Biologics

Background/Objectives: Overactivation of the HGF/c-MET pathway is implicated in various cancers, making its inhibition a promising therapeutic strategy. While several MET-targeting agents are currently approved or in advanced clinical development, patient selection often relies on invasive tissue-based assays. The development of a specific c-MET radioligand for PET imaging and radioligand therapy represents a non-invasive alternative, enabling real-time monitoring of target expression and offering a pathway to personalized treatment. Methods: Radiosynthesis of [⁶⁸Ga]Ga-DOTA-EMP100 was performed using a GMP-certified ⁶⁸Ge/⁶⁸Ga generator connected to an automated synthesis module. The radiopharmaceutical production was optimized by scaling down the amount of DOTA-EMP-100 from 50 to 20 μg. Synthesis efficiency and release criteria were assessed according to Ph. Eur. for all the final products by evaluating radiochemical yield (RY%), radiochemical purity, presence of free gallium (by Radio-UV-HPLC) and gallium colloids (by Radio-TLC), molar activity (Am), chemical purity, pH, and LAL test results. Results: An optimized formulation of [⁶⁸Ga]Ga-DOTA-EMP-100, using 40 μg of precursor, provided the best outcome in terms of radiochemical performance. Process validation across three independent productions confirmed a consistent radiochemical yield of 64.5% ± 0.5, high radiochemical purity (>99.99%), and a molar activity of 53.41 GBq/µmol ± 0.8. Conclusions: [⁶⁸Ga]Ga-DOTA-EMP-100 was successfully synthesized with high purity and reproducibility, supporting its potential for multi-dose application in clinical PET imaging and targeted radioligand therapy. Full article

Introduction: Patients with inflammatory bowel disease (IBD) have an increased risk of Clostridioides difficile infection (CDI). While antibiotic exposure has been considered the most prominent risk factor for CDI, proton pump inhibitor (PPI) use is another potential risk factor. Methods: From January 2017 to April 2021, we examined the University of Missouri’s IBD patients’ medical records. Laboratory-confirmed CDI diagnosis was the main outcome of interest. The usage of PPIs was the exposure of interest. The odds ratio between CDI risk in PPI users and non-users was estimated using logistic regression models. We investigated CDI risk with PPI use duration using stratified analysis. Results: Overall prevalence of CDI was 9%. 358 patients (42%) reported using PPI, with an average duration of ~30 months, with a range of 0.1 to 255. PPI use was associated with a higher risk of CDI in both the unadjusted (OR = 1.58 [0.98–2.53]; p = 0.06) and adjusted models (9.23 [2.11–40.34]; p = 0.003). Only those who used PPIs for less than 30 months had a greater risk of CDI in the stratified analysis (OR = 2.10 [1.16–3.38], p = 0.014). Long-term use (≥30 months) did not increase the incidence of CDI (OR = 0.74 [0.29, 1.83]; p = 0.510). Discussion: This is the single largest study of the US general IBD population to evaluate the association between PPI use and risk of developing CDI. PPI therapy was linked to a significant elevation in CDI risk, restricted to PPI use for up to 30 months. Histamine-2 receptor antagonists (H2RAs) did not increase the risk of CDI. Full article

Mesenchymal stem cells are multipotent stromal cells with immunomodulatory, anti-inflammatory, and trophic properties that support tissue repair and regeneration. Increasing evidence suggests that their therapeutic effects are primarily mediated by paracrine signaling, especially through extracellular vesicles, which can cross the blood–brain barrier and act as cell-free therapeutic agents. Preclinical and clinical studies in stroke, multiple sclerosis, spinal cord injury, and neurodegenerative diseases report encouraging outcomes but also reveal major challenges, including limited engraftment, donor-related heterogeneity, incomplete understanding of mechanisms, and potential oncogenic risks. Recent advances in biotechnology—such as mesenchymal stem cell-derived extracellular vesicles, genetic engineering using CRISPR/Cas9 or viral vectors, 3D culture systems, and bioengineered delivery platforms—offer new opportunities to overcome these limitations. Early clinical trials demonstrate promising safety and functional improvements, yet results remain inconsistent, highlighting the need for standardized protocols and large-scale controlled studies. This review outlines current knowledge, key challenges, and emerging strategies aimed at optimizing mesenchymal stem cell-based approaches for regenerative neurology. Full article

Lyophilization (freeze-drying) has become a cornerstone pharmaceutical technology for stabilizing biopharmaceuticals, overcoming the inherent instability of biologics, vaccines, and complex drug formulations in aqueous environments. The appropriate literature for this review was identified through a structured search of several databases (such as PubMed, Scopus) covering publications from late 1990s till date, with inclusion limited to peer-reviewed studies on lyophilization processes, formulation development, and process analytical technologies. This succinct review examines both fundamental principles and cutting-edge advancements in lyophilization technology, with particular emphasis on Quality by Design (QbD) frameworks for optimizing formulation development and manufacturing processes. The work systematically analyzes the critical three-stage lyophilization cycle—freezing, primary drying, and secondary drying—while detailing how key parameters (shelf temperature, chamber pressure, annealing) influence critical quality attributes (CQAs) including cake morphology, residual moisture content, and reconstitution behavior. Special attention is given to formulation strategies employing synthetic surfactants, cryoprotectants, and stabilizers for complex delivery systems such as liposomes, nanoparticles, and biologics. The review highlights transformative technological innovations, including artificial intelligence (AI)-driven cycle optimization, digital twin simulations, and automated visual inspection systems, which are revolutionizing process control and quality assurance. Practical case studies demonstrate successful applications across diverse therapeutic categories, from small molecules to monoclonal antibodies and vaccines, showcasing improved stability profiles and manufacturing efficiency. Finally, the discussion addresses current regulatory expectations (FDA/ICH) and compliance considerations, particularly regarding cGMP implementation and the evolving landscape of AI/ML (machine learning) validation in pharmaceutical manufacturing. By integrating QbD-driven process design with AI-enabled modeling, process analytical technology (PAT) implementation, and regulatory alignment, this review provides both a strategic roadmap and practical insights for advancing lyophilized drug product development to meet contemporary challenges in biopharmaceutical stabilization and global distribution. Despite several publications addressing individual aspects of lyophilization, there is currently no comprehensive synthesis that integrates formulation science, QbD principles, and emerging digital technologies such as AI/ML and digital twins within a unified framework for process optimization. Future work should integrate advanced technologies, AI/ML standardization, and global access initiatives within a QbD framework to enable next-generation lyophilized products with improved stability and patient focus. Full article

Background: Various thiolactones are known as biologically active compounds, capable of stimulating the development of several human diseases and quorum sensing of Gram–positive bacteria. The enzymatic hydrolysis of thiolactones represents a promising approach to preventing their action. Methods: Thirteen enzymes, including various lactonases and serine hydrolases were studied in this work using several substrates including the homocysteine thiolactone (HTL), and its derivatives the N–acetylhomocysteine thiolactone (C₂–HTL) and the isobutyryl–homocystein thiolactone (i–but–HTL). The potential interactions of the ligands with the surface of enzymes molecules were predicted in silico using computational modeling and checked in wet experiments in vitro. Results: Based on the data obtained several enzymes were selected with localization of the thiolactones near their active sites, indicating the possibility of effective catalysis. The lactonase (AiiA), metallo-β-lactamase (NDM-1) and the organophosphate hydrolase with hexahistidine tag (His₆–OPH) were among them. Determination of catalytic characteristics of enzymes in the hydrolytic reactions with the HTL and the C₂–HTL revealed the maximal value of catalytic efficiency constant for the NDM-1 in the hydrolysis of the HTL (826 M⁻¹ s⁻¹). The maximal activity in the hydrolysis of C₂–HTL was established for AiiA (137 M⁻¹ s⁻¹). The polyaspartic (PLD₅₀) and the polyglutamic (PLE₅₀) acids were used to obtain polyelectrolyte complexes with enzymes. The further combination of these complexes with the clotrimazole and polymyxin B possessing antimicrobial properties resulted in notable improvement of their action in relation to Staphylococcus cells. Conclusions: It was revealed that the antimicrobial activity of the polymyxin B is enhanced by 9–10 times against bacteria and yeast when combined with the His₆–OPH polyelectrolyte complexes. The antimicrobial activity of clotrimazole was increased by ~7 times against Candida tropicalis cells in the case of the AiiA/PLE₅₀/Clotrimazole combination. These results make the obtained biology attractive and promising for their further advancement to practical application. Full article

Background/Objectives: Omalizumab is a monoclonal anti-IgE antibody approved for the treatment of chronic urticaria. There are no established or validated prognostic markers currently available to identify likely responders. The aim of this study was to retrospectively analyze a cohort of chronic urticaria patients treated with omalizumab, in order to determine the clinical and laboratory characteristics associated with complete response to therapy. Methods: Medical records of chronic urticaria patients receiving omalizumab were reviewed. The following parameters were collected: age, sex, disease duration, Urticaria Activity Score over 7 days (UAS7), time to response, total serum IgE levels, presence or absence of atopy, neutrophil-to-lymphocyte ratio, eosinophil and basophil counts, presence or absence of autoimmune conditions, and treatment duration. Complete response was classified as dependent on continued drug administration or drug-free (sustained remission after discontinuation). Adverse events were also recorded. Results: Omalizumab was well tolerated by all patients, with no serious adverse events reported. Complete response was achieved in 81.3% of patients; partial and no responses were observed in 8.3% and 10.1%, respectively. The majority of responders (~79.5%) maintained complete control of hives with low-dose omalizumab; subsequently, most of these patients eventually achieved sustained, drug-free remission. Total serum IgE levels appeared to predict complete response, with 164.7 IU/mL identified as the cut-off value potentially distinguishing responders from nonresponders. Conclusions: Omalizumab is a safe and effective treatment for chronic urticaria. Total serum IgE levels may help identify complete responders. Long-term low-dose regimens could be considered to reduce the economic burden on healthcare systems, although this is currently an off-label approach. Full article

Background/Objectives: Obesity increases reactive oxygen species (ROS), thereby triggering oxidative stress. Coriander seeds contain polyphenolic compounds that act as natural antioxidants to reduce oxidative stress. Coriander seed ethanolic extract has been proven to decrease malondialdehyde and increase catalase activity in the liver of high-fat-diet-fed rats. Thus, coriander seeds are thought to protect against obesity-induced oxidative liver damage; however, their molecular mechanism has not been revealed. Nuclear factor erythroid 2-related factor 2 (Nrf2) and Forkhead Box O3 (FOXO3) are transcription factors involved in cellular antioxidant regulation (e.g., superoxide dismutase/SOD, glutathione peroxidase/GPx expression, and reduced glutathione/GSH) that are negatively regulated by Kelch-like ECH-associated Protein 1 (Keap1) and 14-3-3 protein to maintain cellular homeostasis. This study aimed to analyze the regulation of antioxidant expression through in silico and in vivo experiments. Methods: The in silico study assessed the potential of coriander seed ethanolic extract to inhibit Keap1 and 14-3-3 using molecular docking. Then, the drug-likeness, pharmacokinetics, and toxicity of the top three compounds were analyzed. Meanwhile, the in vivo study investigated how the coriander seed ethanolic extract impacted the level of Nrf2, FOXO3, and their downstream effectors (T-SOD, MnSOD, GPx, and GSH). The in vivo study involved five groups of rats with obesity induced by a high-fat diet that were fed with 100 mg/kgBW coriander seed ethanolic extract for 12 weeks. Results: The in silico tests revealed that shionoside b had the highest potential to inhibit Keap1 (ΔG = −8.90 kcal/mol; Ki = 298.01 nM) and 14-3-3 protein (ΔG = −6.85 kcal/mol; Ki = 9.46 µM). The in vivo tests showed that the Nrf2, FOXO3, MnSOD, and GPx mRNA expression was significantly different between the groups (p < 0.05). Meanwhile, T-SOD, MnSOD, GPx, and GSH activity were not significantly different between the groups (p > 0.05). Nrf2 was significantly correlated with FOXO3 as well as the T-SOD, MnSOD, and GPx activity, and FOXO3 was significantly correlated with the T-SOD, MnSOD, GPx, and GSH activity. Conclusions: In obese rats, coriander seeds tend to increase Nrf2 and FOXO3 expression, which is positively correlated with their downstream enzymatic and nonenzymatic antioxidant activity. This is possibly due to the interaction between the coriander seed phytoconstituents and protein inhibitors (Keap1 and 14-3-3), which contribute to the stability and nuclear mobilization of Nrf2 and FOXO3. Full article

Background/Objectives: Sera from patients before and after organ transplantation were tested at two different temperatures, 21 °C and 37 °C. Currently, organs are transported under normothermic conditions (37 °C). This observational pilot study was conducted to define the effect of the incubation at 37 °C, comparing the results to the usual temperature of 21 °C for serum–bead incubation. Methods: We used the Luminex-based assay for the identification and characterization of HLA-specific antibodies. The assays were performed using single antigen beads for HLA class I and HLA class II. A total of 42 sera were assessed and tested, and 38 were analyzed on the Luminex 200 platform at both temperatures. Results: We noted varying outcomes: both an increase and a decrease in mean fluorescence intensity values. A shift from negative to positive values (n = 6) and vice versa (n = 1) was observed. Several sera (n = 4 for HLA class I and n = 5 for HLA class II) exhibited no alterations. In general, we observed an increase in the mean fluorescence intensity values by incubation at 37 °C. The analysis at the bead level revealed a significant deviation (37 °C vs. 21 °C) for the bead carrying HLA-A80 (p = 0.0006) and two HLA-DQ beads, DQA1*05:01-DQB1*02:01 (p = 0.0438) and DQA1*01:03-DQB1*06:03 (p = 0.0438). Conclusions: Mimicking physiological temperature conditions for the testing of HLA-specific antibodies will lead to the better and more accurate interpretation of the results. This method shows potential for use in the delisting strategy for highly sensitized patients as well, thus allowing a better and more reliable option for the patient awaiting a suitable crossmatch-negative organ. Full article

Background: Rituximab is a monoclonal antibody targeting CD20, commonly used to treat autoimmune diseases such as granulomatosis with polyangiitis (GPA) and rheumatoid arthritis. While generally well-tolerated, serious adverse events, including infusion reactions and infections, are well-documented. Case Summary: We report a rare case of rituximab-induced ST-elevation myocardial infarction (STEMI) in a 26-year-old woman with no cardiovascular risk factors. She developed crushing chest pain after her first 1 g rituximab infusion, with recurrent symptoms upon re-exposure. Cardiac catheterization revealed a left circumflex artery occlusion. Additional workup showed c-ANCA positivity, cryoglobulinemia, pauci-immune glomerulonephritis, and findings consistent with GPA. Rituximab was discontinued, and she was transitioned to steroids, cyclophosphamide, and leuprolide, with no further cardiac events. Discussion: This is the first reported case in a young, previously healthy woman. Clinicians should consider rituximab-associated myocardial injury, especially in autoimmune or hypercoagulable states. Take-Home Message: Remain vigilant for cardiac events during rituximab infusions in patients with inflammatory diseases. Full article

Background and Objectives: Probiotics are live microorganisms that promote health when consumed in adequate amounts, ensure the balance of bacterial composition in the digestive system, and suppress harmful pathogenic bacteria, with overall implications for animal and human health, welfare and performance. However, a lot remains unclear about their functional mechanisms. Materials and Methods: In this study, 14 uncharacterized proteins of Lactobacillus acidophilus were analyzed for subcellular localization, structural and safety profiling and interleukin-6-(IL-6)-inducing potential. Results: Aliphatic index scores were generally high, ranging between 138.39 (LBA1705) and 78.39 (LBA1825). The instability index scores were less than 40 for all the query proteins except for LBA0995. All the proteins produced immunogenic IL-6-inducing peptides, except for LBA0037, LBA1825 and LBA1788. Conclusions: The findings provide insight into understanding the functional mechanism of probiotic Lactobacillus, laying a strong foundation for more experimental studies. Full article

Extracellular matrix (ECM) bioscaffolds have demonstrated therapeutic potential across a variety of clinical and preclinical applications for tissue repair and regeneration. In parallel, these scaffolds and their components have shown the capacity to modulate the immune response. Unlike synthetic implants, which are often associated with chronic inflammation or fibrotic encapsulation, ECM bioscaffolds interact dynamically with host cells, promoting constructive tissue remodeling. This effect is largely attributed to the preservation of structural and biochemical cues—such as degradation products and matrix-bound nanovesicles (MBV). These cues influence immune cell behavior and support the transition from inflammation to resolution and functional tissue regeneration. However, the immunomodulatory properties of ECM bioscaffolds are dependent on the source tissue and, critically, on the methods used for decellularization. Inadequate removal of cellular components or the presence of residual chemicals can shift the host response towards a pro-inflammatory, non-constructive phenotype, ultimately compromising therapeutic outcomes. This review synthesizes current basic concepts on the innate immune response to ECM bioscaffolds, with particular attention to the inflammatory, proliferative, and remodeling phases following implantation. We explore how specific ECM features shape these responses and distinguish between pro-remodeling and pro-inflammatory outcomes. Additionally, we examine the impact of manufacturing practices and quality control on the preservation of ECM bioactivity. These insights challenge the conventional classification of ECM bioscaffolds as medical devices and support their recognition as biologically active materials with distinct immunoregulatory potential. A deeper understanding of these properties is critical for optimizing clinical applications and guiding the development of updated regulatory frameworks in regenerative medicine. Full article

Osteoarthritis (OA) is a multifactorial chronic musculoskeletal disorder characterised by cartilage degradation, synovial inflammation, and subchondral bone remodelling. Conventional diagnostic modalities, including radiographic imaging and symptom-based assessments, primarily detect disease in its later stages, limiting the potential for timely intervention. Inflammatory biomarkers, particularly Interleukin-6 (IL-6), Tumour Necrosis Factor-alpha (TNF-α), and Myeloperoxidase (MPO), have emerged as biologically relevant indicators of disease activity, with potential applications as companion diagnostics in precision medicine. This review examines the diagnostic and prognostic relevance of IL-6, TNF-α, and MPO in OA, focusing on their mechanistic roles in inflammation and joint degeneration, particularly through the activity of fibroblast-like synoviocytes (FLSs). The influence of sample type (serum, plasma, synovial fluid) and analytical performance, including enzyme-linked immunosorbent assay (ELISA), is discussed in the context of biomarker detectability. Advanced statistical and computational methodologies, including rank-based analysis of covariance (ANCOVA), discriminant function analysis (DFA), and Cox proportional hazards modelling, are explored for their capacity to validate biomarker associations, adjust for demographic variability, and stratify patient risk. Further, the utility of synthetic data generation, hierarchical clustering, and dimensionality reduction techniques (e.g., t-distributed stochastic neighbour embedding) in addressing inter-individual variability and enhancing model generalisability is also examined. Collectively, this synthesis supports the integration of biomarker profiling with advanced analytical modelling to improve early OA detection, enable patient-specific classification, and inform the development of targeted therapeutic strategies. Full article

Background: The peach allergen Pru p 7, a member of the Gibberellin-Regulated Protein (GRP) family, has emerged as a key marker of severe fruit-induced allergies. It is hypothesized to mediate cross-reactivity between fruit allergens and cypress pollen. Given the increasing prevalence of food allergies and the complex patterns of cross-sensitization, the role of Pru p 7 in clinical allergy diagnostics warrants further investigation. Objective: This study aims to characterize the sensitization profile to Pru p 7 in a cohort of patients with suspected fruit allergy and to assess its relationship with cypress pollen allergy, particularly to Cup s 7, a homologous GRP from Cupressus sempervirens. Methods: A retrospective analysis was conducted on 20 patients evaluated at the Allergy Unit of the Fondazione IRCCS Policlinico San Matteo. Specific IgE (sIgE) levels to peach extract, Pru p 7, and Cup a 1 (cypress extract) were assessed using the ImmunoCAP^® system (Thermo Fisher Scientific Inc., Waltham, MA, USA). Statistical associations between sensitizations were evaluated using chi-square tests and Spearman’s correlation. Results: Sensitization to peach extract, Pru p 7, and cypress pollen was detected in 38%, 30%, and 45% of patients, respectively. Significant associations were observed between peach and cypress (χ² = 8.80, p = 0.003), peach and Pru p 7 (χ² = 8.23, p = 0.004), and cypress and Pru p 7 (χ² = 6.55, p = 0.01). Notably, all patients sensitized to Pru p 7 also tested positive for both peach and cypress allergens, supporting the hypothesis of pollen–food cross-reactivity. Conclusions: Pru p 7 is a clinically relevant allergen that may account for severe allergic responses in patients not sensitized to classical peach allergens. Its cross-reactivity with Cupressaceae-derived GRPs, such as Cup s 7, highlights the importance of molecular diagnostics in evaluating food allergies, particularly in regions with significant exposure to cypress pollen. Full article

Background/Objectives: The relative efficacy of 8 mg aflibercept compared to 2 mg in treating neovascular age-related macular degeneration (nAMD) has not been fully established. This study aims to compare the visual and anatomical outcomes of aflibercept 8 mg versus 2 mg in patients with nAMD in both treatment-naïve individuals with no history of anti-VEGF treatment and those previously treated with intravitreal injections. Methods: This retrospective study included 13 eyes treated with aflibercept 8 mg and 14 eyes with aflibercept 2 mg in treatment-naïve patients, along with 15 eyes switched to aflibercept 8 mg previously treated with other intravitreal injections and 15 eyes continued on aflibercept 2 mg in patients. Baseline and one-month post-injection changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed. Results: In treatment-naïve patients, the aflibercept 8 mg group showed a significant improvement in BCVA (logMAR 0.19 ± 0.23 to 0.13 ± 0.20, p = 0.0156), while the 2 mg group did not. Both doses reduced CMT significantly, with a greater reduction in the 8 mg group (dCMT 28.60% vs. 24.08%, p = 0.0220). In previously treated patients, no significant changes in BCVA were noted in either group; however, both groups showed significant reductions in CMT. Conclusions: Real-world data demonstrated that aflibercept 8 mg led to substantial improvements in anatomical outcomes one month after injection, irrespective of previous intravitreal injection history. However, significant improvements in visual outcomes were observed exclusively in treatment-naïve patients. Further large-scale, long-term studies are required to determine the proportion of patients who experience improvement and to assess whether these improvements are maintained over time. Full article

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