Biologics (Basel, Switzerland)最新文献

{"title":"De Novo Protein Design Enables Targeting of Intractable Oncogenic Protein-Protein Interfaces.","authors":"Varshika Ram Prakash, Yusuf Najy, Kalel Garrett, Brian F P Edwards, Benjamin L Kidder","doi":"10.3390/biologics6010009","DOIUrl":"10.3390/biologics6010009","url":null,"abstract":"<p><strong>Background/objectives: </strong>Protein-protein interactions (PPIs) involving oncogenic drivers remain among the most intractable targets in cancer biology due to their dynamic conformations and limited accessibility to conventional small molecules. Although antibodies and inhibitors have achieved clinical success against targets such as PD-1/PD-L1 and MYC, challenges persist related to tissue penetration, intracellular delivery, resistance, and incomplete blockade of key interface hotspots. The objective of this study is to develop an integrated computational framework for systematically designing hotspot-conditioned de novo miniprotein binders to target these interfaces.</p><p><strong>Methods: </strong>We present DesignForge, a computational protein design pipeline that integrates energetic hotspot identification, generative backbone design, sequence optimization, and structural confidence evaluation. The framework combines hotspot mapping using an open force-field-based energetic analysis module with generative backbone sampling using BindCraft, sequence optimization using ProteinMPNN, and structural validation using AlphaFold2. This in silico pipeline was applied to three representative oncogenic interfaces: PD-1/PD-L1, MYC/MAX, and KRAS/RAF.</p><p><strong>Results: </strong>Computationally generated designs exhibited high predicted structural confidence, favorable interface energetics, and consistent engagement of identified hotspot residues across targets. AlphaFold2-Multimer structural modeling indicated that the candidate PD-1 mimetic scaffolds, MYC/MAX interface binders, and KRAS interaction candidates can adopt conformations compatible with the target interfaces. Energetic contact analysis further supported predicted engagement of key hotspot residues. These findings support the computational feasibility of hotspot-conditioned binder generation using a unified design workflow.</p><p><strong>Conclusions: </strong>DesignForge provides a reproducible computational framework for hotspot-guided de novo protein binder design targeting oncogenic protein-protein interfaces. The designs reported here represent computational predictions derived from structural modeling and energetic analysis. Experimental biochemical and cellular validation will be required to determine the functional activity of the proposed binders.</p>","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13221196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148140256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review","authors":"Daniela Judith Romero, George S. Hussey, Héctor Capella‐Monsonís","doi":"10.3390/biologics5030028","DOIUrl":"https://doi.org/10.3390/biologics5030028","url":null,"abstract":"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.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":"5 3","pages":"28-28"},"PeriodicalIF":0.0,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.mdpi.com/2673-8449/5/3/28/pdf?version=1757041271","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147883757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Anti-DFS70 in the Diagnosis of Systemic Autoimmune Rheumatic Diseases","authors":"Liudmila Zotova, Victoria Kotova, Zakhar Kuznetsov","doi":"10.3390/biologics3040019","DOIUrl":"https://doi.org/10.3390/biologics3040019","url":null,"abstract":"The diagnosis of systemic autoimmune rheumatic disease (SARD) or its exclusion is carried out taking into account the results of immunological studies, primarily antinuclear antibodies (ANA) and specific autoantibodies. Often, during ANA analysis via indirect immunofluorescence reaction on cellular and tissue substrates, a dense fine speckled 70 (DFS70) fluorescence pattern is observed. Studies on the diagnostic significance of antibodies to anti-DFS70 allow for optimizing the stepwise diagnosis of SARD. Currently, a two-step strategy for laboratory diagnostic investigation is recommended: in the first step, ANA screening is performed, and in the second step, patients with positive results undergo confirmatory tests to detect specific antibodies against individual nuclear antigens. The detection of anti-DFS70 in ANA-seropositive patients without clinical and/or other specific serological markers characteristic of a particular disease within the SARD group may be considered a negative prognostic marker. Also, in the process of decision making in clinical practice, we should remember that anti-DFS70 can be found in the blood of patients with a different, non-SARD pathology and that most people showing anti-DFS70 are healthy individuals.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":"8 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134992172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Metagenomics the Future Routine Diagnosis Tool for Brain Abscesses? About a Case","authors":"William Lars, Claudie Lamoureux, Jérémy Picard, Christophe Rodriguez, Clémence Beauruelle, Luc Quaesaet, Geneviève Héry-Arnaud, Séverine Ansart, Anne Coste","doi":"10.3390/biologics3040018","DOIUrl":"https://doi.org/10.3390/biologics3040018","url":null,"abstract":"Shotgun metagenomics (SMg) usefulness for brain abscess diagnosis is not known. We describe a case of brain abscess diagnosed with SMg and provide a review of the literature. A 70-year-old woman was diagnosed with multiple brain abscesses. Standard culture techniques and 16S rRNA gene sequencing of abscess samples remained negative. SMg finally revealed the presence of sequences from Streptococcus anginosus and Fusobacterium nucleatum, leading to antimicrobial treatment adaptation and corticosteroids initiation. The patient finally recovered. A literature review retrieved fifteen other cases of brain abscesses diagnosed with SMg. SMg results led to changes in patient management in most cases. The existing literature about the performances of SMg, its advantages, future evolutions, and limitations is then discussed. SMg place in routine should be evaluated and defined through prospective studies.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":"142 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136263597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoantigens: The Novel Precision Cancer Immunotherapy","authors":"Tiantian Zhang, Esaw Kurban, Zhe Wang","doi":"10.3390/biologics3040017","DOIUrl":"https://doi.org/10.3390/biologics3040017","url":null,"abstract":"The past few decades have witnessed the remarkable progress of cancer immunotherapy. Neoantigens, also known as tumor-specific antigens, are novel antigens originating from tumor-specific alterations such as genomic mutations, dysregulated RNA splicing, and post-translational modifications. Neoantigens, recognized as non-self entities, trigger immune responses that evade central and peripheral tolerance mechanisms. With the notable strides in cancer genomics facilitated by next-generation sequencing technologies, neoantigens have emerged as a promising avenue for tumor-specific immunotherapy grounded in genomic profiling-based precision medicine. Furthermore, a growing number of preclinical and clinical investigations are harnessing the potential synergies between neoantigens and other immunotherapies such as adoptive cell therapy and immune checkpoint inhibitors. In this review, we will provide a comprehensive perspective encompassing the trajectory of neoantigens, neoantigen design strategies, and the diverse array of clinical applications inherent in immunotherapy strategies centered around neoantigens. Moreover, we delve into the inherent prospects and challenges that accompany the clinical adoption of neoantigen-based immunotherapies while also putting forth potential solutions to address these challenges.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":"31 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135883243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose-Dependency of the Glycemic Response to Polyphenol-Rich Sugarcane Extract (PRSE)","authors":"Matthew Flavel, Julian Neoh, Kosta Fremielle Lim","doi":"10.3390/biologics3040016","DOIUrl":"https://doi.org/10.3390/biologics3040016","url":null,"abstract":"Foods high in available carbohydrates, such as plain white sugar or sucrose, increase the postprandial blood glucose levels that may aggravate the risk of developing Type 2 Diabetes. One class of compounds that is gaining popularity due to its potential application in reducing the release of sugars for absorption into the body is polyphenols. The study aimed to investigate the effect of adding different doses of polyphenol-rich sugarcane extract (PRSE) to sucrose to lower the postprandial glycemia of the participants in a non-randomized study. The four test samples’ Glycemic Index (GI) values were calculated based on the standardized recommended methodology by comparing the area under the curve (AUC) of the test samples against the glucose standard. The glucose concentration curves were similar for the four test foods. The glucose response curves, and GI values were decreased in a dose-dependent manner. The results of this study indicate that PRSE-coated sugar can lower postprandial glycemia in normal individuals. Additionally, decreasing GI values with an increasing concentration of polyphenols suggests a dose-dependent effect between polyphenol levels and GI.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":"124 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136358385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robust Porcine GFR Measurement with Radiotracers and Only Late Blood Samples","authors":"Lars Jødal, Juan Ignacio Brignone, Pui-Ki Chan Ladefoged, Lars Lund, Trine Borup Andersen","doi":"10.3390/biologics3040015","DOIUrl":"https://doi.org/10.3390/biologics3040015","url":null,"abstract":"(1) Pigs are physiologically very relevant as animal models of human physiology. Radiotracer methods for porcine GFR (glomerular filtration rate) determination exist but require full-curve blood sampling or the application of correction formulas, which vary among studies. (2) We used porcine GFR data (40 datapoints from 20 juvenile pigs) for which the GFR was measured as the plasma clearance of [99mTc]Tc-DTPA. The reference clearance (Cl, GFR; range 41–85 mL/min) was measured from the full curve under the data. For simpler determination, an approximate clearance, Cl1, was based on the last five blood samples (acquired 120–240 min post injection). (3) The following formula for the GFR was developed: Cl = 1.27 · (Cl1)0.92. The spread (SD) was within 4% of the reference GFR. A comparison with the literature data showed that our correction formula was robust in pigs of various breeds, sizes up to approximately 200 kg, and GFRs up to approximately 400 mL/min, with a spread of up to 8%. The formula was also applicable for iohexol as the tracer. (4) A formula was developed that allows porcine GFR to be measured using only 4–5 late blood samples. This new formula can be applied across a wide range of swine breeds, animal sizes, and GFR ranges, allowing for robust determination of the GFR in pigs without full-curve blood sampling and without urine collection.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135246713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dawn of In Vivo Gene Editing Era: A Revolution in the Making","authors":"Sarfaraz K. Niazi","doi":"10.3390/biologics3040014","DOIUrl":"https://doi.org/10.3390/biologics3040014","url":null,"abstract":"Gene or genome editing (GE) revises, removes, or replaces a mutated gene at the DNA level; it is a tool. Gene therapy (GT) offsets mutations by introducing a “normal” version of the gene into the body while the diseased gene remains in the genome; it is a medicine. So far, no in vivo GE product has been approved, as opposed to 22 GT products approved by the FDA, and many more are under development. No GE product has been approved globally; however, critical regulatory agencies are encouraging their entry, as evidenced by the FDA issuing a guideline specific to GE products. The potential of GE in treating diseases far supersedes any other modality conceived in history. Still, it also presents unparalleled risks—from off-target impact, delivery consistency and long-term effects of gene-fixing leading to designer babies and species transformation that will keep the bar high for the approval of these products. These challenges will come to the light of resolution only after the FDA begins approving them and opening the door to a revolution in treating hundreds of untreatable diseases that will be tantamount to a revolution in the making. This article brings a perspective and a future analysis of GE to educate and motivate developers to expand GE products to fulfill the needs of patients.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135769267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Immunopathogenesis of Multiple Sclerosis: The Dynamic Dance of Plasmablasts and Pathogenic T Cells","authors":"Yasunari Matsuzaka, Ryu Yashiro","doi":"10.3390/biologics3030013","DOIUrl":"https://doi.org/10.3390/biologics3030013","url":null,"abstract":"Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, characterized by multiple lesions occurring temporally and spatially. Additionally, MS is a disease that predominates in the white population. In recent years, there has been a rapid increase in the number of patients, and it often occurs in young people, with an average age of onset of around 30 years old, but it can also occur in children and the elderly. It is more common in women than men, with a male-to-female ratio of approximately 1:3. As the immunopathogenesis of MS, a group of B cells called plasmablasts controls encephalomyelitis via IL-10 production. These IL-10-producing B cells, called regulatory B cells, suppress inflammatory responses in experimental mouse models of autoimmune diseases including MS. Since it has been clarified that these regulatory B cells are plasmablasts, it is expected that the artificial control of plasmablast differentiation will lead to the development of new treatments for MS. Among CD8-positive T cells in the peripheral blood, the proportion of PD-1-positive cells is decreased in MS patients compared with healthy controls. The dysfunction of inhibitory receptors expressed on T cells is known to be the core of MS immunopathology and may be the cause of chronic persistent inflammation. The PD-1+ CD8+ T cells may also serve as indicators that reflect the condition of each patient in other immunological neurological diseases such as MS. Th17 cells also regulate the development of various autoimmune diseases, including MS. Thus, the restoration of weakened immune regulatory functions may be a true disease-modifying treatment. So far, steroids and immunosuppressants have been the mainstream for autoimmune diseases, but the problem is that this kills not only pathogenic T cells, but also lymphocytes, which are necessary for the body. From this understanding of the immune regulation of MS, we can expect the development of therapeutic strategies that target only pathogenic immune cells.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134913564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Current Review on the Role of Prebiotics in Colorectal Cancer","authors":"Anna Shrifteylik, Morgan Maiolini, Matthew E. Dufault, Daniel L Austin, B. Subhadra, Purushottam Lamichhane, Rahul Renukadas Deshmukh","doi":"10.3390/biologics3030012","DOIUrl":"https://doi.org/10.3390/biologics3030012","url":null,"abstract":"Colorectal cancer (CRC) is one of the leading causes of death in the United States and worldwide. Recent evidence has corroborated a strong correlation between poor diet and the development of CRC, and further research is being conducted to investigate the association between intestinal microbiome and the development of cancer. New studies have established links with certain foods and synthetic food compounds that may be effective in reducing the risk for carcinogenesis by providing protection against cancer cell proliferation and antagonizing oncogenic pathways. Prebiotics are gaining popularity as studies have demonstrated chemo-preventive as well as anticancer potential of prebiotics. This paper aims to discuss the wide definition and scope of prebiotics by reviewing the studies that provide insights into their effects on human health in the context of colorectal cancer.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43790048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}