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17 pages, 2237 KB  
Article
Assessment of Population Immunity Against Peste des Petits Ruminants in Goats and Sheep in India After the Second Annual Mass Vaccination Implemented Under the National PPR Eradication Programme
by Kirubakaran Vinod Kumar, Rakshit Ojha, Ramachandra Deshpande, Shweta Priya, Akshatha Lokanath Goudar, Umathul Ayesha, Ponnidurai Malini, Prajakta Prashant Bokade, Anand Asha, Gangarajareddy Deekshitha, Annett Helcita Dsouza, Archana Pal, Akula Dakshitha, Shakuntala Krishnaiah Harshitha, Mahadevappa Swathi, Roopa Anandamurthy Hemanth, Lakshmipathy Archudhan, Shanmugam ChandraSekar, Kuralayanapalya Puttahonnappa Suresh, GurrappaNaidu Govindaraj, Nayakvadi Shivasharanappa, Paramanandham Krishnamoorthy, Sujit Nayak, Njeumi Felix, Baldev Raj Gulati, Satya Parida and Vinayagamurthy Balamuruganadd Show full author list remove Hide full author list
Viruses 2026, 18(8), 839; https://doi.org/10.3390/v18080839 - 30 Jul 2026
Abstract
This study evaluated population immunity against peste des petits ruminants (PPR) in sheep and goats in India following the second annual round of mass vaccination conducted under the National PPR Eradication Programme (PPR EP), launched in 2023 in accordance with the national strategic [...] Read more.
This study evaluated population immunity against peste des petits ruminants (PPR) in sheep and goats in India following the second annual round of mass vaccination conducted under the National PPR Eradication Programme (PPR EP), launched in 2023 in accordance with the national strategic plan. A cross-sectional post-vaccination evaluation (PVE) was conducted during August 2024 and April 2026 to assess the herd or population immunity under field conditions, in line with the WOAH and FAO Global Control and Eradication Strategy (GCES) of the PPR Global Eradication Programme (PPR GEP) 2030. A total of 52,133 serum samples were collected within 90 days post vaccination from sheep and goats across three age groups, 6–12 months (n = 18,002), 1–2 years (n = 17,316), and >2 years (n = 16,842), representing 1666 epidemiological units across multiple taluks and districts in 20 Indian states and Union Territories. Serum samples were tested for antibodies against PPR virus using in-house IVRI developed hemagglutinin (H) protein monoclonal antibody based competitive ELISA. The study revealed an overall population immunity of 72%, with age-wise PPRV antibody prevalence of 70.8%, 71.8%, and 72.6% in the 6–12-month, 1–2-year, and >2-year age groups, respectively. Statistical analysis showed significant associations (p < 0.005) between PPRV seropositivity and host factors, including species. Population immunity increased markedly from 41% (pre-vaccination sero-prevalence) in 2023 to nearly 72% by 2025-26 following two consecutive rounds of annual vaccination, accompanied by a substantial reduction in confirmed outbreaks from 57 during 2023 to 20 in 2025 in these 20 states/Union Territories. Notably, about 14.5% of epidemiological units remained below 30% seroprevalence, indicating targeted gaps requiring intensified vaccination. Overall animal vaccination coverage exceeded 95% among small ruminants aged above four months, approaching the population immunity threshold of 70 to 80%. These findings highlight the critical role of sustained successive mass vaccination campaigns in achieving and maintaining protective herd/population immunity, thereby supporting national and global PPR eradication goals. Full article
(This article belongs to the Section Animal Viruses)
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41 pages, 2484 KB  
Review
Targeting EGFR Endocytosis and Signaling for Cancer Drug Delivery and Cancer Treatment
by Xinmei Chen and Zhixiang Wang
Cancers 2026, 18(15), 2451; https://doi.org/10.3390/cancers18152451 - 30 Jul 2026
Abstract
The epidermal growth factor receptor (EGFR) was the first receptor tyrosine kinase identified soon after v-Src was recognized as a tyrosine kinase. EGFR signaling begins when EGF binds to EGFR at the cell surface, inducing receptor dimerization, activation, and autophosphorylation. The resulting phosphotyrosine [...] Read more.
The epidermal growth factor receptor (EGFR) was the first receptor tyrosine kinase identified soon after v-Src was recognized as a tyrosine kinase. EGFR signaling begins when EGF binds to EGFR at the cell surface, inducing receptor dimerization, activation, and autophosphorylation. The resulting phosphotyrosine sites recruit downstream effectors that activate signaling cascades such as the RAS-RAF-MEK-ERK and PI3K-Akt pathways, thereby regulating cell growth, proliferation, and survival. EGF binding also promotes EGFR endocytosis, which can direct the receptor to lysosomal degradation. Aberrant EGFR activity is associated with many cancers, and the receptor has been therapeutically targeted using small-molecule tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs). Furthermore, EGFR endocytosis has been exploited for the targeted delivery of anticancer agents into EGFR-expressing cancer cells through antibody–drug conjugates (ADCs) and antibody–nanoparticle conjugates (ANCs). Although ADCs and ANCs both utilize mAbs as homing mechanisms to recognize cancer-associated antigens, they further harness EGFR endocytosis to deliver therapeutic payloads directly into target cells. In this review, we briefly discuss EGFR structure, activation, signaling, and endocytosis, as well as the mechanisms underlying EGFR function in cancer development. We then focus on current advances and future perspectives in using EGFR endocytosis pathways to improve targeted cancer drug delivery and therapy, particularly in the context of ANCs. Full article
(This article belongs to the Collection Cell Signaling in Cancer and Cancer Therapy)
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18 pages, 2384 KB  
Article
A Panel of VHH Antibodies Against Sabin Type 1 Poliovirus D-Antigen Reveals Strain-Specific and Cross-Serotype Reactivity
by Maya Ermakova, Sergey Ivanov, Olga Shmeleva, Nadezhda Borisenko, Anna Zyrina, Stepan Chumakov, Igor Levin, Regina Yakupova, Marina Merkulova, Anna Shishova, Yury Ivin, Anastasia Piniaeva, Alexandra Siniugina and Aydar Ishmukhametov
Viruses 2026, 18(8), 833; https://doi.org/10.3390/v18080833 - 29 Jul 2026
Abstract
Vaccination remains the primary strategy for poliomyelitis prevention. The D-antigen of poliovirus is a critical component of inactivated polio vaccines, as it induces the production of neutralizing antibodies and provides protective immunity. Therefore, the development of quantitative immunoassays for monitoring D-antigen content during [...] Read more.
Vaccination remains the primary strategy for poliomyelitis prevention. The D-antigen of poliovirus is a critical component of inactivated polio vaccines, as it induces the production of neutralizing antibodies and provides protective immunity. Therefore, the development of quantitative immunoassays for monitoring D-antigen content during vaccine production is an important task. In this study, we generated recombinant camelid single-domain antibodies (VHHs) specific for the D-antigen of Sabin poliovirus type 1 and evaluated their antigen specificity. The obtained VHH antibodies demonstrated strong binding to the native D-antigen of Sabin type 1 poliovirus. Furthermore, the use of clone S1-C7 as a capture antibody in combination with Sabin type 1-specific polyclonal antibodies for detection revealed differential recognition of the vaccine-derived Sabin type 1 and homologous wild-type Mahoney strains. Notably, such discrimination was not observed when polyclonal antibodies were used alone, indicating that incorporation of VHH S1-C7 into the assay enhances strain-specific antigen recognition. In a neutralization assay, clone S1-C7 exhibited in vitro neutralizing activity against Sabin type 1 poliovirus. One clone, S1-D9, demonstrated cross-reactivity with all three poliovirus serotypes, suggesting recognition of a conserved epitope in the capsid and potential utility as a universal detection antibody. The generated VHH antibodies represent promising analytical tools for poliovirus antigen characterization. Together with S1-C7, they enable the discrimination of both D- and C-antigen forms as well as vaccine-derived and wild-type strains. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research, 2nd Edition)
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33 pages, 8691 KB  
Review
Virulence and Resistance Mechanisms in Multidrug-Resistant Acinetobacter baumannii
by Priya Rajendran, Rameshkumar Marimuthu Ragavan, Renuka James, Bindu Dhanapal, Mullai Venkatachalam, Jeevarahini Reghupathy and Ramachandran Vignesh
Pathogens 2026, 15(8), 798; https://doi.org/10.3390/pathogens15080798 - 28 Jul 2026
Abstract
Acinetobacter baumannii, a Gram-negative opportunistic bacterium in the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, A. baumannii, Pseudomonas aeruginosa and Enterobacter spp.), has emerged as a leading cause of nosocomial infections worldwide. It is known to [...] Read more.
Acinetobacter baumannii, a Gram-negative opportunistic bacterium in the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, A. baumannii, Pseudomonas aeruginosa and Enterobacter spp.), has emerged as a leading cause of nosocomial infections worldwide. It is known to possess diverse virulence traits and antimicrobial resistance, making it a critical priority pathogen on the World Health Organization’s 2024 Bacterial Priority Pathogens List. Carbapenem-resistant A. baumannii (CRAB) is currently endemic across several continents, with global carbapenem resistance exceeding 70% in healthcare settings and multidrug-resistant infections being associated with alarming mortality rates. This review comprehensively discusses the molecular underpinnings of A. baumannii pathogenesis and virulence, detailing the array of factors coordinated by complex regulatory networks. The convergence of this pathogen’s virulence and antimicrobial resistance traits, resulting in multidrug resistance, leaves clinicians with only a handful of therapeutic options. The review also discusses upcoming therapeutic strategies, including phage therapy, antimicrobial peptides, monoclonal antibodies, photodynamic therapy, and vaccine candidates in the pipeline. While emerging therapeutics show promise, several challenges remain, and integrated approaches are warranted to efficiently combat A. baumannii’s virulence and resistance armamentarium. Full article
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15 pages, 3570 KB  
Article
Purifying Bevacizumab via Affinity Precipitation Using Branched Peptide
by Joaquin Amir Eloy, Jésica Ayelén Rodríguez, Gabriela Romina Barredo-Vacchelli, Magalí Sol García-Cabanas, Débora Eugenia Rinaldi, Barbara Richichi, Marco Marradi and Silvia Andrea Camperi
J. Pharm. BioTech Ind. 2026, 3(3), 18; https://doi.org/10.3390/jpbi3030018 - 28 Jul 2026
Abstract
The therapeutic monoclonal antibody bevacizumab is typically purified using protein A affinity chromatography, a highly effective but costly method. Affinity-based precipitation for antibody purification is a lower-cost approach. In this work, a precipitation protocol was developed for bevacizumab purification using a branched peptide [...] Read more.
The therapeutic monoclonal antibody bevacizumab is typically purified using protein A affinity chromatography, a highly effective but costly method. Affinity-based precipitation for antibody purification is a lower-cost approach. In this work, a precipitation protocol was developed for bevacizumab purification using a branched peptide (Ac-PHQGQHIG-Ahx3)2-K-Ahx3-PHQGQHIG-NH2, which contains the epitope PHQGQHIG that is responsible for interacting with bevacizumab. The peptide was synthesised by a microwave-assisted solid-phase peptide method, employing LiCl as an additive to prevent aggregation and ensure high purity and yield. Three molecules of 6-aminohexanoic acid were introduced between each epitope branch as spacer arms to promote the formation of cyclic complexes. Bevacizumab purification from cell-free culture broth was achieved through a fractional precipitation process. First, a negative precipitation step using (NH4)2SO4 1.18 M was performed to remove contaminants. Afterwards, 5 moles of peptide per mol of bevacizumab was added to the supernatant, together with additional (NH4)2SO4, to reach a final concentration of 1.20 M. Under these conditions, bevacizumab was recovered in the precipitate with 98% purity and a yield of 73%. In addition to being recyclable, the peptide’s relatively low production cost could enable the development of a single-use purification process, which would be particularly advantageous for biopharmaceutical manufacturing. Full article
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21 pages, 2947 KB  
Article
Efficacy of Bioengineered PD-L1 siRNA for Immunotherapy Against Non-Small Cell Lung Cancer Cells
by Neelu Batra, Mei-Juan Tu, Su Guan, Jonathan W. Riess and Ai-Ming Yu
Non-Coding RNA 2026, 12(4), 26; https://doi.org/10.3390/ncrna12040026 - 27 Jul 2026
Viewed by 75
Abstract
Background/Objectives: Recent advances in immunotherapy have revolutionized cancer treatment, as exemplified by multiple monoclonal antibodies against programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1). Nevertheless, immunotherapeutic antibodies exhibit certain limitations, which drives the development of alternative approaches, such as [...] Read more.
Background/Objectives: Recent advances in immunotherapy have revolutionized cancer treatment, as exemplified by multiple monoclonal antibodies against programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1). Nevertheless, immunotherapeutic antibodies exhibit certain limitations, which drives the development of alternative approaches, such as small interfering RNA (siRNA)-based therapeutics. The aim of this study was to design and produce new biological PD-L1 siRNA (BioRNA/PD-L1-siRNA) molecules and further define their immunotherapeutic efficacy against non-small cell lung cancer (NSCLC) in vitro. Methods: A novel RNA molecular bioengineering platform was employed to produce new BioRNA/PD-L1-siRNA agents. The functions of BioRNA/PD-L1-siRNAs were determined by quantitative PCR, Western blot, immunofluorescence confocal imaging, flow cytometry, and PD-1/PD-L1 blockade assays in human NSCLC cells, alone and co-cultured with human peripheral blood mononuclear cells (PBMCs). Results: After heterologous overexpression and purification of five BioRNA molecules, one siRNA named BioRNA/PD-L1-siRNA-1 was identified as the most effective to selectively suppress human PD-L1 mRNA and protein levels in H460 and H1975 cells. Disruption of PD-1/PD-L1 interactions by BioRNA/PD-L1-siRNA-1 was further demonstrated via a PD-1/PD-L1 blockade bioassay. In addition, the immunomodulatory effectiveness of BioRNA/PD-L1-siRNA-1 was established in co-culture models, as indicated by the induction of T-cell and natural killer cell populations and an increase in specific cytokines and cytotoxic granules, and subsequent enhancement of apoptosis and greater inhibition of NSCLC cell viability. Conclusions: Overall, these findings demonstrate the potential of bioengineered PD-L1 siRNA entities for NSCLC immunotherapy. Full article
(This article belongs to the Section Small Non-Coding RNA)
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18 pages, 6159 KB  
Article
Mass Spectrometry-Based Comparative Evaluation of Forced Glycation Profiles of Therapeutic Monoclonal Antibodies
by Ceren Pamukcu and Ahmet Emin Atik
Biomedicines 2026, 14(8), 1683; https://doi.org/10.3390/biomedicines14081683 - 27 Jul 2026
Viewed by 155
Abstract
Background/Objectives: Glycation, a non-enzymatic post-translational modification, can increase structural heterogeneity in therapeutic monoclonal antibodies (mAbs) and is considered a critical quality attribute in biosimilar (BS) development. Despite extensive studies on glycation in individual mAbs, comparative reports on originator (OR) and BS mAbs [...] Read more.
Background/Objectives: Glycation, a non-enzymatic post-translational modification, can increase structural heterogeneity in therapeutic monoclonal antibodies (mAbs) and is considered a critical quality attribute in biosimilar (BS) development. Despite extensive studies on glycation in individual mAbs, comparative reports on originator (OR) and BS mAbs under forced glycation conditions remain limited. This study aimed to comparatively evaluate the glycation profiles of one OR and three BS anti-tumor necrosis factor-alpha (anti TNF-α) mAb products using integrated mass spectrometry-based methods. Methods: Forced glycation was induced by incubating mAbs with 200 mM D-glucose at 37 °C for 7 days. Intact mass analysis and peptide mapping were used to assess glycation extent and site distribution, respectively. Results: Intact mass analysis revealed a consistent mass increase of approximately 486 Da across all major glycoform species for each mAb product, indicating predominant formation of the tri-glycated mAb population under the applied stress conditions. The overall glycation levels were comparable at the intact level, ranging from 67% to 73% among the OR and BS mAb products. Peptide mapping identified nine glycated lysine (K)-containing peptides, among which three major glycation hotspots (LC:V5 K145/K149, LC:V7 K183, and HC:V7 K250/K252) showed elevated occupancies (~10–16%). These sites collectively accounted for the dominant intact level mass shift. The remaining glycated peptides exhibited only minimal modification levels (<2%). Despite their distinct manufacturing processes, all tested mAb products showed nearly identical site-specific glycation profiles. Conclusions: Forced glycation susceptibility in the studied mAbs was driven by a limited set of structurally preferred K hotspots, leading to highly comparable glycation profiles across OR and BS mAb products. The combined intact mass and peptide mapping strategy provides a robust analytical platform for comparative glycation assessment in BS characterization. Full article
(This article belongs to the Special Issue Advances in Drug Discovery and Development Using Mass Spectrometry)
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12 pages, 412 KB  
Case Report
Anesthetic Management of a Patient with Advanced Anti-Myelin-Associated Glycoprotein Antibody Neuropathy in the Absence of Measurable Quantitative Neuromuscular Responses: A Case Report
by Jun Yamaguchi, Joho Tokumine, Kiyoshi Moriyama and Harumasa Nakazawa
Reports 2026, 9(3), 242; https://doi.org/10.3390/reports9030242 - 27 Jul 2026
Viewed by 125
Abstract
Background and Clinical Significance: Anti–myelin-associated glycoprotein (MAG) antibody polyneuropathy is a rare, chronic IgM-mediated demyelinating peripheral neuropathy predominantly affecting sensory nerves in older adults, commonly in association with monoclonal gammopathy of undetermined significance. Reports describing anesthetic management in patients with this condition remain [...] Read more.
Background and Clinical Significance: Anti–myelin-associated glycoprotein (MAG) antibody polyneuropathy is a rare, chronic IgM-mediated demyelinating peripheral neuropathy predominantly affecting sensory nerves in older adults, commonly in association with monoclonal gammopathy of undetermined significance. Reports describing anesthetic management in patients with this condition remain extremely limited, and no specific guidelines currently exist regarding neuromuscular blocking agent (NMBA) use or neuromuscular monitoring in this population. Case Presentation: A 79-year-old man with anti-MAG antibody polyneuropathy (diagnosed in 2007) and IgM monoclonal gammopathy of undetermined significance developed disproportionate progressive lower-extremity weakness and became wheelchair-dependent following COVID-19 infection in 2020. Preoperative evaluation revealed mildly reduced left ventricular function (ejection fraction 49%), mild chronic kidney disease, and marked intrinsic hand muscle atrophy with absent deep tendon reflexes. He was scheduled for robot-assisted radical cystectomy with ileal conduit diversion under combined general and thoracic epidural anesthesia. Before NMBA administration, neuromuscular monitoring was systematically attempted at the ulnar nerve (electromyography and acceleromyography, up to 60 mA/300 μs) and the corrugator supercilii; despite visible muscle contractions following peripheral nerve stimulation, neither modality produced reliable responses at either site. Given the inability to establish reliable monitoring, the administration of NMBAs was considered to carry an unacceptable risk of a prolonged, undetectable blockade. Anesthesia was maintained with deep sevoflurane (2.0–2.5% end-tidal) and remifentanil infusion without NMBAs, titrated to a bispectral index of 40–60. Tracheal intubation was accomplished via video laryngoscopy without NMBA. The 7 h and 30 min surgery was completed without patient movement or surgical compromise. Postoperatively, the patient developed transient upper airway obstruction attributed to glossoptosis, managed successfully with head elevation and nasopharyngeal airway insertion; supplemental oxygen was required until postoperative day 3, and the patient was discharged from the high-dependency unit on postoperative day 5. Conclusions: No measurable quantitative neuromuscular response could be obtained in this patient with advanced anti-MAG antibody neuropathy, despite appropriate application of electromyography- and acceleromyography-based monitoring and the presence of visible muscle contractions following peripheral nerve stimulation. In such circumstances, avoiding NMBA administration in favor of deep volatile or intravenous anesthesia with opioid supplementation may represent a reasonable, hypothesis-generating approach in carefully selected patients; this observation does not establish the general superiority of an NMBA-free strategy, and caution is warranted before generalizing it to procedures such as robotic surgery, in which profound neuromuscular blockade is often considered desirable. Full article
(This article belongs to the Section Anaesthesia)
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23 pages, 400 KB  
Review
The Use of Biological Therapies in the Treatment of Chronic Rhinosinusitis with Nasal Polyps: Current State of Knowledge
by Joanna Wrona, Zuzanna Krupa, Marta Zawadzka, Julia Rydzek, Adrian Muzyka, Karolina Dorobisz and Katarzyna Pazdro-Zastawny
J. Clin. Med. 2026, 15(15), 5837; https://doi.org/10.3390/jcm15155837 - 26 Jul 2026
Viewed by 361
Abstract
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease with a complex pathogenesis that significantly affects patients’ quality of life. Type 2 inflammation plays a dominant role in its course and is associated with the activation of immune pathways involving interleukins [...] Read more.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease with a complex pathogenesis that significantly affects patients’ quality of life. Type 2 inflammation plays a dominant role in its course and is associated with the activation of immune pathways involving interleukins IL-4, IL-5 and IL-13, eosinophils, and immunoglobulin E. Standard treatment methods, including corticosteroids and surgical interventions, despite their proven efficacy, often fail to provide sustained disease control and are associated with a high rate of recurrence. The aim of this review is not only to summarize the available evidence on biological therapies in CRSwNP, but also to critically evaluate their current position within treatment algorithms, with particular emphasis on patient selection, integration with endoscopic sinus surgery, comparison of available biologic mechanisms, and remaining challenges in personalized treatment strategies. The paper discusses available monoclonal antibodies, such as dupilumab, omalizumab, mepolizumab, and benralizumab, which act by selectively inhibiting key mediators of type 2 inflammation. Analysis of clinical trial results indicates that biological therapies lead to a significant reduction in nasal polyp size, improvement in nasal patency, restoration of olfactory function, and enhancement of quality of life as measured by the SNOT-22 scale. Furthermore, they demonstrate a favourable safety profile and may represent an effective therapeutic option for patients with severe, treatment-resistant disease, particularly in cases with coexisting eosinophilic asthma. Biological therapies represent a breakthrough in the treatment of CRSwNP and align with the concept of personalised medicine. Their role in clinical practice continues to expand; however, further research is required to optimise patient selection and assess long-term treatment outcomes. Full article
(This article belongs to the Section Otolaryngology)
61 pages, 11791 KB  
Review
Therapeutic Applications of Immunobiologics in Autoimmune and Inflammatory Diseases
by Kannan Badri Narayanan
Pharmaceutics 2026, 18(8), 917; https://doi.org/10.3390/pharmaceutics18080917 - 25 Jul 2026
Viewed by 139
Abstract
Immunobiologics or biologics have revolutionized the therapeutic paradigm of autoimmune and inflammatory diseases by selectively targeting and modulating dysregulated immune pathways. Compared with conventional broad-spectrum immunosuppressants, biologics provide a more specific and mechanism-based rational approach, often associated with improved efficacy and reduced adverse [...] Read more.
Immunobiologics or biologics have revolutionized the therapeutic paradigm of autoimmune and inflammatory diseases by selectively targeting and modulating dysregulated immune pathways. Compared with conventional broad-spectrum immunosuppressants, biologics provide a more specific and mechanism-based rational approach, often associated with improved efficacy and reduced adverse events. This review provides a comprehensive overview of the repertoire of therapeutic biologics, their mechanisms of action, pivotal clinical trials, and clinical applications. We discuss biologics targeting T-cell activation, depletion, and adhesion, as well as agents neutralizing pro-inflammatory cytokines, including tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, IL-12, IL-17, IL-22, and IL-23, in addition to B-cell-directed therapies and IgE-modulating agents. Evidence from randomized clinical trials and observational studies highlights the profound therapeutic impact of these agents across a broad spectrum of immune-mediated diseases, including rheumatoid arthritis, psoriasis, systemic lupus erythematosus (SLE), ankylosing spondylitis, chronic spontaneous urticaria, asthma, ulcerative colitis, Crohn’s disease, and other forms of inflammatory bowel disease (IBD). Pharmacodynamic parameters, including receptor-binding affinity and downstream pathway modulation, are critical determinants of therapeutic efficacy, whereas pharmacovigilance remains indispensable for monitoring risks such as immunogenicity, opportunistic infections, and manufacturing-related variability. Continuous regulatory oversight by agencies such as the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) safeguards standards of safety, efficacy, and quality. In parallel, the expanding development of biosimilars offers a key opportunity to enhance affordability and broaden global access to biologic therapies. Despite substantial clinical progress, important challenges persist, including disease heterogeneity, variability in therapeutic response, long-term safety concerns, and issues of cost-effectiveness. Future directions emphasize precision medicine strategies, including biomarker-guided treatment, rationally designed biologic combinations, next-generation antibody engineering, and the development of high-quality biosimilars to improve therapeutic durability, safety, and accessibility equity. By integrating mechanistic insights with clinical outcomes, this review underscores the transformative role of immunobiologics and delineates strategies to optimize their application in the management of autoimmune and inflammatory diseases. Full article
(This article belongs to the Special Issue Medical Applications of Biologic Drugs)
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14 pages, 2324 KB  
Article
Serological Detection of Antibodies Against Mycoplasma bovis Infection by Competitive Enzyme-Linked Immunosorbent Assay (cELISA)
by Wentao Fei, Li Yang, Yuhao Zhao, Zhijie Xiang, Chengwei Fang, Yingyu Chen, Changmin Hu and Aizhen Guo
Vet. Sci. 2026, 13(8), 741; https://doi.org/10.3390/vetsci13080741 - 25 Jul 2026
Viewed by 156
Abstract
Mycoplasma bovis (M. bovis) is a major pathogen in cattle, primarily responsible for bovine respiratory disease complex (BRDC). Characterized by high infectivity and morbidity, M. bovis spreads rapidly within herds and is challenging to control and eradicate, underscoring the need for [...] Read more.
Mycoplasma bovis (M. bovis) is a major pathogen in cattle, primarily responsible for bovine respiratory disease complex (BRDC). Characterized by high infectivity and morbidity, M. bovis spreads rapidly within herds and is challenging to control and eradicate, underscoring the need for early and accurate diagnosis. To address this, we developed a competitive enzyme-linked immunosorbent assay (cELISA) for detecting M. bovis-specific antibodies in bovine sera. The assay uses recombinant MbovP579 protein (1 μg/mL) as the coating antigen and an HRP-conjugated 1A2 monoclonal antibody against MbovP579 (mAb, 0.35 μg/mL) as the competitor. With a cut-off value of 40.69% (percentage inhibition, PI), the cELISA demonstrated apparent sensitivity (90%; 95% CI: 78.64–95.65%) and specificity (96.15%; 95% CI: 90.53–98.49%) using the known background positive and negative sera. In addition, it yielded 100% positivity (9/9) against sera collected from 21 days post-immunization. The assay showed no cross-reactivity with other Mycoplasma species or two common bovine bacterial pathogens, confirming its high specificity. The intra- and inter-assay coefficients of variation (CVs) were below 10%. In clinical evaluations, this cELISA generated a 55.57% positivity rate for field samples (n = 1069) and exhibited 90.46% overall agreement (967/1069; 95% CI: 88.54–92.15%) with the commercial indirect ELISA kit, demonstrating strong diagnostic consistency. Discrepant specimens were further analyzed by a metabolic inhibition test (MIT), which suggested improved specificity, although further validation is required of this cELISA. Full article
(This article belongs to the Special Issue Diagnosis and Epidemiology of Cattle Infectious Diseases)
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13 pages, 1442 KB  
Review
Amyloidosis and Thoracic Aortic Disease: A Scoping Review
by Vasiliki Androutsopoulou, Konstantinos Spanos, Ioanna Giannouka, Konstantinos Tzimkas-Dakis, Konstantinos Karakoussis and Athanasios D. Giannoukas
J. Clin. Med. 2026, 15(15), 5817; https://doi.org/10.3390/jcm15155817 - 25 Jul 2026
Viewed by 150
Abstract
Background and Objectives: Amyloidosis is a systemic disorder characterized by extracellular deposition of misfolded protein fibrils, most commonly light-chain (AL) or transthyretin-derived (ATTR) ones. Cardiac involvement is well recognized, but large-vessel complications, including thoracic aortic aneurysms (TAA) and dissections, are rare and [...] Read more.
Background and Objectives: Amyloidosis is a systemic disorder characterized by extracellular deposition of misfolded protein fibrils, most commonly light-chain (AL) or transthyretin-derived (ATTR) ones. Cardiac involvement is well recognized, but large-vessel complications, including thoracic aortic aneurysms (TAA) and dissections, are rare and under-reported. The aim of this review article is to provide insights into pathophysiology, clinical diagnosis and the therapeutic opportunities in amyloidosis-related thoracic aortic diseases. Methods and Materials: The PRISMA Extension for Scoping Reviews (PRISMA-ScR) Guidelines were followed. An extensive search of the available literature in the English language, published between 1 January 2000, and 31 December 2025, in three large-scale scientific databases was undertaken by two independent reviewers. The terms “amyloidosis”, “thoracic aorta”, “thoracic aortic aneurysm”, “aortic dissection”, and “aortopathy” were used both as specific items, as well as in MeSH Terms. Studies reporting on the pathophysiology, diagnosis, clinical manifestations, treatment options and prognosis of amyloid deposition on the thoracic aorta were included in the review. Because of the nature of the existing literature, only a narrative review was possible. Results: Twenty-nine studies were included. Owing to the rarity of reporting, data was derived mainly from case reports and series, as well as autopsy studies. Amyloid infiltration of the aortic wall has been associated with medial architectural disruption, degeneration of elastic fibers, impairment of vasa vasorum perfusion, and arterial stiffness, all of which could contribute to aneurysmal dilation and aortic lesions. Amyloidosis management combines targeted anti-plasma cell therapy with supportive care. In AL amyloidosis, melphalan–dexamethasone (MDex) was historically standard, but regimens such as cyclophosphamide, bortezomib, and dexamethasone (CyBorD) and bortezomib, melphalan, and dexamethasone (BMDex) achieve higher complete response rates. Immunotherapy with Daratumumab has shown high overall and complete response rates. Fibril-directed approaches, including doxycycline and epigallocatechin gallate, and monoclonal antibodies, are under evaluation. Acute management of large-vessel manifestations follows conventional protocols, but prognosis is often dominated by underlying cardiac and systemic involvement. Conclusions: Management of thoracic aortic involvement follows standard imaging surveillance and surgical criteria, though operative risk is increased. Multidisciplinary care, early recognition, and individualized risk stratification are essential to improve outcomes, particularly given frequent cardiac involvement. Full article
(This article belongs to the Special Issue Machine Learning in Vascular Surgery)
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19 pages, 3323 KB  
Review
Mechanistic and Clinical Differences Between Daratumumab and Isatuximab in Multiple Myeloma: Emerging Roles of 1q Gain and Immune Remodeling
by Jiro Kikuchi and Hiroshi Yasui
Cells 2026, 15(15), 1331; https://doi.org/10.3390/cells15151331 - 24 Jul 2026
Viewed by 181
Abstract
Anti-CD38 monoclonal antibodies have substantially improved outcomes in multiple myeloma (MM). Although daratumumab and isatuximab target the same antigen, accumulating evidence indicates that they differ in epitope recognition, biological activity, and immunomodulatory properties, suggesting these agents may not be therapeutically interchangeable. This review [...] Read more.
Anti-CD38 monoclonal antibodies have substantially improved outcomes in multiple myeloma (MM). Although daratumumab and isatuximab target the same antigen, accumulating evidence indicates that they differ in epitope recognition, biological activity, and immunomodulatory properties, suggesting these agents may not be therapeutically interchangeable. This review summarizes the molecular and immunological mechanisms underlying their distinct antitumor effects and their implications for treatment selection. Isatuximab binds near the catalytic site of CD38, resulting in potent enzymatic inhibition, enhanced antibody internalization, FOXM1 suppression, and reactive oxygen species-mediated cytotoxicity, which may preferentially target MM cells harboring 1q21 amplification. In contrast, daratumumab exerts prominent Fc-dependent immune effects, including trogocytosis-mediated downregulation of CD38 and VLA-4, suppression of cell adhesion-mediated drug resistance, and modulation of the immune microenvironment, potentially enhancing subsequent T-cell-redirecting therapies. We further discuss the relevance of these mechanistic differences to measurable residual disease, extramedullary disease, and sequencing with BCMA- and GPRC5D-directed immunotherapies. Finally, we propose a biology-guided treatment-selection model integrating genomic alterations, tumor biology, and immune remodeling to support precision medicine for patients with MM. Full article
(This article belongs to the Section Cellular Immunology)
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11 pages, 673 KB  
Article
Rapid Onset of Clinical Response to Eculizumab in a Single-Center Cohort of Older Patients with Refractory Generalized Myasthenia Gravis
by Giulia D’Alvano, Salvatore Del Giudice, Francesca D’Anna, Vincenzo Todisco, Alessandro Tessitore and Alvino Bisecco
NeuroSci 2026, 7(4), 85; https://doi.org/10.3390/neurosci7040085 - 24 Jul 2026
Viewed by 101
Abstract
Background: Current treatments for myasthenia gravis (MG), while improving outcomes, are often associated with adverse effects, and a proportion of patients remain refractory to standard therapies. Eculizumab, a humanized monoclonal antibody targeting complement protein C5, is approved for refractory anti-acetylcholine receptor antibody-positive generalized [...] Read more.
Background: Current treatments for myasthenia gravis (MG), while improving outcomes, are often associated with adverse effects, and a proportion of patients remain refractory to standard therapies. Eculizumab, a humanized monoclonal antibody targeting complement protein C5, is approved for refractory anti-acetylcholine receptor antibody-positive generalized MG (AChR-Ab+ gMG). Aim of the present study is to explore the rapidity of onset of eculizumab efficacy in a single-center cohort of MG patients. Methods: This retrospective, observational, single-center study evaluated the real-world effectiveness and rapidity of response to eculizumab in patients with AChR-Ab+ gMG. Patients received eculizumab according to the approved regimen and were assessed at baseline (T0), 5 weeks (T1), and 3 months (T2) using the Myasthenia Gravis Activities of Daily Living (MG-ADL) score, Quantitative Myasthenia Gravis (QMG) score, and Myasthenia Gravis Foundation of America (MGFA) classification. Results: Eight patients were eligible for the study with a mean age of 73.1 years. A rapid clinical improvement was observed after treatment initiation. Mean MG-ADL scores decreased from 8.38 at T0 to 2.13 at T1 (p < 0.001; Cohen’s d = 2.075), while QMG scores declined from 13.75 to 5.63 (p = 0.001; Cohen’s d = 1.824). Improvements were maintained at T2. Mean percentage reductions from T0 to T1 were 73.5% for MG-ADL and 60.6% for QMG. Eculizumab was well tolerated. Conclusions: These real-world findings confirm a rapid and clinically meaningful response to eculizumab in elderly patients with refractory gMG. These findings highlight its potential role in achieving early symptom control and reducing disease burden in this clinically vulnerable population. Full article
(This article belongs to the Special Issue Expanding the Clinical Landscape of Autoimmune Neurology)
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13 pages, 5276 KB  
Article
Development of a Quantum Dot-Based Immunochromatographic Assay for Rapid and Sensitive Detection of Non-Medical Etomidate Abuse
by Xin Yan, Liwei Jiang, Xiaolong Zhang, Yizhe Zhao, Zixin Wan, Jun Ma, Chunhui Song, Yikai Wang and Xingliang Liu
Biosensors 2026, 16(8), 404; https://doi.org/10.3390/bios16080404 - 24 Jul 2026
Viewed by 157
Abstract
Etomidate is an ultrashort-acting imidazole-derived intravenous anesthetic. The non-medical abuse of etomidate as a new psychoactive substance has emerged as a critical public health challenge globally, particularly among adolescents, necessitating sensitive, rapid detection methods for forensic analysis. This study developed a quantum dot-based [...] Read more.
Etomidate is an ultrashort-acting imidazole-derived intravenous anesthetic. The non-medical abuse of etomidate as a new psychoactive substance has emerged as a critical public health challenge globally, particularly among adolescents, necessitating sensitive, rapid detection methods for forensic analysis. This study developed a quantum dot-based immunochromatographic test strip and a corresponding rapid detection method for the sensitive detection of etomidate acid in urine. CdSe/ZnS fluorescent quantum dot microspheres were used as labeling probes combined with specific monoclonal antibodies, and the detection protocol utilized a portable fluorescence reader. The method’s validation demonstrated a linear range of 10–2000 ng/mL (y = −0.231lnx + 0.5241, r = −0.991), with intra-batch and inter-batch coefficients of variation below 12%. The spike recovery rates ranged from 88.24% to 95.69%. Cross-reactivity testing against 12 common drugs and structural analogs showed no interference. The detection limit of 10 ng/mL represents a substantial improvement over conventional colloidal gold strips and approaches LC-MS/MS sensitivity. Assays of real urine specimens confirmed that the immunochromatographic test strip and detection method possess favorable accuracy and reliability. This fluorescent quantum dot-based immunochromatographic assay provides rapid, quantitative, and highly specific etomidate screening suitable for on-site forensic applications, effectively bridging front-end rapid testing with confirmatory laboratory analysis. Full article
(This article belongs to the Special Issue Biosensing Technologies in Medical Diagnosis—2nd Edition)
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