflammation, augmenting the immune response for immunotherapeutic efficacy. Through this approach, the patient's immune system can better recognize and eliminate cancer cells, simultaneously reducing tumor evasion mechanisms against the immune system. This review delves deeply into the latest research progress concerning the integration of oncolytic virus with diverse treatments and its role in various types of cancer therapy. We aim to analyze the mechanisms, advantages, potential challenges, and future research directions of this combination therapy. By extensively exploring this field, we aim to instill renewed hope in the fight against cancer. [ABSTRACT FROM AUTHOR]

Immunonutrition, which focuses on specific nutrients in breast milk and post-weaning diets, plays a crucial role in supporting infants' immune system development. This study explored the impact of maternal supplementation with Bifidobacterium breve M-16V and a combination of short-chain galacto-oligosaccharide (scGOS) and long-chain fructo-oligosaccharide (lcFOS) from pregnancy through lactation, extending into the early childhood of the offspring. The synbiotic supplementation's effects were examined at both mucosal and systemic levels. While the supplementation did not influence their overall growth, water intake, or food consumption, a trophic effect was observed in the small intestine, enhancing its weight, length, width, and microscopic structures. A gene expression analysis indicated a reduction in FcRn and Blimp1 and an increase in Zo1 and Tlr9, suggesting enhanced maturation and barrier function. Intestinal immunoglobulin (Ig) A levels remained unaffected, while cecal IgA levels decreased. The synbiotic supplementation led to an increased abundance of total bacteria and Ig-coated bacteria in the cecum. The abundance of Bifidobacterium increased in both the intestine and cecum. Short-chain fatty acid production decreased in the intestine but increased in the cecum due to the synbiotic supplementation. Systemically, the Ig profiles remained unaffected. In conclusion, maternal synbiotic supplementation during gestation, lactation, and early life is established as a new strategy to improve the maturation and functionality of the gastrointestinal barrier. Additionally, it participates in the microbiota colonization of the gut, leading to a healthier composition. [ABSTRACT FROM AUTHOR]

The immune system comprises a complex yet tightly regulated network of cells and molecules that play a critical role in protecting the body from infection and disease. The activity and development of each immune cell is regulated in a myriad of ways including through the cytokine milieu, the availability of key receptors, via tailored intracellular signalling cascades, dedicated transcription factors and even by directly modulating gene accessibility and expression; the latter is more commonly known as epigenetic regulation. In recent years, epigenetic regulators have begun to emerge as key players involved in modulating the immune system. Among these, the lysine methyltransferase DOT1L has gained significant attention for its involvement in orchestrating immune cell formation and function. In this review we provide an overview of the role of DOT1L across the immune system and the implications of this role on health and disease. We begin by elucidating the general mechanisms of DOT1Lmediated histone methylation and its impact on gene expression within immune cells. Subsequently, we provide a detailed and comprehensive overview of recent studies that identify DOT1L as a crucial regulator of immune cell development, differentiation, and activation. Next, we discuss the potential mechanisms of DOT1L-mediated regulation of immune cell function and shed light on how DOT1L might be contributing to immune cell homeostasis and dysfunction. We then provide food for thought by highlighting some of the current obstacles and technical limitations precluding a more in-depth elucidation of DOT1L's role. Finally, we explore the potential therapeutic implications of targeting DOT1L in the context of immune-related diseases and discuss ongoing research efforts to this end. Overall, this review consolidates the current paradigm regarding DOT1L's role across the immune network and emphasises its critical role in governing the healthy immune system and its potential as a novel therapeutic target for immune-related diseases. A deeper understanding of DOT1L's immunomodulatory functions could pave the way for innovative therapeutic approaches which fine-tune the immune response to enhance or restore human health. [ABSTRACT FROM AUTHOR]

The molecular mechanisms underlying neuronal dysfunction in Alzheimer's disease (AD) remain uncharacterized. Here, we identify genes, molecular pathways and cellular components associated with whole-brain dysregulation caused by amyloid-beta (Aβ) and tau deposits in the living human brain. We obtained in-vivo resting-state functional MRI (rs-fMRI), Aβ- and tau-PET for 47 cognitively unimpaired and 16 AD participants from the Translational Biomarkers in Aging and Dementia cohort. Adverse neuronal activity impacts by Aβ and tau were quantified with personalized dynamical models by fitting pathology-mediated computational signals to the participant's real rs-fMRIs. Then, we detected robust brain-wide associations between the spatial profiles of Aβ-tau impacts and gene expression in the neurotypical transcriptome (Allen Human Brain Atlas). Within the obtained distinctive signature of in-vivo neuronal dysfunction, several genes have prominent roles in microglial activation and in interactions with Aβ and tau. Moreover, cellular vulnerability estimations revealed strong association of microglial expression patterns with Aβ and tau's synergistic impact on neuronal activity (q < 0.001). These results further support the central role of the immune system and neuroinflammatory pathways in AD pathogenesis. Neuronal dysregulation by AD pathologies also associated with neurotypical synaptic and developmental processes. In addition, we identified drug candidates from the vast LINCS library to halt or reduce the observed Aβ-tau effects on neuronal activity. Top-ranked pharmacological interventions target inflammatory, cancer and cardiovascular pathways, including specific medications undergoing clinical evaluation in AD. Our findings, based on the examination of molecular-pathological-functional interactions in humans, may accelerate the process of bringing effective therapies into clinical practice. [ABSTRACT FROM AUTHOR]

The growth of aquaculture demands intense consumption of formulated foods, scarce natural resources such as water and land. The increase in aquaculture production needs to be sustainable in several aspects of the activity, including the use of more sustainable farming systems that provide reduced water demand, less space dependence for increased production, and availability of complementary natural food. In this perspective, the biofloc system (BFT), presents itself as a more friendly cultivation technology as a way to mitigate some impacts of aquaculture production. Much research has been carried out, addressing different aspects important to the production of fish in BFT. In this review, we address how stocking density, carbon sources and carbon nitrogen ration (C/N) affect animal performance and the nutritional value of bioflocs; the use of microbial aggregates as "in situ" and "ex situ" food and the benefits in feed conversion, and their influence on the immune system and disease resistance. [ABSTRACT FROM AUTHOR]

Purpose: No study to date has investigated the prognostic ability of the recently introduced "systemic immune-inflammation index" (SII) in thoracic empyema. Therefore, we aimed to evaluate the association between SII and outcome in such patients. Methods: The single-center retrospective study involved 84 patients with thoracic empyema admitted to the Clinic of Thoracic Surgery at a University Hospital Stara Zagora between January 2021 and October 2023. Clinical and laboratory parameters were recorded at admission. We analyzed the area under receiver operating characteristics (AUROC) curves of SII, qSOFA, and SIRS and compared their prognostic value. Results: The observed in-hospital mortality was 10.7%. As a predictor of death, SII showed the best prognostic ability compared to SIRS (AUROC = 0.782 vs. 0.676) and qSOFA (AUROC = 0.782 vs. 0.747). At the optimal cut-off value of > 3269 x 109/L, we identified a sensitivity of 71.4% and a specificity of 78.7%. Conclusion: In thoracic empyema, SII could be routinely used as a simple, low-cost, and easily assessable indicator for patients at higher risk of poor outcome. [ABSTRACT FROM AUTHOR]

This article provides an overview of recent advancements in veterinary cancer immunology, focusing on how the immune system interacts with animal cancer cells. It discusses novel immunotherapeutic approaches, such as cancer vaccines and monoclonal antibodies, that have shown promise in treating canine cancers. Comparative oncology, which examines cancer across different species, is highlighted as a valuable approach for identifying common mechanisms and potential treatments. The article also mentions the potential of chimeric antigen receptors (CARs) in veterinary immuno-oncology, although their use in veterinary medicine is still under development. The document is a collection of research articles covering various topics related to cancer treatment in animals, providing new insights and potential therapeutic strategies for veterinary oncology. Ongoing research in this field is crucial for improving cancer management and treatment options for dogs. [Extracted from the article]

Multi-host parasites pose greater health risks to wildlife, livestock, and humans than single-host parasites, yet our understanding of how ecological and biological factors influence a parasite's host range remains limited. Here, we assemble the largest and most complete dataset on permanently parasitic mammalian mites and build a predictive model assessing the probability of single-host parasites to become multi-hosts, while accounting for potentially unobserved host-parasite links and class imbalance. This model identifies statistically significant predictors related to parasites, hosts, climate, and habitat disturbance. The most important predictors include the parasite's contact level with the host immune system and two variables characterizing host phylogenetic similarity and spatial co-distribution. Our model reveals an overrepresentation of mites associated with Rodentia (rodents), Chiroptera (bats), and Carnivora in the multi-host risk group. This highlights both the potential vulnerability of these hosts to parasitic infestations and the risk of serving as reservoirs of parasites for new hosts. In addition, we find independent macroevolutionary evidence that supports our prediction of several single-host species of Notoedres, the bat skin parasites, to be in the multi-host risk group, demonstrating the forecasting potential of our model. Some mite species infect only one mammal host, while other typically more dangerous species, infect multiple hosts. This study developed a model using parasite, host, climate, and habitat data to predict potential host range expansions in single-host mites and the probability of single-host parasites to become multi-hosts. [ABSTRACT FROM AUTHOR]

Adult neurogenesis, which takes place in both vertebrate and invertebrate species, is the process by which new neurons are born and integrated into existing functional neural circuits, long after embryonic development. Most studies in mammals suggest that self-renewing stem cells are the source of the new neurons, although the extent of self-renewal is a matter of debate. In contrast, research in the crayfish Procambarus clarkii has demonstrated that the neural progenitors producing adult-born neurons are capable of both self-renewing and consuming (non-self-renewing) divisions. However, self-renewing divisions are relatively rare, and therefore the production of adult-born neurons depends heavily on progenitors that are not replenishing themselves. Because the small pool of neural progenitors in the neurogenic niche is never exhausted throughout the long lives of these animals, we hypothesized that there must also be an extrinsic source of these cells. It was subsequently demonstrated that the neural progenitors originate in hemocytes (blood cells) produced by the immune system that travel in the circulation before ultimately integrating into niches where the neural lineage begins. The current study examines the developmental lineage of the three hemocyte types — hyaline (HC), semigranular (SGC) and granular (GC) cells — with the goal of understanding the origins of the progenitor cells that produce adult-born neurons. Longstanding qualitative metrics for hemocyte classification were validated quantitatively. Then, in a longitudinal study, proliferation markers were used to label the hemocytes in vivo, followed by sampling the circulating hemocyte population over the course of two months. Hemolymph samples were taken at intervals to track the frequencies of the different hemocyte types. These data reveal sequential peaks in the relative frequencies of HCs, SGCs and GCs, which were identified using qualitative and quantitative measures. These findings suggest that the three hemocyte types comprise a single cellular lineage that occurs in the circulation, with each type as a sequential progressive stage in hemocyte maturation beginning with HCs and ending with GCs. When combined with previously published data, this timeline provides additional evidence that HCs serve as the primary neural progenitor during adult neurogenesis in P. clarkii. [ABSTRACT FROM AUTHOR]

Various metabolites, including phytohormones, phytoalexins, and amino acids, take part in the plant immune system. Herein, we analyzed the effects of L-methionine (Met), a sulfur-containing amino acid, on the plant immune system in tomato. Treatment with low concentrations of Met enhanced the resistance of tomato to a broad range of diseases caused by the hemi-biotrophic bacterial pathogen Pseudomonas syringae pv. tomato (Pst) and the necrotrophic fungal pathogen Botrytis cinerea (Bc), although it did not induce the production of any antimicrobial substances against these pathogens in tomato leaf tissues. Analyses of gene expression and phytohormone accumulation indicated that Met treatment alone did not activate the defense signals mediated by salicylic acid, jasmonic acid, and ethylene. However, the salicylic acid-responsive defense gene and the jasmonic acid-responsive gene were induced more rapidly in Met-treated plants after infection with Pst and Bc, respectively. These findings suggest that low concentrations of Met have a priming effect on the phytohormone-mediated immune system in tomato. [ABSTRACT FROM AUTHOR]

Polygalae Radix: is the dried root of Polygala tenuifolia Willd. or Polygala sibirica L., which has the effect of improving memory and cognitive function in traditional Chinese medicine. Modern pharmacological studies indicated that Polygalae Radix has rich pharmacological activities in vitro and in vivo, including protective effects on the nervous system, immune system, cardiovascular system and respiratory system, as well as antioxidant and antiepileptic pharmacological activities. Up to now, more than 160 metabolites from Polygalae Radix were identified, including triterpenoid saponins, xanthones, oligosaccharide esters and et al. The clinical practice of traditional Chinese medicine has proved that Polygalae Radix has a certain irritation to the throat, and a large or long-term use will stimulate the digestive tract, and the main toxic metabolite is saponins. Therefore, Polygalae Radix should be pr ocessed or used in combination with other Chinese herbal medicines to reduce the irritation to the throat and reduce gastrointestinal irritation. This article provides a review of the metabolites, pharmacological activity, and toxicology of Polygalae Radix. It also discusses the future research prospects and existing problems of Polygalae Radix, providing reference for further research on Polygalae Radix. [ABSTRACT FROM AUTHOR]

Ionizing radiation and microgravity are two considerable health risks encountered during deep space exploration. Both have deleterious effects on the human body. On one hand, weightlessness is known to induce a weakening of the immune system, delayed wound healing and musculoskeletal, cardiovascular, and sensorimotor deconditioning. On the other hand, radiation exposure can lead to long-term health effects such as cancer and cataracts as well as have an adverse effect on the central nervous and cardiovascular systems. Ionizing radiation originates from three main sources in space: galactic cosmic radiation, solar particle events and solar winds. Furthermore, inside the spacecraft and inside certain space habitats on Lunar and Martian surfaces, the crew is exposed to intravehicular radiation, which arises from nuclear reactions between space radiation and matter. Besides the approaches already in use, such as radiation shielding materials (such as aluminium, water or polyethylene), alternative shielding materials (including boron nanotubes, complex hybrids, composite hybrid materials, and regolith) and active shielding (using fields to deflect radiation particles) are being investigated for their abilities to mitigate the effects of ionizing radiation. From a biological point of view, it can be predicted that exposure to ionizing radiation during missions beyond Low Earth Orbit (LEO) will affect the human body in undesirable ways, e.g., increasing the risks of cataracts, cardiovascular and central nervous system diseases, carcinogenesis, as well as accelerated ageing. Therefore, it is necessary to assess the risks related to deep space exploration and to develop mitigation strategies to reduce these risks to a tolerable level. By using biomarkers for radiation sensitivity, space agencies are developing extensive personalised medical examination programmes to determine an astronaut's vulnerability to radiation. Moreover, researchers are developing pharmacological solutions (e.g., radioprotectors and radiomitigators) to proactively or reactively protect astronauts during deep space exploration. Finally, research is necessary to develop more effective countermeasures for use in future human space missions, which can also lead to improvements to medical care on Earth. This review will discuss the risks space travel beyond LEO poses to astronauts, methods to monitor astronauts' health, and possible approaches to mitigate these risks. [ABSTRACT FROM AUTHOR]

The major histocompatibility complex (MHC) plays a key role in the adaptive immune system of vertebrates, and is known to influence mate choice in many species. In birds, the MHC has been extensively examined but mainly in galliforms and passerines while other taxa that represent specific ecological and evolutionary life-histories, like seabirds, are underexamined. Here, we characterized diversity of MHC Class II B exon 2 in a colonial pelagic seabird, the Little Auk (or Dovekie Alle alle). We further examined whether MHC variation could be maintained through balancing selection and disassortative mating. We found high polymorphism at the genotyped MHC fragment, characterizing 99 distinct alleles across 140 individuals from three populations. The alleles frequencies exhibited a similar skewed distribution in both sexes, with the four most commonly occurring alleles representing approximately 35% of allelic variation. The results of a Bayesian site-by-site selection analysis suggest evidence of balancing selection and no direct evidence for MHC-dependent disassortative mating preferences in the Little Auk. The latter result might be attributed to the high overall polymorphism of the examined fragment, which itself may be maintained by the large population size of the species. [ABSTRACT FROM AUTHOR]

Background: Low immunity and sleep disorders are prevalent suboptimal health conditions in contemporary populations, which render them susceptible to the infiltration of pathogenic factors. LJC, which has a long history in traditional Chinese medicine for nourishing the Yin and blood and calming the mind, is obtained by modifying Qiyuan paste. Dendrobium officinale Kimura et Migo has been shown to improve the immune function in sleep-deprived mice. In this study, based on the traditional Chinese medicine theory, LJC was prepared by adding D. officinale Kimura et Migo to Qiyuan paste decoction. Methods: Indicators of Yin deficiency syndrome, such as back temperature and grip strength, were measured in each group of mice; furthermore, behavioral tests and pentobarbital sodium-induced sleep tests were performed. An automatic biochemical analyzer, enzyme-linked immunosorbent assay kit, and other methods were used to determine routine blood parameters, serum immunoglobulin (IgG, IgA, and IgM), cont (C3, C4), acid phosphatase (ACP) and lactate dehydrogenase (LDH) levels in the spleen, serum hemolysin, and delayed-type hypersensitivity (DTH) levels. In addition, serum levels of γ-aminobutyric acid (GABA) and glutamate (Glu) were detected using high-performance liquid chromatography (HPLC). Hematoxylin–eosin staining and Nissl staining were used to assess the histological alterations in the hypothalamus tissue. Western blot and immunohistochemistry were used to detect the expressions of the GABA pathway proteins GABRA1, GAD, GAT1, and GABAT1 and those of CD4+ and CD8+ proteins in the thymus and spleen tissues. Results: The findings indicated that LJC prolonged the sleep duration, improved the pathological changes in the hippocampus, effectively upregulated the GABA content in the serum of mice, downregulated the Glu content and Glu/GABA ratio, enhanced the expressions of GABRA1, GAT1, and GAD, and decreased the expression of GABAT1 to assuage sleep disorders. Importantly, LJC alleviated the damage to the thymus and spleen tissues in the model mice and enhanced the activities of ACP and LDH in the spleen of the immunocompromised mice. Moreover, serum hemolysin levels and serum IgG, IgA, and IgM levels increased after LJC administration, which manifested as increased CD4+ content, decreased CD8+ content, and enhanced DTH response. In addition, LJC significantly increased the levels of complement C3 and C4, increased the number of white blood cells and lymphocytes, and decreased the percentage of neutrophils in the blood. Conclusions: LJC can lead to improvements in immunocompromised mice models with insufficient sleep. The underlying mechanism may involve regulation of the GABA/Glu content and the expression levels of GABA metabolism pathway-related proteins in the brain of mice, enhancing their specific and nonspecific immune functions. [ABSTRACT FROM AUTHOR]

A short prokaryotic Argonaute (pAgo) TIR-APAZ (SPARTA) defense system, activated by invading DNA to unleash its TIR domain for NAD(P)+ hydrolysis, was recently identified in bacteria. We report the crystal structure of SPARTA heterodimer in the absence of guide-RNA/target-ssDNA (2.66 Å) and a cryo-EM structure of the SPARTA oligomer (tetramer of heterodimers) bound to guide-RNA/target-ssDNA at nominal 3.15–3.35 Å resolution. The crystal structure provides a high-resolution view of SPARTA, revealing the APAZ domain as equivalent to the N, L1, and L2 regions of long pAgos and the MID domain containing a unique insertion (insert57). Cryo-EM structure reveals regions of the PIWI (loop10-9) and APAZ (helix αN) domains that reconfigure for nucleic-acid binding and decrypts regions/residues that reorganize to expose a positively charged pocket for higher-order assembly. The TIR domains amass in a parallel-strands arrangement for catalysis. We visualize SPARTA before and after RNA/ssDNA binding and uncover the basis of its active assembly leading to abortive infection. The SPARTA defense system, activated by invading DNA for NAD(P)+ hydrolysis, was recently identified in bacteria. Here, authors visualize SPARTA before and after nucleic acid binding and uncover the basis of its active assembly leading to abortive infection. [ABSTRACT FROM AUTHOR]

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Autoimmune thyroid diseases (AITD) are among the most frequent autoimmune disorders, with a multifactorial etiology in which both genetic and environmental determinants are probably involved. Celiac disease (CeD) also represents a public concern, given its increasing prevalence due to the recent improvement of screening programs, leading to the detection of silent subtypes. The two conditions may be closely associated due to common risk factors, including genetic setting, changes in the composition and diversity of the gut microbiota, and deficiency of nutrients like vitamin D. This comprehensive review discussed the current evidence on the pivotal role of vitamin D in modulating both gut microbiota dysbiosis and immune system dysfunction, shedding light on the possible relevance of an adequate intake of this nutrient in the primary prevention of AITD and CeD. While future technology-based strategies for proper vitamin D supplementation could be attractive in the context of personalized medicine, several issues remain to be defined, including standardized assays for vitamin D determination, timely recommendations on vitamin D intake for immune system functioning, and longitudinal studies and randomized controlled trials to definitely establish a causal relationship between serum vitamin D levels and the onset of AITD and CeD. [ABSTRACT FROM AUTHOR]

Background/Objectives: As heart failure (HF) patients face increased vulnerability to respiratory infections, optimizing pneumococcal and influenza vaccination coverage becomes pivotal for mitigating additional health risks and reducing hospitalizations, morbidity, and mortality rates within this population. In this specific subpopulation of patients, vaccination coverage for pneumococcal and influenza holds heightened significance compared to other vaccines due to their susceptibility to respiratory infections, which can exacerbate existing cardiovascular conditions and lead to severe complications or even death. However, despite the recognized benefits, vaccination coverage among HF patients remains below expectations. The aim of the present systematic review was to assess the vaccination coverage for influenza and pneumococcus in HF patients from 2005 to 2023 and the vaccination's effects on survival and hospitalizations. Methods: The authors developed the protocol of the review in accordance with the PRISMA guidelines, and the search was performed in databases including PubMed and Scopus. After the initial search, 851 studies were found in PubMed Library and 1961 in Scopus (total of 2812 studies). Results: After the initial evaluation, 23 publications were finally included in the analysis. The total study population consisted of 6,093,497 participants. Regarding the influenza vaccine, vaccination coverage ranged from low rates of 2.5% to very high rates of 97%, while the respective pneumococcal vaccination coverage ranged from 20% to 84.6%. Most studies demonstrated a beneficial effect of vaccination on survival and hospitalizations. Conclusions: The present systematic review study showed a wide variety of vaccination coverage among patients with heart failure. [ABSTRACT FROM AUTHOR]

Background: Suboptimal influenza and pneumococcal vaccination rates have been reported before the COVID-19 pandemics in certain populations at risk for severe infection. The aim of this longitudinal cohort study was to investigate changes in influenza and pneumococcal vaccination rates and patient perceptions in patients with psoriasis (PsO) before and during the pandemic. Methods: Data on vaccination, patient and disease characteristics, comorbidity, and patient perceptions were collected with questionnaires before and during the pandemic approximately one year later. Results: Over the whole cohort who participated in the follow-up visit (n = 287; 59.2% male; mean age: 56.3 years), both influenza and pneumococcal lifetime vaccination prevalences increased significantly from 50.5% to 66.2% and from 16.0% to 41.5%, respectively. A total of 88.5% of PsO patients were interested in a COVID-19 vaccination or had already received it. The reasons for and against vaccinations changed significantly before and during the pandemic. Conclusions: Despite a promising increase in the vaccination prevalence in our PsO cohort, it remains important that awareness for vaccinations is encouraged and closely monitored in future research, particularly in populations at risk. [ABSTRACT FROM AUTHOR]

Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine, and oncology applications, Ad-based platforms offer advantages, including ease of genetic manipulation, scale of production, and well-established safety profiles, making them attractive tools for therapeutic development. However, the immune system often poses a significant challenge that must be overcome for adenovirus-based therapies to be truly efficacious. Both pre-existing anti-Ad immunity in the population as well as the rapid development of an immune response against engineered adenoviral vectors can have detrimental effects on the downstream impact of an adenovirus-based therapeutic. This review focuses on the different challenges posed, including pre-existing natural immunity and anti-vector immunity induced by a therapeutic, in the context of innate and adaptive immune responses. We summarise different approaches developed with the aim of tackling these problems, as well as their outcomes and potential future applications. [ABSTRACT FROM AUTHOR]

Illicit drug and alcohol abuse have significant negative consequences for individuals who inject drugs/use drugs (PWID/UDs), including decreased immune system function and increased viral pathogenesis. PWID/UDs are at high risk of contracting or transmitting viral illnesses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). In South Africa, a dangerous drug-taking method known as "Bluetoothing" has emerged among nyaope users, whereby the users of this drug, after injecting, withdraw blood from their veins and then reinject it into another user. Hence, the transmission of blood-borne viruses (BBVs) is exacerbated by this "Bluetooth" practice among nyaope users. Moreover, several substances of abuse promote HIV, HBV, and HCV replication. With a specific focus on the nyaope drug, viral replication, and transmission, we address the important influence of abused addictive substances and polysubstance use in this review. [ABSTRACT FROM AUTHOR]