Search Results (3,295)

Postbiotics, which are preparations of inanimate microorganisms and their components, have emerged as a promising functional ingredient in animal health and nutrition. Postbiotics are primarily composed of microbial cell fractions, metabolites, enzymes, vitamins, polysaccharides, and short-chain fatty acids. Unlike probiotics, postbiotics do not contain live microorganisms, which strengthens their greater stability and safety in feed/food formulations. Postbiotics offer several beneficial effects, including antioxidant, anti-inflammatory, immune-modulatory, and antimicrobial actions. They enhance antioxidant enzymes, neutralize reactive oxygen species, and inhibit lipid peroxidation, thereby protecting tissues from oxidative damage. Postbiotics also inhibit pro-inflammatory molecules like TNF-α and IL-6, while enhancing the anti-inflammatory cytokine IL-10, promoting the maturation and function of immune cells, and increasing secretory IgA production. They suppress a variety of pathogenic bacteria, including Escherichia coli, Salmonella, Staphylococcus, Campylobacter, etc., both in vitro and in vivo. Moreover, they increase beneficial gut bacteria and improve the digestion and integrity of the intestine. This article outlines the beneficial effects of postbiotics in animals including poultry, swine, canine, feline, horses, and ruminant animals, either as feed/food or as a supplement. The integration of postbiotics into animal feed improves growth performance, feed conversion ratios, and disease resistance in animals. Thus, the multifunctional benefits of postbiotics make them a valuable tool for healthy companion animals and sustainable livestock production, supporting both animal welfare and productivity without the drawbacks associated with antibiotic growth promoters. Full article

The JAK/STAT (Janus kinase/signal transducer and activator of transcription) signaling pathway transfers signals at the surface of cell membranes to the nucleus, triggering the expression of a myriad of factors implicated in immunity, cell proliferation, and apoptosis. Owing to this central role in cell homeostasis, its dysregulation is extensively reported in tumorigenesis, particularly in hematological cancers, justifying the development of specific inhibitors. It has more recently also been implicated in the development of solid cancers, including breast cancer. However, so far, clinical trials testing drugs targeting actors of JAK/STAT signaling yielded disappointing results, advocating in favor of a better understanding of this pathway in breast cancer. Herein, we exhaustively reviewed the current tools available to target this pathway in clinical trials and we offer several perspectives to gain further insight into the role of JAK2 in breast cancer and more particularly in the resistance to endocrine therapy in hormone-dependent breast cancers. Full article

Streptococcus pneumoniae contributes significantly to morbidity, mortality, and healthcare costs worldwide due to severe Invasive Pneumococcal Disease (IPD), particularly among young children and vulnerable populations. This review critically examines the current state of pneumococcal disease epidemiology, the evolution of vaccine strategies, and persistent challenges to achieve global control of the disease. The implementation of Pneumococcal Conjugate Vaccines (PCVs) has yielded substantial public health gains, establishing herd protection and sharply reducing vaccine-type IPD incidence. However, this success has been fundamentally challenged by serotype replacement, where non-vaccine serotypes have subsequently emerged to cause a significant proportion of the residual disease burden. This epidemiological shift has necessitated the development and deployment of higher-valency PCVs (PCV15, PCV20, and PCV21) to expand serotype coverage. Furthermore, optimal protection requires personalized strategies for high-risk cohorts where vaccine effectiveness can be compromised. In this context, the review details how pneumococcal vaccination—and particularly PPSV23—serves as an indispensable diagnostic tool to evaluate a broad spectrum of Inborn Errors of Immunity (IEI) and in particular humoral defects. Diagnostic challenges are strained by non-standardized assays and the limited panel of unique serotypes available for testing in the PCV era. The scientific priority is now the development of universal protein-based vaccines, to provide protection against all serotypes and non-encapsulated strains by targeting conserved virulence factors. This integrated approach, combining expanded PCV coverage with novel vaccine technology, is essential to mitigate the ongoing public health burden of pneumococcal disease. Full article

The diagnosis and treatment of rheumatoid arthritis (RA) have been constantly evolving for decades, pointing towards early diagnostic and therapeutic interventions. Synovial biopsy has emerged as a pivotal tool in precision medicine, transitioning from a research procedure to a clinically feasible approach. Modern ultrasound-guided techniques allow safe, reproducible access to inflamed joints, enabling direct analysis of the synovial tissue, which reveals biological heterogeneity undetectable in peripheral blood. Histological scoring, including the Krenn synovitis score, discriminates inflammatory from non-inflammatory pathology, supporting targeted escalation of immunosuppressive therapy. Molecular and histological profiling has defined distinct synovial pathotypes—lympho-myeloid, diffuse-myeloid, and fibroid/pauci-immune—with reproducible associations to therapeutic responsiveness. Moreover, biopsy-driven trials, such as R4RA and STRAP, demonstrate that pathotype-guided strategies can predict outcomes: diffuse-myeloid synovitis responds to IL-6 receptor blockade, lympho-myeloid synovitis to B cell depletion, and fibroid synovitis exhibits multidrug resistance. In difficult-to-treat RA, synovial biopsy differentiates inflammatory from non-inflammatory drivers of persistent symptoms, providing a rational basis for therapy selection. Ongoing biomarker-driven initiatives, including PRECISion and 3TR Precis-The-RA, aim to embed biopsy findings into clinical decision-making. In this review, it is underscored that the integration of histology, molecular profiling, and clinical context positions synovial biopsy as a patient-centered precision approach, guiding individualized therapy and bridging RA stratification with clinical practice. Full article

Homozygous deletion of the 9p21.3 genomic locus spanning the CDKN2A/B and MTAP genes is an event affecting 15% of cancers. While CDKN2A is a well-established tumor suppressor gene, the role of MTAP in tumorigenesis varies across cancer types. MTAP codes for methylthioadenosine phosphorylase, a key enzyme in the methionine salvage pathway, and its loss has been associated with several downstream synthetic vulnerabilities. Despite multiple efforts to exploit MTAP loss for targeted therapies, none of these efforts have yielded substantial results in clinical trials. In this review, we consolidate the existing literature along with our systematic analysis to provide an updated perspective on the incidence of MTAP loss in different cancers and elucidate its impact on metabolism, immune microenvironment, and tumor progression. In addition, we summarize the therapeutic strategies that have been investigated preclinically on MTAP-null tumors before and after the advent of functional genomic screening tools. We further assess the current landscape of clinical trials investigating MTAP-targeted inhibitors, evaluating their limitations and potential avenues for improvement. The insights gained from this review will inform future research directions beyond the promising PRMT5/MAT2A axis for rational combination therapies that would work synergistically to eradicate this devastating disease. Full article

Single-cell sequencing (scRNA-seq) has emerged as a pivotal technology for deciphering the complex cellular heterogeneity and tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC), positioning it as a critical tool for informing novel therapeutic strategies. This review explores how scRNA-seq reveals diverse cellular subpopulations and their functional roles within the PDAC TME, including malignant epithelial cells with transitional phenotypes, heterogeneous cancer-associated fibroblasts (CAFs), functionally distinct immune cells such as tumor-associated neutrophils (TANs) and macrophages (TAMs), and actively participating neural components like Schwann cells. These cellular constituents form specialized functional units that drive tumor progression, immune evasion, neural invasion, and therapy resistance through metabolic reprogramming, immunosuppressive signaling, and cellular plasticity. The review further examines technological advances in single-cell sequencing from 2023 to 2025, focusing on sample preprocessing innovations, multi-omics integration (combining transcriptomics with epigenomics and proteomics), spatial resolution enhancements, and customized computational tools that address PDAC-specific challenges. Clinically, single-cell sequencing enables precise cellular subtyping, identification of novel biomarkers, and development of personalized therapeutic approaches, including combination therapies targeting specific cellular subpopulations and their interactions. Despite these advances, significant challenges remain in standardizing clinical applications such as liquid biopsy for early detection and tumor microenvironment assessment for diagnostic staging, validating biomarkers like CLIC4, GAS2L1, Cytokeratins, Vimentin and N-cadherin in circulating tumor cells, and comprehensively integrating multi-omics data. Future research focusing on both technology refinement and biological validation will be essential for translating single-cell insights into improved diagnostic and therapeutic outcomes for pancreatic cancer. Full article

Diabetes mellitus (DM) is a chronic non-communicable disease associated with macroangiopathy and microangiopathy, with disabling or even life-threatening complications. In the present study, we aimed to analyze the association between insulin resistance (IR) and inflammation biomarkers and peripheral arterial disease (PAD) and diabetic peripheral neuropathy (DPN), respectively. The study had a cross-sectional design and evaluated a panel of IR related indices and inflammatory biomarkers commonly used in clinical and epidemiological research, including the triglyceride-glucose (TyG) index and its obesity related derivates, cholesterol, HDL, glucose (CHG) index, lipid-derived ratios, and composite inflammatory indices, together with interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα) and C-reactive protein (CRP) in 110 subjects, according to the presence or absence of PAD and DPN, respectively. In the PAD (+) group, TyG-waist-to-height-ratio (TyG−WHtR) and CHG recorded significantly increased values (p = 0.042, respectively p < 0.001), compared to PAD (−). CHG recorded significantly increased values in DPN (+) subjects (p = 0.007). In addition, in the PAD (+) subjects, IL-6 and systemic immune inflammation index (SII) recorded significantly increased values (p = 0.026, respectively, p = 0.015) and TNFα, monocyte to lymphocyte ratio (MLR) and C-reactive protein to albumin ratio (CAR) recorded significantly increased values in DPN (+) subjects (p = 0.028, respectively, p = 0.008, and p = 0.038). We developed a score with a good discriminatory performance for PAD and DPN, including DM duration, TyG−WHtR, SII, MLR and CAR (AUROC 0.822 in PAD, respectively 0.848 in DPN, p < 0.001). A composite score combining IR and inflammatory biomarkers showed strong discriminatory performance for lower limb complications in type 2 diabetes, suggesting a valuable tool for early detection and prevention. Full article

Personalized cancer vaccines are a key strategy for training the immune system to recognize and respond to tumor-specific antigens. Our earlier software release, AutoEpiCollect 1.0, was designed to accelerate the vaccine design process, but the identification of tumor-specific genetic variants remains a manual process and is highly burdensome. In this study, we introduce AutoEpiCollect 2.0, an improved version with integrated genetic analysis capabilities that automate the identification and prioritization of tumorigenic variants from individual tumor samples. AutoEpiCollect 2.0 connects with RNA sequencing and cross-references the resulting RNAseq data for efficient determination of cancer-specific and prognostic gene variants. Using AutoEpiCollect 2.0, we conducted two case studies to design personalized peptide vaccines for two distinct cancer types: cervical squamous cell carcinoma and breast carcinoma. Case 1 analyzed five cervical tumor samples from different stages, ranging from CIN1 to cervical cancer stage IIB. CIN3 was selected for detailed analysis due to its pre-invasive status and clinical relevance, as it is the earliest stage where patients typically present symptoms. Case 2 examined five breast tumor samples, including HER2-negative, ER-positive, PR-positive, and triple-negative subtypes. In three of these breast samples, the same epitope was identified and was synthesized by identical gene variants. This finding suggests the presence of shared antigenic targets across subtypes. We identified the top MHC class I and class II epitopes for both cancer types. In cervical carcinoma, the most immunogenic epitopes were found in proteins expressed by HSPG2 and MUC5AC. In breast carcinoma, epitopes with the highest potential were derived from proteins expressed by BRCA2 and AHNAK2. These epitopes were further validated through pMHC-TCR modeling analysis. Despite differences in cancer type and tumor subtype, both case studies successfully identified high-potential epitopes suitable for personalized vaccine design. The integration of AutoEpiCollect 2.0 streamlined the variant analysis workflow and reduced the time required to identify key tumor antigens. This study demonstrates the value of automated data integration in genomic analysis for cancer vaccine development. Furthermore, by applying RNAseq in a standardized workflow, the approach enables both patient-specific and population-level vaccine design, based on statistically frequent gene variants observed across tumor datasets. AutoEpiCollect 2.0 is freely available as a website based tool for user to design vaccine. Full article

Prolonged Grief Disorder (PGD) is marked by enduring and disruptive grief symptoms following the death of a significant other. Although PGD has been recognized as a distinct psychopathological entity within the trauma dimension in the DSM-5-TR, its neurobiological underpinnings remain not fully defined. A systematic literature review was conducted up to September 2025 following PRISMA 2020 guidelines. PubMed, Scopus, Embase and Web of Science were searched using a comprehensive strategy combining MeSH terms and free-text keywords. Eligible studies included human participants, validated grief assessment tools and biomarker assessments. Out of 2140 initial records, 12 studies published between 1989 and 2022 met inclusion criteria. Investigated neuro–psycho–endocrine systems included the hypothalamic–pituitary–adrenal (HPA) axis, catecholamines, oxytocin, endocannabinoids and immune/inflammatory markers. Key findings in pathological grief reactions included altered cortisol rhythms, elevated oxytocin levels, increased pro-inflammatory cytokines and immune system dysregulation. Results are limited by heterogeneity in study designs, small sample sizes, inconsistent use of diagnostic criteria prior to DSM-5-TR and lack of control for psychiatric comorbidities. This review highlights emerging biological correlates of PGD, particularly those involving the stress response, reward-attachment networks and immune/inflammatory pathways. Further standardized, longitudinal research is essential to gain a more defined picture of PGD, to clarify causal mechanisms and to guide targeted therapeutic interventions. Full article

Varicella Zoster Virus (VZV), responsible for chickenpox and herpes zoster, has emerged as a significant contributor to cerebrovascular disease. Mounting evidence indicates that VZV reactivation may precipitate ischemic and hemorrhagic stroke through mechanisms of viral vasculopathy, immune evasion, and vascular inflammation. While antiviral therapy remains the cornerstone of treatment, several adjunctive regimens exhibit encouraging results in controlling endothelial inflammatory response. This targeted review synthesized findings from 31 studies, including clinical cohorts, in vitro models, and pathological analyses, to evaluate the relationship between VZV and stroke, with emphasis on treatment management beyond antivirals. Evidence demonstrates that VZV antigens are frequently detected within cerebral arteries, where they induce transmural inflammation, endothelial dysfunction, and thrombosis, thereby increasing stroke risk, particularly in the weeks following herpes zoster. Adjunctive therapies such as corticosteroids, statins, and resveratrol show promise in mitigating vascular inflammation, though clinical validation is limited. Preventive measures, especially zoster vaccination, significantly reduce herpes zoster incidence and may lower subsequent stroke risk, yet global uptake remains insufficient. Collectively, the data underscore the need for improved diagnostic tools, combination treatment strategies, and expanded vaccination programs to address the substantial public health burden of VZV-associated stroke. Full article

Brain tumors encompass a heterogeneous group of neoplasms, including primary and secondary metastatic lesions, with glioblastoma multiforme (GBM) representing the most aggressive primary malignancy. Despite advancements in surgical resection, radiotherapy, and chemotherapy, the prognosis for GBM remains poor due to its infiltrative nature, tumor heterogeneity and resistance mechanisms. Emerging diagnostic tools, such as liquid biopsies, and therapeutic strategies leveraging extracellular vesicles (EVs) are reshaping the field of neuro-oncology. EVs, lipid bilayer-enclosed particles secreted by cells, carry oncogenic cargo such as microRNAs and molecular chaperones, influencing tumor progression, immune evasion, and therapy resistance. Recent research highlights their potential as biomarkers for early diagnosis and vehicles for targeted drug delivery across the blood–brain barrier (BBB). EV-based nanotherapeutics show promise in improving treatment precision, reducing systemic toxicity, and advancing precision medicine in brain tumor management. However, challenges related to EV heterogeneity, cargo-loading efficiency, and large-scale production must be addressed to fully realize their therapeutic potential. This review explores the multifaceted roles of EVs in brain tumors, emphasizing their diagnostic, prognostic, and therapeutic applications. Full article

Anal cancer is high in men who have sex with men living with human immunodeficiency virus (MSM-LWHIV). This cancer is strongly associated with high-risk human papillomavirus (HR-HPV) infection. Anal cancer screening using cytology and high-resolution anoscopy (HRA) for diagnosis of anal intraepithelial neoplasia requires specialized expertise. Biomarkers for the diagnosis of abnormal anal cells are of interest. Thyrotropin-releasing hormone (TRH) methylation at cg01009664 was detected using a pyrosequencing assay to compare methylation patterns among different anal lesions. Our results demonstrated that TRH methylation was significantly hypermethylated in anal intraepithelial neoplasia (AIN3) (>20%) and AIN1-2 (>10%) but less methylated in normal (<10%) (p < 0.001). TRH gene methylation showed higher sensitivity than the cytology for predicting AIN1+ (75.96% vs. 25.37%, respectively) and AIN2+ (78.95%% vs. 19.23%, respectively). There was no significant correlation between TRH methylation and the percentage of CD4 in patients with HIV (p > 0.05). TRH methylation in anal swabs reflects the presence of anal intraepithelial neoplasia. Methylation analysis showed higher sensitivity than cytology for high-grade lesions and was independent of immune status. These findings support its use as a screening tool to preselect patients for HRA, potentially reducing unnecessary procedures while maintaining diagnostic accuracy. Full article

Cell migration plays a central role in physiological processes such as wound healing, tissue regeneration, and immune responses, as well as in pathological conditions like chronic inflammation and tumor metastasis. Among the in vitro approaches to study this phenomenon, the conventional wound healing assay (scratch assay) has been widely used due to its simplicity and low cost. However, its limitations, including poor reproducibility, damage to the extracellular matrix (ECM), and lack of dynamic physiological conditions, have prompted the development of microfluidic alternatives. Scratch-on-a-chip platforms integrate engineering and microtechnology to provide standardized, non-destructive methods for wound generation, preserve ECM integrity, and allow precise control of the cellular microenvironment. These systems also enable miniaturization, reducing reagent and cell consumption, while facilitating the application of biochemical or physical stimuli and real-time monitoring. This review synthesizes advances reported in the literature, addressing the different wound induction strategies (enzymatic depletion, physical depletion, and physical exclusion), the role of ECM composition, and the impact of mechanical forces such as shear stress. Overall, scratch-on-a-chip assays emerge as promising tools that enhance reproducibility, better mimic in vivo conditions, and broaden applications for therapeutic testing and mechanistic studies in cell migration. Full article

Omics sciences are revolutionizing the field of biomedical and dental research by allowing for an integrated understanding of the molecular basis of health and disease. This narrative review analyzes the role of these novel technologies supporting the diagnosis, prognosis, and treatment of the most noteworthy oral diseases, such as dental caries, periodontitis, and oral squamous cell carcinoma. The review discusses the characterization of disease-associated genetic variations and polygenic risk scores as evidenced by genomic studies. It further examines how transcriptomic analyses can identify diagnostic gene expression signatures of immune dysregulation and tumor heterogeneity. The contribution of proteomics and metabolomics studies to the discovery of diagnostic and prognostic protein and metabolites biomarkers is also analyzed. Finally, the integration of different omics datasets within multi-omics frameworks is discussed as a key approach for a holistic interpretation of oral pathogenesis and data-driven precision dentistry. The review also addresses current limitations in the clinical translation of omics sciences into tools for early diagnosis, personalized prevention, and targeted therapy. Full article

Background: Antibodies have the unique ability to recognize antigens and to be recognized as antigens by other antibodies, creating a balanced network that regulates the humoral part of the immune system. An antibody that uniquely identifies another antibody of a given specificity as its antigen is referred to as an anti-idiotypic antibody. Methods: A descriptive literature review was conducted using the PubMed database, including publications up to 2025. Results: This review examines the formation mechanisms of anti-idiotypic antibodies, their functional attributes, and their importance in diverse pathologies. A key focus is their capacity to neutralize pathogenic autoantibodies, offering a novel strategy for treating autoimmune diseases. Conversely, the generation of anti-Id Abs against therapeutic monoclonal antibodies (anti-drug antibodies) represents a significant challenge for biologic therapy, a complication addressed in a dedicated section on detection methods. Furthermore, consideration is given to the application of anti-Id Abs as innovative tools for vaccine design, particularly in oncology. By mimicking tumor-associated antigens, anti-Id Abs can induce a potent, targeted immune response against cancer with minimal side effects, presenting an alternative to conventional chemotherapy and radiation. Conclusions: Anti-Id Abs hold significant therapeutic promise. Their ability to selectively suppress pathogenic autoantibodies allows for precise immune intervention without broad immunosuppression. Additionally, their utility extends to vaccine development for various diseases. Further research into anti-Id Abs will deepen our understanding of immune regulation and open new avenues for targeted therapies. Full article