Search Results (101)

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

The molecular regulation and therapeutic applications of brain-derived neurotrophic factor (BDNF)–tropomyosin-related kinase B (TrkB) signaling in major depressive disorder (MDD) through interaction with vascular endothelial growth factor (VEGF) and N-methyl-D-aspartic acid (NMDA) receptors show promise. While BDNF-TrkB signaling is implicated in antidepressant action, the association between BDNFs and depression has not yielded conclusive results. Some studies show decreased BDNF levels in depression, while others indicate that increased BDNF expression in certain brain regions can induce depression susceptibility. The role of BDNFs varies across different brain regions, necessitating further study of individual mechanisms. This regional variability complicates the development of targeted therapies. The antidepressant-like and neurotrophic actions of BDNFs require VEGF signaling, but there is also a reciprocal interdependence, as VEGF actions are dependent on BDNFs. This complex relationship complicates the development of targeted therapies. Full article

Background: Biosimilars are designed to closely resemble their reference biologics in terms of quality, safety, and efficacy, with only minor variations in clinically inactive components and manufacturing methods. Evaluating the safety of switching between these products is critical for healthcare providers and patients. Concerns may arise when transitioning patients from a reference biologic to a biosimilar or between different biosimilars. Objective: This systematic review and meta-analysis aims to evaluate the frequency of adverse events associated with switching from a reference biologic to its biosimilar, using data derived from randomized controlled trials (RCTs). Methods: A comprehensive search was conducted in MEDLINE and Cochrane Central databases from their inception to December 2024. Studies included RCTs that reported adverse reactions related to switching between reference-to-reference biologics and reference-to-biosimilar biologics. Record screening, data extraction, and risk of bias assessment were performed independently by two reviewers. Random effects models were applied to pool crude outcome data. Results: The search identified 668 abstracts, with an additional 14 studies found through hand-searching review articles. Of these, 12 trials involving 1326 participants in the reference–reference group and 1176 participants in the reference–biosimilar group met the inclusion criteria. The frequency of adverse events, serious adverse events, and treatment-related adverse events did not differ significantly between the reference–reference and reference–biosimilar groups: relative risk (RR) = 0.96 (95% confidence interval [CI], 0.85–1.08), RR = 1.06 (95% CI, 0.68–1.65), and RR = 1.03 (95% CI, 0.66–1.59), respectively. Heterogeneity was generally low to moderate across outcomes, and subgroup analyses based on disease type and reference product showed no differences. Conclusions: Switching between reference biologics and biosimilars demonstrates a comparable safety profile, suggesting that both options are viable. However, the findings are limited by the small number of trials and the scope of patient populations and products studied. PROSPERO registration number: CRD42021267205. Full article

Background/Objectives: Dupilumab was recently approved to treat eosinophilic phenotypes of chronic obstructive pulmonary disease (COPD). This systematic review aimed to collect and appraise the efficacy and safety of dupilumab to treat patients with COPD. Methods: Databases searched included Ovid Medline, Embase, Web of Science, Directory of Open Access Journals, and International Pharmaceutical Abstracts. Experimental and observational studies, including case reports/series, were eligible for inclusion. Reports were independently screened, appraised, and extracted by three investigators; disagreements were resolved through discussion and agreement. Quality appraisal was conducted using the Cochrane Risk of Bias Tool 2.0, Newcastle–Ottawa Scale, and JBI Checklist for experimental, observational, and case studies, respectively. Results: A total of 307 unique reports were identified, of which 17 were included in this systematic review. The majority (n = 11, 64.7%) of reports presented evidence from the BOREAS and NOTUS trials, the landmark trials serving as the basis for dupilumab’s approval to treat refractory eosinophilic COPD. The results from this systematic review found that dupilumab reduced exacerbations of COPD in patients treated with inhaled triple therapy and it was well tolerated. Conclusions: When added to inhaled triple therapy, dupilumab may decrease patients’ risk for acute exacerbations of COPD. Additional research is necessary to substantiate these findings for broader generalizability, including populations with non-eosinophilic COPD phenotypes. Full article

Idiopathic nephrotic syndrome (INS) and other pediatric kidney diseases represent significant challenges due to their complex pathogenesis, often involving dysregulated immune responses and renal injury. Biologic therapies, defined as targeted treatments derived from living organisms, have gained traction in managing these conditions, offering a potential shift in therapeutic paradigms. This review examines the current and emerging role of biologics in treating pediatric kidney diseases, focusing on indications, contraindications, adverse effects, therapeutic positioning, and a comparison with alternative immunosuppressive treatments. Full article

Background: Dupilumab, a fully human monoclonal antibody targeting the interleukin (IL)-4/IL-13 pathway, is able to dampen T helper (Th)2-mediated inflammation in several conditions characterized by this particular type of phlogosis. The aim of this study was to review the efficacy and safety of dupilumab treatment in conditions underpinned by Th2-type inflammation in a cohort of real-world patients referred to our outpatient clinic. Methods: Data from all patients with atopic dermatitis, chronic rhinosinusitis with nasal polyps, asthma, and other Th2-type-mediated inflammatory conditions treated with dupilumab were retrospectively reviewed. Results: Twenty-two patients were included in the study: 14 with atopic dermatitis, 5 with chronic rhinosinusitis with nasal polyps, 2 with asthma, and 1 with prurigo nodularis; some of the patients had more than one atopic condition. A complete response was observed in 13 out of 22 patients (59.1%); when partial responses were included in the analysis, the overall response rate was 86.4%. No adverse events were recorded, either locally or systemically. Total IgE levels dropped in all patients, in some cases reaching values close to those typically observed in nonatopic subjects. When eosinophilia was present at baseline, this also normalized during dupilumab treatment. Conclusions: Dupilumab was safe and effective across multiple conditions driven by Th2-type chronic inflammation; effective interference with the Th2-type pathway was inferred by the progressive reduction in serum total IgE levels, which reached the normal range in a fraction of patients, and by the reduction in peripheral blood eosinophil counts. Further studies in different Th2-mediated diseases are warranted. Full article

Background/Objectives: Perilla frutescens has historically been used to protect against inflammation and redox stress. This has been partly attributed to its high polyphenolic content; however, polyphenolic components in Perilla extract remain incompletely defined. This study aimed to characterise the polyphenolic composition in Perilla extract and evaluate its effect on the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), regulating antioxidant defenses during inflammation and oxidative stress. Methods: Hot water extraction from Perilla leaves was followed by fractionation using four solvents of different polarity, namely methanol, butanol, ethyl acetate and ether. The polyphenolic composition of these fractions was analysed using RP-HPLC, and some of these compounds were quantified. The total phenolic, flavonoid, and ortho-diphenolic contents of each Perilla fraction were determined. The antioxidant activity was assessed using metal cation reduction and radical scavenging assays. A dual-luciferase assay using a human NQO1 ARE-luciferase reporter plasmid was employed to quantify Nrf2 activation by the Perilla fractions. Results: HPLC analysis identified 35 polyphenolic compounds, with the highest phenolic content present in the polar fractions and rosmarinic acid being the major constituent. Radical scavenging tests (DPPH and ABTS) confirmed the highest antioxidant capacity in the polar fractions. On cells in vitro, the methanol Perilla fraction displayed the strongest antioxidant activity, showing up to a 1.5-fold increase in human NQO1 ARE-luciferase reporter induction. Conclusions: This study has shown that Perilla extract contains a diversity of polyphenolic compounds contributing to its potent antioxidant effects, with methanol and butanol being the most efficient extraction solvents. While rosmarinic acid is expected to be the major contributor towards providing protection against inflammation and redox stress, further work is required on the synergystic effects between different polyphenols. Full article

Psoriatic arthritis (PsA) is a systemic inflammatory condition affecting the joints, spine, and entheses, as well as the skin and nails. It affects about 6–42% of patients with psoriasis (PsO), with a prevalence of 1–2 per 1000. PsA can precede skin disease in 7–14% of patients. Different clinical domains may be involved, including psoriatic skin disease, peripheral arthritis, axial involvement, dactylitis, enthesitis, and nail disease. Psoriatic arthritis is a complex, systemic inflammatory condition. While the exact mechanisms underlying PsA are not fully understood, it is believed that the disease arises from a combination of genetic predisposition and environmental triggers that lead to inflammatory processes in both the skin and joints. The treatment approach for PsA focuses on controlling inflammation, improving symptoms, and preventing joint damage. Early initiation of treatment is crucial for achieving better functional outcomes. Various therapeutic agents are available that target different inflammatory pathways. In this review article, various treatment options, focusing on biologic and targeted synthetic disease-modifying antirheumatic drugs, are discussed. Full article

Glandirana is a genus of frogs that includes G. rugosa, G. emeljanovi, G. minima, G. tientaiensis, G. susurra, G. nakamurai and G. reliquia. These frogs produce antimicrobial peptides (AMPs), which are endogenous antibiotics that possess antibacterial, antifungal, antiviral and anti-endotoxin activity and help keep the hosts free from infections. In these activities, microbial death is promoted by membranolytic mechanisms that are mediated by the cationic charge and amphiphilic α-helical structures of these peptides. In general, these peptides are selective for microbes, showing low levels of hemolytic and cytotoxic activity, as well as possessing other biological activities, including anticancer, antioxidative and insulinotrophic action. In this review, a brief overview of AMPs with a focus on those from amphibians is provided, along with the phylogeny and nomenclature of frogs and AMPs from the Glandirana genus. This review then provides a comprehensive, in-depth description of the antimicrobial and other biological activities of all AMPs produced by known frogs of the Glandirana for the period 1994 to 2024. This description includes a detailed discussion of the structure/function relationships and mechanisms involved in the membrane interactions that drive these biological activities, with comparisons between AMPs from the same frog and between frogs across the genus. Based on their biological properties, AMPs from frogs of the Glandirana genus have been proposed for investigation as potential therapeutic agents, such as in the treatment of cancers and diabetes, as well as antimicrobial agents in areas, including crop protection, the food industry and oral hygiene. Full article

Background: Introducing unnatural base pairs into a natural, double-stranded DNA construct is a powerful tool within synthetic biology. Accordingly, the ability to detect these unnatural base pairs has many applications, including the study and detection of semisynthetic organisms. Objective and Methods: The work described here aimed to select human antibodies for the specific recognition of Hirao’s base pair dDs–dPn in various natural DNA contexts by using a combination of phage and yeast display technologies. Results: We selected a total of six antibodies in yeast-displayed scFv format, and further tested three of these antibodies in soluble form as minibodies and IgGs. We also describe an assay that can be used to detect plasmids containing dDs–dPn pair. Conclusions: Our antibodies did not afford the desired specificity or sensitivity for detection of a single unnatural base pair among thousands of natural. However, our data indicate not only that such detection is possible but also that these antibodies may be candidates for further affinity and specificity maturation. Full article

Ustekinumab is a fully human IgG1k monoclonal antibody that binds with high affinity and specificity to the p40 subunit of interleukins (IL-) 12 and 23, inhibiting their activity by preventing binding to their receptors. The European extension of the patent (Supplementary Protection Certificate) of ustekinumab expired on 20 July 2024. Biosimilar alternatives to ustekinumab are now an additional option for treating patients. The efficacy data for this drug in moderate-to-severe psoriasis obtained both from clinical trials and indirect comparisons through meta-analyses, are superior to those of etanercept and adalimumab, and its safety profile is more favorable than that of tumor necrosis factor (TNF) inhibitors. Several ustekinumab biosimilars have already been approved by regulatory agencies: between October 2023 and October 2024, Wezlana^® (Amgen ABP 654), Uzpruvo^® (Alvotech AVT04) and Pyzchiva^® (Samsung/Bioepis SB17) have been approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). SteQeyma^® (Celltrion Healthcare CT-P43) was approved by the EMA in August 2024. Otulfi^® (Fresenius Kabi/Formycon) was approved by the FDA in October 2024. Several other potential biosimilar candidates are under development, including BAT2206 (Bio-Thera), DMB-3115 (Dong-A ST), QX001S (Qyuns Therapeutic), BFI-751 (BioFactura), NeuLara (Neuclone), ONS3040 (Oncobiologics), and BOW090 (Epirus Biopharmaceuticals). In most cases, these monoclonal antibodies are expressed in cell lines (e.g., Chinese Hamster Ovary, CHO) different from those used for the originator (Sp2/0 spleen cell murine myeloma); of note, the cell line of origin is not a requirement for biosimilarity in the totality-of-evidence comparison exercise and may facilitate the production and reduce the immunogenicity of biosimilars originated in CHO cultures. This narrative review summarizes the available data on characteristics of the full comparability exercises and comparative clinical trials of these drugs. Full article

Antiretroviral therapy (ART) has significantly extended the lifespan of people living with Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS), thereby transforming the disease into a manageable chronic condition. However, this increased longevity has led to a higher incidence of non-AIDS-defining cancers (NADCs) among this population. In this holistic review, we explore the complex interactions between HIV, ART, and cancer development, focusing on how ART influences tumor initiation and progression in people living with HIV/AIDS (PLWHA). Our findings from this reveal several critical aspects of cancer risk in PLWHA. Firstly, while ART restores immune function, it does not fully normalize it. Chronic immune activation and persistent inflammation continue to be prevalent, creating a conducive environment for oncogenesis. Additionally, PLWHA are more susceptible to persistent infections with oncogenic viruses such as human papillomavirus (HPV) and Epstein–Barr virus (EBV), further increasing cancer risk. Some ART drugs have been implicated in genotoxicity and mitochondrial dysfunction, potentially promoting tumorigenesis. ART-induced metabolic changes, including insulin resistance and dyslipidemia, are also associated with heightened cancer risk. Common NADCs in PLWHA include lung cancer, liver cancer, anal cancer, and Hodgkin lymphoma, each with distinct etiologies linked to both HIV-related and ART-related factors. The interplay between HIV infection, chronic inflammation, immune restoration via ART, and the direct effects of ART drugs creates a unique cancer risk profile in PLWHA. Although ART reduces the incidence of AIDS-defining cancers, it does not confer the same protective effect against NADCs. Persistent HIV-related inflammation and immune activation, despite viral suppression, are key factors in cancer development. Additionally, long-term exposure to ART may introduce new oncogenic risks. These insights highlight the need for integrated cancer screening and prevention strategies tailored to PLWHA. Future research is needed to focus on identifying biomarkers for early cancer detection and developing ART regimens with lower oncogenic potential. Healthcare providers should be vigilant in monitoring PLWHA for cancer and adopt comprehensive screening protocols to mitigate the increased cancer risk associated with ART. Full article

Protein aggregation may lead to detrimental changes in brain and several other tissues. Amyloids or large protein aggregates are formed in different brain areas under multiple diseases classified as proteinopathies. However, our understanding of the initiation, elongation, and spread of amyloid aggregates is limited. Our current knowledge about these diseases is generic and we lack specific mechanisms for several diseases affecting memory, movement, and behavior. Multiple studies have indicated the involvement of vesicular transport in the spread of aggregates formed inside the brain. For example, the trafficking of amyloid precursor protein (APP) occurs from Golgi to Endosome using an adapter protein complex. Amyloids, once formed, may also affect cholesterol (an important membrane constituent), homeostasis, and overall membranous transport. A disruption of vesicular transport could be deleterious for synaptic neurotransmission. Alterations caused by amyloid proteins in vesicular transport may form a feedback loop and thus contribute further to the pathogenesis of Alzheimer’s disease (AD) and many others. In this review, we are providing recent updates on this crisscross puzzle and exploring an evolving correlation between amyloid formation and vesicular transport. Full article