Search Results (113)

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

Background: Recombinant monoclonal antibodies represent a vital category of biologics, constituting the largest class of molecules used to treat autoimmune disorders, cancers, rheumatoid arthritis, and other chronic conditions. The IgG1 subclass is the most potent among all the immunoglobulin gamma (IgG) antibodies, inducing Fc-related effector functions. N-linked glycan distribution of therapeutic IgG1s affects Fc-related effector functions such as CDC (complement-dependent cytotoxicity) and ADCC (antibody dependent cell-mediated cytotoxicity) biological activities and efficacy in vivo. Hence, as a critical quality attribute (CQA), the glycosylation profile of therapeutic IgG1s must be consistently preserved, which is primarily influenced by manufacturing process factors. In the era of biosimilars, it is challenging for biopharmaceutical manufacturers to not only obtain the desired glycan distribution consistently but also to meet the innovator molecule specifications as per the regulatory agencies. Methods: This study investigates the CHO fed-batch process parameters that affect the titer and terminal galactosylation of the TNF-α blocker-IgG1. It was hypothesized that galactose supplementation would enhance the galactosylation of TNF-α blocker-IgG1. Results: It was observed that such in-cultivation process shift does not affect cell culture parameters yet significantly enhances the galactosylation of TNF-α blocker-IgG1. Interestingly, the results indicate that supplementing D-galactose from the exponential phase of the CHO fed-batch process had the greatest effect on Fc galactosylation, increasing the amount of total galactosylated TNF-α blocker-IgG1 from 7.7% to 15.8%. Conclusions: Our results demonstrate a relatively easy and viable technique for cell culture engineering that is more appropriate for industrial production than costly in vitro glycoengineering. Full article

Background: Dissolvable Microneedle Patches (DMP) have emerged as a promising approach for improved topical delivery of skincare agents with dermatological values (dermo-cosmetics), effectively addressing the various skin concerns. These patches enable minimally invasive penetration of the skin’s outer layer, facilitating efficient transdermal delivery of actives by overcoming skin barrier for successful outcomes. Objectives: The aim of this work was to assess the efficacy and safety of hyaluronic acid-based microneedle patches (HA-MNP) with agents for the managements of an inflammatory disorder of acne. A particular focus was on helping individuals with moderate inflammatory acne. Methods: A single-center clinical trial was conducted over a period of four weeks on acne patients. Measurable skin properties, including sebum content, redness, and severity of inflammation, were evaluated to gauge the overall usefulness of the MN patches. Results: The application of the patches resulted in a significant decrease in sebum content, with reductions of −4.9% and −36.8% observed after two and four weeks of use, respectively. The redness of localized acne lesions also showed a marked decline, with reductions of −47.2% and −65.5% observed after two and four weeks of use, respectively. Additionally, the severity of inflammatory signs in acne lesions showed significant improvements, with reductions of −68.8% and −83.3% observed for the application periods. The patches utilized in this investigation exhibited highly encouraging results, displaying a notable synergistic effect in the context of combating acne without adverse effects. Conclusions: The patches have the potential to be broadly applied as a modular and adaptable approach for therapeutic delivery of actives for various skin diseases and concerns. Full article

C-terminal-binding proteins (CtBPs) dimerize and function predominantly as transcriptional corepressors by recruiting various chromatin-modifying factors to promoter-bound repressors. Hypotonia, ataxia, developmental delay, and tooth enamel defects syndrome (HADDTS) is a recently discovered neurodevelopmental disorder resulting from a heterozygous missense mutation in CTBP1. It is often associated with the early onset of profound cerebellar atrophy in patients. Allen Institute’s Allen Brain Cell (ABC) atlas of human brain data was used to localize CTBP1 expression in the brain to elucidate the etiology of HADDTS. Based on the ABC atlas, CTBP1 is highly expressed in the upper rhombic lip supercluster, which gives rise to cerebellar cells and provides insights into the cerebellar pathophysiology observed in HADDTS patients. Full article

Sherpabodies are a novel class of antibody-mimetic proteins and represent the third generation of SH3 domain-based targeting scaffolds. Sherpabodies have several advantageous biophysical properties, and molecular libraries based on this scaffold provide a rich and facile source of high-quality binders against diverse target proteins of interest. Recent studies have successfully exploited sherpabodies for developing potent antivirals to block SARS-CoV-2 infection and for the advanced guiding of cancer cell killing by chimeric antigen receptor (CAR)-T cells, but many other applications for sherpabody-mediated targeting in biomedicine and biotechnology can be anticipated. Full article

Background and Objectives: Canakinumab, a human recombinant monoclonal antibody against interleukin-1ß (IL-1ß), is indicated for the treatment of selected autoinflammatory periodic fever syndromes and rheumatic diseases. Data on its use during pregnancy remain limited and all are primarily derived from case reports. Although animal studies indicate no evidence of reproductive toxicity, the risk to the fetus or mother remains unknown. This study aims to provide more findings about this important topic. Methods: A retrospective analysis was conducted on three patients followed and treated in the National Center for Periodic Fever Syndromes. Although due to the small sample size, no general conclusions regarding the safety of canakinumab during pregnancy can be drawn. Results: Three maternal-exposed pregnancies were assessed, with no paternal exposure. Diagnoses included mevalonate kinase deficiency, familiar Mediterranean fever and TNF-receptor-associated periodic syndrome. All mothers were treated with canakinumab, and two of those continued the canakinumab treatment during the whole course of pregnancy. The diseases remained under full control during pregnancy, enabling conception in two cases where attempts prior to treatment were unsuccessful. The therapy led to disease control, a reduction in inflammation and subsequently successful conception. One patient underwent IVF repeatedly. All pregnancies resulted in three healthy infants, with no reported miscarriages during the canakinumab-exposed pregnancies, no complications during pregnancies and no serious infections in the newborns. The children had normal development, without any developmental delays or chronic illnesses. Conclusions: The current data, including our findings, indicate no harmful effects of canakinumab during pregnancy. However, because of the scarcity of data, the use of canakinumab during pregnancy should be carefully managed, and women who want to become pregnant should continue treatment only after a thorough benefit–risk evaluation. Full article

Background: Alopecia areata (AA) is an autoimmune disease affecting 2% of the global population, often causing localized scalp hair loss that can progress to alopecia totalis or universalis. While corticosteroids and JAK inhibitors are effective, their significant side effects highlight the need for safer, more targeted treatments. Recently, biologics have gained attention as potential treatments for AA. Methods: A review of clinical trials, case series, and case reports published on PubMed was conducted to assess the efficacy of cytokine-targeting biologics for the treatment of AA. Data on the mechanism of action, treatment outcomes, and safety were extracted and analyzed. Results: Cytokine-targeting biologics identified included Dupilumab, Secukinumab, Tralokinumab, Etanercept, Ustekinumab, Infliximab, Adalimumab, and Tildrakizumab. Dupilumab and ustekinumab demonstrated strong efficacy, with dupilumab showing significant regrowth in 89% of cases and ustekinumab in all patients. Tralokinumab demonstrated a 33.75% improvement, with no patients achieving SALT₅₀. Limited efficacy was observed with secukinumab, tildrakizumab, and adalimumab, with 71.4%, 77.8%, and 50% of patients, respectively, showing no response. Disease worsening was observed in patients who received etanercept (29%) and infliximab (50%). Conclusions: Further research is necessary to optimize treatment protocols, identify predictive biomarkers, and, crucially, discover novel and more effective cytokine targets to advance biologics as a cornerstone therapy for AA. Full article

Vertebrate cell surfaces exhibit intricate arrangements of glycosaminoglycan polymers, which are primarily linked to lipids and proteins. Numerous soluble secreted proteins are also decorated with either individual sugar molecules or their polymers. The carbohydrate polymers commonly possess terminal nine-carbon sugars, known as sialic acids. Due to their widespread distribution and strategic positioning, sialic acids play a crucial role in mediating and regulating a wide range of physiologic processes and pathologic conditions. Human- or animal-based investigations predominantly concentrate on the effects of sialic acids during infections, inflammations, vascular disorders, or cancers. Further investigations encompass a variety of applications, including cell–cell interactions, signaling, host–pathogen interactions, and other biological functions associated with nutrition, metabolism, or genetic disorders. Nevertheless, future mechanistic investigations are needed to clarify the specific roles of sialic acids in these varied contexts, so that more effective interventions may be developed. Full article

Background: Biologics is an exciting and growing area of medicine. Within the larger field of biologics, the use of viral vectors and virus-like particles (VLPs) is increasingly common, making it crucial to develop innovative and practical unit operations for the related purification process. Objective: Some scientists and engineers propose that membrane-based downstream virus purification (MVP) platforms would allow for more scalable and cost-effective production of these critical particles. However, the so-cial, political, and ethical implications of these advancements remain largely unex-plored. This paper aims to explore various pivotal facets of MVP technology govern-ance and regulations within the U.S. context, including (1) government policy ar-rangements related to the implementation of the technologies, (2) stakeholder atti-tudes, policy preferences, and behaviors, and (3) the fundamental factors that shape these attitudes, policy preferences, and behaviors. Methods: In doing so, we analyze publicly available federal and state government documents pertaining to biomanu-facturing, healthcare, and legislative attempts. Additionally, we will perform a stake-holder analysis on relevant industries, healthcare service providers, and recipients. Conclusions: Our goal is to outline the socio-political, ethical, and regulatory factors pertaining to the regulation and governance of these technologies. Full article

Background/Objectives: Oleuropein (OLP), the key bioactive in olive leaf extracts, has demonstrated various biological benefits. We previously reported on the pro-melanogenic action with increased dendricity of a patented olive leaf extract (Benolea^®) that was standardized to 16–24% OLP. In this study, purified OLP was evaluated to identify if it might be the bioactive responsible for the stimulating effects on melanocytes. Moreover, previous studies on OLP have never reported the effects on melanocyte dendricity or melanin export in the medium. Methods: Herein, the effect of OLP on melanogenesis was first evaluated using the B16F10 cell model and validated using the physiological model of normal human melanocytes from Caucasian (lightly pigmented; LP) and Asian (moderately pigmented; MP) skin. The effects of OLP on melanin export in LP and MP cells were indirectly evaluated by dendricity indices. Results: OLP lowered the intracellular melanin content in B16F10 cells by 26.36%, 24.48%, and 27.71% at 100, 150, and 200 µg/mL (all p < 0.01), respectively, with no effect on the intracellular melanin contents of LP or MP cells. OLP treatment did not influence tyrosinase activity in B16F10 cells or MP cells but significantly enhanced the activity in LP cells. The measurement of extracellular melanin showed significantly higher levels for all three cells, although the levels were considerably higher in MP cells, after the adjustment for OLP autoxidation observed in the cell-free system, which caused melanin-like brown coloration. Furthermore, OLP induced morphological alterations of extended dendrites of B16F10 cells that were retained in LP and MP cells. The quantitation of the dendricity of cells treated with OLP at 200 μg/mL revealed that the total dendrite length was increased by 35.24% (p < 0.05) in LP cells and by 58.45% (p < 0.001) in MP cells without any change in the dendrite number. Conclusions: This is the first study to demonstrate the novel finding that OLP possesses a hitherto unreported unique capacity to stimulate melanocyte dendricity, hence establishing the efficacy for use in increasing human pigmentation. Our findings show significance, with a potential application of the compound OLP for addressing human hypopigmentation disorders in clinical settings or for cosmetic uses related to sunless tanning. Full article