Biologics, Volume 5, Issue 3 (September 2025) – 8 articles

Background/Objectives: Fasting-induced elevation of blood ketone body levels suppresses allergic reactions; however, the underlying mechanism remains unclear. This study investigated whether elevated ketone body levels affect allergic contact dermatitis (ACD) and explored nutritional interventions that effectively increase β-hydroxybutyrate (BHB) levels. Additionally, we examined the role of GPR109A, a receptor for β-hydroxybutyrate (BHB), in ketone body-induced allergy suppression through ingestion of a ketogenic substrate. Methods: To evaluate the effects of ketone body precursors, medium-chain triglyceride (MCT) oil or 1,3-butanediol (BD) was administered as a single oral dose (2 g/kg body weight) under fed conditions. Blood BHB concentrations were measured at the time of euthanasia. ACD was induced using 2,4-dinitrofluorobenzene (DNFB), and its severity was assessed by measuring ear swelling and mast cell (MC) degranulation. To determine whether GPR109A mediates ketone body-induced allergy suppression, mepenzolate bromide (MPN), a GPR109A antagonist, was subcutaneously administered before BD treatment. Results: Both MCT oil and BD significantly increased the blood BHB levels. Elevated BHB concentrations were accompanied by reduced ear swelling and MC degranulation in DNFB-treated mice. The anti-allergic effects of BD were abolished by MPN administration, indicating that these effects were mediated by GPR109A activation. Conclusions: Nutritional supplementation with ketogenic substrates, such as MCT oil and BD, may serve as a dietary intervention for ACD by elevating blood BHB levels. GPR109A activation appears to be involved in ketone body-induced allergy suppression, suggesting a mechanistic link between ketone metabolism and immunomodulation. Full article

Background: Chronic eosinophilic pneumonia (CEP) is a rare inflammatory lung disease typically responsive to glucocorticoids, but is prone to relapse and, in some cases, progressive deterioration. A subset of patients develops fibrosing CEP, a distinct phenotype characterized by irreversible parenchymal remodeling and declining lung function, for which no standard treatment exists. Although biologic therapies targeting interleukin-5 (IL-5) are effective in relapsing CEP, their role in fibrosing forms remains unclear. Case Presentation: We report the case of a 43-year-old man with idiopathic CEP initially treated with systemic glucocorticoids, which were discontinued due to severe adverse effects. Despite subsequent therapy with inhaled steroids and azathioprine, the disease relapsed and progressed to a fibrosing phenotype, as confirmed by radiologic and functional assessments. An off-label treatment with subcutaneous mepolizumab, 100 mg, every 4 weeks was started. After eight months of therapy, the patient achieved clinical stability, improved lung function, and the radiologic stabilization of fibrotic changes, without the need for any further treatment with a corticosteroid. Conclusions: This is, to the best of our knowledge, the first documented case of fibrosing CEP treated with an anti-IL-5 monoclonal antibody, highlighting its potential role as a steroid-sparing agent and immunomodulator even in the fibrotic phase of disease. Further research is warranted to define the place of biologics in the management of CEP with a fibrosing evolution and possible combinations with antifibrotic drugs. Full article

Background and Objectives: The cytokine IL-6, methyltransferase NSD2, pro-protein convertase Furin, and growth factor receptor IGF-1R are essential factors in the proliferation of cancer cells. These proteins are involved in the tumor process by generating several cell-signaling pathways. However, the interactions of these oncogenic biomarkers, Furin, IL-6, and NSD2, and their links with the inhibitor SERPINA-1 remain largely unknown. Materials and Methods: Cell proliferation is measured by colorimetric and enzymatic methods. The genetic expressions of SERPINA-1, Furin, IL-6, and NSD2 are measured by qRT-PCR, while the expression of IGF-1R on the cell surface is measured by flow cytometry. Results: The proliferation of cells overexpressing SERPINA-1 (JP7pSer+) is decreased by more than 90% compared to control cells (JP7pSer-). The kinetics of the gene expression ratios of Furin, IL-6, and NSD2 show an increase for 48 h, followed by a decrease after 72 h for the three biomarkers in JP7pSer+ cells compared to JP7pSer- cells. The expression of IGF-1R on the cell surface in both cell lines is low, with JP7pSer- cells expressing 1.33 times more IGF-1R than JP7pSer+ cells. Conclusions: These results suggest gene correlations of SERPINA-1 overexpression with decreased cell proliferation and modulation of gene expression of Furin, IL-6, and NSD2. This study should be complemented by molecular transcriptomic and proteomic experiments to better understand the interaction of SERPINA-1 with IL-6, Furin, and NSD2, and their effect on tumor progression. Full article

Background: Immunological strategies for antibody-guided vaccine design intend to enhance viral neutralization and protection and increase efficacy. Here, we discuss advances in antibody-guided vaccine design and current antibody-guided strategies, including epitope-based, nanoparticle-based, and scaffold-based vaccine approaches. We review the challenges and limitations of vaccines against different pathogens, such as influenza A virus, HIV-1 virus, single-celled malaria parasite, respiratory syncytial virus, and SARS-CoV-2. We summarize the available literature guidance, including emerging techniques in immunological vaccine design, to help understand and improve antibody-based immunity. The search strategy we applied is a comprehensive literature review of major databases, with specific search terms related to antibody-mediated vaccine design, viral neutralization, and immune protection. We discuss the how future directions for next-generation vaccine platforms and personalized vaccines based on immunogenetics will help improve vaccine design for increased specificity and potency of antibodies that neutralize pathogens, offering more precise and effective immune responses and, therefore, protection. Full article

Objectives: The aim of this study was to assess the association of diabetes mellitus and its medications with overall response (ORR) and mortality or cancer-specific survival (CSS) in patients with metastatic urothelial cancer receiving enfortumab vedotin monotherapy. Methods: This multicentre retrospective cohort study was designed according to the guidelines for the synthesis of qualitative research (ENTREQ). Eligible patients were adults (≥18) years treated with enfortumab vedotin monotherapy for metastatic urothelial cancer between June 2024 and January 2025. A total of 125 patients were reported across 11 centres. Results: The cohort included 93 males (74.4%) and 32 females (25.6%), with a mean age of 68.3 years (SD 9.3). The primary tumour site was the bladder in 109 (87.2%) cases and the upper tract (UTUC) in 16 (12.8%) cases. Interestingly, medication with metformin was significantly associated with cancer-specific mortality (37.9% versus 77.8%; p = 0.019), while patients with insulin-dependent diabetes mellitus had a significantly better CSS (Log Rank = 0.004). Upon comparing only patients who already had diabetes mellitus and then received anti-diabetic medication, there was a significant association between patients with diabetes mellitus receiving metformin and a worse 3-month ORR (80.0% versus 55.6%; p = 0.039). Regarding the subpopulation of UTUC, cancer-specific mortality was significantly associated with metformin medication (p = 0.033). Conclusions: Despite recent reports that metformin has protective effects in urothelial cancer, our findings suggest that metformin use may be linked to worse responses and survival outcomes in patients treated with enfortumab vedotin monotherapy. Further research, particularly translational research into the underlying diabetic and pharmacologic pathways, is warranted. Full article

Background/Objectives: Natural products are important in healthcare due to their accessibility and linkage to a healthy lifestyle. However, their effectiveness is uncertain due to insufficient scientific data. Cancer patients are frequent users of natural products to relieve symptoms or for chemoprevention. Eugenia uniflora leaf essential oil (EO), traditionally used for digestive disorders, emerges as a potential antineoplastic agent. We investigated the cytotoxic and antiproliferative effects of E. uniflora EO in human normal CCD 841 CoN and tumoral Caco-2 colonic cell lines. Methods: CCD 841 CoN and Caco-2 cells were exposed to different concentrations of E. uniflora EO, and the cytotoxicity was determined by MTT and Trypan Blue assays. Cell proliferation kinetics were analyzed at a low EO concentration, and the induction of DNA damage and oxidative stress was assessed by Comet and Cellular ROS assays. Results: Both cell lines exhibited cytotoxicity produced by the EO and decreased cell viability of the exposed cells and their progeny. CCD 841 CoN proliferation was impaired by low EO concentration, while the proliferation kinetics of the Caco-2 cells was modified. EO treatment induced variable DNA damage and oxidative stress depending on the cell line. Conclusions: Our results suggest that E. uniflora EO may prevent the proliferation of normal cells, inducing loss of viability. The EO produced cytotoxic and antiproliferative effects in tumoral cells by inducing DNA damage and increased oxidative stress. These effects support the consideration of E. uniflora EO (or its bioactive compounds) as a potential agent for the chemoprevention and treatment of colorectal cancer. Full article

Background/Objectives: Keloid treatment remains challenging due to limited effectiveness and patient dissatisfaction. Herbal-based therapy offers promising alternatives that require further investigation. Uncaria gambir (W.Hunter) Roxb., an original plant from Indonesia, possesses an antifibrotic effect. However, its potential as an antifibrotic agent in keloid management remains unclear. This study aims to bridge this gap by evaluating the bioactive compound from gambir and its effects on keloid fibroblast primary culture. Methods: The bioactive compounds of gambir extract and fractions (ethanol, hexane, and ethyl acetate fractions) were identified by using liquid chromatography–mass spectrometry (LCMS/MS) analysis. The mechanism of gambir bioactive compounds for keloid was predicted using the compound–protein interaction network and enrichment analysis, and validated using molecular docking and dynamic simulation. The experimental study results, including cytotoxic and bioactivity effects, were represented as IC₅₀ and selectivity index (SI) values, and the ex vivo analysis of keloid tissue explants. Results: Uncariagambiriine was identified as the most potent compound with the lowest binding energy and high stability to the core protein targets: AKT1 and TGFB1. The ethanol fraction was determined to have the highest abundance of gambir’s typical bioactive compounds, with the lowest IC₅₀ (128.76 ± 0.24 µg/mL) and the highest SI (6.32) value. Furthermore, the results of the ex vivo analysis indicated the significant inhibition of keloid fibroblast proliferation and migration by the gambir ethanolic fraction. Conclusions: This study underlines the potential of the gambir ethanolic fraction as an antifibrotic agent in keloid, warranting further investigation and development for clinical applications. Full article

Background/Objectives: Research efforts and substantial funding have been dedicated to finding cost-effective and sustainable alternatives to antibiotics. Probiotics have been proposed as promising substitutes for antibiotics in human nutrition and livestock production; however, their functional mechanisms remain incompletely understood, limiting their sustainable applications as food supplements, feed additives and for therapeutic and cosmetic purposes. Methods: In this study, the probiotic potential of two bacterial genomes, Ligilactobacillus saerimneri and Ligilactobacillus salivarius, were explored. Their protein-coding hypothetical proteins were analyzed for their potential to induce interleukin-5 (IL-5) and interleukin-13 (IL-13). Results: The IL-5- and IL-13-inducing peptides were identified as immunogens against bacterial and tumor peptides. Conclusions: These findings provide insights into the probiotic bacteria’s immune functionality pathways, sustainability and potential as therapeutic feed additives, food supplements and candidates for vaccine development. Full article