Mechanistic insights into the anti-restenotic effects of HSP27 and HO1 modulated by reconstituted HDL on neointimal hyperplasia.

High-density lipoprotein (HDL) therapy has demonstrated beneficial effects in acute stroke and acute myocardial infarction models by reducing infarct size. In this study, we investigated the inhibitory effects of reconstituted HDL (rHDL) on neointimal hyperplasia and elucidated its underlying mechanism using a balloon injury rat model. Our finding revealed a significant 37% reduction in the intima to media ratio in the arteries treated with 80 mg/kg rHDL compared to those subjected to injury alone (p < 0.05), indicating a specific inhibition of neointimal hyperplasia. In vivo analysis further supported the positive effects of rHDL by demonstrating a reduction in smooth muscle cell (SMC) proliferation and an increase in endothelial cell (EC) proliferation. Additionally, rHDL treatment led to decreased infiltration of leukocytes and downregulated the expression of matrix metallopeptidase 9 (MMP9) in the neointimal area. Notably, rHDL administration resulted in decreased expression of VCAM1 and HIF1α, alongside increased expression of heme oxygenase 1 (HO1) and heat shock protein 27 (HSP27). Overexpression of HSP27 and HO1 effectively inhibited SMC proliferation. Moreover, rHDL-mediated suppression of injury-induced HIF1α coincided with upregulation of HSP27. Interestingly, HSP27 and HO1 had varying effects on the expression of chemokine receptors and rHDL did not exert significant effect on chemokine receptor expression in THP1 cells. These findings underscore the distinct roles of HSP27 and HO1 as potential regulatory factors in the progression of restenosis. Collectively, our study demonstrates that rHDL exerts a potent anti-neointimal hyperplasia effect by reducing leukocytes infiltration and SMC proliferation while promoting EC proliferation.

Evaluation of Implant Stability According to Implant Placement Site and Duration in Elderly Patients: A Prospective Multi-Center Cohort Study.

The aim of this prospective study is to investigate implant stability and the reliability of different measuring devices according to implant placement site and duration in patients aged over 65 years. The study evaluated 60 implants (diameter: 3.5/4.0/4.5/5.0 mm and length: 8.5/10.0/11.5 mm) in 60 patients aged ≥ 65 years. The implant placement sites were divided into six evenly distributed sections (n = 10), i.e., maxillary right-posterior, A; maxillary anterior, B; maxillary left-posterior, C; mandibular right-posterior, D; mandibular anterior, E; mandibular left-posterior, F. Participants visited the hospital six times: implant surgery, 1V; stitch removal, 2V; 1-month follow-up, 3V; 2-month follow-up, 4V; before final restoration delivery, 5V; and after final restoration delivery, 6V. The implant stability was evaluated with the Osstell Mentor (ISQ), Periotest M (PTV), and Anycheck (IST). The mean values of ISQ, PTV, and IST were analyzed (α = 0.05). ISQ, PTV, and IST results of 4V and 5V were significantly higher than those of 1V (p < 0.05). The lowest ISQ results occurred in the E location at 4V and 5V (p < 0.05). In all mandibular locations, IST results of 6V were significantly higher than those of 1V, 2V, 3V, and 4V (p < 0.05). ISQ results were negatively correlated with PTV and positively correlated with IST, and PTV was negatively correlated with IST. By considering various factors affecting the stability of the implant, it is necessary to determine the appropriate implant load application time. This could help increase the implant success rate in elderly patients. And as a diagnostic device for implant stability and the evaluation of osseointegration in elderly patients, Anycheck was also able to prove its relative reliability compared to Osstell ISQ Mentor and Periotest M.

Peptide-Assembled Single-Chain Atomic Crystal Enhances Pluripotent Stem Cell Differentiation to Neurons.

Nanomaterials hybridized with biological components have widespread applications. among many candidates, peptides are attractive in that their peptide sequences can self-assemble with the surface of target materials with high specificity without perturbing the intrinsic properties of nanomaterials. Here, a 1D hybrid nanomaterial was developed through self-assembly of a designed peptide. A hexagonal coiled-coil motif geometrically matched to the diameter of the inorganic nanomaterial was fabricated, whose hydrophobic surface was wrapped along the axis of the hydrophobic core of the coiled coil. Our morphological and spectroscopic analyses revealed rod-shaped, homogeneous peptide-inorganic nanomaterial complexes. Culturing embryonic stem cells on surfaces coated with this peptide-assembled single-chain atomic crystal increased the growth and adhesion of the embryonic stem cells. The hybridized nanomaterial also served as an ECM for brain organoids, accelerating the maturation of neurons. New methods to fabricate hybrid materials through peptide assembly can be applied.

Bilateral Cervical Lymphadenopathy after mRNA COVID-19 Vaccination on Oral Squamous Cell Carcinoma Patient: A Case Report.

We report the case of a 59-year-old man with squamous cell carcinoma (SCC) of the right mandibular gingiva, who presented with bilateral cervical lymphadenopathy (CLA) after mRNA coronavirus disease 2019 (COVID-19) vaccination. The patient was diagnosed. Imaging studies performed prior to surgery revealed bilateral CLA and axillary lymphadenopathy (LA) ipsilateral to the vaccination site. Fine-needle aspiration (FNA) biopsy of the left CLA revealed reactive lymph nodes. The patient underwent surgical intervention for the malignant tumor, and the specimen was sent for histopathologic evaluation. The biopsy-proven cancer stage was pT3N0Mx. Positron emission tomography (PET-CT), performed six months after surgery, showed persistent bilateral CLA. However, FNA of the left axillary LA once again showed no evidence of metastasis or recurrence. Since the treatment plan may change based on the type of LA, it is important to figure out whether an mRNA vaccine has been administered to patients with head and neck cancer.

Diagnostic value of presepsin in odontogenic infection: a retrospective study.

BACKGROUND: Most head and neck infections originate from odontogenic causes; therefore, it is important to determine the severity of odontogenic infections. Since severe infection can cause sepsis, a systemic examination should be performed when evaluating a patient with odontogenic infection. C-reactive protein (CRP), white blood cell count (WBC), procalcitonin (PCT), and presepsin (PSEP) can be used to evaluate the severity of inflammatory status and sepsis in patients in the early stages of visiting the emergency room. Moreover, sepsis can be diagnosed based on the systemic inflammatory response syndrome (SIRS) classification. In relation to PSEP, significant study results on sepsis have been reported in other organ infections. However, there has been no progress in odontogenic infection; therefore, this study aimed to determine the diagnostic value of sepsis derived from odontogenic infection. METHODS: This study was conducted from March 2021 to October 2021 on 43 patients admitted to the Department of Oral and Maxillofacial Surgery, Dankook University Hospital, in the emergency room for odontogenic infection. All patients underwent vital sign assessment and diagnostic tests (CRP, WBC, PCT, PSEP) in the emergency room. Sepsis was classified according to the SIRS criteria, and CRP, WBC, PCT, and PSEP levels were measured. The Statistical Package for the Social Sciences was used for statistical analyses. RESULTS: The results of this study showed a moderately positive correlation between CRP and PCT, CRP and PSEP, and CT and PSEP levels. In addition, PCT and PSEP levels showed a positive correlation with sepsis. The odds ratios of sepsis and PCT and sepsis and PSEP were statistically significant. The optimal cut-off values obtained through the receiver operating characteristic curve were 0.24 and 671.5 for PCT and PSEP, respectively. Finally, there were positive correlations between CRP level and length of stay, WBC and Flynn scores, PCT level and Flynn scores, PCT level and length of stay, and PSEP level and length of stay. CONCLUSION: WBC and CRP and PCT levels have been used in the past to determine the severity of infection and sepsis in patients with odontogenic infection, but PSEP was also found to have diagnostic value in this study. According to this study, a PSEP level of 671.5 pg/ml or higher for odontogenic infection can be considered an abnormal level.

Supramolecular Peptide Hydrogel-Based Soft Neural Interface Augments Brain Signals through a Three-Dimensional Electrical Network.

Recording neural activity from the living brain is of great interest in neuroscience for interpreting cognitive processing or neurological disorders. Despite recent advances in neural technologies, development of a soft neural interface that integrates with neural tissues, increases recording sensitivity, and prevents signal dissipation still remains a major challenge. Here, we introduce a biocompatible, conductive, and biostable neural interface, a supramolecular ß-peptide-based hydrogel that allows signal amplification via tight neural/hydrogel contact without neuroinflammation. The non-biodegradable ß-peptide forms a multihierarchical structure with conductive nanomaterial, creating a three-dimensional electrical network, which can augment brain signal efficiently. By achieving seamless integration in brain tissue with increased contact area and tight neural tissue coupling, the epidural and intracortical neural signals recorded with the hydrogel were augmented, especially in the high frequency range. Overall, our tissuelike chronic neural interface will facilitate a deeper understanding of brain oscillation in broad brain states and further lead to more efficient brain-computer interfaces.

Lipopeptide-Based Nanosome-Mediated Delivery of Hyperaccurate CRISPR/Cas9 Ribonucleoprotein for Gene Editing.

A transient cytosolic delivery system for accurate Cas9 ribonucleoprotein is a key factor for target specificity of the CRIPSR/Cas9 toolkit. Owing to the large size of the Cas9 protein and a long negative strand RNA, the development of the delivery system is still a major challenge. Here, a size-controlled lipopeptide-based nanosome system is reported, derived from the blood-brain barrier-permeable dNP2 peptide which is capable of delivering a hyperaccurate Cas9 ribonucleoprotein complex (HypaRNP) into human cells for gene editing. Each nanosome is capable of encapsulating and delivering ≈2 HypaRNP molecules into the cytoplasm, followed by nuclear localization at 4 h post-treatment without significant cytotoxicity. The HypaRNP thus efficiently enacts endogenous eGFP silencing and editing in human embryonic kidney cells (up to 27.6%) and glioblastoma (up to 19.7% frequency of modification). The lipopeptide-based nanosome system shows superior delivery efficiency, high controllability, and simplicity, thus providing biocompatibility and versatile platform approach for CRISPR-mediated transient gene editing applications.

Peptide-Programmable Nanoparticle Superstructures with Tailored Electrocatalytic Activity.

Biomaterials derived via programmable supramolecular protein assembly provide a viable means of constructing precisely defined structures. Here, we present programmed superstructures of AuPt nanoparticles (NPs) on carbon nanotubes (CNTs) that exhibit distinct electrocatalytic activities with respect to the nanoparticle positions via rationally modulated peptide-mediated assembly. De novo designed peptides assemble into six-helix bundles along the CNT axis to form a suprahelical structure. Surface cysteine residues of the peptides create AuPt-specific nucleation site, which allow for precise positioning of NPs onto helical geometries, as confirmed by 3-D reconstruction using electron tomography. The electrocatalytic model system, i.e., AuPt for oxygen reduction, yields electrochemical response signals that reflect the controlled arrangement of NPs in the intended assemblies. Our design approach can be expanded to versatile fields to build sophisticated functional assemblies.

An injectable collagen/poly(γ-glutamic acid) hydrogel as a scaffold of stem cells and α-lipoic acid for enhanced protection against renal dysfunction.

Mesenchymal stem cells (MSCs) can ameliorate renal injury and accelerate repair of acute kidney injury. Herein, we developed a collagen/poly(γ-glutamic acid) (γ-PGA) hydrogel as an injectable scaffold for the delivery of mouse MSCs (mMSCs) and anti-oxidant drugs into injured sites. By the introduction of γ-PGA into conventional collagen, the viscosity of collagen was reduced at ambient temperature for easy handling, while the elastic and viscous moduli of collagen were increased and a new porous structure was generated near body temperature. When in situ gel-forming collagen/γ-PGA hydrogels loaded with mMSCs and α-lipoic acid (LA) were administered to a mouse model of renal dysfunction, they significantly attenuated the level of blood urea nitrogen and creatinine, which resulted from the increased retention of therapeutic mMSCs and the controlled release of anti-oxidant drugs at the injured site. These findings suggested that this novel type of hydrogel could be applied as an injectable scaffold for use in regenerative medicine.

Synergistic Effect of Detection and Separation for Pathogen Using Magnetic Clusters.

Early diagnosis of infectious diseases is important for treatment; therefore, selective and rapid detection of pathogenic bacteria is essential for human health. We report a strategy for highly selective detection and rapid separation of pathogenic microorganisms using magnetic nanoparticle clusters. Our approach to develop probes for pathogenic bacteria, including Salmonella, is based on a theoretically optimized model for the size of clustered magnetic nanoparticles. The clusters were modified to provide enhanced aqueous solubility and versatile conjugation sites for antibody immobilization. The clusters with the desired magnetic property were then prepared at critical micelle concentration (CMC) by evaporation-induced self-assembly (EISA). Two different types of target-specific antibodies for H- and O-antigens were incorporated on the cluster surface for selective binding to biological compartments of the flagella and cell body, respectively. For the two different specific binding properties, Salmonella were effectively captured with the O-antibody-coated polysorbate 80-coated magnetic nanoclusters (PCMNCs). The synergistic effect of combining selective targeting and the clustered magnetic probe leads to both selective and rapid detection of infectious pathogens.

Increased in vivo immunological potency of HB-110, a novel therapeutic HBV DNA vaccine, by electroporation.

Pulse-induced permeabilization of cellular membranes, generally referred to as electroporation (EP), has been used for years as a tool to increase macromolecule uptake in tissues, including nucleic acids, for gene therapeutic applications, and this technique has been shown to result in improved immunogenicity. In this study, we assessed the utility of EP as a tool to improve the efficacy of HB-110, a novel therapeutic DNA vaccine against chronic hepatitis B, now in phase 1 of clinical study in South Korea. The potency of HB-110 in mice was shown to be improved by EP. The rapid onset of antigen expression and higher magnitude of humoral and cellular responses in electric pulse-treated mice revealed that EP may enable a substantial reduction in the dosage of DNA vaccine required to elicit a response similar in magnitude to that achievable via conventional administration. This study also showed that EP-based vaccination at 4-week-intervals elicited a cellular immune response which was about two-fold higher than the response elicited by conventional vaccination at 2-week intervals. These results may provide a rationale to reduce the clinical dose and increase the interval between the doses in the multidose vaccination schedule. Electric pulsing also elicited a more balanced immune response against four antigens expressed by HB-110: S, preS, Core, and Pol.

In vivo kinetics and biodistribution of HB-110, a novel HBV DNA vaccine, after administration in mice.

This study investigated the pharmacokinetic profile and biodistribution of HB-110, a novel HBV therapeutic vaccine candidate, in mice. HB-110 was rapidly degraded in the blood after i.v. injection with a half-life of 1.9+/-0.083 min, and was no longer detected at 60 min except in one individual near the detection limit. In the i.m. injection, plasmid DNA was detectable at the injection site until 11 days after administration, but the amounts were just above the detection limit. The blood concentration of HB-110 showed a maximum of 604 pg/mL at 15 min after i.m. injection, which was followed by degradation to undetectable levels at 90 min. The plasmid DNA in tissues peaked at 90 min after administration. The highest concentration of plasmid DNA was detected in the liver (24.172 pg/mg tissue), and considerable amounts were also observed in the lung (9.467 pg/mg tissue) and spleen (7.688 pg/mg tissue). The amount of plasmid DNA in tissues was 2 to 3 orders of magnitude lower than in the injection site at the same time points. The HB-110 concentration in tissues, including gonads, decreased rapidly and was undetectable 24 h after administration.