Immuno

Antiphospholipid syndrome (APS) is a thrombo-inflammatory disease propelled by circulating autoantibodies that recognize cell surface phospholipids and phospholipid-binding proteins. APS is an autoimmune disorder associated with recurrent thrombosis of arterial or venous vessels and/or recurrent obstetric complications as miscarriages. APS can be divided into primary or secondary clinical syndrome because of the possible association with other autoimmune systemic diseases as systemic lupus erythematosus (SLE). Vitamin K antagonists remain the mainstay of treatment for most patients with APS and, based on current data, appear superior to the more targeted direct oral anticoagulants. However, the choice of the type of antithrombotic drug is based on the anamnesis of affected patients: patients with previous arterial or venous thrombosis may benefit from anticoagulants, while patients with previous obstetric diseases may benefit from aspirin, but several clinical exceptions may be evaluated. This short review is dedicated to underlining the main clinical evidence for patients affected by APS or CAPS (catastrophic antiphospholipid syndrome) in order to prevent recurrent thrombosis. Full article

Human immunodeficiency virus (HIV) has troubled humankind for many years. The rate of new HIV cases is decreasing steadily, mostly because of safer sexual practices and scientific advances in medicine. However, the number of HIV-related trials has significantly increased, as the search for a definite cure for HIV is still fruitless. Our current treatment options involve antiretroviral therapy (ART) with various drug combinations that lower the patients’ viral load in order for the immune system to reconstitute itself. This way, adherent patients achieve a life expectancy similar to the general population. Besides the established treatment protocols, the focus has currently shifted towards secondary pharmaceutical regimen programs that enhance a patient’s immune system and response to opportunistic infections. Vitamins C and D are easily obtainable even in the developing world and are known to improve an individual’s daily life, with vitamin D enhancing the human immune response and vitamin C having an assisting role in both the immune response and as an important antioxidant. Recently, many studies assessing the effect of these vitamins on the progression of HIV have been performed. We aimed to collect and review these studies in order to determine the necessity of the supplementation of these vitamins in HIV-infected patients, which might complement the existing ART. To this day, the scientific community is conflicted, and more studies must be conducted before a definite conclusion about these vitamins’ effects on HIV patients can be reached. Full article

Background and Aim: Monkeypox (Mpox) is a viral disease mainly found in central and western Africa, with symptoms similar to variola virus (smallpox) but distinguished by the early lymph node swelling specific to Mpox. This review summarizes the neuropsychiatric manifestations of Mpox infection and vaccination, along with management approaches. Method: We searched different databases such as PubMed, Scopus, WoS, and Google Scholar about the neuropsychiatric manifestations of Mpox disease and the associated strategies of management. Results and conclusions: Mpox can cause a wide range of neurological symptoms. These range from mild symptoms like headaches, muscle aches, fatigue, and pain to severe symptoms, including seizures, blindness, photophobia, delirium, coma, encephalitis, and transverse myelitis. It is essential to distinguish Mpox from smallpox and other orthopox viruses. Psychiatric issues, such as stigma, disfigurement, isolation, and physical pain, are common in Mpox patients. To address these, healthcare providers should provide accurate information, counseling, and virtual support. Neurological side effects were associated with the previous smallpox vaccine, which offered cross-protection against Mpox. This vaccine has since been replaced by JYNNEOS, which does not pose any neurological risks. Mpox-related neurological symptoms are generally managed with supportive care, including NSAIDs, antibiotics, antiepileptics, and sedatives for seizures. Antivirals like acyclovir are also used. Severe cases may require hospitalization or intubation. So, we recommend early diagnosis, isolation, and prompt treatment, as Mpox spreading to the central nervous system can lead to serious and potentially fatal complications. Full article

DENV belongs to the Flaviviridae family and possesses a single-stranded RNA genome of positive polarity. DENV infection manifests in mild subclinical forms or severe forms that may be dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Despite a lot of effort worldwide, the exact mechanism underlying the pathogenesis of severe DENV infection remains elusive. It is believed that both host and viral factors contribute to the outcome of dengue disease. The host factors are age at the time of infection, sex, nutrition, and immune status, including the presence of pre-existing antibodies or reactive T cells. Viral factors include the serotype, genotype, and mutation(s) due to error-prone RNA-dependent polymerase leading to the development of quasispecies. Accumulating bodies of literature have depicted that DENV has many ways to invade and escape the immune system of the host. These invading strategies are directed to overcome innate and adaptive immune responses. Like other viruses, once the infection is established, the host also mounts a series of antiviral responses to combat and eliminate the virus replication. Nevertheless, DENV has evolved a variety of mechanisms to evade the immune system. In this review, we have emphasized the strategies that DENV employs to hijack the host innate (interferon, IFN; toll-like receptors, TLR; major histocompatibility complex, MHC; autophagy; complement; apoptosis; RNAi) and adaptive (antibody-dependent enhancement, ADE; T cell immunity) immune responses, which contribute to the severity of DENV disease. Full article

The metabolism of T-lymphocytes has recently emerged as a pivotal area of investigation, offering insights into the supra-genic modulations that can influence the genetic mechanisms underlying lymphocyte clustering processes. Furthermore, it has become a crucial aspect in understanding lymphocyte plasticity within the immune microenvironment, both in physiological and pathological contexts. T-lymphocyte metabolism has recently emerged as a pivotal factor in both targeted therapy and the genetic signature of the T-lymphocyte, as a result of its influence on gatekeeper processes. From this perspective, the interconnections between the metabolic processes traditionally associated with energy production and the capacity to influence the genetic fate of the T lymphocyte have identified purine metabolism and nuclear/cytoplasmic signaling as pivotal elements in comprehending the intricacies of these molecular phenomena. The two aspects of purine metabolism and metabolic/molecular control of the nuclear envelope have been the subject of a number of significant studies published in recent years. However, from a certain perspective, the existing evidence remains sparse and inconclusive, hindering a comprehensive understanding of the subject matter. In this review, we endeavor to establish a connection between these aspects for the first time and to present a review of the molecular, immunological and genetic events that determine how these aspects, which have hitherto received insufficient attention, may represent a new avenue for lymphocyte reprogramming in the therapeutic field. This will be achieved by understanding the connections between nuclear control and purine flux within and outside the cell. Full article

Background. Several research findings suggest that sodium–glucose co-transporter 1 (SGLT1) is implicated in the progression and control of infections and inflammation processes at the pulmonary level. Moreover, our previous works indicate an engagement of SGLT1 in inhibiting the inflammatory response induced in intestinal epithelial cells by TLR agonists. In this study, we report the anti-inflammatory effects observed in the lung upon engagement of the transporter, and upon the use of glucose and BLF501, a synthetic SGLT1 ligand, for the treatment of animal models of lung inflammation, including a model of allergic asthma. Methods. In vitro experiments were carried out on human pneumocytes stimulated with LPS from Pseudomonas aeruginosa and co-treated with glucose or BLF501, and the production of IL-8 was determined. The anti-inflammatory effect associated with SGLT1 engagement was then assessed in in vivo models of LPS-induced lung injury, as well as in a murine model of ovalbumin (OVA)-induced asthma, treating mice with aerosolized LPS and the synthetic ligand. After the treatments, lung samples were collected and analyzed for morphological alterations by histological examination and immunohistochemical analysis; serum and BALF samples were collected for the determination of several pro- and anti-inflammatory markers. Results. In vitro experiments on human pneumocytes treated with LPS showed significant inhibition of IL-8 production. The results of two in vivo experimental models, mice exposed to aerosolized LPS and OVA-induced asthma, revealed that the engagement of glucose transport protein 1 (SGLT1) induced a significant anti-inflammatory effect in the lungs. In the first model, the acute respiratory distress induced in mice was abrogated by co-treatment with the ligand, with almost complete recovery of the lung morphology and physiology. Similar results were observed in the OVA-induced model of allergic asthma, both with aerosolized and oral BLF501, suggesting an engagement of SGLT1 expressed both in intestinal and alveolar cells. Conclusions. Our results confirmed the engagement of SGLT1 in lung inflammation processes and suggested that BLF501, a non-metabolizable synthetic ligand of the co-transporter, might represent a drug candidate for therapeutic intervention against lung inflammation states. Full article

The aim of this review was to gather pieces of information from available critically evaluated published articles concerning any interplay in which the spleen could be involved. For many years, the spleen has been alleged as an unnecessary biological structure, even though splenomegaly is an objective finding of many illnesses. Indeed, the previous opinion has been completely changed. In fact, the spleen is not a passive participant in or a simple bystander to a relationship that exists between the immune system and other organs. Recently, it has been evidenced in many preclinical and clinical studies that there are close associations between the spleen and other parts of the body, leading to various spleen–organ axes. Among them, the gut–spleen axis, the liver–spleen axis, the gut–spleen–skin axis, the brain–spleen axis, and the cardio-splenic axis are the most explored and present in the medical literature. Such recent sources of evidence have led to revolutionary new ideas being developed about the spleen. What is more, these observations may enable the identification of novel therapeutic strategies targeted at various current diseases. The time has come to make clear that the spleen is not a superfluous body part, while health system operators and physicians should pay more attention to this organ. Indeed, much work remains to be performed to assess further roles that this biological structure could play. Full article

Rheumatoid arthritis (RA) is an autoimmune disorder causing chronic inflammation primarily due to collagen regulation and transport imbalances. Collagen VII A1(COL7A1), a major component of anchoring fibrils, regulates inflammation via interacting with its transporter protein Transport and Golgi organization 2 homologs (TANGO1). The study revealed a significant increase in COL7A1 levels in both the plasma and PBMCs of RA patients. Additionally, a positive correlation between COL7A1 and ACCPA (anti-cyclic citrullinated peptide antibody) levels was observed among RA patients. TANGO1 mRNA expression was also found to be elevated in PBMCs. The knockdown of COL7A1 in RA synoviocytes using siRNA affected the expression of TANGO1 and inflammatory genes. Western blot analysis showed that COL7A1 si-RNA in TNF-α-induced SW982 cells reduced the expression of COL7A1, TANGO1, and NF-kBp65. The mRNA expression of inflammatory genes TNF-α, NF-kB p65, and IL-6 simultaneously decreased after the knockdown of COL7A1, as measured by qRT-PCR. An in silico analysis found 20 common interacting proteins of COL7A1 and TANGO1, with pathway enrichment analysis linking them to antigen presentation, class I and II MHC, and adaptive immunity pathways in RA. Among the common proteins, The DisGeNET database depicted that COL1A1, MIA3, SERPINH1, and GORASP1 are directly linked to RA. The molecular docking analysis of COL7A1 and TANGO1 revealed strong interaction with a −1013.4 energy-weighted score. Common RA-used drugs such as Adalimumab, Golimumab, and Infliximab were found to inhibit the interaction between COL7A1 and TANGO1, which can further impede the transport of COL7A1 from ER exit sites, indicating COL7A1 and TANGO1 as potential therapeutic targets to diminish RA progression. Full article

PTEN (phosphatase and tensin homolog) is a frequently lost tumor suppressor gene in prostate cancer, leading to aggressive tumor behavior and poor clinical outcomes. PTEN loss results in aberrant activation of the PI3K/AKT/mTOR pathway, promoting oncogenesis. These alterations also lead to an immunosuppressive tumor microenvironment with altered immune cell infiltration, cytokine profiles, and immune checkpoint regulation. This review aims to provide a comprehensive overview of the mechanisms underlying PTEN loss in prostate cancer and the consequent immune alterations observed in this subtype, thus underscoring the importance of understanding PTEN-mediated immune modulation for the development of effective therapeutic interventions in prostate cancer. Full article

Propolis, a complex natural product that honey bees produce by mastication to protect and maintain their hive structures, comprises various bioactive constituents, including phenolic acids, flavonoids, diterpenes, sesquiterpenes, lignans, vitamins, minerals, etc. The objective of the current research was to extract crude propolis to enrich the total polyphenolic and flavonoid content, conduct preliminary phytochemical screening, and develop and evaluate dosage form to improve formulation characteristics and immunomodulatory potential. Total balsam, polyphenols, and flavonoids were found to be 46% w/w, 34.82 ± 0.078 mg equivalent of gallic acid/g, and 23.61 ± 0.045 mg equivalent of quercetin/g, respectively. DSC and FTIR studies demonstrated molecular dispersion of the propolis extract. Formulation was optimized with a 3² factorial design, and an optimized batch showed 92.20 ± 1.72% drug release in 1 h, an elevated hypersensitivity (DTH) response (p < 0.0001), increased phagocytic activity (p < 0.01), and a significantly (p < 0.001) higher total leukocyte count ((5.015 ± 0.19) × 10³/mm³). The developed formulation showed significantly modulated immune modulatory potential compared with the propolis extract and conventional levamisole. This study can be further extended for clinical evaluations. Full article

Inflammatory bowel disease (IBD) is a chronic complicated inflammatory gut pathological disorder and is categorized into ulcerative colitis (UC) and Crohn’s disease (CD). Although the cause of IBD is unclear, dysbiosis of the gut microbiota is thought to be a key factor in the disease’s progression. The gut microbiome serves as a metabolic organ and promotes wellness by carrying out several biological activities. Any modification in the makeup of the gut microbiome leads to several pathological conditions, including IBD. In this review, we emphasize the key metabolic processes that control host–microbiome interaction and its impact on host health. We also discuss the association between microbiome dysbiosis (bacteriome, virome, and mycobiome) and the progression of IBD. Finally, we will highlight microbiome-based therapy as a novel and promising strategy to treat and manage IBD. Full article

Background: Previous research has suggested that modulated electro-hyperthermia (mEHT) can be used to induce anti-tumor immune effects and to extend patient survival. The use of mEHT in advanced pancreatic cancer is beneficial; however, its immune-mediating effects were never investigated. Methods: A retrospective observational study was conducted. Leukocyte counts, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and granulocyte-to-lymphocyte ratio (GLR) were measured at baseline, midpoint, and after mEHT treatment. Results: A total of 73 mEHT treated pancreatic cancer patients were included. The time elapsed between tumor diagnosis and the first mEHT treatment was 4.40 ± 5.70 months. While no change could be observed between the baseline and the first follow-up visits, the total white blood cell (WBC), neutrophil, and granulocyte count, CRP, NLR, and GLR were significantly higher at the second follow-up compared to both previous visits. Higher levels of the latter parameters following the last mEHT treatment were signaling significantly poor prognostic signs, and so were their longitudinal changes. Conclusions: After the initiation of mEHT, immune markers stabilize with the treatment, but this positive effect is eroded over time by progressive disease. Monitoring the changes in these markers and the occurrence of their increase is a prognostic marker of shorter survival. Full article

Bovine brucellosis and neosporosis are reported as potential abortifacient infections in cattle worldwide. Brucellosis is additionally a zoonotic bacterial infection caused by numerous Brucella species. Meanwhile, neosporosis is a protozoan parasitic disease that is implicated in causing high economic losses in the cattle industry. Herein, we attempted to investigate the seroprevalence of specific antibodies to Brucella spp. and Neospora caninum using commercially available ELISAs. In addition, we conducted risk factor analysis and estimated the correlation of seropositivity of both pathogens with the recorded abortions in the tested herds. Serum samples from cattle (n = 460) collected from various governorates in the Delta region, northern Egypt, were targeted in this study. Overall, a seroprevalence of 5.4%, 33.3%, and 1.3% was revealed for Brucella spp., N. caninum, and mixed seropositivity, respectively. The location (Kafr El Sheikh vs. Dakahlia vs. Al-Qalyubiya vs. Damietta governorates) and a history of abortion (yes vs. no vs. unknown) were analyzed as risk factors of infection. Kafr El Sheikh governorate (57.7%, p = < 0.0001) and a history of abortion (54.1%, p = < 0.0001) were considered risk factors for Brucella spp. seropositivity compared to the reference factors Al-Qalyubiya (1.1%) and unknown abortion history (0.6%). In the case of N. caninum, the location was also considered a risk factor because the seropositive rates were significantly higher in Damietta (51%, p = 0.001) and Dakahlia (33.4%, p = 0.026) compared to Kafr El Sheikh (11.3%, set as a reference). Conversely to Brucella, animals without a history of abortion exhibited a higher seropositive rate for N. caninum (47.6%, p = 0.009) compared to those with a history of abortion (21.6%, set as reference). For further investigations into the association between abortion and the obtained seropositive rates, we also analyzed the reactivity by comparing samples of animals with, without, and unknown history of abortion. We detected high seroreactivity for Brucella spp. in samples collected from animals with a history of abortion, as demonstrated in the recorded antibody levels and correlation coefficient (Pearson r = 0.919). Based on our data, despite the higher seroprevalence of N. caninum compared to that of Brucella species, Brucella spp. might be the primary cause of abortion in our tested cattle population. Full article

The immune system is inexperienced before birth and tends to be tolerogenic, rather than immunogenic. After birth, the adaptive immune system develops while facing microbial challenges, but it can become impaired as old age progresses and persistent inflammation can lead to chronic morbidity, disability and frailty. To investigate the potential contributions of lymphocyte subsets to immunity from birth until old age, we enumerated circulating innate and conventional lymphocytes and measured serum cytokine levels in 10 cord blood samples and in peripheral blood from 10 healthy term neonates, 23 healthy school-age children, 25 young adults and 11 older subjects. Flow cytometric analysis revealed that B cell frequencies increase during childhood and gradually decrease into adulthood, whereas natural killer cell frequencies increase throughout life. T cell frequencies remained relatively constant throughout life, as did their expression of CD4 and CD8. However, all four innate T cell populations studied—invariant natural killer T cells, mucosa-associated invariant T cells and the Vδ1 and the Vδ2 subsets of γδ T cells—were extremely rare in cord blood and in peripheral blood of neonates, but they expanded after birth reaching highest levels in adulthood. Analysis of serum cytokine levels revealed that proinflammatory and T helper type 1 (Th1) cytokine levels increase in adulthood, whereas Th2 and Th17 cytokine levels remain relatively constant. These changes in lymphocyte numbers and cytokine levels across the lifetime are likely to affect immunocompetence, leaving newborn and elderly people susceptible to infection, cancer and immune-mediated disease. Full article

Deep-sea mineral water (DSW) consists of different compositions and properties. The composition can be varied in different seas all around the world. However, previous studies have investigated that DSW is a potential candidate that can be used to prevent different inflammatory diseases. Even though inflammation is an important protective mechanism in an animal, excessive inflammation causes organ failure and ultimate death. Therefore, the present study was carried out to investigate the anti-inflammatory effect of DSW extracted from the South Korean Sea to unveil its potential as an anti-inflammatory drug. To perform this, first, we have compared the cytotoxic effect of DSW on RAW 264.7 murine macrophage cells with NaCl and normal-sea water (NSW). Results reveal that DSW enhances cell survival while other treatments negatively affect cell survival. Furthermore, we have investigated that DSW reduces the LPS-induced cell apoptosis compared to the NaCl- and NSW-treated cells. Moreover, DSW has the ability to suppress the pro-inflammatory cytokine transcription (TNF-α, IL-1β, and IL-6) and NO production upon LPS treatment. In-vivo survival assay in zebrafish larvae shows a more than 50% survival rate in 10, 20, 30, 40, or 50% concentrations of DSW-treated larvae compared to NaCl- or NSW-treated larvae. Further investigations unveiled that DSW can negatively regulate the neutrophil and macrophage recruitment to the inflammatory site, which was induced by fin-fold amputation in zebrafish larvae and pro-inflammatory cytokine (tnf-α, il-1β, and il-6) secretion. Taken together, the present study concluded that DSW may have the ability to act as an anti-inflammatory drug to suppress excessive inflammation and subsequent consequences. Full article

Vaccination is credited as a significant medical achievement contributing to the decline in morbidity and mortality of infectious diseases. Traditional vaccines composed of inactivated and live-attenuated whole pathogens confer the induction of potent and long-term immune responses; however, traditional vaccines pose a high risk of eliciting autoimmune and allergic responses as well as inflammations. New modern vaccines, such as subunit vaccines, employ minimum pathogenic components (such as carbohydrates, proteins, or peptides), overcome the drawbacks of traditional vaccines and stimulate effective immunity against infections. However, the low immunogenicity of subunit vaccines requires effective immune stimulants (adjuvants), which are an indispensable factor in vaccine development. Although there are several approved adjuvants in human vaccines, the challenges of matching and designing appropriate adjuvants for specific vaccines, along with managing the side effects and toxicity of existing adjuvants in humans, are driving the development of new adjuvants. Self-assembling peptides are a promising biomaterial rapidly emerging in the fields of biomedicine, vaccination and material science. Here, peptides self-assemble into ordered supramolecular structures, forming different building blocks in nanoparticle size, including fibrils, tapes, nanotubes, micelles, hydrogels or nanocages, with great biostability, biocompatibility, low toxicity and effectiveness at controlled release. Self-assembling peptides are effective immunostimulatory agents used in vaccine development to enhance and prolong immune responses. This review describes the predominant structures of self-assembling peptides and summarises their recent applications as vaccine adjuvants. Challenges and future perspectives on self-assembled peptides as vaccine adjuvants are also highlighted. Full article

Recent advances in organoid technology have revolutionized cancer biology and therapeutic interventions, offering personalized immunotherapy treatment. Organoids, three-dimensional cell cultures derived from patient tumors, accurately replicate the tumor microenvironment, providing unprecedented insights into tumor-immune interactions and therapeutic responses. In this literature-based study, we discuss various culture methods for the diverse applications of organoids in cancer immunotherapy, including drug screening, personalized treatment strategies, and mechanistic studies. Additionally, we address the technological challenges associated with these methods and propose potential future solutions to accelerate the development of novel immunotherapeutic approaches. This review highlights the transformative potential of organoid models in advancing preclinical cancer immunotherapy modeling, screening, and evaluation, paving the way for more effective and personalized cancer treatments. Full article

In recurrent pregnancy loss (RPL), peripheral and local immune cells are activated, decreasing the leukocyte tolerogenic response in the uterus and decidua. The aim was to examine the role of IL-17 in RPL critically. The study included genetic polymorphism, the analysis of the number of circulating IL-17 lymphocyte populations, before and after cell priming, serum cytokine quantification, and the assessment of T-reg cells in a group of 50 RPL and 50 normal women from the admixed Venezuelan population. The study found no differences in the genetic polymorphisms rs2275913 and rs763780. However, when IL-17+ cell populations of controls and RPL patients were compared, a significant increase was observed in the cell populations CD3+ and CD4+ (p < 0.001), while the contrary was recorded in CD8+ and CD56+ cells. Upon cell priming, all IL-17+ populations were significantly decreased (p < 0.001) in RPL patients compared to controls. The increase in IL-17A in the serum of RPL patients may be due to the CD4+ population, while cell exhaustion after activation could be responsible for decreased CD8+ cell population. The number of CD4CD25 FoxP3+ cells was significantly reduced (p < 0.001), and the number of activated HLADR+ cells was significantly increased (p < 0.001) in RPL patients. The absence of differences in the genetic polymorphism compared to controls suggests that biological factors influence IL-17 levels in RPL patients. This finding has significant implications for the understanding and potential treatment of RPL. Full article

VEXAS syndrome is a new disease entity with symptoms that can mimic hematological, rheumatic and dermatological diseases. It is important to take a multidisciplinary approach to patient care, taking into account genetic testing, in which the presence of mutations in the UBA1 gene can confirm the diagnosis. UBA1 mutation has been shown to be involved in the induction of the inflammatory response through many different mechanisms. NF-κB and TNF-α pathways appear to be the most important in VEXAS syndrome. There are many different UBA1 mutations which can result in different outcomes, suggesting it is a possible prognostic factor. Furthermore, mutations differ in how they impair UBA1 function. Cytokines have been shown to be significantly altered in VEXAS patients; however, their exact expression and importance were not clearly defined. Interleukins, such as interleukin (IL)-6, IL-1, IL-2R and others, were reported to be expressed at an altered level, similarly to other cytokines, such as IFN-γ or TNF-α. It is worth noting that the expression of certain cytokines can vary between patients, which poses therapeutic difficulties in selecting the right drug. Therefore, the aim of this review was to describe the cytokines involved in VEXAS syndrome and associate their expression with UBA1 mutation. Full article