Development of mRNA Lipid Nanoparticles: Targeting and Therapeutic Aspects.

Lipid nanoparticles (LNPs) have emerged as leading non-viral carriers for messenger RNA (mRNA) delivery in clinical applications. Overcoming challenges in safe and effective mRNA delivery to target tissues and cells, along with controlling release from the delivery vehicle, remains pivotal in mRNA-based therapies. This review elucidates the structure of LNPs, the mechanism for mRNA delivery, and the targeted delivery of LNPs to various cells and tissues, including leukocytes, T-cells, dendritic cells, Kupffer cells, hepatic endothelial cells, and hepatic and extrahepatic tissues.

Therapeutic effect of E-Lip-siRNA-sFlt1 on pre-eclampsia: targeted gene silencing and improved pregnancy outcomes.

To evaluate a liposome complex conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for the treatment of pre-eclampsia (PE). In experiments, the transfection rate, silencing effect and cytotoxicity were determined. In the PE model, the siRNA distribution, mean arterial pressure, 24-h urine protein concentration, serum sFlt1 concentration, number of viable fetuses and placental weight were measured.

Detection of calcitonin gene-related peptide based on increased antigen-driven interaction with antibody variable regions.

Calcitonin gene-related peptide (CGRP) is involved in trigeminal neuralgia and migraine, and measuring the CGRP concentration in the serum is crucial for the early prediction of these conditions. Current methods for CGRP detection are primarily radioimmunoassay, which needs radioactive substances and enzyme-linked immunosorbent assays (ELISAs) which need long detection time and some have a narrow detection range. The genes of anti-CGRP antibody variable regions were cloned into pDong1 vector to obtain pDong1/Fab-CGRP, with which phage-Fab was prepared, and the concentration of CGRP was detected by competitive ELISA.

Multifunctional hydrogels based on photothermal therapy: A prospective platform for the postoperative management of melanoma.

Preventing the recurrence of melanoma after surgery and accelerating wound healing are among the most challenging aspects of melanoma management. Photothermal therapy has been widely used to treat tumors and bacterial infections and promote wound healing. Owing to its efficacy and specificity, it may be used for postoperative management of tumors.

Development of nanoparticle vaccines utilizing designed Fc-binding homo-oligomers and RBD-Fc of SARS-CoV-2.

The Fc-fused receptor binding domain (RBD-Fc) vaccine for SARS-CoV-2 has garnered significant attention for its capacity to provide effective and specific immune protection. However, its immunogenicity is limited, highlighting the need for improvement in clinical application. Nanoparticle delivery has been shown to be an effective method for enhancing antigen immunogenicity.

Innovative Biomaterials for Bone Tumor Treatment and Regeneration: Tackling Postoperative Challenges and Charting the Path Forward.

Surgical resection of bone tumors is the primary approach employed in the treatment of bone cancer. Simultaneously, perioperative interventions, particularly postoperative adjuvant anticancer strategies, play a crucial role in achieving satisfactory therapeutic outcomes. However, the occurrence of postoperative bone tumor recurrence, metastasis, extensive bone defects, and infection are significant risks that can result in unfavorable prognoses or even treatment failure.

Molecular and structural basis of anti-DNA antibody specificity for pyrrolated proteins.

Anti-DNA antibodies (Abs), serological hallmarks of systemic lupus erythematosus (SLE) and markers for diagnosis and disease activity, show a specificity for non-nucleic acid molecules, such as N-pyrrolated proteins (pyrP) containing N-pyrrole-L-lysine (pyrK) residues. However, the detailed mechanism for the binding of anti-DNA Abs to pyrP remains unknown. In the present study, to gain structural insights into the dual-specificity of anti-DNA Abs, we used phage display to obtain DNA-binding, single-chain variable fragments (scFvs) from SLE-prone mice and found that they also cross-reacted with pyrP.

Fluorescence quenching-based immunological probe for ticagrelor monitoring.

Ticagrelor is extensively utilized for the treatment of acute coronary syndromes (ACS), but its platelet aggregation inhibitory effects can potentially result in tissue bleeding, posing a serious risk to patients' lives. In this study, we developed highly sensitive full length anti-ticagrelor Quenchbodies (Q-bodies) for fast monitoring of ticagrelor both in solution and serum for the first time. Ticagrelor coupled with N- hydroxysuccinimide (Ticagrelor-NHS) ester was also designed and synthesized for interaction and biological activity detection.

Quantitative SERS detection of multiple breast cancer miRNAs based on duplex specific nuclease-mediated signal amplification.

Simultaneous and ultrasensitive detection of multiple microRNA (miRNA) biomarkers is an essential precondition for early cancer diagnosis and treatment. Here we developed a sandwich surface-enhanced Raman scattering (SERS) sensor based on Au@Ag core-shell nanorods combined with duplex specific nuclease-mediated signal amplification (DSNSA) for quantitative detection of multiple breast cancer miRNA biomarkers. The DSNSA strategy enables quantitative detection of target miRNA through rehybridizing the capture probe DNA-SERSnanotag conjugates to trigger signal amplification.

Immunosensor for Rapid and Sensitive Detection of Digoxin.

Digoxin is a cardiac glycosylated steroid-like drug with a positive inotropic effect and has been widely used in treating congestive heart failure, atrial fibrillation, atrial flutter, and other heart diseases. Digoxin is also a dangerous drug, which can cause drug poisoning at a low blood drug concentration (2.73-3.

Mussel-Inspired Multifunctional Hydrogels with Adhesive, Self-Healing, Antioxidative, and Antibacterial Activity for Wound Healing.

Antibacterial hydrogel wound dressings with adhesive and antioxidant activity are desirable for treating skin injuries in clinical care. Hereby, a series of multifunctional hydrogel wound dressings with high adhesive, self-healing, antioxidant, and antibacterial activity were designed and fabricated using dopamine (DA) and quercetin (QT). The multifunctional hydrogels were constructed by the interpenetrated quaternized chitosan chain segments and polyacrylamide network.

V-Based Mini Q-Body: A Novel Quench-Based Immunosensor.

Quenchbodies (Q-bodies), a type of biosensor, are antibodies labeled with a fluorescent dye near the antigen recognition site. In the absence of an antigen, the dye is quenched by tryptophans in the antibody sequence; however, in its presence, the dye is displaced and therefore de-quenched. Although scFv and Fab are mainly used to create Q-bodies, this is the first report where a single-domain heavy chain V from a semi-synthetic human antibody library formed the basis.

Immunosensor for realtime monitoring of the expression of recombinant proteins during bioprocess.

Recombinant protein expression and purification are crucial in modern life sciences research. A fluorescent immunosensor termed Quenchbody (Q-body) was developed for real-time monitoring of FLAG-fused protein expression. Detection results showed that the limit of detection of the 3 × FLAG peptide detected by the TAMRA-labeled anti-FLAG Q-body was as low as 3.

Quarternized chitosan/quercetin/polyacrylamide semi-interpenetrating network hydrogel with recoverability, toughness and antibacterial properties for wound healing.

Antibiotic abuse has posed enormous burdens on patients and healthcare systems. Hence, the design and development of non-antibiotic wound dressings to meet clinical demand are urgently desired. However, there remains one of the impediments to hydrogel wound dressings that integrated with good recoverability, toughness, and excellent antibacterial properties.

The Patrol Yeast: A new biosensor armed with antibody-receptor chimera detecting a range of toxic substances associated with food poisoning.

Baker's yeast is an attractive host with established safety and stability characteristics. Many yeast-based biosensors have been developed, but transmembrane signal transduction has not been used to detect membrane-impermeable substances using antigen-antibody interactions. Therefore, we created Patrol Yeast, a novel yeast-based immunosensor of various targets, particularly toxic substances in food.

Rapid and sensitive SARS-CoV-2 detection using a homogeneous fluorescent immunosensor Quenchbody with crowding agents.

Antigen tests for SARS-CoV-2 are widely used by the public during the ongoing COVID-19 pandemic, which demonstrates the societal impact of homogeneous immunosensor-related technologies. In this study, we used the PM Q-probe and Quenchbody technologies to develop a SARS-CoV-2 nucleocapsid protein (N protein) homogeneous immunosensor based on a human anti-N protein antibody. For the first time, we uncovered the crowding agent's role in improving the performance of the double-labeled Quenchbody, and the possible mechanisms behind this improvement are discussed.

Isolation of a human SARS-CoV-2 neutralizing antibody from a synthetic phage library and its conversion to fluorescent biosensors.

Since late 2019, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resultant spread of COVID-19 have given rise to a worldwide health crisis that is posing great challenges to public health and clinical treatment, in addition to serving as a formidable threat to the global economy. To obtain an effective tool to prevent and diagnose viral infections, we attempted to obtain human antibody fragments that can effectively neutralize viral infection and be utilized for rapid virus detection. To this end, several human monoclonal antibodies were isolated by bio-panning a phage-displayed human antibody library, Tomlinson I.

Synthesis and Anti-Neuroinflammatory Activity of 1,7-diphenyl-1,4-heptadien-3-ones in LPS-Stimulated BV2 Microglia Via Inhibiting NF-B/MAPK Signaling Pathways.

A series of 1,7-diphenyl-1,4-heptadien-3-ones with various substituents (HO-, CHO-, CH-, Cl-) on the phenyl rings were synthesized and evaluated for anti-neuroinflammatory effects in LPS-stimulated BV2 microglia. The pharmacological results showed that the target compounds bearing methoxy groups greatly inhibited LPS-induced NO release, and that the active compounds and reduced the level of NO, TNF-, IL-6 and PGE-2, downregulated the expression of COX-2 and iNOS in LPS-stimulated BV2 cells. A study of the mechanism of action revealed that and inhibited the nuclear translocation of NF-B and phosphorylation of MAPKs (ERK, JNK, and p38).

Creation of a quick and sensitive fluorescent immunosensor for detecting the mineralocorticoid steroid hormone aldosterone.

Aldosterone (ALD) is a steroid hormone secreted by the zona glomerulosa of the adrenal cortex that mainly acts on the kidney to regulate sodium ion and water reabsorption. Detection of ALD plays an important role in the diagnosis of primary aldosteronism in patients with hypertension. For the first time, the gene encoding the anti-ALD antibody, A2E11, was successfully cloned and analyzed using phage display technology.

DNAzyme signal amplification based on Au@Ag core-shell nanorods for highly sensitive SERS sensing miRNA-21.

Here, we developed a surface-enhanced Raman scattering (SERS) sensor based on functionalized Au@Ag core-shell nanorods (Au@Ag NRs) and cascade DNAzyme amplifier (CSA) for sensitive and accurate determination of microRNA-21 (miRNA-21). The as-prepared SERS nanoprobes were composed of a thiol-modification hairpin probe (HP2)-functionalized Au@Ag NRs and hairpin DNAzyme (HP1-Dz). Compared with original gold nanorods, the silver shell caused an enhancement of plasmonic properties, resulting in a significant enhancement of Raman signals.

Isolation of a Monoclonal Antibody and its Derived Immunosensor for Rapid and Sensitive Detection of 17β-Estradiol.

Estrogens are effective for stimulating several functions in living organisms and for regulating cancer development by promoting cell proliferation. Estradiol can disrupt the reproductive and endocrine systems, leading to the development of various diseases. In this study, the monoclonal antibody ESC9 was developed by immunizing mice with a 17β-estradiol (E2) conjugate, preparing an antibody phage display library, and screening monoclonal antibodies from the prepared library.

Maternal serum-derived exosomal lactoferrin as a marker in detecting and predicting ventricular septal defect in fetuses.

Among different types of congenital heart diseases, ventricular septal defect is the most frequently diagnosed type and is frequently missed in early prenatal screening programs. Herein, we explored the role of maternal serum-derived exosomes in detecting and predicting ventricular septal defect in fetuses in the early stage of pregnancy. A total of 104 pregnant women consisting of 52 ventricular septal defect cases and 52 healthy controls were recruited.

Advances in the application of Let-7 microRNAs in the diagnosis, treatment and prognosis of leukemia.

The lethal-7 (Let-7) family of microRNAs (miRNAs) controls the process of development and differentiation, but is also related to the occurrence of tumors and a poor prognosis of patients with tumors. Thus, a more comprehensive exploration of its functions will provide further insights into these processes, and may promote the diagnosis and treatment of tumors. Leukemia is a type of progressive malignant disease, and its pathogenesis involves a variety of epigenetic factors.

Universal probe-based intermediate primer-triggered qPCR (UPIP-qPCR) for SNP genotyping.

Background: The detection and identification of single nucleotide polymorphism (SNP) is essential for determining patient disease susceptibility and the delivery of medicines targeted to the individual. At present, SNP genotyping technology includes Sanger sequencing, TaqMan-probe quantitative polymerase chain reaction (qPCR), amplification-refractory mutation system (ARMS)-PCR, and Kompetitive Allele-Specific PCR (KASP). However, these technologies have some disadvantages: the high cost of development and detection, long and time consuming protocols, and high false positive rates.