Search Results (11,012)

With the rapid progression of global industrialization and urbanization, heavy metal contamination has emerged as a major global threat, especially cadmium pollution. Consequently, optimizing remediation measures has become a pivotal means to solve cadmium contamination. Compared to traditional physical and chemical remediation methods, microbial remediation has great potential in addressing cadmium pollution. In this study, a novel bacterial strain, Chryseobacterium sp. HGX-24, exhibiting high cadmium resistance was successfully isolated and screened from cadmium-contaminated environments. A preliminary discussion of the response mechanisms of this strain under cadmium stress is provided. Additionally, preliminarily explored the synergistic remediation of microbial-plant in cadmium-contaminated soil. Under conditions of high cadmium concentration, cadmium ions were effectively adsorbed by strain HGX-24 through extracellular polymers and functional groups on the cell wall surface, including −COOH, −CONH−, −NH, −OH, and >C=O. Extracellular proteins and polysaccharides were secreted by strain HGX-24 to regulate the adverse effects of heavy-metal cadmium ions on bacterial growth. Furthermore, the expression of genes such as antioxidant defense and ROS scavenging (katG, fabG, ybjT), Fe-S cluster assembly (sufB, sufD), sulfur metabolism (cysAU), amino acid metabolism (hisA, cysD, aspC), phenylacetic acid catabolism (paaC), and ribosomal proteins (rplC, rpsC, rpsL, rplA, rplY, rpmC) was regulated, affecting the synthesis and metabolism of membrane transporters (ABC transporters and efflux RND transporters), antioxidant enzymes (SOD, COT, POD), Fe-S clusters, thioredoxin family proteins, and ribosomal proteins, thereby enhancing resistance to cadmium toxicity. Moreover, strain HGX-24 was found to regulate the activities of redox enzymes in Zea mays L., thereby alleviating oxidative stress and reducing the negative feedback effects of reactive oxygen species in Z. mays. Full article

We propose a dimensionally consistent fractional spatio-temporal PDE framework for modelling immune-mediated demyelination in multiple sclerosis (MS). The system couples effector and regulatory T cells, M1/M2 macrophage polarisation, pro- and anti-inflammatory cytokines, oligodendrocyte dynamics, and time-dependent therapeutic controls within a unified distributed-parameter structure. In contrast to ad hoc replacements of integerorder derivatives by Caputo fractional derivatives, the fractional extension proposed here is derived from an underlying continuous-time random walk (CTRW) process with Mittag–Leffler-distributed residence times. This stochastic derivation yields a governing system in which a single commensurate fractional order α ∈ (0, 1], together with a characteristic memory timescale τ0, ensures dimensional consistency and mass balance across all coupled components. The model is formulated as a system of nonlinear reaction–diffusion equations with cross-regulatory and multiplicative interaction terms governing immune amplification, cytokine feedback, and the demyelination–remyelination balance. Analytical interpretation shows how non-Markovian residence times induce Mittag–Leffler-type relaxation and thereby modify effective growth, decay, and stability properties. Numerical simulations compare classical and fractional dynamics, revealing that memory-driven kinetics prolong effector T-cell and M1-macrophage activity, attenuate reparative M2 and oligodendrocyte responses, and extend the effective action of bang–bang therapy inputs representing IFN-β and glatiramer acetate beyond their dosing windows. The results indicate that integer-order models may underestimate chronic inflammatory persistence and demyelination severity, while providing a mathematically and physically well-posed platform for memory-aware immune modelling and therapy evaluation in MS. Full article

Increasing evidence suggests pancreatic cancer develops within a host–microbe ecosystem in which microbial communities across anatomical niches interact with tumour biology, immune regulation, metabolism, and therapeutic response. This review examines pancreatic cancer through the lens of humans as holobionts, integrating evidence from the oral, gut, biliary, and intratumoural microbiomes. Epidemiological and sequencing studies demonstrate consistent microbial alterations across these niches in pancreatic cancer, including oral dysbiosis associated with periodontal pathogens, gut microbial shifts toward pro-inflammatory taxa, disease-specific biliary microbial signatures, and the presence of distinct intratumoural microbial communities. Mechanistic studies indicate that intestinal barrier disruption, microbial translocation, immune and metabolite signalling can influence tumour immune architecture, macrophage polarisation, T-cell infiltration, oncogenic signalling pathways, and chemotherapeutic metabolism, particularly inactivation by tumour-associated bacteria. Microbiome-driven shifts in immunometabolism can reprogramme immune-cell metabolic pathways, impairing effective T-cell activation, promoting tumour-supportive macrophage phenotypes. Emerging therapeutic strategies aim to modulate the microbiome–tumour axis, including dietary interventions, probiotics and immunonutrition, faecal microbiota transplantation, engineered microbial therapies, and microbiome-informed antibiotic strategies. While pre-clinical findings are compelling and early-phase clinical studies suggest feasibility, most evidence remains associative and heterogeneous across cohorts and methodologies. Understanding pancreatic cancer as a multi-site ecological system may help explain inter-patient variability in disease progression and treatment response. This could usher in a new era for therapeutic manipulation where future progress will depend on longitudinal, multi-omic, and interventional studies to determine whether microbiome-targeted strategies can produce clinically meaningful improvements in pancreatic cancer outcomes. Full article

Background: Kinkeliba (Combretum micranthum G. Don), commonly used in West African traditional pharmacopeia for its anti-inflammatory and gastrointestinal properties, remains poorly studied regarding its potential role in the prevention or treatment of ulcerative colitis. Objective: This study evaluated the therapeutic potential of the ethanolic extract of Combretum micranthum (EECM) in a murine model of chronic DSS-induced colitis. Methods: Male C57BL/6 mice were subjected to three cycles of 1.5% DSS administration over nine weeks to induce chronic colitis. EECM was administered orally at 50, 100, or 200 mg/kg during the final week. Disease severity was evaluated using the Disease Activity Index (DAI), colon length, biochemical and hematological markers, along with histopathological and immunohistochemical assessment of colonic tissue. Results: EECM treatment significantly improved clinical parameters and prevented colon shortening in chronic DSS-induced colitis. These improvements were associated with the restoration of serum biochemical and hematological profiles, along with reduced histopathological damage and preservation of colonic tissue architecture. Immunohistochemical analysis further demonstrated decreased CD3-positive T-lymphocyte infiltration in colonic tissue, suggesting modulation of local immune cell responses. Conclusions: These findings highlight the therapeutic potential EECM in ulcerative colitis and support further investigations to elucidate its mechanisms of action and evaluate its efficacy in future translational studies. Full article

Sjögren’s disease (SjD) is a chronic autoimmune disorder characterized by progressive dysfunction of the exocrine glands, driven primarily by aberrant T- and B-cell activation. Current therapeutic strategies remain largely symptomatic and are frequently limited by off-target effects and long-term toxicity, underscoring an urgent need for safer, mechanism-based adjunctive approaches. In recent years, nutritional interventions and medicinal herbs have emerged as promising complementary strategies, owing to their capacity to modulate immune–metabolic pathways and restore immune homeostasis. Nutrients such as n-3 polyunsaturated fatty acids (PUFAs) and short-chain fatty acids (SCFAs) exert well-documented anti-inflammatory effects and influence immune cell differentiation via immunometabolic reprogramming. Concurrently, bioactive constituents derived from medicinal herbs offer multi-target regulation of inflammatory signaling and lymphocyte function. This review synthesizes current advances in the immunomodulatory roles of dietary components and edible herbs in the context of SjD, focusing on their mechanistic convergence on T-cell subsets, B-cell responses, and the gut–immune axis. By integrating traditional knowledge with contemporary immunological insights, this article aims to provide a conceptual framework for the rational integration of nutritional and herbal strategies into the clinical management of SjD. Full article

Background/Objectives: Immune aging has been associated with survival outcomes in patients with lung adenocarcinoma (LUAD), but its relevance within the tumor microenvironment (TME) remains unclear. Methods: Clinical, RNA-sequencing, and somatic mutation data from the TCGA LUAD cohort were analyzed. Immune aging score within the TME was quantified using a predefined blood-driven 121-gene immune aging signature (IAS-121), and patients were categorized into the lowest versus the highest IAS-121 tertiles. Immune cell composition in the TME was inferred using xCell. Overall survival (OS) was evaluated using Kaplan–Meier analysis, Cox proportional hazards models adjusted for age, sex, tumor stage, smoking status, and EGFR mutation status, and restricted cubic spline analysis to examine the dose–response relationship between IAS-121 and mortality risk. Sensitivity analyses comparing the highest versus lowest quartiles or higher than median versus lower than median of IAS-121 were performed. Two independent LUAD cohorts (GSE68465 and GSE50081) were employed for validation. Results: A total of 518 patients with LUAD from the TCGA cohort were analyzed. Restricted cubic spline analysis showed a linear association between IAS-121 and OS. Patients in the highest IAS-121 tertile showed significantly better survival than those in the lowest tertile in both the TCGA cohort (p < 0.001) and the external validation cohorts (p = 0.003). In multivariable-adjusted Cox models, the lowest IAS-121 tertile was associated with worse survival in TCGA (adjusted HR 1.87, 95% CI 1.20–2.92) and in the pooled external cohorts (adjusted HR 1.57, 95% CI 1.02–2.43). Subgroup analyses showed generally consistent associations across clinical strata. Tumors with higher IAS-121 exhibited lower CD8⁺ and CD4⁺ naïve T-cell enrichment but higher neutrophil infiltration. Conclusions: Immune aging within TME is associated with poorer survival in LUAD. Given this study is hypothesis-generating, further investigations integrating tissue- and blood-based measures of immune aging are warranted to clarify its clinical and biological implications. Full article

The utilization of immunomodulatory nanomaterials, i.e., leveraging their unique properties to enhance immune responses, represents a transformative approach for the treatment of various diseases. Recent advancements in nanotechnology have enabled the design of nanomaterials capable of delivering immunomodulatory agents in a targeted manner, such as cytokines, antibodies, and nucleic acids, to specific cells or tissues involved in immune regulation. These nanomaterials, including nanoparticles, liposomes, nanogels, nanoemulsions, dendrimers, MXenes and extracellular vesicles, have been increasingly tailored to modulate immune responses with precision and efficacy. This targeted approach not only enhances therapeutic outcomes but also reduces off-target effects, minimizing systemic toxicity. In this review, an overview of immunomodulatory nanomaterials and their biomedical applications are highlighted. Herein, we have discussed different types of nanomaterials and their design strategies, interactions with different immune system components (macrophages, dendritic cells (DCs), neutrophils, T lymphocytes (CD4⁺ helper T-cells, CD8⁺ cytotoxic T-cells, regulatory T-cells/Tregs, and memory T-cells), and B lymphocytes), and immunomodulation mechanisms. Furthermore, nanomaterial-based immunomodulation strategies to enhance cancer immunotherapy, wound healing, and bone regeneration and the treatment of infectious diseases, autoimmune diseases, and allergy and are discussed in detail. In addition to therapeutic applications, selected nanomaterial platforms demonstrate significant potential in pharmaceutical formulations by improving drug stability, controlled release, and bioavailability, as well as in cosmetology through skin-targeted delivery, anti-inflammatory activity, immune protection, and enhanced tissue regeneration. Finally, clinical trial updates, challenges and future prospects are outlined. Key findings indicate that lipid-based, polymeric, inorganic nanoparticles and dendrimers provide complementary advantages for immunomodulation, including efficient delivery, controlled release, multifunctionality, and precise immune targeting. Despite safety, regulatory, and scalability challenges, these systems show strong potential for advancing precision and personalized medicine. Taken together, these innovations hold great promise for personalized medicine approaches, wherein nanomaterials can be tailored to individual patient profiles for more effective and precise disease treatment and prevention strategies. This review focuses primarily on the mechanistic interactions between immunomodulatory nanomaterials and immune cells, including macrophages, dendritic cells, neutrophils, T lymphocytes, and B lymphocytes, rather than providing an exhaustive treatment of physicochemical optimization parameters such as particle size or surface modification chemistry, which fall outside the defined scope of this work. Full article

Background: Ulcerative colitis (UC) is a multifactorial disease characterized by aberrant mucosal immune activation in response to intestinal dysbiosis. Contemporary management strategies aim to target inflammation and microbiome alterations while reducing relapse risk. A multidimensional assessment integrating clinical, inflammatory, immune, and microbial endpoints may better capture therapeutic effects beyond symptom control. Aims: To evaluate whether supplementation with Lactobacillus rhamnosus GG co-formulated with vitamin D3 (Dicoflor IBD Immuno) as an adjunct to optimized mesalamine (5-ASA) is associated with coordinated changes across clinical and biological domains in mild-to-moderate UC, using a multidimensional assessment framework. Methods: This single-center, randomized, double-blind, placebo-controlled pilot trial was conducted at Fondazione Ca’ Granda IRCCS Policlinico di Milano between May 2022 and May 2024. Thirty-six patients with mild-to-moderate UC receiving optimized 5-ASA were randomized to LGG+VitD3 (ALD3) or placebo (AP) for 4 weeks. Clinical activity, health-related quality of life (HRQoL), fecal calprotectin, peripheral immune cell subsets, and gut microbiota composition were assessed at baseline and week 4. Results: Both 5-ASA-LGG+VitD3 (ALD3)- and 5-ASA-placebo (AP)-treated patients showed significant improvement in clinical activity and HRQoL, without between-group differences. A higher proportion of clinical responders was observed in the ALD3 group, although this was not statistically significant. LGG+VitD3-supplemented patients showed reduced fecal calprotectin levels and increased frequencies of IL-22-producing CD4⁺ T cells. Microbiome analysis revealed enrichment of short-chain fatty acid-producing taxa, including Coprococcus and Fusicatenibacter, in ALD3-treated patients. Conclusions: In patients with mild UC receiving optimized 5-ASA, LGG+VitD3 supplementation does not improve short-term clinical outcomes beyond placebo but is associated with favorable modulation of inflammatory, immune, and microbial parameters, supporting the relevance of multidimensional biological endpoints in adjunctive UC management. Full article

Type 2 diabetes mellitus (T2DM) affects approximately 10–25% of patients undergoing orthopedic procedures and is associated with impaired tissue healing, increased complication rates, and reduced responsiveness to orthobiologic therapies, including platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), and mesenchymal stem cell (MSC) preparations. The underlying mechanisms include advanced glycation end-product accumulation, NF-κB-driven chronic inflammation, Nrf2 pathway impairment, mitochondrial dysfunction, and epigenetic diabetic memory, collectively compromising both orthobiologic product quality and the tissue microenvironment. Emerging, predominantly mechanistic evidence suggests that targeted nutritional interventions, including bioactive compounds targeting mitochondrial biogenesis pathways, anti-inflammatory dietary patterns, and specific micronutrients, may modulate these pathological processes and potentially improve orthobiologic outcomes. This narrative review synthesizes evidence from diabetic pathophysiology, orthobiologic outcomes research, and nutritional science to propose a conceptual clinical framework for regenerative medicine optimization in T2DM patients. Critical knowledge gaps are identified, and a research agenda is proposed. The proposed framework, based primarily on mechanistic and preclinical evidence, should be interpreted as a foundation for research prioritization and hypothesis generation rather than as a clinical protocol. Rigorous randomized trials directly evaluating nutritional optimization in orthobiologic therapy for diabetic patients are required before evidence-based recommendations can be established. Full article

The most common complication of active brucellosis in humans is osteoarticular injury. In the bone marrow microenvironment, mesenchymal stem cells (MSCs) can differentiate into either adipocytes or osteoblasts, and this balance is tightly regulated because an increase in adipogenesis may negatively affect bone formation and favor bone loss. The differentiation of MSCs into adipocytes or osteoblasts is tightly regulated by mechanisms that promote cell fate toward one lineage while repressing the other. Our study demonstrated that Brucella abortus infects MSCs but does not affect the deposition of organic and mineral matrix during osteoblast differentiation. However, the infection upregulates Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) expression in osteoblasts, which may contribute to osteoclast activation and bone resorption. Conversely, B. abortus infection significantly influences adipocyte differentiation by modulating lipolysis, lipogenesis, and interactions between lipid droplets and mitochondria. This leads to increased cellular cholesterol levels and reduced intracellular triglycerides, accompanied by glycerol release. These changes result in more differentiated adipocytes and larger lipid droplets. Consequently, we observed increased IL-6 secretion and a higher leptin/adiponectin ratio. Importantly, these effects were independent of a functional type IV secretion system (T4SS), as purified Brucella DNA fully reproduced the adipogenic phenotype. Moreover, inhibition of TLR9—the primary sensor of bacterial DNA—significantly reduced the DNA-induced adipogenic response, demonstrating that adipocyte modulation is at least in part mediated through TLR9 signaling. In summary, B. abortus promotes MSC differentiation toward an inflammatory adipocyte phenotype. It involves a TLR-9-mediated DNA detection. It may contribute to osteoarticular injury and infection-associated bone resorption. Full article

Background/Objectives: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and chronic neuroinflammation. Increasing evidence suggests that the imbalance between pro-inflammatory Th17 cells and anti-inflammatory regulatory T (Treg) cells plays a critical role in AD pathogenesis. However, a comprehensive synthesis of how natural compounds modulate Th17/Treg balance in AD remains lacking. This review aims to summarize current preclinical evidence on Th17/Treg dysregulation and evaluate the immunomodulatory potential of natural compounds in AD. Methods: This review focuses on preclinical evidence derived from experimental AD models and related inflammatory models to evaluate how natural compounds modulate Th17/Treg balance, neuroinflammation, and cognitive function, with an emphasis on underlying molecular and immunometabolic mechanisms. Results: Th17/Treg imbalance contributes significantly to AD-associated neuroinflammation and disease progression. Representative natural compounds, including paeoniflorin, quercetin, and ganoderic acid A, have demonstrated the ability to rebalance Th17/Treg responses, suppress neuroinflammation, and improve neuronal survival in experimental models. These compounds are highlighted due to their relatively stronger evidence in AD-related models and more clearly defined immunomodulatory mechanisms. These effects are partially mediated through modulation of key signaling pathways and immunometabolic reprogramming. Conclusions: Targeting Th17/Treg balance with natural compounds represents a promising multi-target immunomodulatory strategy for AD. However, most current evidence is derived from preclinical or non-AD models, and clinical validation remains limited. Future studies should prioritize AD-specific models and translational research to evaluate therapeutic potential in humans. Full article

Background: Hematological patients have a high risk of developing severe COVID-19 (37%). Most mRNA vaccine trials in hematological patients showed a low immunogenicity after two doses, while long-term data are scarce. Methods: In this monocentric retrospective observational study, we evaluated humoral and T cell-mediated immune responses in 230 hematological patients after three doses of the Pfizer-BioNTech mRNA COVID-19 vaccine. Patients were stratified by age, disease type/state, prior COVID-19 infection, and treatment status and regimens (anti-CD20 monoclonal antibodies, BTK and BCL-2 inhibitors, and treatment line). Antibody titer to SARS-CoV-2 was assessed by electrochemiluminescence immunoassay and T cell response by QuantiFERON interferon-γ release assay (IGRA). Data were analyzed using univariate (Fisher’s exact test) and Firth’s bias-reduced penalized-likelihood logistic regression. Results: A robust humoral response was observed with 91.55% of patients developing anti-spike antibodies (GMT 988.83 U/mL). Anti-CD20-bendamustine treatment was associated with a significantly lower antibody positivity compared to untreated subjects. Prior COVID-19 infection significantly boosted both antibody positivity (95.9% vs. 85.2%) and GMT (847.02 U/mL vs. 258.79 U/mL). Conversely, T cell response was suboptimal (36.1% positive), particularly in anti-CD20-bendamustine-treated and multi-treated patients (27.1%), but highest in those treated with BTK inhibitors (50%). Multivariable logistic regression analysis linked multiple treatments to lower T cell response. Following vaccination, 29.1% of patients contracted SARS-CoV-2, but only 0.89% developed severe COVID-19. Conclusions: Three doses of mRNA vaccine elicit a strong humoral but a low T cell response, as detected by IGRA, in hematological patients. These findings underscore the importance of completing vaccination before initiating immunosuppressive therapies. Full article

Hapten-based immunotherapies represent a promising strategy to enhance the immunogenicity of tumor antigens and promote antitumor immune responses. Chemical conjugation of small haptens to antigens generates novel antigenic determinants that increase immune recognition. Mechanistic studies indicate that haptenation enhances antigen uptake, dendritic cell maturation, and the activation of both cellular and humoral immunity. In preclinical models, hapten-modified antigens induce robust immune activation, tumor regression, and durable immune memory. Clinically, dinitrophenyl-modified autologous tumor cell vaccines elicit delayed-type hypersensitivity responses and clonal T-cell expansion, with evidence of clinical activity and a favorable safety profile. However, their clinical benefit remains to be confirmed in larger, randomized studies. Emerging strategies include in situ haptenation and bihaptenized or stressed hapten-modified allogeneic platforms, which aim to expand epitope diversity and enhance immune priming. Hapten-based immunotherapies offer a clinically feasible approach to converting poorly immunogenic tumors into effective immune targets. Full article

Gluten allergy is linked to high risk of anaphylaxis. The relative allergenicity of glutens (alcohol-soluble gliadin and acid-soluble glutenin) from the three commercially grown wheat species (diploid Triticum monococcum, tetraploid Triticum durum, hexaploid Triticum aestivum) is unknown. A comparative gluten allergenicity map (CGAM) from these species will enable the identification of potentially hyper-/hypo-/iso-allergenic species/varieties of wheat as well as the determination of substantial equivalence of genetically engineered (GE) or other novel wheat lines. Here, using a recently described novel mouse model, we tested the hypothesis that the three different wheat species will exhibit natural variation in their gluten allergenicity. Groups of Balb/c mice were transdermally sensitized to alcohol-soluble or acid-soluble gluten extracts followed by elicitation of systemic anaphylaxis. Initial studies were performed to validate the model for glutens from the three wheat species. Both glutens from all three wheat species elicited robust specific IgE responses, as well as systemic anaphylaxis. However, comparative mapping analysis revealed differences in capacity to elicit specific IgE among the three wheat species with T. aestivum being the most potent in both gluten extracts. Hypothermic shock response analysis revealed that the three species elicited similar kinetics and intensity of anaphylaxis. Nevertheless, when analyzing mucosal mast cell response, it was revealed that the glutens from T. aestivum emerged as the most potent elicitor. Collectively, these results yield the first CGAM that may be utilized for preclinical testing of the allergenic potential of glutens from novel (e.g., GE) wheats and processed wheat products against existing wheat glutens. Full article

The immunosuppression inherent to chronic lymphocytic leukemia (CLL) is the most frequent cause of morbidity and mortality associated with this pathology. Both the innate and adaptive immune responses exhibit marked functional alterations, with a bias towards a tolerant environment that favors the spread of the disease. This condition is reflected in increased risk of infections, immune-mediated cytopenias, and associated second malignancies. Knowledge of these alterations, both in the molecular pathways that modulate T cell activity in CLL (the T lymphocyte cytotoxic antigen-4 (CTLA-4) axis and programmed cell death 1 (PD-1)) and at the T cell immunoreceptor level, could be of interest as therapeutic targets in CLL. In this review, we will analyze the main consequences of this dysfunction and its management strategies. Full article