Search Results (88)

Tinea incognito is an incorrectly diagnosed form of fungal infection due to a changed clinical picture as a result of systemic or topical corticosteroids or even local immunomodulators. This type of skin lesion is most often located on the trunk but can affect any part of the body. We present a case report of 76-year-old woman with a history of systemic lupus erythematosus who was admitted to hospital because of extensive, painful, and burning erythematous and papular lesions in an annular pattern, covered with a thick, yellow crust, located on the scalp and neck. The skin lesions were accompanied by extensive hair loss. The patient had previously undergone intensified treatment of the underlying disease due to the exacerbation of skin lesions of a subacute cutaneous lupus erythematosus type. A suspicion of tinea incognito was raised, and direct mycological examination and culture confirmed the presence of dermatophytes (Microsporum spp.). Tinea incognito can be difficult to diagnose because the clinical picture is relatively nonspecific and can mimic other dermatoses, such as subacute lupus erythematosus. Therefore, in doubtful cases it is necessary to perform a direct test and culture for fungal infection, especially before initiating treatment with glucocorticosteroids and other immunosuppressive agents. Full article

Superoxide dismutases (SODs) maintain redox homeostasis through the catalytic dismutation of superoxide anions, thereby affording protection to organisms against oxidative damage. The SOD family, encompassing Cu/Zn-SOD, Mn-SOD, Fe-SOD, and Ni-SOD, exhibits structural diversity and constitutes a multilevel antioxidant defense system with discrete subcellular localizations. Beyond their antioxidant functions, SODs also function as immunomodulatory proteins, regulating the maturation, proliferation, and differentiation of immune cells. They further fulfill a crucial role in host responses to parasitic infections. The current review synthesizes and critically evaluates extant research to comprehensively delineate the molecular architecture of SODs, their intricate post-translational modification (PTM) networks, and their dual regulatory mechanisms at the interface of immunomodulation and pathological processes. This review establishes a critical framework for elucidating the biological significance of redox homeostasis maintenance. Full article

Diabetic foot ulcers (DFUs) constitute a severe and debilitating complication of diabetes, imposing a substantial global health burden due to their intricate pathophysiology and impaired wound healing processes. Vitamin D deficiency is highly prevalent among diabetic populations, and accumulating evidence indicates its potential involvement in the pathogenesis and prognosis of DFUs. This review comprehensively explores the diverse roles of vitamin D in DFUs, encompassing its molecular mechanisms such as immunomodulation, promotion of angiogenesis, neuroprotection, and induction of antimicrobial peptides, as well as the metabolic characteristics associated with various vitamin D forms and compromised vitamin D receptor (VDR) signaling pathways. Although robust observational studies have established an association between vitamin D deficiency and adverse outcomes in DFUs, the clinical validation of supplementation efficacy through randomized controlled trials (RCTs) remains constrained by limitations such as small sample sizes, heterogeneity in study protocols, and insufficient long-term follow-up. This highlights the critical need for large-scale, high-quality studies to ascertain optimal treatment regimens and to cater to individualized patient requirements, particularly for individuals with obesity or those with renal impairments. Innovative strategies, such as the topical administration of vitamin D through intelligent delivery systems leveraging advanced biomaterials like nanofibers and hydrogels, exhibit substantial preclinical potential in enhancing stability, achieving targeted controlled release, and augmenting local biological effects, including the induction of antimicrobial peptides. Nevertheless, significant challenges persist in conclusively establishing clinical efficacy, comprehensively elucidating the underlying mechanisms, ensuring the safe translation of novel delivery systems, and developing personalized therapeutic strategies. The future success of these interventions hinges on meticulous research and interdisciplinary collaboration to seamlessly integrate validated vitamin D-based interventions into a comprehensive multidisciplinary management framework for DFUs, thereby holding promise for improving the clinical outcomes of this debilitating condition. Full article

Background/Objectives: Microneedles represent an innovative transdermal drug delivery approach, especially for protein antigens. This study aimed to develop a dual-functional, dissolvable microneedle system loaded with β-glucan and fucoidan in a hyaluronic acid matrix to achieve transdermal immunomodulation and reactive oxygen species (ROS) regulation, exploring its potential in inflammatory disease management and antigen delivery. Methods: The microneedles were fabricated using a two-step casting method. Their morphology, mechanical strength, and dissolution kinetics were characterized. In vitro experiments evaluated the ROS-modulating effects on human dermal fibroblasts, while in vivo studies on C57 mice investigated immune activation and lymph node accumulation of ovalbumin antigen. Results: The microneedles exhibited a mechanical strength exceeding 7.45 N/needle and dissolved within 50 s. β-glucan transiently reduced ROS levels at 6 h followed by a rebound, whereas fucoidan sustained ROS suppression after 12 h. In mice, β-glucan-loaded microneedles triggered local immune activation, and fucoidan-incorporated microneedles enhanced ovalbumin accumulation in lymph nodes by 2.1-fold compared to controls. Conclusions: Integrating β-glucan’s immunostimulatory and fucoidan’s ROS-scavenging/lymphatic-targeting properties within a single microneedle platform offers a promising multifunctional strategy for treating inflammatory diseases and delivering protein antigens. Full article

Deep-seated tumors present significant diagnostic challenges and pose substantial mortality risks due to their occult anatomical localization. Current diagnostic paradigms predominantly depend on conventional imaging modalities; nevertheless, inherent technical constraints persistently compromise diagnostic precision and therapeutic efficacy. In contrast to traditional methodologies, near-infrared (NIR; 700–1700 nm) fluorescence imaging (FLI) demonstrates superior sensitivity and spatiotemporal resolution, facilitating real-time intraoperative visualization and precision-guided surgical interventions. This paper explores fluorescence materials with tailored structures for tumors at different depths. We critically analyze optimization strategies for NIR fluorescence materials while evaluating their comparative advantages in stratified tissue imaging. This study presents a systematic evaluation of NIR fluorescence molecular tomography (FMT) systems and image reconstruction methodologies. These insights provide feasible ideas for detecting and treating tumors at varying depths in clinical practice. Furthermore, the application of NIR fluorescent materials in tumor diagnosis, navigation-guided surgery, and phototherapy (including photothermal, photodynamic, and immunomodulation therapies) is discussed. Finally, the prospects and challenges of clinical transformation are summarized. Full article

Spinal motor nerve root lesions can happen after avulsion or crush, generating acute motoneuron death and synaptic loss, consequently, causing motor and sensory dysfunctions. Local response is mediated by astroglial and microglial cells, giving rise to a pro-inflammatory profile. TEMPOL and DMF are drugs that have been studied in our laboratory after spinal cord nerve root injuries and have demonstrated significant results in terms of neuroprotection and immunomodulation, decreasing the inflammation process. In the present work, a flow cytometry approach was used to evaluate cellular responses to injury and immunomodulation. For this, injured animals received TEMPOL, DMF or vehicle once a day for 7, 14 or 28 days of treatment. Flow cytometry multiparametric analysis allowed the quantification of different pro- and anti-inflammatory glial, macrophage and lymphocyte markers. Contrasting with the vehicle treated counterpart, TEMPOL and DMF led to downregulation of pro-inflammatory cytokines in astrocytes and microglia subpopulations, but did not show significant results in increasing anti-inflammatory phenotypes. As for macrophage and lymphocyte subpopulations, both treatments showed a balance between pro- and anti-inflammatory phenotypes. Therefore, it was concluded that both drugs exhibit immunomodulatory action, contributing to a pro-regenerative profile in the tissue. Full article

Autoimmune diseases present complex therapeutic challenges due to their chronic nature, systemic impact, and requirement for precise immunomodulation to avoid adverse side effects. Recent advancements in biodegradable and stimuli-responsive nanomaterials have opened new avenues for targeted drug delivery systems capable of addressing these challenges. This review provides a comprehensive analysis of state-of-the-art biodegradable nanocarriers such as polymeric nanoparticles, liposomes, and hydrogels engineered for targeted delivery in autoimmune therapies. These nanomaterials are designed to degrade safely in the body while releasing therapeutic agents in response to specific stimuli, including pH, temperature, redox conditions, and enzymatic activity. By achieving localized and controlled release of anti-inflammatory and immunosuppressive agents, these systems minimize systemic toxicity and enhance therapeutic efficacy. We discuss the underlying mechanisms of stimuli-responsive nanomaterials, recent applications in treating diseases such as rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease, and the design considerations essential for clinical translation. Additionally, we address current challenges, including biocompatibility, scalability, and regulatory hurdles, as well as future directions for integrating advanced nanotechnology with personalized medicine in autoimmune treatment. This review highlights the transformative potential of biodegradable and stimuli-responsive nanomaterials, presenting them as a promising strategy to advance precision medicine and improve patient outcomes in autoimmune disease management. Full article

Toll-like receptor 2 (TLR2) signaling is a pivotal component of immune system activation, and it is closely linked to the lipidation of bacterial proteins. This lipidation is guided by bacterial signal peptides (SPs), which ensure the precise targeting and membrane anchoring of these proteins. The lipidation process is essential for TLR2 recognition and the activation of robust immune responses, positioning lipidated bacterial proteins as potent immunomodulators and adjuvants for vaccines against bacterial-, viral-, and cancer-related antigens. The structural diversity and cleavage pathways of bacterial SPs are critical in determining lipidation efficiency and protein localization, influencing their immunogenic potential. Recent advances in bioinformatics have significantly improved the prediction of SP structures and cleavage sites, facilitating the rational design of recombinant lipoproteins optimized for immune activation. Moreover, the use of SP-containing lipobox motifs, as adjuvants to lipidate heterologous proteins, has expanded the potential of vaccines targeting a broad range of pathogens. However, challenges persist in expressing lipidated proteins, particularly within heterologous systems. These challenges can be addressed by optimizing expression systems, such as engineering E. coli strains for enhanced lipidation. Thus, lipoprotein signal peptides (SPs) demonstrate remarkable versatility as adjuvants in vaccine development, diagnostics, and immune therapeutics, highlighting their essential role in advancing immune-based strategies to combat diverse pathogens. Full article

Background/Objectives: Intranasal vaccination enhances protection against respiratory viruses by providing stimuli to the immune system at the primary site of infection, promoting a balanced and effective response. Influenza vectors with truncated NS1 are a promising vaccine approach that ensures a pronounced local CD8+ T-cellular immune response. Here, we describe the protective and immunomodulating properties of an influenza vector FluVec-N carrying the C-terminal fragment of the SARS-CoV-2 nucleoprotein within a truncated NS1 open reading frame. Methods: We generated several FluVec-N recombinant vectors by reverse genetics and confirmed the vector’s genetic stability, antigen expression in vitro, attenuation, and immunogenicity in a mouse model. We tested the protective potential of FluVec-N intranasal immunization in naïve mice and seropositive Th2-prone mice, primed with aluminium-adjuvanted inactivated SARS-CoV-2. Immune response in immunized and challenged mice was analyzed through serological methods and flow cytometry. Results: Double intranasal immunization of naïve mice with FluVec-N reduced weight loss and viral load in the lungs following infection with the SARS-CoV-2 beta variant. Mice primed with alum-adjuvanted inactivated coronavirus experienced substantial early weight loss and eosinophilia in the lungs during infection, demonstrating signs of enhanced disease. A single intranasal boost immunization with FluVec-N prevented the disease enhancement in primed mice by modulating the local immune response. Protection was associated with the formation of specific IgA and the early activation of virus-specific effector and resident CD8+ lymphocytes in mouse lungs. Conclusions: Our study supports the potential of immunization with influenza vector vaccines to prevent respiratory diseases and associated immunopathology. Full article

According to a modern view, cancer no longer follows a purely mechanistic model. Rather, a tumor is conceived as a more complex structure, composed of cancer cells, the activities of which may interact and reshape the so-called tumor microenvironment (TME), leading to preservation of specific tumoral niches and promoting the survival of tumoral stem cells. Background/Objective: Therapeutic strategies must deal with this unique cancer architecture in the near future by widening their range of activities outside the cancer cells and rewiring a TME to ensure it is hostile to cancer growth. Therefore, an intratumoral therapeutic strategy may open the door to a new type of anticancer activity, one that directly injures the tumoral structure while also eliciting an influence on the TME through local and systemic immunomodulation. This review would like to assess the current situation of intratumoral strategies and their clinical implications. Methods We analyzed data from phase I, II, and III trials, comprehensive reviews and relevant clinical and preclinical research, from robust databases, like PUBMED, EMBASE, Cochrane Library, and clinicaltrials.gov. Results: Intratumoral strategies can be quite variable. It is possible the injection and inhalation of traditional antiblastic agents or immunomodulant agents, or intrapleural administration. Ablation strategy is available, both thermal and photodynamic method. Moreover, TTfields and NPs are analyzed and also brachytherapy is mentioned. Intratumoral therapy can find space in “adjuvant”/perioperative or metastatic settings. Finally, intratumoral strategies allow to synergize their activities with systemic therapies, guaranteeing better local and systemic disease control. Conclusions: Intratumoral strategies are overall promising. Antiblastic/immunomodulant injection and NPs use are especially interesting and intriguing. But, there is generally a lack of phase II and III trials, in particular NPs use need additional experimentation and clinical studies. Full article

Secreted phospholipase 2 (sPLA2) is the largest family of phospholipase A2 (PLA2) enzymes with 11 mammalian isoforms. Each sPLA2 exhibits different localizations and specific properties, being involved in a very wide spectrum of biological processes. The enzymatic activity of sPLA2 has been well described; however, recent findings have shown that they could regulate different signaling pathways by acting directly as ligands. Arachidonic acid (AA) and its derivatives are produced by sPLA2 in collaboration with other molecules in the extracellular space, making important impacts on the cellular environment, being especially relevant in the contexts of immunity and cancer. For these reasons, this review focuses on sPLA2 functions in processes such as the promotion of EMT, angiogenesis, and immunomodulation in the context of tumor initiation and progression. Finally, we will also describe how this knowledge has been applied in the search for new sPLA2 inhibitory compounds that can be used for cancer treatment. Full article

Mesenchymal stem cells are used most in regenerative medicine due to their capacities in differentiation and immune modulation. The intraosseous injection of MSC into the bone has been recommended because of expected outcomes for retention, bioavailability, and enhanced therapeutic efficacy, particularly in conditions involving the bone, such as osteoporosis and osteonecrosis. A review of the intraosseous delivery of mesenchymal stem cells in comparison with intravenous and intra-arterial delivery methods will be subjected to critical examination. This delivery mode fares better regarding paracrine signaling and immunomodulation attributes, which are the cornerstone of tissue regeneration and inflammation reduction. The local complications and technical challenges still apply with this method. This study was more focused on further research soon to be conducted to further elucidate long-term safety and efficacy of intraosseous mesenchymal stem cell therapy. Though much has been achieved with very impressive progress in this field, it is worth noting that more studies need to be put into place so that this technique can be established as a routine approach, especially with further research in biomaterials, gene therapy, and personalized medicine. Full article

Chronic inflammation alters lipoprotein metabolism and causes changes in the serum concentrations of lipids, C-reactive protein (CRP), and paraoxonase-1 activity (PON-1), an enzyme that may act as a local detoxifier, antioxidant, and immunomodulator in the gastrointestinal tract. Scarce information is available in dogs with protein-losing enteropathy secondary to chronic enteropathy (iPLE). The first aim was to describe and compare the lipid profiles, CRP concentrations and PON-1 activities in healthy dogs and in dogs with iPLE. The second aim was to evaluate correlations among clinicopathological, histologic data and lipid profiles in dogs with iPLE. Serum samples from 51 iPLE and 40 healthy dogs were used to study albumin, total protein, CRP, PON-1 activity, cholesterol, triglycerides and lipoprotein classes. Serum concentrations of albumin, total protein, cholesterol, PON-1 activity, and high-density and very-low-density lipoproteins were lower in iPLE dogs compared to healthy controls, while those of triglycerides, low-density lipoproteins, chylomicrons and CRP were higher. Significant correlations between the lipid profile and the existing chronic enteropathy activity index were not found. High-density and low-density lipoproteins correlated with CRP and PON-1. Triglycerides were significantly higher in dogs with both inflammation and lymphangiectasia. The results need to be confirmed in further studies. Full article

Interstitial lung diseases (ILDs) encompass a heterogeneous group of over 200 disorders that require individualized treatment. Antifibrotic agents, such as nintedanib and pirfenidone, have remarkably revolutionized the treatment landscape of patients with idiopathic pulmonary fibrosis (IPF). Moreover, the approval of nintedanib has also expanded the therapeutic options for patients with progressive pulmonary fibrosis other than IPF. However, despite recent advances, current therapeutic strategies based on antifibrotic agents and/or immunomodulation are associated with non-negligible side effects. Therefore, several studies have explored the inhalation route aiming to spread higher local concentrations while limiting systemic toxicity. In this review, we examined the currently available literature about preclinical and clinical studies testing the efficacy and safety of inhalation-based antifibrotics, immunomodulatory agents, antioxidants, mucolytics, bronchodilators, and vasodilator agents in ILDs. Full article

Cationic vaccines of nanometric sizes can directly perform the delivery of antigen(s) and immunomodulator(s) to dendritic cells in the lymph nodes. The positively charged nanovaccines are taken up by antigen-presenting cells (APCs) of the lymphatic system often originating the cellular immunological defense required to fight intracellular microbial infections and the proliferation of cancers. Cationic molecules imparting the positive charges to nanovaccines exhibit a dose-dependent toxicity which needs to be systematically addressed. Against the coronavirus, mRNA cationic nanovaccines evolved rapidly. Nowadays cationic nanovaccines have been formulated against several infections with the advantage of cationic compounds granting protection of nucleic acids in vivo against biodegradation by nucleases. Up to the threshold concentration of cationic molecules for nanovaccine delivery, cationic nanovaccines perform well eliciting the desired Th 1 improved immune response in the absence of cytotoxicity. A second strategy in the literature involves dilution of cationic components in biocompatible polymeric matrixes. Polymeric nanoparticles incorporating cationic molecules at reduced concentrations for the cationic component often result in an absence of toxic effects. The progress in vaccinology against cancer involves in situ designs for cationic nanovaccines. The lysis of transformed cancer cells releases several tumoral antigens, which in the presence of cationic nanoadjuvants can be systemically presented for the prevention of metastatic cancer. In addition, these local cationic nanovaccines allow immunotherapeutic tumor treatment. Full article