-
Molecules (Basel, Switzerland) Apr 2024The COVID-19 pandemic over recent years has shown a great need for the rapid, low-cost, and on-site detection of severe acute respiratory syndrome coronavirus 2...
The COVID-19 pandemic over recent years has shown a great need for the rapid, low-cost, and on-site detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, an aptamer-based colloidal gold nanoparticle lateral flow test strip was well developed to realize the visual detection of wild-type SARS-CoV-2 spike proteins (SPs) and multiple variants. Under the optimal reaction conditions, a low detection limit of SARS-CoV-2 S proteins of 0.68 nM was acquired, and the actual detection recovery was 83.3% to 108.8% for real-world samples. This suggests a potential tool for the prompt detection of SARS-CoV-2 with good sensitivity and accuracy, and a new method for the development of alternative antibody test strips for the detection of other viral targets.
Topics: Humans; Aptamers, Nucleotide; COVID-19; Gold; Limit of Detection; Metal Nanoparticles; Reagent Strips; SARS-CoV-2; Spike Glycoprotein, Coronavirus
PubMed: 38675595
DOI: 10.3390/molecules29081776 -
Polymers Apr 2024Natural and synthetic polymers are a versatile platform for developing biomaterials in the biomedical and environmental fields. Natural polymers are organic compounds... (Review)
Review
Natural and synthetic polymers are a versatile platform for developing biomaterials in the biomedical and environmental fields. Natural polymers are organic compounds that are found in nature. The most common natural polymers include polysaccharides, such as alginate, hyaluronic acid, and starch, proteins, e.g., collagen, silk, and fibrin, and bacterial polyesters. Natural polymers have already been applied in numerous sectors, such as carriers for drug delivery, tissue engineering, stem cell morphogenesis, wound healing, regenerative medicine, food packaging, etc. Various synthetic polymers, including poly(lactic acid), poly(acrylic acid), poly(vinyl alcohol), polyethylene glycol, etc., are biocompatible and biodegradable; therefore, they are studied and applied in controlled drug release systems, nano-carriers, tissue engineering, dispersion of bacterial biofilms, gene delivery systems, bio-ink in 3D-printing, textiles in medicine, agriculture, heavy metals removal, and food packaging. In the following review, recent advancements in polymer chemistry, which enable the imparting of specific biomedical functions of polymers, will be discussed in detail, including antiviral, anticancer, and antimicrobial activities. This work contains the authors' experimental contributions to biomedical and environmental polymer applications. This review is a vast overview of natural and synthetic polymers used in biomedical and environmental fields, polymer synthesis, and isolation methods, critically assessessing their advantages, limitations, and prospects.
PubMed: 38675078
DOI: 10.3390/polym16081159 -
PloS One 2024Empty large volume parenteral (LVP) bottle has irregular shape and narrow opening, and its detection accuracy of the foreign substances at the bottom is higher than that...
Empty large volume parenteral (LVP) bottle has irregular shape and narrow opening, and its detection accuracy of the foreign substances at the bottom is higher than that of ordinary packaging bottles. The current traditional detection method for the bottom of LVP bottles is to directly use manual visual inspection, which involves high labor intensity and is prone to visual fatigue and quality fluctuations, resulting in limited applicability for the detection of the bottom of LVP bottles. A geometric constraint-based detection model (GCBDM) has been proposed, which combines the imaging model and the shape characteristics of the bottle to construct a constraint model of the imaging parameters, according to the detection accuracy and the field of view. Then, the imaging model is designed and optimized for the detection. Further, the generalized GCBDM has been adopted to different bottle bottom detection scenarios, such as cough syrup and capsule medicine bottles by changing the target parameters of the model. The GCBDM, on the one hand, can avoid the information at the bottom being blocked by the narrow opening in the imaging optical path. On the other hand, by calculating the maximum position deviation between the center of visual inspection and the center of the bottom, it can provide the basis for the accuracy design of the transmission mechanism in the inspection, thus further ensuring the stability of the detection.
Topics: Drug Packaging; Humans; Models, Theoretical
PubMed: 38669295
DOI: 10.1371/journal.pone.0298108 -
Archives of Microbiology Apr 2024Bacteriocins are highly diverse, abundant, and heterogeneous antimicrobial peptides that are ribosomally synthesized by bacteria and archaea. Since their discovery about... (Review)
Review
Bacteriocins are highly diverse, abundant, and heterogeneous antimicrobial peptides that are ribosomally synthesized by bacteria and archaea. Since their discovery about a century ago, there has been a growing interest in bacteriocin research and applications. This is mainly due to their high antimicrobial properties, narrow or broad spectrum of activity, specificity, low cytotoxicity, and stability. Though initially used to improve food quality and safety, bacteriocins are now globally exploited for innovative applications in human, animal, and food systems as sustainable alternatives to antibiotics. Bacteriocins have the potential to beneficially modulate microbiota, providing viable microbiome-based solutions for the treatment, management, and non-invasive bio-diagnosis of infectious and non-infectious diseases. The use of bacteriocins holds great promise in the modulation of food microbiomes, antimicrobial food packaging, bio-sanitizers and antibiofilm, pre/post-harvest biocontrol, functional food, growth promotion, and sustainable aquaculture. This can undoubtedly improve food security, safety, and quality globally. This review highlights the current trends in bacteriocin research, especially the increasing research outputs and funding, which we believe may proportionate the soaring global interest in bacteriocins. The use of cutting-edge technologies, such as bioengineering, can further enhance the exploitation of bacteriocins for innovative applications in human, animal, and food systems.
Topics: Bacteriocins; Humans; Animals; Anti-Bacterial Agents; Bacteria; Food Microbiology; Microbiota; Food Packaging; Food Safety
PubMed: 38662051
DOI: 10.1007/s00203-024-03948-y -
Mucosal adjuvanticity and mucosal booster effect of colibactin-depleted probiotic membrane vesicles.Human Vaccines & Immunotherapeutics Dec 2024There is a growing interest in development of novel vaccines against respiratory tract infections, due to COVID-19 pandemic. Here, we examined mucosal adjuvanticity and...
There is a growing interest in development of novel vaccines against respiratory tract infections, due to COVID-19 pandemic. Here, we examined mucosal adjuvanticity and the mucosal booster effect of membrane vesicles (MVs) of a novel probiotic derivative lacking both flagella and potentially carcinogenic colibactin (ΔΔ). ΔΔ-derived MVs showed rather strong mucosal adjuvanticity as compared to those of a single flagellar mutant strain (Δ-MVs). In addition, glycoengineered ΔΔ-MVs displaying serotype-14 pneumococcal capsular polysaccharide (CPS14MVs) were well-characterized based on biological and physicochemical parameters. Subcutaneous (SC) and intranasal (IN) booster effects of CPS14MVs on systemic and mucosal immunity were evaluated in mice that have already been subcutaneously prime-immunized with the same MVs. With a two-dose regimen, an IN boost (SC-IN) elicited stronger IgA responses than homologous prime-boost immunization (SC-SC). With a three-dose regimen, serum IgG levels were comparable among all tested regimens. Homologous immunization (SC-SC-SC) elicited the highest IgM responses among all regimens tested, whereas SC-SC-SC failed to elicit IgA responses in blood and saliva. Furthermore, serum IgA and salivary SIgA levels were increased with an increased number of IN doses administrated. Notably, SC-IN-IN induced not only robust IgG response, but also the highest IgA response in both serum and saliva among the groups. The present findings suggest the potential of a heterologous three-dose administration for building both systemic and mucosal immunity, . an SC-IN-IN vaccine regimen could be beneficial. Another important observation was abundant packaging of colibactin in MVs, suggesting increased applicability of ΔΔ-MVs in the context of vaccine safety.
Topics: Animals; Mice; Immunity, Mucosal; Probiotics; Escherichia coli; Immunization, Secondary; Female; Adjuvants, Immunologic; Polyketides; Mice, Inbred BALB C; Immunoglobulin A; Peptides; Administration, Intranasal; Immunoglobulin G; Immunoglobulin M; COVID-19 Vaccines
PubMed: 38658133
DOI: 10.1080/21645515.2024.2337987 -
ACS Nano May 2024Pharmacological activation of the retinoic acid-inducible gene I (RIG-I) pathway holds promise for increasing tumor immunogenicity and improving the response to immune...
Pharmacological activation of the retinoic acid-inducible gene I (RIG-I) pathway holds promise for increasing tumor immunogenicity and improving the response to immune checkpoint inhibitors (ICIs). However, the potency and clinical efficacy of 5'-triphosphate RNA (3pRNA) agonists of RIG-I are hindered by multiple pharmacological barriers, including poor pharmacokinetics, nuclease degradation, and inefficient delivery to the cytosol where RIG-I is localized. Here, we address these challenges through the design and evaluation of ionizable lipid nanoparticles (LNPs) for the delivery of 3p-modified stem-loop RNAs (SLRs). Packaging of SLRs into LNPs (SLR-LNPs) yielded surface charge-neutral nanoparticles with a size of ∼100 nm that activated RIG-I signaling in vitro and in vivo. SLR-LNPs were safely administered to mice via both intratumoral and intravenous routes, resulting in RIG-I activation in the tumor microenvironment (TME) and the inhibition of tumor growth in mouse models of poorly immunogenic melanoma and breast cancer. Significantly, we found that systemic administration of SLR-LNPs reprogrammed the breast TME to enhance the infiltration of CD8 and CD4 T cells with antitumor function, resulting in enhanced response to αPD-1 ICI in an orthotopic EO771 model of triple-negative breast cancer. Therapeutic efficacy was further demonstrated in a metastatic B16.F10 melanoma model, with systemically administered SLR-LNPs significantly reducing lung metastatic burden compared to combined αPD-1 + αCTLA-4 ICI. Collectively, these studies have established SLR-LNPs as a translationally promising immunotherapeutic nanomedicine for potent and selective activation of RIG-I with the potential to enhance response to ICIs and other immunotherapeutic modalities.
Topics: Animals; Female; Humans; Mice; Cell Line, Tumor; Immunotherapy; Lipids; Mice, Inbred C57BL; Nanoparticles; Tumor Microenvironment
PubMed: 38652829
DOI: 10.1021/acsnano.3c06225 -
Clinical and Translational Science Apr 2024Drug safety communications (DSCs) are essential tools for communicating important postmarket serious drug safety information to healthcare professionals and patients....
Drug safety communications (DSCs) are essential tools for communicating important postmarket serious drug safety information to healthcare professionals and patients. Previous studies characterized DSCs issued by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA); however, knowledge about the activities of the Pharmaceuticals and Medical Devices Agency (PMDA)/the Ministry of Health, Labor and Welfare (MHLW) is limited. This study characterized DSCs by the PMDA/MHLW in comparison with previously reported DSCs by the FDA and the EMA. We retrospectively analyzed 37 DSCs of 41 adverse drug reactions (ADRs) for 33 drugs in Japan from 1997 to 2022. Most DSCs were related to non-oncology drugs (30/37, 81.1%), and the median (interquartile range) time from approval to DSC issuance was 19 (10-51) months. Notably, the regulatory review reports and the latest labels before DSC issuance did not describe 16/28 (57.1%) and 12/37 (32.4%) of the ADRs related to DSCs, respectively. Most DSCs resulted in label revisions (36/37, 97.3%) and seven drugs were eventually withdrawn. Some DSC characteristics are similar among the PMDA/MHLW, the FDA, and the EMA; however, the number, contents, and range of new safety issues addressed by DSCs differ among the three jurisdictions. Our study emphasized the importance of continuous efforts to gather postmarket drug safety information because substantial ADRs that led to DSCs were recognized after approval and were associated with critical label revisions and withdrawals. Future studies are required to address global challenges for regulatory harmonization of safety-related regulatory actions.
Topics: Japan; Humans; Drug Approval; Product Surveillance, Postmarketing; Retrospective Studies; Drug-Related Side Effects and Adverse Reactions; United States Food and Drug Administration; Drug Labeling; United States; Adverse Drug Reaction Reporting Systems
PubMed: 38651283
DOI: 10.1111/cts.13803 -
Indian Journal of Ophthalmology May 2024
Topics: Humans; Drug Labeling; Presbyopia; Ophthalmic Solutions
PubMed: 38648444
DOI: 10.4103/IJO.IJO_1476_23 -
PLoS Computational Biology Apr 2024Influenza A virus contains regions of its segmented genome associated with ability to package the segments into virions, but many such regions are poorly characterised....
Locations and structures of influenza A virus packaging-associated signals and other functional elements via an in silico pipeline for predicting constrained features in RNA viruses.
Influenza A virus contains regions of its segmented genome associated with ability to package the segments into virions, but many such regions are poorly characterised. We provide detailed predictions of the key locations within these packaging-associated regions, and their structures, by applying a recently-improved pipeline for delineating constrained regions in RNA viruses and applying structural prediction algorithms. We find and characterise other known constrained regions within influenza A genomes, including the region associated with the PA-X frameshift, regions associated with alternative splicing, and constraint around the initiation motif for a truncated PB1 protein, PB1-N92, associated with avian viruses. We further predict the presence of constrained regions that have not previously been described. The extra characterisation our work provides allows investigation of these key regions for drug target potential, and points towards determinants of packaging compatibility between segments.
Topics: Influenza A virus; Virus Assembly; Computational Biology; Genome, Viral; Algorithms; Computer Simulation; RNA, Viral; Humans; RNA Viruses
PubMed: 38648223
DOI: 10.1371/journal.pcbi.1012009 -
Scientific Reports Apr 2024For the majority of cytotoxic drug preparations, such as bortezomib, the unit dose information is not available. In addition, there is a lack of information on the...
For the majority of cytotoxic drug preparations, such as bortezomib, the unit dose information is not available. In addition, there is a lack of information on the physicochemical stability of the pharmaceutical preparation after opening; this information is crucial for its administration to patients in successive visits, and the per-patient cost can be affected. The purpose of our proposed physicochemical stability study is to determine the shelf life of the reconstituted liquid product under refrigeration and clinical practice conditions. This evaluation was extended to both vials and ready-to-use syringes prefilled with the contents of the open vial. The stability test design includes the specified storage conditions and the critical physicochemical parameters of reconstituted injectable bortezomib. Furthermore, this approach includes the determination of impurities, the monitoring of the purity of the mean peak using a photodiode array, the control of the mass balance, the monitoring of subvisible particles using a laser diffraction analyser, and the setting of stability specifications. For the chemical stability study, the amount of bortezomib and its degradation products were determined using a stability-indicating HPLC method. The physical inspection of the samples was performed throughout the stability study, and their pH values were also monitored. Bortezomib (2.5 mg/mL) in 0.9% sodium chloride remained stable for 7 days when stored in both polypropylene syringes and vials at 5 ± 3 °C (refrigeration) and shielded from light. Additionally, it exhibits stability for 24 h under storage conditions simulating clinical use (20-30 °C and protected from light). The proposed protocol provides the stability in the vials once reconstituted and in prefilled refrigerated syringes; this protocol can be used to reduce waste and increase cost savings.
Topics: Humans; Bortezomib; Drug Packaging; Antineoplastic Agents; Polypropylenes; Drug Stability; Syringes; Chromatography, High Pressure Liquid; Pharmaceutical Solutions
PubMed: 38637597
DOI: 10.1038/s41598-024-58473-1