Nociplastic pain is the fourth category of pain defined in recent years. It is a pain arising from altered nociception, despite the lack of clear evidence of actual or threatened tissue damage that causes activation of peripheral nociceptors nor evidence for disease or lesion of the somatosensory system causing the pain. This type of pain is usually multifocal, more diffuse or intense than expected and it is usually associated with other central nervous system-derived symptoms, such as fatigue, sleep, memory, and mood problems. It can occur in isolation or as part of a mixed-pain state in combination with ongoing nociceptive or neuropathic pain. It is associated with increased social and sanitary costs due to the difficulty of adequately treating it. Its pathogenesis is still poorly understood, even if a mounting body of evidence suggests a pivotal role in inflammation and immunity, which may be triggered by an infection and/or a trauma. This narrative review aims to summarise the current knowledge about the interplay of the immune system and nociplastic pathways activation and amplification. The challenge for the future will be to identify the exact role of inflammation and immunity, the cause of this activation, and its link to other pathogenetic factors of nociplastic pain, such as diet or microbiota alteration, social and phycological factors, together with a genetic and epigenetic predisposition.

Aim:Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality and is characterized by T-cell exhaustion, particularly in effector CD8+ T-cells. This exhaustion, driven by persistent immunosuppressive signals in the tumor microenvironment, impairs immune function and hinders effective immunotherapy. This study aimed to identify key exhaustion-related marker genes in CD8+ T-cells linked to PDAC and assess the potential of repurposing anti-inflammatory drugs to counteract T-cell exhaustion and enhance immune responses against PDAC.

Methods:We employed a multi-omics approach, integrating single-cell RNA sequencing data with whole genome sequencing to identify dysregulated exhaustion-related immune markers in CD8+ T-cells in PDAC. We examined gene expression profiles and conducted functional enrichment analysis to evaluate their roles in immune exhaustion. We analyzed mutations in the shortlisted biomarkers from The Cancer Genome Atlas (TCGA) and performed in silico mutational analysis using Maestro to evaluate the impact of an IL7R mutation (K110N) on protein function. Virtual screening using a deep learning framework, GNINA, explored the inhibitory features of the anti-inflammatory drugs oxaprozin and celecoxib on IL7R.

Results:Key dysregulated exhaustion-related immune markers were identified including PRF1, GZMA, CD8A, CD3D, NKG7, IL7R, and IL2RG. Pathway enrichment analysis indicated significant involvement in T-cell receptor signaling, Th1 and Th2 differentiation, and Th17 differentiation pathways, correlating with reported poor survival outcomes in PDAC patients. Mutational analysis of IL7R revealed a likely pathogenic mutation (K110N) located in the IL-7Ralpha fibronectin type III domain. Drug repurposing of oxaprozin and celecoxib showed favorable binding interactions with both wild and mutant IL7R proteins.

Conclusions:The K110N mutation, despite not causing significant structural changes, may impact T-cell and B-cell homeostasis and development. Our findings suggest that oxaprozin and celecoxib could effectively inhibit T-cell exhaustion through favorable interactions with IL7R. Further clinical studies are necessary to validate the therapeutic potential of these anti-inflammatory drugs in enhancing immune responses in pancreatic cancer.

Aim:This study aims to identify the factors affecting the formation of neutralizing antibodies (NAbs) in healthy adults four weeks post-COVID-19 vaccination.

Methods:A cross-sectional study was conducted among mass vaccination attendees using inactivated CoronaVac. Collected the peripheral blood serum four weeks following the second vaccine dose. Forty-four adults aged 26–85 were split into two groups based on age (≤ 60 years and > 60 years) and BMI (non-obese ≤ 25 kg/m² and obese > 25 kg/m²). Variables like age, gender, BMI, and the presence of comorbidities were recorded. CD4/CD8 ratio and vitamin D levels were examined for their influence on NAbs formation. NAbs were measured using ELISA, T-cells via flow cytometry, and vitamin D through radioimmunoassay. Descriptive data analysis was performed as mean ± standard deviation to show the characteristics of the sample. Students’t-tests and multivariate and univariate regression analyses were used to evaluate the data.

Results:Significant variations in NAbs levels were observed with age (P = 0.013), BMI (P = 0.004), and comorbidities (P = 0.034). The elderly demonstrated higher NAb levels, potentially due to the high vitamin D levels compared to the adult group. The vitamin D levels strongly correlated with NAb titer (P < 0.001; R = 0.843). A collective correlation was found between NAb levels and the factors of age, BMI, and CD4/CD8 ratio (P = 0.033). A negative correlation existed between BMI and NAb levels (P = 0.018; R = –0.356) and between age and the CD4/CD8 ratio (P = 0.440; R = –0.119), but age alone did not correlate with NAb titer.

Conclusions:Age, BMI, CD4/CD8 ratio, and comorbidities influence the production of post-vaccination NAbs. Sufficient vitamin D levels in the elderly significantly boost post-vaccination NAb levels. Maintaining a healthy body weight is also vital, as studies have revealed a significant and negative correlation between BMI and the level of NAbs, suggesting a possible need for adjusted vaccine doses in obese individuals.

Aim:Immunization with meningococcal vaccine (MV) is the most effective measure to control and prevent the transmission of meningococcal infections. In this study, in order to support the appropriate use of various MVs in the prevention of meningococcal meningitis (MM), the effects of MVs, especially single-dose and inter-booster administered, on inflammatory parameters in < 5-year-old children were investigated.

Methods:A total of 464 healthy children were included in this study. The data of those who received the first 2 doses at 2-month intervals and the next dose between 8–12 months were included. Nimenrix^® (Pfizer) administered as a single dose to children from 12 months of age. Bexsero^® (GSK) was administered as 2 + 1 doses under 2 years of age and 2 doses 2 months apart over 2 years of age. Neutrophil, lymphocyte, monocyte, platelet counts, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation response index (SIR-I), and systemic immune inflammation index (SII) were evaluated.

Results:Of the 464 participants, 58.2% were male, with a mean age of 3.81 years, and both sex ratios and ages were similar across the Nimenrix and Bexsero groups. The laboratory and inflammatory parameters of the two vaccine groups were similar. In both vaccine groups, changes in laboratory parameters before and 3-months after vaccination were similar. The changes in laboratory parameters over time between vaccine groups and their interactions were not significant.

Conclusions:The NLR, dNLR, PLR, SIR-I, and SII are useful biomarkers indicating the inflammatory response of Nimenrix and Bexsero vaccines. Inflammatory markers can be used as both a safety endpoint and a protection endpoint for MVs (Nimenrix and Bexsero). However, further studies involving larger patient cohorts as well as detailed laboratory data on specific markers of inflammation are needed to draw comprehensive conclusions regarding the inflammatory response following vaccination.

Coronavirus disease 2019 (COVID-19) infected individuals showed either mild symptoms or were paucisymptomatic, with severe impact on human health, revealing heightened risk and direct effects on health. Among various factors contributing to complications, bacterial and fungal co-infection remains very common and is highly lethal. This narrative review aims to focus on the collective role of gut microbiota and mycobiota in COVID-19. Fungal infection has been identified as a key risk factor for the spread of COVID-19 and mortality. Gut mycobiomes diversity and abundance also vary due to the different types of SARS-CoV-2 variant infection. Their cross-talk plays a vital role in immune regulation and disease severity, with an emphasis on understanding the altered condition as a predictive marker. On the other hand, the gut microbiome is well known for shaping metabolic functions, generating immune responses, and deciphering the signal to decide the healthy state and disease condition of an individual. Immune response during COVID-19 infection was also linked with metabolites produced by the gut microflora, specifically amino acids, sugar metabolites, and neurotransmitters. The cross-talk between gut microbiota and gut mycobiota for clinical implications in terms of early detection, identification of the disease severity, and even therapeutic alternatives will open newer avenues. A deep dive understanding of the cross-talk between the microbiome and mycobiome, and their role in immune response will take scientific discovery knowledge to develop gut-targeted safe therapeutic approaches in the form of FMT (fecal microbiota transplantation) probiotics, peptides, antibacterial, and antifungal metabolites. Overall cross-talk and immune interplay are critical determinants of host immunity, providing insights into their role and key take home lessons for better management of crisis in the future.

Wound healing is an area of growing importance in the healthcare field, especially chronic wounds associated with comorbidities like diabetes mellitus (DM), hypoxic stress, obesity, and malnutrition. Chronic wounds significantly increase healthcare costs and reduce patients’ quality of life. Cytokines are a promising therapeutic target, as they regulate all stages of wound healing, and dysfunction in cytokine production can cause inflammatory non-healing wounds. Interleukin-1 (IL-1), IL-2, IL-6, IL-8, and tumour necrosis factor-α (TNF-α) facilitate leukocyte recruitment and clear dead cells during the initial inflammation stage while transforming growth factor-β (TGF-β), IL-4, and IL-13 inhibit inflammation and stimulate proliferation of fibroblasts to begin extracellular matrix (ECM) deposition. Given the complexity of cytokine interactions and their diverse cellular targets, a comprehensive understanding of these signaling pathways is crucial. This review examines the multifaceted roles of cytokines in wound healing and discusses recent advancements in the therapeutic application of cytokine modulation for improved wound care outcomes. Despite significant advancements in improving the specificity of cytokine therapies, further research is needed to focus on targeting downstream signaling pathways or specific receptors to minimize the adverse effects associated with these treatments.

Aim:The objectives of our study were to evaluate a range of circulating biomarkers in COVID-19-related long-term neurological dysfunction.

Methods:The study involved 30 patients with post-COVID syndrome (PCS) and 28 patients after COVID-19 without PCS. The third cohort consisted of 29 patients with acute COVID-19 of varying severity. The severity of COVID-19 was classified as mild and moderate to severe. The Montreal Cognitive Assessment (MOCA) and the SAGE test were used to study cognitive functions. The Hospital Anxiety and Depression Scale (HADS), the Sheehan Anxiety Scale, and the Beck Depression Inventory were used to study affective functions. The levels of serum cytokines and IgM, IgG, IgA to the SARS-CoV-2 coronavirus were determined using the Vector-Best test systems (Novosibirsk, Russia). We also studied the IgG subclasses to the spike protein of the SARS-CoV-2.

Results:А mild to moderate COVID-19 infection primarily increases the risk of affective disorders and asthenia and, to a lesser extent, the development of cognitive impairment. The levels of IFN-α, IL-6, as well as serum antibodies to the SARS-CoV-2 among patients with PCS were significantly higher compared to convalescents without PCS. IgM to the SARS-CoV-2 was detected in the blood of patients with PCS during 2–7 months after the disease. After moderate and severe COVID-19, IgG2 and IgG4 were predominant in the blood of patients with PCS and neurological symptoms. The levels of IL-1, IL-4, IL-6, IL-8 in the blood serum of patients with PCS were higher after moderate and severe COVID-19 compared to patients who had mild COVID-19.

Conclusions:The obtained data on an elevated level of cytokines and IFN-α in the blood of PCS patients can suggest the hypothesis about the participation of chronic inflammation in neurological disorders. The main limitation of the study is the relatively small sample size, which limits the statistical analyses.

In hematological malignancies, autologous immunotherapy with T lymphocytes expressing a chimeric antigen receptor (CAR-T) has been successfully applied. CAR enhances the immuno-cellular effector system directly against cells expressing target antigens. The objective here was to discuss the prospects of applying CAR-T and its variants in autoimmune diseases (AIDs) to deplete pathogenic autoantibodies by eliminating B lymphocytes and plasma cells. B cells play a crucial role in the pathogenesis of AID through the production of autoantibodies, cytokine dysregulation, antigen presentation, and regulatory dysfunction. In AID with numerous autoreactive clones against various autoantigens, such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, myositis, and systemic sclerosis, CAR-T targeting CD19/CD20 and B-cell maturation antigen (BCMA) have shown success in preclinical and clinical studies, representing an innovative option for refractory patients when standard treatments fail. The suppression of B lymphocytes reactive against specific antigens using cytolytic T cells carrying a chimeric autoantibody receptor (CAAR-T) offers a promising approach for managing various AIDs, especially those with characterized pathogenic autoantibodies, such as pemphigus vulgaris, myasthenia gravis, and anti-NMDAR autoimmune encephalitis. CAAR-T allows the elimination of autoreactive B lymphocytes without compromising the general functionality of the immune system, minimizing common side effects in general immunosuppressive therapies, including immunobiologicals and CAR-T. In vitro, preclinical, and clinical (phase 1) studies have demonstrated the efficacy and specificity of CAR-T and CAAR-T in several AIDs; however, extensive clinical trials (phase 3) are required to assess their safety and clinical applicability. These advances promise to enhance precision medicine in the management of AIDs, offering personalized treatments for individual patients.

Aim:Plasma cell disorders (PCD), a group of B-cell neoplasms, have undefined etiology. Mast cells (MC) have been found to promote the proliferation and differentiation of B cells in several B cell lymphoproliferative disorders; however, their role in PCD is unclear. The study therefore aims to evaluate bone marrow MC (BM-MC) in the context of PCD.

Methods:Thirty patients with PCD and 20 control subjects were selected. The BM sample was collected and mononuclear cells were isolated to identify the MC percentage among mononuclear cells using flow cytometry. A 24-hour BM culture was also performed and tryptase levels in the culture supernatant were measured by an enzyme immunoassay.

Results:In the patient group, the median of MC was 0.04% compared to 0.002% in the control group (p = 0.00001). Median BM-MC tryptase levels were also high in patients (10.1 ng/mL) against the control levels of 7.0 ng/mL (p = 0.011). While 50% of patients were found to have raised tryptase levels, only 10% of controls had tryptase levels beyond the cutoff levels of (p = 0.003).

Conclusions:BM-MC number and tryptase levels are increased in PCD, suggesting their role in disease pathogenesis.

Immune response, inflammation, and lipid metabolism have important effects on cancer development and progression. Several proteins in tumoral cells and/or tumor microenvironment are involved in any of these processes, whereas some of them participate in all three, such as the zinc finger E-box-binding homeobox 1 (ZEB1) protein. This protein has been proposed to have an important role in invasion and metastasis of cancer cells, as well as to be involved in malignant transformation and resistance to cancer treatments. So, in this study, we present the participation of ZEB1 in immune, inflammatory, and membrane remodeling (lipid metabolism) processes, as well as its interaction with proteins that participate in them. Due to the importance of ZEB1 in cancer progression, it may be a potential biomarker of cancer prognosis and a target for the development of new cancer therapies.

Cutaneous reactions present a diagnostic challenge, mainly when multiple factors, such as infections, medications, and environmental triggers, contribute to the clinical picture. Erythema multiforme (EM) is an acute, self-limiting mucocutaneous disorder that is most commonly triggered by herpes simplex virus (HSV) but can also be associated with drug-induced hypersensitivity reactions. Diagnosing EM becomes even more complex in patients taking photosensitizing medications, such as doxycycline, which can cause phototoxic or photoallergic reactions. Differentiating between drug-induced and infection-associated EM, as well as distinguishing it from more severe conditions like Stevens-Johnson syndrome (SJS), is crucial for appropriate management. This case report presents a case of a 57-year-old Caucasian female with a history of penicillin allergy who developed a phototoxic reaction to doxycycline following sun exposure. She was treated with silver sulfadiazine for her skin lesions but subsequently developed EM, with target-like lesions predominantly on the legs and a concurrent herpes simplex labialis infection. Laboratory findings were unremarkable, and there was no mucosal involvement. Given the suspected drug-induced nature of the reaction and the presence of HSV, a cautious approach was taken. Treatment with oral prednisone led to the resolution of symptoms without recurrence. Patch testing for doxycycline and silver sulfadiazine was omitted due to the risk of severe cutaneous adverse drug reactions (SCARs) and their non-essential status. Instead, penicillin testing was prioritized due to its clinical importance, and the patient successfully passed the oral amoxicillin challenge. This case highlights the diagnostic challenges of differentiating between drug-induced, infection-triggered, and photosensitivity-related cutaneous reactions. A careful evaluation of medication history, infection status, and clinical presentation is essential to guide the management of this condition.

Aim:To assess circulating levels of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) in mid-gestation pregnant women from South India, with (RPL) and without history of recurrent pregnancy loss (non-RPL) and its correlation with neutrophil to lymphocyte ratio (NLR).

Methods:Blood samples were collected from 400 pregnant women attending government maternity hospital, Hyderabad, and subjected to enzyme linked immunosorbent assay (ELISA) for cytokines. NLR was calculated from absolute cell counts obtained from hospital records. Mann-Whitney U and Spearman r correlation was conducted as data followed non-normal distribution.

Results:We found significantly decreased level of TGF-β and elevated TNF-α, TNF-α/TGF-β (P < 0.0001), and NLR ( P = 0.0007) in patients over controls. Receiver operating curve characteristics of TNF-α/TGF-β (area under curve: 0.96) were superior to individual cytokines and NLR for patients when compared to the control group. A negative correlation was noted between NLR and TGF-β in the RPL group (P = 0.0041).

Conclusions:Our results are indicative of predominant pro-inflammatory environment during mid-gestation in patients contrary to the anti-inflammatory milieu in controls. This is first study that attempted to connect cytokines with cellular ratio in RPL. The affordability of NLR to track inflammation is promised by its inverse correlation with TGF-β. However, further longitudinal studies are warranted spanning all stages of gestation in normal pregnant and RPL women to establish our observations. The limitations of the study include other factors that drive pro-inflammatory status like emotional dysregulation in women associated with chronic pro-inflammatory status is unexplored.

Neoantigen vaccines are a promising strategy in cancer immunotherapy that leverage tumor-specific mutations to elicit targeted immune responses. Although they have considerable potential, development challenges related to antigen prediction accuracy, manufacturing complexity, and scalability remain key obstacles to their widespread clinical use. This literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar databases to identify relevant studies. Keywords included “neoantigen vaccines,” “personalized cancer immunotherapy,” “tumor heterogeneity,” “bioinformatics pipelines,” and “prediction algorithms”. Clinical trial data were sourced from ClinicalTrials.gov, Trialtrove, and other publicly available registries. Eligible studies included peer-reviewed research articles, systematic reviews, and clinical trials focusing on neoantigen vaccine development, bioinformatic strategies, and immunotherapy. Tumor heterogeneity and clonal evolution significantly impact vaccine efficacy, necessitating multi-epitope targeting and adaptive vaccine design. Current neoantigen prediction algorithms suffer from high false-positive and false-negative rates, requiring further integration with multi-omics data and machine learning to enhance accuracy. Manufacturing remains complex, time-intensive, and costly, necessitating advancements in standardization and automation. Combination therapies, such as immune checkpoint inhibitors and adoptive cell therapies, counteract the immunosuppressive tumor microenvironment, improving treatment outcomes. Neoantigen vaccines hold great potential for personalized cancer therapy but require advancements in bioinformatics, manufacturing scalability, and immunomodulatory strategies to enhance clinical efficacy. Continued research and interdisciplinary collaboration are essential for refining clinical applications.

Diet plays a complex role in the management of inflammatory bowel disease (IBD), significantly influencing the microbiome and metabolome. Three key metabolites implicated in IBD are short chain fatty acids, bile acids and tryptophan, all of which can be modulated through diet. This study analyses the impact of various diets on these metabolites. Despite the anti-inflammatory effects of short chain fatty acids, their levels do not increase during successful remission with exclusive enteral nutrition. Additionally, changes in tryptophan and bile acids are non-specific across different diets, suggesting these metabolic shifts are secondary to dietary efficacy in IBD. Dietary therapies vary in efficacy across individuals, as the established microbiome may not produce the desired metabolites. This variability is further compounded by differences in immune responses influenced by genetic factors and disease duration. Furthermore, inflammation and symptom resolution do not always coincide, revealing a discrepancy in dietary impacts on IBD. These limitations highlight the need for a deeper understanding of the interconnectedness of disease heterogeneity, dietary effects, the microbiome, and their influence on the mucosal immune system to develop more personalised dietary therapies. While no single diet is universally effective for all IBD patients, future research should focus on establishing a more rigid definition of dietary interventions for IBD and their long-term effects on clinical outcomes.

Monogenic muscular dystrophies (MDs), such as Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophy (LGMD), are characterized by chronic inflammation, progressive fibrosis, and impaired muscle regeneration. Central to these pathological processes are macrophages, which exhibit dynamic polarization states that influence the dystrophic microenvironment. In early disease stages, macrophages support tissue repair and regeneration, but chronic inflammation skews their activity toward pro-fibrotic phenotypes, driving excessive extracellular matrix (ECM) deposition and muscle dysfunction. Macrophages also interact with other immune cells, such as T cells and neutrophils, and non-immune cells, including fibroblasts and satellite cells, to regulate inflammatory and fibrotic responses. These interactions establish a dysregulated immune environment that exacerbates muscle damage and impairs effective regeneration. Preclinical studies using themdx mouse model of DMD highlight the critical role of macrophages in sustaining inflammation and fibrosis, particularly through transforming growth factor-beta (TGF-β) signaling and fibro-adipogenic progenitor (FAP) activation. Therapeutically, targeting macrophages offers significant potential to mitigate disease progression. Strategies include modulating macrophage polarization toward a pro-regenerative M2 phenotype, inhibiting macrophage recruitment via chemokine signaling, and reprogramming macrophage metabolism to support oxidative phosphorylation and mitochondrial function. Additionally, anti-fibrotic interventions targeting TGF-β signaling or macrophage-FAP crosstalk have shown promise in reducing ECM deposition and preserving muscle architecture. In this review, we curate relevant studies and provide insights into the molecular mechanisms governing macrophage behavior in dystrophic muscle. Herein, we discuss how emerging therapeutic strategies targeting macrophage-mediated pathways can be leveraged to mitigate inflammation and fibrosis, enhance muscle regeneration, and improve clinical outcomes.

Primary immunodeficiency disease (PID) now known as inborn errors of immunity (IEI) is genetic disorder(s) that impair the immune system. IEI is a heterogeneous group of diseases of more than 485 lifelong genetic disorders mainly due to intrinsic defect(s) in human immune system. Adults, children, and neonates can be affected by IEI diseases. The first IEI defects were reported in the 1950s, but Bruton’s use of immunoglobulin in 1952 to treat an 8-year-old boy suffering from pneumonia and other bacterial sino-pulmonary infections brought the PID or IEI and associated diseases into limelight. This review will focus on a general description of IEI (history, epidemiology, pathophysiology, and diagnosis), inborn errors of metabolism, and the management (cure or therapy) of IEI diseases.

Aim:Mutations in key regulators of apoptosis have necessitated exploring the alternative cell death pathways like necroptosis in breast cancer (BC). Necroptosis is immunogenic due to the release of damage-associated molecular patterns (DAMPs) into extracellular environment, which can trigger pro- or anti-tumor immune responses. Inducing necroptosis in estrogen receptor-positive (ER+) BC cells leads to the release of DAMPs, which can influence macrophages polarisation within the tumor microenvironment. The study aims to identify and characterize the DAMPs released from ER+ BC cells after necroptosis induction and to investigate their effects on macrophage properties.

Methods:Necroptosis was induced by treating T-47D cells with Z-VAD-FMK and TNF-α (24 hours). The culture medium was collected as induction medium (IM). Necrostatin-1 alongside Z-VAD-FMK and TNF-α was added to inhibit necroptosis, the culture medium was collected as inhibition medium (InM) and used as a negative control for necroptosis. IM also referred as conditioned medium (CM), was analyzed using LC-MS/MS for the identification of DAMPs. THP-1 macrophages were incubated with the CM (24 hours), and their differentiation into M1 or M2 subtypes was assessed using qPCR, by evaluating the expression of specific M1 and M2 markers.

Results:A total of 35 unique proteins with potential DAMP activity were identified in the IM. Functional and pathway analyses using PANTHER and DAVID revealed their involvement in immune regulation, metabolism, stress responses, and key pathways such as glycolysis, signaling, and inflammation. These proteins were primarily intracellular or secretory and included cytoskeletal components, chaperones, and binding modulators. Furthermore, IM treatment promoted THP-1 monocyte differentiation into both M1 and M2 macrophage subtypes.

Conclusions:These findings highlight the role of necroptosis in generating DAMPs, which can modulate macrophage differentiation within the BC microenvironment. The identified DAMPs hold potential for further investigation as prognostic or predictive biomarkers and therapeutic targets in future studies.

Aim:This study aims to analyze the impact of sucrose consumption on inflammatory and immunological parameters of newborn offspring of females with gestational diabetes mellitus (GDM).

Methods:4 groups of pregnant female CD1 mice were created (n = 6): A, without GDM, without sucrose supplementation; B, without GDM, with sucrose supplementation; C, with GDM, without sucrose supplementation; and D, with GDM, with sucrose supplementation. GDM was induced by subcutaneous injection of streptozotocin, with a dose of 230 mg/kg. Sucrose supplementation was administered at a concentration of 41.66 mg/mL per oral stool (500 μL volume) to each female daily at 8:00 am from confirmation of gestational diabetes until the end of pregnancy. Immediately after birth, the pups were sacrificed in the first 2 h of life. The following were quantified in each group of 8 newborns: body weight, glycaemia, leptin, adiponectin, insulin, HOMA-IR index, percentage of lymphocytes: CD3, CD4, and CD8, immunoglobulins (IgA and IgG), cytokines (IL-1β, IL-6, TNF-α, and IFN-γ), and redox activity: (carbonylated proteins, malondialdehyde, superoxide dismutase, catalase, reduced glutathione, total antioxidant capacity).

Results:Sucrose consumption increased the levels of adiponectin, IL-1β, IL-6 and decreased the concentration of IgA in the offspring. Group C and D caused lower body weight and higher concentration of carbonylated proteins. The combination of sucrose and GDM favored an increase in blood glucose, the HOMA-IR index, the percentage of T lymphocytes, the concentration of proinflammatory cytokines, and reduced glutathione, with reduction of catalase.

Conclusions:Sucrose consumption by mothers during pregnancy and the presence of GDM generate alterations at the cellular, immunological, metabolic, hormonal, and redox levels in newborns. This results in an inflammatory state, with an imbalance in the redox state, which predisposes the newborn to short and medium-term metabolic problems from birth.

The introduction of immune checkpoint inhibitors (ICIs) has transformed the landscape of oncology, offering significant improvements in patient survival and achieving remarkable long-term outcomes. Despite these advances, the therapeutic benefits of ICIs are not universal, and existing biomarkers often fall short in accurately predicting patient responses. A comprehensive understanding of the mechanisms underlying resistance to ICIs is essential for the development of strategies to mitigate these challenges and enhance therapeutic efficacy. This review provides a detailed exploration of the resistance mechanisms associated with ICIs, focusing on the role of the tumor microenvironment and intrinsic tumor cell alterations in mediating both primary and secondary resistance. Furthermore, it evaluates emerging strategies to overcome resistance, including combination therapies and innovative therapeutic approaches. By dissecting the molecular and immunological pathways implicated in ICI resistance, this review aims to highlight novel predictive and prognostic biomarkers and outline optimized therapeutic strategies to maximize the clinical impact of ICIs in cancer management.

Aim:The high levels of anti-SSA/Ro and anti-SSB/La autoantibodies are closely associated with a group of diseases related to connective tissues, also known as connective tissue diseases (CTD). The current study attested to profile the multifactorial association between interleukin IL-6 and IL-10 in sera from the study cohort to underline its putative prognostic and therapeutic characteristics for future application in CTD.

Methods:The study cohort was recruited from government hospitals and screened for autoantibody using Enzyme Immunoassay (EIA) and Immunofluorescence Assay (IFA) while cytokine levels were measured using ELISA.

Results:Our data showed the mean age of female patients is 38.1 years. Higher mean levels of both cytokines were observed in the first year of disease onset and menopause autoimmune-CTD patients. The mean levels of IL-6 and IL-10 were significantly higher in positive anti-Ro/La compared to the control group (p < 0.05). Also, the significant correlation of IL-6 and IL-10 in CTD patients as opposed to healthy control has underlined the putative role of these biologics.

Conclusions:These data suggest the putative manipulation of IL-6 and IL-10 as prognostic and therapeutics molecules in managing CTD, as an alternative to steroid-based medications to control the disease manifestations.

Aim:Tungiasis caused by Tunga penetrans is a neglected tropical disease that majorly affects children, the elderly and persons living with disabilities in rural homes in sub-Saharan Africa. The disease is characterized by swelling and inflammation symptoms, especially on the hands and feet. However, it is unclear whether inflammatory responses induced by T. penetrans may be associated with alterations of cytokine and antibody profiles. The study evaluated the immunological changes: cytokine and antibody profiles of experimentally raised guinea pigs exposed to T. penetrans.

Methods:A total of 24 guinea pigs were experimented on; 16 were exposed to T. penetrans while 8 were controls. Blood samples were collected before and after exposure. Enzyme-linked immunosorbent assay (ELISA) technique was used to quantify cytokines and antibodies. Data analysis was performed using GraphPad Prism 10.4.

Results:At day 10 of post-infection, guinea pigs showed significant elevation (p < 0.05) of pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α) (235 pg/mL), and interferon gamma (IFN-γ) (425 pg/mL) in the serum. Anti-inflammatory cytokine had a delayed elevation, with interleukin-4 (IL-4) peaking to 357 pg/mL by day 15, while IL-10 rose to 367 pg/mL by day 15 of post-infection. Total systemic circulating levels of antibodies in serum were significantly elevated ( p < 0.05), with immunoglobulin E (IgE) elevating to 232 ng/mL while IgG peaking at 272 ng/mL on day 15 post-infection.

Conclusions:Pro-inflammatory cytokines elevated during the early stages of infection may serve as early markers for the infection, and their potential role in the pathogenesis of tungiasis needs to be explored further. The study has established that IgE and IgG are important antibodies that are produced in response to tungiasis, and their efficacy in controlling the infection needs to be further explored for potential alleviation of severe forms of the infection.

The immune system is a masterclass in balance and adaptation. Its ability to distinguish self from non-self, to tolerate internal diversity, to learn from past encounters, and to respond to environmental cues offers more than just biological insight-it offers a framework for thinking about resilient societies. In this perspective, I reflect on the parallels between immune function and the ways communities withstand adversity, adapt, and rebuild. When the immune system falters-through intolerance, loss of memory, or failure to regulate-it mirrors the kinds of dysfunction we see in divided or unjust societies. By learning from the immune system’s strengths and failures, we may find guidance for healing fractured communities and fostering more cohesive, adaptable, and resilient social systems.

The mixed leukocyte reaction (MLR) is a pivotal in vitro assay for evaluating T-cell responses stimulated by allogeneic antigen-presenting cells (APCs). Dendritic cells (DCs) are the most efficient stimulatory cells. However, the scarcity of circulating DCs in peripheral blood limits their isolation for research or clinical use. In contrast, monocytes, which are abundant and easily accessible, can be differentiated into monocyte-derived DCs (moDCs) in vitro and have emerged as the most practical and efficient stimulatory cells for MLR due to their accessibility and robust allostimulatory capabilities. This review aims to describe the scientific rationale and evidence for using moDCs in MLR assays to assess T-cell alloreactivity. Its methodology outlines the protocols for experimental, preclinical, and biosafety assays that have demonstrated the practicality of moDCs in evaluating and quantifying the alloresponse of naïve and memory CD4⁺ and CD8⁺ T cells, as well as the effects of immunomodulatory factors, immune monitoring, and tolerogenic strategies in the context of transplantation. Additionally, it illustrates how moDC-mediated MLRs have provided critical insights into understanding alloimmunity processes and antigen-specific T-cell responses in cancer immunotherapy, autoimmune diseases, and vaccine development, with potential implications for personalized medicine and immunotherapy optimization. In conclusion, despite ongoing challenges such as standardization and scalability in massive cell production, the current understanding and reproducible results of moDC applications in MLRs highlight their potential to develop innovative strategies focused on immune monitoring.

The global socioeconomic and health impacts of microbial diseases cannot be overemphasized. The emergence of the coronavirus in 2019 and the ongoing threat of infectious diseases, such as HIV/AIDS, tuberculosis, and hepatitis, remind us of the impact these infections have on economic stability and global health. Gaps in the treatment of microbial infections and their contribution to increased mortality necessitate holistic and long-term solutions, as opposed to antibiotics, which were previously relied upon. Immunotherapy is becoming increasingly promising for the treatment of microbial infections. This study reviews recent advances in immunotherapeutic strategies, particularly cytokine-based therapies, adoptive cell therapy, monoclonal antibodies, and immune checkpoint inhibitors, for the control of antimicrobial resistance. New inventive approaches, such as chimeric antigen receptor T cell therapy and mucosal-associated invariant T cells, have been discussed in the context of bacterial and viral infections, highlighting promising results from clinical trials and addressing the challenges of toxicity, immune evasion, and therapy resistance that are inherent in these diseases. Future priorities include optimizing combination therapies and exploring new immunomodulatory targets to improve the effectiveness of these interventions in treating antimicrobial resistance and other infectious diseases.

Advancements in viral vaccine development have revolutionized public health by reducing the burden of infectious diseases worldwide. The development of vaccinology started with Jenner’s smallpox vaccine and Salk’s polio vaccine among other live attenuated and inactivated vaccines before shifting to modern platforms that include subunit, protein-based, and viral vector vaccines as well as messenger RNA (m-RNA) vaccines. Subunit and protein-based vaccines are the ones that protect specific subpopulations and contain low risks; reverse vaccinology, built on genome sequencing and using computational methods for identification of the antigens, helps to cut the time for vaccination development. The COVID-19 experience by itself has shown the feasibility of faster and easily scalable m-RNA development that provides a very strong immunogenicity and safety profile. These advancements are crucial in the fight against new and resurging pathogens, for example, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV), and influenza. They allow the creation of vaccines for highly mutable pathogens or those that evolve strategies to avoid the immune system. Truly innovational approaches in delivering vaccines are lipid nanoparticles, microneedle patches, and thermostability that improve the stability, accessibility, and administration of vaccines in low- and middle-income countries (LMICs). Furthermore, computational immunology, artificial intelligence, and bioinformatics are involved in creating precision vaccines that are likely to suit different populations in society. This review presents solutions to critical barriers including vaccine refusal among the population and unequal distribution systems and transportation requirements along with clinical trial gender bias. Recent strategies employing nanotechnology-based delivery methods and universal vaccines receive assessment regarding their solutions to present challenges. The need for joint public-private collaborations combined with strong health programs and systematic research investments stands essential for developing extensive scalable vaccination strategies. These findings present a detailed guide for improving both the effectiveness and accessibility of vaccines as well as readiness against current and future viral infections.

Oncolytic virotherapy (OVT) employs genetically engineered or naturally occurring viruses to selectively replicate within tumor cells, leading to direct lysis and induction of systemic anti-tumor immune responses. This dual mechanism distinguishes OVT from conventional therapies and positions it as a promising candidate in precision oncology. This review synthesizes recent advancements in understanding the molecular mechanisms underlying OVT efficacy, including viral entry, replication kinetics, immunogenic cell death, and modulation of the tumor microenvironment. We highlight innovations in viral engineering, such as promoter targeting, microRNA control, and immune-modulatory gene insertions that enhance tumor specificity and therapeutic safety. Clinically, OVT has shown measurable benefits in various solid tumors, with several viruses, such as talimogene laherparepvec, entering regulatory approval and others progressing through late-phase clinical trials. When combined with immune checkpoint inhibitors, OVT has demonstrated synergistic effects by improving antigen presentation and reversing immunosuppressive signaling. Integration with targeted therapies and nanotechnology-based delivery systems has further refined viral biodistribution and pharmacodynamics. However, therapeutic resistance, immune clearance, stromal barriers, and heterogeneous tumor responses remain key limitations. Overcoming these challenges requires optimized delivery routes, predictive biomarkers, and combination strategies tailored to immune and genetic tumor profiles. As OVT evolves from proof-of-concept to a platform-based therapeutic strategy, its integration into multimodal cancer treatment protocols will depend on refined bridge oncolytic activity with durable immunotherapy effects.

Cancer remains one of the leading causes of morbidity and mortality globally, driven by genetic alterations, uncontrolled cell proliferation, and metabolic reprogramming. The tumor microenvironment (TME) is a highly dynamic and heterogeneous system composed of tumor cells, immune cells, stromal cells, and extracellular matrix (ECM) components, which influence cancer progression. Tumor-associated macrophages (TAMs), especially those polarized into the M2 phenotype, play a critical role in modulating this environment. M2 macrophages promote tumor progression through mechanisms such as immune suppression, angiogenesis, and metastasis. This polarization is heavily influenced by the altered metabolic landscape of tumors, where the Warburg effect leads to excessive lactate production, which in turn drives M2 polarization through G protein-coupled receptor 132 (GPR132). M2 macrophages secrete cytokines like IL-10, transforming growth factor β (TGF-β), and vascular endothelial growth factor (VEGF), which contribute to immune escape, tumor growth, and metastasis. The metabolic shifts within TAMs, especially the transition from oxidative phosphorylation to glycolysis, further support the pro-tumoral functions of these cells. This review explores the intricate relationship between M2 macrophage polarization bias, tumor metabolism, and the resulting impact on cancer progression, highlighting the potential of targeting these pathways for therapeutic strategies. The findings suggest that M2 macrophage polarization could serve as a key prognostic factor for cancer outcomes and provide a basis for future research into therapeutic interventions that target macrophage polarization and the tumor metabolic milieu.

Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread musculoskeletal pain, fatigue, cognitive impairments, and sleep disturbances. Although traditionally considered psychogenic, recent research supports a multifactorial etiology involving central nervous system (CNS) dysregulation and significant immune involvement. This narrative review synthesizes current evidence regarding the role of immune mechanisms in FMS, with comparative insights into chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and irritable bowel syndrome (IBS)-previously grouped under functional somatic syndromes (FSS). In FMS, immune dysregulation is evidenced by elevated levels of pro-inflammatory cytokines (e.g., IL-6, IL-8, TNF-α) and decreased anti-inflammatory mediators such as IL-10, contributing to symptomatology including pain amplification and fatigue. Neuroinflammation, as indicated by microglial activation in pain-processing CNS regions, further supports the role of immune signaling in central sensitization. Other contributing factors include oxidative stress, mitochondrial dysfunction, and immune cell alterations, particularly involving regulatory T cells and natural killer (NK) cells. Compared to FMS, CFS/ME exhibits greater systemic immune activation and more severe mitochondrial impairment, correlating with profound fatigue and cognitive decline. IBS, on the other hand, shows immune activation localized to the gastrointestinal tract, emphasizing the gut-brain axis. These findings highlight both shared and syndrome-specific immune features. To better reflect their systemic and immunological complexity, this review refers to these conditions collectively as chronic multisystem immune-related disorders (CMIRDs). The evidence supports the development of biomarker-based diagnostics and personalized immunomodulatory therapies. A multidisciplinary approach that integrates immunology and neurology is essential to improve outcomes for patients with FMS and related disorders.

Aim:Autoimmune cytopenias are disorders driven by immune-mediated destruction of hematopoietic cells. Recent studies have linked these conditions to inborn errors of immunity (IEI), particularly in patients with recurrent and/or chronic forms. Common variable immunodeficiency (CVID) is the most common IEI in humans, and autoimmune cytopenias represent the most prevalent autoimmune manifestations of the disease.TNFRSF13B/TACI alterations are the most common genetic defects in CVID patients. The aim of this study was to investigate both the incidence of hypogammaglobulinemia-including immunoglobulin subclass deficiencies-in patients with autoimmune cytopenias, as well as possible correlations with commonTNFRSF13B/TACI defects in selective patients.

Methods:A cohort of 123 patients (110 adults and 13 children, male/female: 58/65, median age at diagnosis: 50.0 years, range: 1.5–87.0) with autoimmune cytopenias [113 with autoimmune thrombocytopenia (AIT), 8 with autoimmune hemolytic anemia (AHA), and 2 with Evans syndrome] were enrolled in the study. The main immunoglobulin types (IgG, IgM, and IgA) were measured in all patients, while serum for the estimation of IgG subclass levels was available in 84 patients. Genetic analysis ofTNFRSF13B/TACI was performed by PCR and Sanger sequencing.

Results:Although no deficiency of main immunoglobulin types was detected in any patient, 8 of 84 patients (9.5%) displayed selective IgG4 deficiency (sIgG4D). Among them, three suffered from acute/newly diagnosed AIT, three from chronic AIT, and two from AHA. Interestingly, two patients with sIgG4D exhibited a family history of IEI. Furthermore, one patient (12.5%) carried a pathogenic missense mutation (c.542C>A, p.A181E, rs72553883) in a heterozygous state, while the remaining patients carried only common polymorphisms.

Conclusions:IgG4 could be considered a useful biomarker in patients with autoimmune cytopenias, while further studies may elucidate its precise role in disease pathogenesis and prognosis.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder characterised by synovial joint destruction and systemic complications. Central to its pathogenesis is the formation and deposition of immune complexes (ICs), which result from antigen-antibody interactions involving autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs). These ICs infiltrate joint tissues, activate the complement system, and initiate a cascade of inflammatory responses. The ensuing recruitment of polymorphonuclear leukocytes and release of pro-inflammatory cytokines and chemokines contribute to sustained inflammation, tissue degradation, and joint deformity. RA is thus classified as a type III hypersensitivity disorder, wherein IC-mediated mechanisms perpetuate a self-amplifying inflammatory loop. This review explores the evolving understanding of IC-driven pathophysiology in RA, emphasising the three-stage progression of IC formation, deposition, and inflammatory activation. By elucidating the interplay between hypersensitivity reactions and immune-mediated mechanisms in RA, the review underscores potential therapeutic targets that may help disrupt this pathogenic cycle. Enhanced comprehension of IC dynamics not only deepens insight into RA progression but also opens avenues for more precise and effective interventions in autoimmune diseases.

Aim:Recurrent pregnancy loss (RPL) is defined as the loss of two or more clinical pregnancies before the 20th week of gestation. Globally, RPL affects 1–5% of couples, with approximately 50% of cases remaining idiopathic. This study aimed to assess the circulating levels of interleukin-6 (IL-6) and IL-10 cytokines in pregnant women with and without a history of RPL.

Methods:A total of 170 pregnant women in their second trimester with and without a history of RPL were enrolled from Niloufer Hospital, South India. Serum samples isolated from blood were analyzed using a sandwich-enzyme linked immunosorbent assay (ELISA) to estimate IL-6 and IL-10 levels.

Results:The median age was significantly higher in the RPL group (25 years) compared to the non-RPL (NRPL) group (22 years) (p = 0.0001). Similarly, body mass index (BMI) was significantly elevated in the RPL group (25.64 kg/m²) vs. the NRPL group (22.51 kg/m²) (p = 0.0001). The analysis revealed significantly elevated IL-6 and reduced IL-10 levels in the RPL group compared to the NRPL group (p = 0.0001). Additionally, the IL-6/IL-10 ratio differed significantly between the two groups. Receiver operating characteristic (ROC) curve analysis indicated that IL-6 was a better marker for RPL than IL-6/IL-10 ratio and IL-10. IL-10 levels were found to be a reliable marker in relation to the extent of pregnancy loss history.

Conclusions:The study highlights the presence of a pro-inflammatory systemic milieu in mid-gestation among women with a history of RPL, potentially reflecting the immunological environment at the feto-placental interface. Further research to establish a distinct cytokine signature between RPL and NRPL groups may facilitate the development of targeted preventive and therapeutic strategies. However, the current findings are limited by a modest sample size and a homogenous ethnic population, which may affect generalizability. Larger, multi-ethnic studies are warranted to validate these observations and enhance clinical applicability.

Aim:Vitiligo is an autoimmune skin disorder characterized by melanocyte destruction and progressive depigmentation. Cytokine imbalance plays a key role in its pathogenesis. This study aims to evaluate and compare serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) and the pro-inflammatory cytokine IL-17 in vitiligo patients and healthy individuals, to explore their potential as biomarkers of disease activity.

Methods:A total of 60 vitiligo patients and 40 age- and sex-matched healthy controls were recruited. Serum concentrations of IL-10 and IL-17 were measured using enzyme-linked immunosorbent assay (ELISA). Disease severity and duration were also assessed in relation to cytokine levels.

Results:Vitiligo patients showed significantly lower IL-10 levels (9.37 ± 0.17 pg/mL) compared to controls (11.38 ± 0.22 pg/mL,P < 0.01), and significantly higher IL-17 levels (326.48 ± 5.49 pg/mL) compared to controls (270.47 ± 8.48 pg/mL, P < 0.01).

Conclusions:These findings suggest an inflammatory cytokine imbalance in vitiligo, characterized by decreased IL-10 and elevated IL-17 levels. The significant correlation of IL-17 with disease progression supports its role as a potential biomarker of disease activity. Targeting cytokine pathways may offer new directions for immunomodulatory treatment strategies in vitiligo.

Cardiac fibrosis, characterized by excessive extracellular matrix (ECM) deposition, plays a central role in the progression of heart diseases such as myocardial infarction, heart failure, and hypertensive cardiomyopathy. The dynamic interplay between fibroblasts and macrophages is pivotal in regulating ECM remodeling and the fibrotic response. Fibroblasts, as primary ECM producers, undergo phenotypic changes during pathological conditions, transitioning into myofibroblasts that exacerbate fibrosis. Macrophages, both resident and non-resident, contribute to cardiac fibrosis by influencing fibroblast activation through cytokine secretion and direct cell interactions. Emerging evidence from preclinical studies highlights the transformation of macrophages into myofibroblast-like cells, known as macrophage-to-myofibroblast transformation (MMT), a key mechanism linking chronic inflammation to fibrosis. During MMT, macrophages acquire characteristics like myofibroblasts. This process is driven by signaling pathways such as TGF-β/Smad3, ALKBH5, and mineralocorticoid receptor (MR)/connective tissue growth factor (CTGF) pathways. Recent single-cell transcriptomics and lineage-tracing studies have provided deeper insights into the molecular regulation of MMT and its contribution to myocardial remodeling. Additionally, the balance between resident cardiac macrophages and monocyte-derived macrophages plays a crucial role in determining the fibrotic outcome following cardiac injury. This review discusses the cellular composition of the heart, the interactions between macrophages and fibroblasts, and the mechanisms driving MMT. By synthesizing these insights, we aim to evaluate MMT as a therapeutic target for mitigating cardiac fibrosis and improving clinical outcomes in cardiovascular diseases.

Messenger RNA (mRNA) vaccines represent a novel category of vaccinations with significant potential for the future. Recent studies have demonstrated the effectiveness of mRNA vaccines in combating various viral infections and cancer, particularly in cases where traditional vaccine platforms may not produce protective immune responses. In particular, mRNA vaccines have gained attention due to their quick development, scalable manufacturing, and ability to elicit strong immune responses. This review elucidates the synthesis of mRNA and mRNA vaccines, their mechanisms of action, and the strategies to enhance their delivery and address their advantages and limitations for viral disease. Many delivery strategies have been investigated in recent years, concentrating on nanoparticle-mediated mRNA vaccine delivery. The delivery mechanism is crucial for improving mRNA vaccine stability, biocompatibility, and targeting specific cells and tissues. By preventing mRNA degradation and increasing cellular uptake, nanocarriers significantly contribute to the stability and immunogenicity of mRNA vaccines. Nanoformulation functions not only as a carrier but also as a compartment that safeguards the mRNA from biological, chemical, and physical processes that may compromise its safety and efficacy. Despite these advances, challenges such as long-term safety and innate immune activation remain. Eventually, this review concentrated on future considerations necessary for the more efficient and safer deployment of mRNA, emphasizing the merits and drawbacks of the existing viral disease mRNA vaccines, with an eye toward future innovations and clinical applications.

Mpox, caused by the monkeypox virus (MPXV), has re-emerged as a global health concern due to recent outbreaks and the emergence of new variants. Current antiviral options are limited, prompting the search for alternative therapeutic strategies. This review explores the therapeutic potential of marine-derived bioactive compounds as antiviral agents against MPXV, focusing on their mechanisms of action and clinical relevance. Marine phytoconstituents, including mycosporine-like amino acids, carrageenan, fucoidans, and griffithsin, exhibit diverse antiviral, immunomodulatory, and anti-inflammatory properties. Understanding their role may offer innovative solutions for mpox management and address gaps in current treatment approaches. A comprehensive literature search was performed across PubMed, Scopus, and Web of Science to identify peer-reviewed articles published between 2010 and June 2024 using keywords such as “mpox”, “monkeypox virus”, “marine-derived antivirals”, and “orthopoxvirus”. Emphasis was placed on studies from 2021–2024 to capture recent developments in mpox pathogenesis and marine-based therapeutics. Eligible sources included original research, systematic reviews, meta-analyses, and official health reports published in English. Marine-derived compounds demonstrate promising antiviral and immunomodulatory effects against MPXV in preclinical models. While further research is needed to confirm their clinical efficacy and address issues of scalability and safety, these agents represent a valuable adjunct or alternative for future mpox therapeutics.

Aim:Regulatory T (Treg) cells and interleukin-17-producing T helper (Th17) cells play a critical role in successful pregnancy. Treg and Th17 cells differentiate predominantly in the thymus. Despite steroid-induced pregnancy thymic involution, the peripheral blood Treg number increases, indicating peripheral expansion. Thymic atrophy is accompanied by a decrease in T-cell receptor diversity, but is compensated for by activation of RAG2 (recombination activating genes) in the periphery, which initiates extrathymic T-cell differentiation. In addition, naive Treg enhance their suppressive activity during pregnancy, which may play an important role in the development of maternal tolerance to fetal antigens. The changes in naive Th17 thymic output during pregnancy have not been studied. The aim of the study is to determine the percentages of peripheral blood Treg and Th17 and the expression of CD45RA, CD31, RAG2, and Tim-3 on these subsets during physiological pregnancy and in non-pregnant (NP) women.

Methods:Peripheral blood samples (n = 80) from healthy NP and pregnant women (1st, 2nd, and 3rd trimesters) were analyzed by flow cytometry to determine Treg (CD4⁺CD25⁺FOXP3⁺) and Th17 (CD4⁺RORγt⁺IL-17A⁺), and the expression of RAG2 and Tim-3 in these subsets. Treg and Th17 then subdivided into mature naive (MN, CD45RA⁺CD31^–), recent thymic migrants (RTE, CD45RA⁺CD31⁺), CD31^– memory, and CD31⁺ memory cells.

Results:An increase in the Treg percentage, a decrease in Th17, and a shift in the Treg/Th17 ratio shift towards Treg were revealed in pregnant women compared to NP. A Tim-3⁺ Treg increase in the 1st and 3rd trimesters and Tim-3⁺ Th17 in the 3rd trimester were found. There was a decrease in RTE-Treg and RTE-Th17, an increase in the MN-Treg percentage, but MN-Th17 did not change during pregnancy. The RAG2 expression was increased only in Treg.

Conclusions:The obtained data indicate that a healthy pregnancy is characterized by significant changes in the composition of naive Th17 and Tregs in peripheral blood.

Aim: Cytotoxic T lymphocytes (CTL) examine the major histocompatibility complex (MHC) class I ligands on nucleated cells to detect antigens derived from pathogens and cancer cells. Accurate prediction of T-cell epitopes is therefore crucial for the development of a wide range of biopharmaceuticals, including vaccines.

Methods: The present study involved the development of position-specific scoring matrices (PSSM) and artificial neural networks (ANN) based models for 22 MHC class I molecules, including the integrated forecast of CTL epitopes using the EasyPred modeler. Similarity-reduced peptides dataset was used to train and evaluate models with performance assessed using the area under the receiver operating characteristic curve (Aroc) as the primary metric.

Results: Comparative analysis revealed that the ANN-based predictor achieved superior performance for the HLA-A*0202 molecule by achieving the maximum Aroc value of 0.97 as compared to the PSSM predictor, having a value of 0.93. Furthermore, most natural MHC binders were identified within the top 5% with an average relative rank (%) of 2.23 and 3.13 for predictors PSSM and ANN, respectively, on the NetCTLpan dataset. Likewise, evaluation on the SARS-CoV-2 dataset of HLA-A*0201 revealed that the PSSM predictor (2.46%) performed better than the other contemporary CTL epitope forecast methods like naturally eluted ligands (EL) of NetMHCpan 4.0 (2.66%), NetCTLpan 1.1 (2.69%), and binding affinity (BA) of NetMHCpan 4.0 (3.33%), respectively.

Conclusions: The application of these predictive models offers a significant reduction of approximately 97% in the resources typically required for epitope identification, including costs related to materials, labor, and time. As such, these models represent a valuable advancement in the rational design of more efficient, cost-effective, and innovative biotherapeutics.

Aim:Despite advances in lymphoma treatment, resistance to conventional therapies and insufficient immune-mediated tumor clearance remain major challenges. This study investigates the dual antitumor mechanisms of the mushroom-derived triterpenoid, ganoderic acid DM (GA-DM), exploring its ability to induce programmed cell death while enhancing immune recognition in diffuse large B-cell lymphoma (DLBCL).

Methods:DLBCL cells (DB and Toledo) were treated with GA-DM (0–40 μM), and cell viability was assessed via MTS assay. Apoptosis was evaluated through caspase-3 activation and inhibition by ZVAD-FMK, while autophagy was measured via LC3 protein expression. Flow cytometry analyzed HLA class II surface expression and antigen presentation to CD4⁺ T cells (via IL-2 production), with autophagy’s role further confirmed using the inhibitor 3-MA.

Results:GA-DM exhibited potent and dose-dependent cytotoxicity against DLBCL cells, with concentrations of 30–40 μM inducing over 60% cell death within 24 h. Mechanistic studies revealed that GA-DM activated the intrinsic apoptotic pathway, as evidenced by caspase-3 cleavage and the significant reduction in cell death upon ZVAD-FMK treatment. Concurrently, GA-DM treatment upregulated the autophagy marker LC3-II, indicating the induction of autophagy. Strikingly, GA-DM also enhanced the immunogenicity of lymphoma cells by increasing surface expression of HLA class II molecules. This led to improved antigen presentation and subsequent activation of CD4⁺ T cells, as demonstrated by a 2.5-fold increase in IL-2 production (amount of IL-2 in pg/mL) compared to untreated controls. The critical role of autophagy in this process was confirmed by the near-complete abrogation of HLA class II-mediated T-cell activation upon 3-MA treatment.

Conclusions:GA-DM synergistically induces apoptosis and autophagy while promoting immune-mediated tumor clearance through enhanced HLA class II antigen presentation. These findings highlight GA-DM as a promising multi-modal therapeutic candidate for lymphoma immunotherapy.

Aim:This retrospective study was performed to evaluate the efficacy and tolerability of cyproheptadine versus montelukast as adjuncts to ongoing second-generation antihistamines in adults with refractory chronic urticaria.

Methods:This study included adult patients diagnosed with chronic urticaria who did not respond to standard treatment, divided into two groups. Group A received antihistamines plus oral cyproheptadine for one month, and group B received antihistamines in addition to standard-dose montelukast daily (10 mg) for four months. The weekly urticaria activity score (UAS7), chronic urticaria quality of life questionnaire (CU-Q₂oL), and dermatology life quality index (DLQI) scores were measured at the end of grading after four months.

Results:After four months, both groups showed significant improvements in UAS7 and CU-Q₂oL scores, and group A also saw a notable increase in DLQI score compared to baseline. Group A showed more pronounced improvements overall. Both groups saw a reduction in background antihistamine usage, with group A experiencing a more significant decrease. Additionally, more patients in group A reported daytime sedation and weight gain compared to group B.

Conclusions:Cyproheptadine, along with second-generation antihistamines, was found to be efficacious and safe as compared to montelukast along with second-generation antihistamines in patients with chronic urticaria.

The skin covers the entire surface of the body and therefore is the largest organ in humans. The skin has various functions, primarily defence from infections and trauma. With aging, profound changes occur that compromise its key functions, leading to impaired barrier protection and immune responses. This is in part due to the increased low-grade systemic inflammation known as inflammaging, driven by senescent cells, and release of pro-inflammatory cytokines, to which the skin also significantly contributes. As a consequence of inflammaging, the skin’s function is compromized. The cellular and molecular components involved are summarized in this review.

Eosinophilic granulomatosis with polyangiitis (EGPA) is an uncommon form of necrotizing vasculitis that affects the respiratory system and other organs, characterized by asthma, eosinophilia, and multiple organ involvement that complicates the diagnosis and treatment. There are no definitive open-label clinical data on the diagnosis or treatment of EGPA to guide clinicians. The diverse presentation of the disease, distinct from other eosinophilic disorders; the presence of competing conditions such as allergy and asthma, which also have potential biomarkers; lack of a definitive test to confirm diagnosis; difficulties in obtaining endoscopic biopsies for histologic confirmation, etc., are significant barriers to early detection. Even with recent advances in imaging, immunological approaches, and molecular testing to determine the disease’s identity and characteristics, clinicians still misdiagnose or delay treatment, sometimes leading to life-threatening and irreversible complications. Though EGPA is pharmacotherapeutically controlled with glucocorticoids, it has typically included the use of cytotoxic agents such as cyclophosphamide for induction in cases of severity. Recently, several clinical trials have examined targeted biologic treatments (such as mepolizumab, benralizumab, and omalizumab) and demonstrated that these medications can reduce exacerbations, decrease the need for glucocorticoids, and improve asthma control. New drugs such as dupilumab and new anti-IL-5/IL-5R monoclonal antibodies are being studied in phase II and phase III trials, and these drugs may provide additional avenues for refractory disease. Treatment will be organized based on individualization of treatment strategy, depending on disease severity, organ involvement, and biomarker profile. Vertical investment in multicenter longitudinal studies is necessary to formulate therapeutic algorithms and evaluate new targets.

Cancer is a multifaceted and heterogeneous disease characterized by uncontrolled growth, evasion of immune surveillance, and resistance to conventional therapies. The immune system plays a crucial role in tumor surveillance. However, tumors exploit immune checkpoint pathways to inhibit T cell activation and evade immune destruction. Immune checkpoint inhibitors (ICIs) have markedly improved outcomes in certain cancers by restoring T cell function and enhancing anti-tumor immunity. Despite these advances, the presence of immune resistance mechanisms contributes to variability in responses and ongoing challenges in overcoming resistance. Triple-negative breast cancer (TNBC), compared to other breast cancer (BC) subtypes, exhibits higher immunogenicity, but its anti-tumor immunity is profoundly suppressed by immune checkpoint molecules, creating a paradoxical scenario of “high immunogenic potential yet restrained by inhibitory signals”. Consequently, TNBC has become a significant target for ICI therapy. However, response rates vary among BC subtypes, with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-positive (HER2+) BC demonstrating lower immunogenicity. Hematological malignancies, including leukemia, lymphoma, and multiple myeloma, also exhibit distinct immune checkpoint dynamics, influencing their responsiveness to ICIs. This review comprehensively examines the mechanisms of immune checkpoint regulation, their role in cancer immune evasion, and the clinical applications of ICIs in both solid and hematological malignancies. It further discusses emerging strategies to counteract ICI resistance, such as dual checkpoint blockade, tumor microenvironment modulation, metabolic targeting, and epigenetic reprogramming. An enhanced understanding of immune checkpoint biology is essential for optimizing immunotherapy strategies and improving patient outcomes. The literature selection for this study was guided by relevance to the research topic, focusing on peer-reviewed articles, monographs, and conference proceedings published between 2010 and 2025, sourced from databases like PubMed and Google Scholar.

T cell-based immunotherapies increasingly include personalized neoantigen vaccines that target tumor-specific mutations. However, despite their promise, current neoantigen vaccines show limited and unpredictable clinical benefit, with T cell responses observed in only a subset of patients. To overcome these limitations, we developed the VERDI (Vaccine Epitopes Ranked by Digital Intelligence) System-a cloud-based computational platform that integrates a patient’s human leukocyte antigen (HLA) class I and II genotype with selected tumor-associated antigens (TAAs), including cancer-testis antigens (CTAs), to identify peptides with high predicted immunogenicity and low risk of immune-related adverse events (irAEs). Using the VERDI System, we designed ten personalized peptide vaccines for a patient with metastatic signet ring cell carcinoma (SRCC), a rare and aggressive gastric cancer with limited treatment options. All ten VERDI vaccines were well tolerated and consistently induced tumor-specific T cell responses following a single administration, without the need for checkpoint inhibitors. The patient survived for 15 months-substantially longer than the reported median survival of 5.6 months in metastatic SRCC-highlighting the potential of this individualized, predictive vaccine platform to improve outcomes in advanced cancer.

Cutaneous lupus erythematosus (CLE) is the most common organ manifestation in individuals diagnosed with systemic lupus erythematosus (SLE). CLE can occur either alone or in association with SLE; in the latter case, it substantially increases the occurrence of disease flares and can cause disfigurement. The clinical pathogenesis of CLE is well established, as exposure to ultraviolet (UV) light and/or other environmental triggers, such as smoking or drug use, can lead to keratinocyte death in genetically susceptible individuals. This in turn activates cytotoxic T cells, plasmacytoid dendritic cells (pDCs), and B cells, creating a continuous interaction between the innate and adaptive immune systems. This interaction plays a pivotal role in CLE development, driving the formation of skin lesions. However, the molecular mechanisms underlying these cutaneous manifestations are not yet fully understood. While significant advances have been made in SLE treatment over the past few decades, U.S. Food and Drug Administration (FDA)-approved therapies remain limited to hydroxychloroquine, glucocorticoids, belimumab, and anifrolumab. Although new therapies for CLE have emerged, given the highly heterogeneous nature of the condition, personalized medicine is essential to prevent disfigurement and systemic disease flares. Understanding the molecular pathogenesis of CLE is crucial for developing targeted therapies and improving patient outcomes. This review presents current insights into CLE pathogenesis, highlighting key mechanisms driving the disease and exploring recent advances in treatments that have shown promise in clinical practice.

The human vaginal microbiome plays a pivotal role in maintaining female reproductive health through its Lactobacillus-dominated microbial ecology. These bacteria contribute to the acidic pH of the vagina by producing lactic acid, ultimately preventing the colonization of pathogens. Additionally, they produce bacteriocins and hydrogen peroxide, which are detrimental to other microorganisms. Human vaginal microbiota is subjected to alterations with advancement in age, hormonal status, puberty, menstruation cycle, pregnancy and gestation, vaginal tract diseases, exposure to antibiotics, etc. Diet, lifestyle factors, obesity, and gestational diabetes are also reported to cause a shift in vaginal microbiota. This review thoroughly illustrates the perpetually changing dynamics of vaginal microbiota throughout women’s lives, as well as focuses on the impact of dysbiosis in bacterial vaginosis. More emphasis is given on immunological changes observed during bacterial vaginosis, mainly IL-1β, and its involvement in the development of preeclampsia. Thereby, this review highlights a mechanistic link between lower genital tract disease, bacterial vaginosis, and a hypertensive disorder of pregnancy, preeclampsia, via IL-1β–ROR-γt–Th17 axis, which is regulated by vitamin D, with a suggestion on how shifts in vaginal microbial community may pose a risk for preeclampsia.

Cancer treatment regimens are significantly more intricate than commonly perceived. Nonetheless, both immunotherapy and chemotherapy may produce adverse consequences. Immunotherapy represents a significant advancement in the battle against cancer; nonetheless, it is not devoid of challenges. This research elucidates the mechanisms underlying immunotherapy-induced cardiovascular damage, highlighting the significant role of immune regulators, such as soluble urokinase plasminogen activator receptor (suPAR), in inducing vascular leakage. We also examine the role of matrix metalloproteinase (MMP14/15) in this process, and antigens associated with cardiovascular illness and malignancies, including native proteins, mutated tumor antigens, and viral components. Besides, we studied predictive biomarkers, such as circulating T-cell populations associated with the probability of myocarditis. We discuss treatment approaches and strategies to mitigate these issues, particularly through the use of antihypertensive medications to reduce their impact. Losartan alters the tumor microenvironment (TME) to improve immunotherapy. It restores immune effector cells in triple-negative breast cancer (TNBC), overcomes resistance in unresponsive tumors, and modifies TMEs’ immune system suppression in ovarian cancer and melanoma. It is important to note that its effects differ by cancer kind. It may promote fibrosarcoma tumor growth and improve cholangiocarcinoma treatment. This shows that losartan’s dangers in cancer treatment should be carefully considered and that more research is needed. This suggests that there must be careful consideration of the potential risks associated with losartan use in cancer treatment and underscores the requirement for additional research on this topic. This study may enhance our comprehension and management of cardiovascular adverse effects in cancer immunotherapy by integrating novel insights on immunological predictors and vascular dysfunction. Experts assert that oncology programs must provide and promote continuous monitoring of cardiac health for breast cancer patients. To mitigate the risk of cardiovascular disease in this demographic, comprehensive patient care must be administered.

Innate lymphoid cells are lymphocytes that are neither T cells nor B cells. They are relatively rare in lymphoid tissues and peripheral blood and are distinguished by their absence of an adaptive antigen receptor. In the present study, we describe the mechanisms underlying the generation of the various cell populations and highlight the functional importance of their plasticity. These cells are indeed capable of transdifferentiating from one type to another. This adds complexity to their functional program, and this feature appears to be crucial for adapting and modulating immune responses under different conditions. These lymphoid cells are of great hematological interest due to their pathophysiological and therapeutic role in many onco-hematological pathologies such as acute myeloid leukemia, multiple myeloma, and several types of lymphomas. In hematological disorders, innate lymphoid cells may exert differential effects on the pathogenesis of hematologic malignancies. Furthermore, within the same disease, certain cell populations have been shown to play a protective role in antitumor immune responses, whereas others appear to suppress these responses. This review aims to provide an integrated description of innate lymphoid cells, their alterations in hematological malignancies, and potential preventive strategies, by proposing new specific targets for correcting anomalies. We also discuss the use of innate lymphoid cells as new therapies by applying chimeric antigen receptor-modified natural killer cells. We examine the current knowledge and outline future perspectives.

Tumor-infiltrating lymphocytes (TILs) play a critical role in the ability of the immune system to combat cancer, offering a foundation for personalized immunotherapies. However, the effectiveness of TILs is often reduced by problems like becoming less active, the tumor making the immune system weaker, and not lasting long in the tumor environment. Recent advancements in single-cell technologies, including single-cell RNA sequencing (scRNA-seq), single-cell T-cell receptor sequencing (scTCR-seq), and mass cytometry (CyTOF), have revolutionized our understanding of TIL heterogeneity and dynamics. These tools offer new perspectives on the diverse phenotypes, functional states, and spatial organization of TILs, enabling the identification of key exhaustion markers, regulatory pathways, and neoantigen-specific clones. Concurrently, genetic reprogramming strategies have emerged to address TIL limitations by reversing exhaustion, enhancing metabolic resilience, and improving persistence in vivo. This review explores the synergistic integration of single-cell technologies and genetic engineering in refining TIL-based therapies. We talk about how spatial transcriptomics can help us understand how TILs work in different areas of the body and how changing their epigenetics can help them become more effective at fighting cancer. Additionally, we highlight emerging approaches to overcome immunosuppressive barriers in the tumor microenvironment (TME), including targeting regulatory immune cells, neutralizing suppressive cytokines, and enhancing antigen presentation. Together, these strategies promise to unlock the full therapeutic potential of TILs, paving the way for more effective and durable cancer immunotherapy.

Background: Oral squamous cell carcinoma (OSCC), a significant health burden in developing nations, is linked to risk factors such as tobacco use, alcohol consumption, betel nut chewing, HPV infection, and genetic susceptibility. A hallmark of OSCC is impaired T cell function, driven in part by the PD-L1/PD-1 immune checkpoint pathway, which enables tumor immune evasion and progression. Despite growing interest in immunotherapy, a focused synthesis of PD-L1 expression and its clinical implications in OSCC remains limited. This review aims to consolidate existing evidence on PD-L1 in OSCC, evaluating its expression patterns, correlation with disease progression, and therapeutic relevance.

Methods: A systematic search was conducted across multiple databases to identify studies examining PD-L1 expression in OSCC and its relationship with clinicopathological parameters and immune response.

Results: The findings revealed a higher PD-L1 positivity in female patients, non-smokers, and non-drinkers. Positive PD-L1 expression rate correlated with poor differentiation, lymph node metastasis, and advanced TNM stage. Although it didn’t significantly impact overall survival, higher PD-L1 expression was observed in HPV-positive patients and correlated with increased CD8+ TIL levels.

Discussion: Understanding the role of PD-L1 in OSCC elucidates immune evasion mechanisms and offers insights into potential treatments, such as checkpoint inhibitors, for personalized therapies and innovative cancer treatments. This comprehensive synthesis provides valuable insights into the complex interplay between PD-L1 expression and OSCC progression, laying the groundwork for additional studies in this area.

Killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) molecules play an essential role in regulating immune responses against hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. HLA-KIRs interactions are crucial for activating and inhibiting the natural killer (NK) cell system through a modulation that shapes these cells to kill infected cells and release cytokines. Regulation underlies the anti-viral function of the NK cell and profoundly affects viral clearance, immune evasion, and the course of disease. Activating KIRs such as KIR2DS1 and KIR3DS1 cooperate with specific HLA ligands in boosting NK cell responses against the virus, thereby facilitating viral elimination. In contrast, inhibitory KIRs like KIR2DL1 and KIR3DL1 bind to HLA-C2 and HLA-Bw4, respectively, imposing a dampening influence on NK cell activation, which allows the virus to persist and progress to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). These variations in KIRs and HLA genes will also affect an individual’s susceptibility to infections, disease severity, and their response to antiviral therapies. Observation of the role of KIRs and their interaction with HLA at the immunogenetic level provides valuable insight into host-virus dynamics and opens up many therapeutic avenues. Targeting immunotherapies toward NK cell pathways and developing personalized medicine may boost antiviral immune responses and improve treatment outcomes in chronic viral hepatitis patients. This review recognizes HLA-KIRs interactions as potent biomarkers for disease progression and determining treatment strategies.

Aim:Develop A/H1N1pdm09-based live attenuated influenza vaccines (LAIVs) presenting chimeric hemagglutinin (HA) fused to fragments of Streptococcus pneumoniae (PspA, Spr1875) or S. agalactiae (ScaAB) to elicit combined anti-influenza and anti-bacterial immunity.

Methods:Recombinant LAIVs were generated by reverse genetics. Replicative fitness was measured in embryonated chicken eggs (CE; log₁₀EID₅₀/0.1 mL, n = 5 per delution) and MDCK cells (log₁₀TCID₅₀/mL, n = 5). BALB/c mice (n = 20 per group; serology n = 6 per group; lung titers n = 5 per group) received intranasal 10⁶EID₅₀. Systemic IgG and mucosal IgA to influenza and to the recombinant pneumococcal peptide were quantified by ELISA (GMT ± SD). Early cytokine responses were profiled in THP-1 cells.

Results:All recombinant strains replicated in CE at 33°C but were temperature-sensitive at 39°C. H1-ScaAB retained relatively high replication and exhibited a cold-adapted phenotype despite a large N-terminal insert. In MDCK cells, H1-PspA showed significantly reduced replication compared with the parental LAIV. In mouse lungs, replication on day 3 post-immunization was significantly lower for H1-ScaAB and H1-PspA compared with the parental LAIV strain (p < 0.05). The parental LAIV induced robust systemic anti-influenza IgG and, uniquely for H1-ScaAB, significant mucosal anti-influenza IgA ( p < 0.05). H1-Spr generated stronger antibody responses to the inserted pneumococcal peptide ( p < 0.05). THP-1 assays revealed construct-specific cytokine patterns (unmodified H1N1: highest IFN-α; H1-Spr: elevated IL-6; H1-ScaAB: greatest MCP-1).

Conclusions:Multiple A/H1N1pdm09-based recombinant LAIVs with chimeric HA can replicate in eggs and murine respiratory tract and induce dual influenza/pneumococcal antigen responses. Expanded biophysical validation, functional antibody assays and challenge studies are needed to optimize insert design without compromising viral fitness.

Aim:To determine whether PepTivator^® melanoma-associated antigen-A3 (MAGE-A3) primes early T-cell activation and memory skewing in human peripheral blood mononuclear cells (PBMCs).

Methods:PBMCs from 10 donors were stimulated with MAGE-A3 (manufacturer-recommended dose), negative control (NC), or CD3/CD28 and CytoStim™ (PC: positive control). Activation [CD69, CD25, HLA-DR (human leukocyte antigen-DR isotype)], proliferation, cytokines [24 h; GM-CSF (granulocyte-macrophage colony-stimulating factor), IFN-γ (interferon-gamma), IL-2 (interleukin-2), TNF-α (tumor necrosis factor-alpha)], and memory phenotypes (CD45RO/CD27 at days 0/7/14) were quantified by flow cytometry and MACSPlex. Paired statistics used repeated-measures models with Šidák correction; cytokines were analyzed on log10 scale.

Results:MAGE-A3 significantly increased early activation (CD69 ↑, CD25 ↑) and modestly increased proliferation, with selective IL-2/TNF-α rise and minimal IFN-γ and modest HLA-DR. Across two weeks, 6/10 donors showed increased central memory T cell (TCM)/effector memory T cell (TEM) with a corresponding decline in naïve cells relative to NC. Variability across donors was evident.

Conclusions:MAGE-A3 primes partial activation and memory skewing of human T cells in vitro, suggesting utility as a component antigen that likely benefits from professional antigen-presenting cell (APC) presentation and/or costimulation. We discuss limitations (single dose, in vitro context, donor variability) and implications for future dose-response, HLA-stratified, and APC-supported studies.

Inflammatory bowel disease (IBD), consisting of Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gastrointestinal tract with significant clinical impact, leading to debilitating symptoms, impaired quality of life, and an increased risk of complications such as colorectal cancer. This review provides a comprehensive overview of current and emerging therapeutic strategies for IBD. We conducted a narrative review to explore therapeutic advances in IBD treatment, focusing on mechanisms of action, clinical development, and current therapeutic challenges. We analyzed existing knowledge on clinical drug development for IBD, up to July 2025. Our search encompassed databases including PubMed, ClinicalTrials.gov, and Google Scholar, using keywords such as “Inflammatory bowel disease”, “Crohn’s disease”, “Ulcerative colitis”, “therapeutics”, and relevant drug names. We delve into key progress in approved drugs in recent years, including biologic and targeted small molecule therapies, which have advanced the treatment paradigms by offering more precise targeting of inflammatory pathways. This review also covers investigational drugs in clinical development, including biologics and small molecules against novel molecular targets, cell and gene therapies, precision medicine approaches, and microbiome-based interventions. Those novel therapies could potentially address unmet medical needs by achieving deeper and more durable responses, inducing remission, preventing disease progression, and ultimately improving long-term patient outcomes. This review summarizes the latest progress in IBD treatment, outlines the advantages, pitfalls, and research prospects of various drugs and therapies, aiming to provide a foundational understanding for both clinical decision-making and future IBD research.

Aim:The benefit of topical application of probiotics on pain and itching associated with skin disorders has become an increasingly intriguing topic in recent years. These effects are mainly associated with the anti-inflammatory activity of probiotics. Given the crucial role of the endocannabinoid system (ECS) in skin pathophysiology, here, the ability of Streptococcus thermophilus was evaluated, in comparison with Lactobacillus acidophilus, to inhibit two enzymes involved in endocannabinoid (eCB) degradation: fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL).

Methods:Bacterial lysates were obtained from both probiotics. FAAH and MAGL activities were assayed using fluorometric and colorimetric methods. The effect of probiotic lysates on FAAH and MAGL activities was also evaluated on human keratinocytes stimulated with lipopolysaccharide (LPS).

Results: S. thermophilus inhibited both FAAH and MAGL, although to varying extents. In comparison,L. acidophilus had a minimal effect on FAAH and did not influence MAGL activity.

Conclusions:Although preliminary, our findings suggest that S. thermophilus may exert both potential analgesic and anti-inflammatory effects by modulating the ECS and reducing the degradation of EC, known to play a key role in immune regulation and inflammation. Results presented confirm the selective actions of probiotics and propose a novel mechanism that may contribute to the beneficial effects ofS. thermophilus in alleviating signs and symptoms associated with inflammatory skin conditions. Our evidence shows significant inhibitory activity of S. thermophilus on FAAH and MAGL activity, suggesting its ability to influence skin conditions by modulating ECS and preventing the eCB degradation.