Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

Tooth pulpitis is a prevalent oral disorder. Understanding the underlying mechanisms of pulpitis and developing effective treatment strategies hold great significance. Ferroptosis has recently emerged as a new form of cell death, but the role of ferroptosis in pulpitis remains largely unknown. In our study, single-cell RNA sequencing (scRNA-seq) was used to identify cellular heterogeneity between 3 pulpitis tissue and 3 healthy pulp tissue, and explored ferroptosis occurrence in pulpitis tissue and inflamed dental pulp cells (DPCs). In scRNA-seq, 40 231 cells (Pulpitis: 17 814; Healthy pulp: 22 417) were captured, and visualized into 12 distinct cell clusters. Differentially expressed ferroptosis-related genes (DE-FRGs) were almost presented in each cluster in pulpitis vs healthy pulp. ROS and Fe²⁺ levels significantly rose, and immunohistochemistry showed low expression of GPX4 and high expression of PTGS2 in pulpitis. In LPS-stimulated DPCs, thymosin α1 increased the expression of GPX4 and FTL, and decreased expression of TNF-α, IL-1β, IL-6, and Fe²⁺ levels. In rat pulpitis models, both prothymosin α (PTMA, precursor of thymosin α1) gelatin sponge placed at the hole of pulp (LPS-P(gs)) and PTMA injection in pulp (LPS-P(i)) significantly reduced infiltration of inflammatory cells and expression of PTGS2, and increased the expression of GPX4. In RNA sequencing, the expression of DE-FRGs were reversed when thymosin α1 were added in LPS-stimulated DPCs. Collectively, single-cell atlas reveals cellular heterogeneity between pulpitis and healthy pulp, and ferroptosis occurrence in pulpitis. Thymosin α1 may reduce ferroptosis in DPCs to alleviate pulpitis and thus potentially has the ability to treat pulpitis.
Ferroptosis/drug effects* ; Dental Pulp/drug effects* ; Animals ; Pulpitis/pathology* ; Rats ; Thymalfasin/pharmacology* ; Humans ; Male ; Thymosin/pharmacology* ; Disease Models, Animal ; Rats, Sprague-Dawley

Congenital insensitivity to pain with anhidrosis (CIPA)is a rare disease which mainly affects infants, children and adolescents. As an autosomal recessive disorder, CIPA is also known as familial autonomic dysfunction type 2. The diagnosis of CIPA mainly relies on clinical observation and genetic testing. Currently there is a lack of effective treatment, and it is mainly treated by cooling, anti-inflammatory and strengthened guardianization. This article has reviewed the literature and summarized the research on CIPA and progress made in its diagnosis and treatment, with an aim to improve the understanding of this disorder.

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans ; Mice ; Rats ; Cell Proliferation ; Heart/physiology* ; Mammals ; Myocardial Infarction/metabolism* ; Myocytes, Cardiac/metabolism* ; Pericardium/metabolism* ; Single-Cell Analysis ; Zebrafish/metabolism*

Objective To investigate the effect of genistein on the proliferation,migration and invasion of prostate cancer cells and its molecular mechanism.Methods Prostate cancer LNCaP and CWR22RV1 cells were divided into the control group(conventional culture)and the experimental group(50μmol/L genistein treatment).The effect of genistein on the proliferation of prostate cancer cells were analyzed by MTT assay.The effect of genistein on the migration and invasion of prostate cancer cells were analyzed by cell scratch assay and Transwell assay.The protein levels of epithelial interstital transformation(EMT)intermediate markers E-Cadherin,N-Cadherin,Vimentin,and tumor stem cell markers CD44 and Oct-4 were detected by Western blot assay.Results MTT assay showed that genistein could inhibit the proliferation of prostate cancer cells.The scratch closure rates of LNCaP and CWR22RV1 cells were significantly reduced in the experimental group compared with those in the control group,and the number of cells passing through the Transwell membrane was significantly reduced(P＜0.05).Western blot assay showed that genistein could down-regulate the expression levels of N-Cadherin,Vimentin,CD44 and Oct4 in prostate cancer cells,and up-regulate the expression of E-Cadherin in epithelial cells(P＜0.01).Conclusion Genistein reduces the dryness of prostate cancer cells by inhibiting the EMT process,thus reducing the proliferation,migration and invasion of prostate cancer cells.

ObjectiveTo study the current status and development trend of research on the executive function in overweight or obesity， and to grasp the research hotspots in this field. MethodsA total of 1 321 literatures relevant to the executive function in overweight or obesity collected in Web of Science Core Collection database from 2010 to 2021 were selected. CiteSpace and VOSviewer were used to generate knowledge graphs for visualization analysis， then the number of articles issued， countries/regions， institutions and the co-occurrence， clustering and burst of keywords were analyzed. Results①In terms of the trend of the number of articles issued from 2010 to 2021， the annual quantity of published articles about the executive function in overweight or obesity presented a rapid growth over 2010-2014， then entered into a slow growth stage over 2014-2017， and emerged a rapid growth over 2017-2021. ②From the perspective of countries / regions， a total of 64 countries and regions participated in the research. The largest number of articles issued in this field was the USA， which had the most frequent cooperation and exchanges with other countries and regions， and exerted the greatest academic influence， occupying the core position of this research field. ③From the perspective of research institutions， a total of 1 627 institutions participated in this research field， among which the Illinois University published the most papers and closely cooperated with many productive institutions， forming a research group with a certain scale. ④From the perspective of keywords， the research content mainly involved dietary behavior research， prevention and intervention research， risk factor assessment， and analysis of the characteristics of different groups. ConclusionResearches on executive function in overweight or obesity have been developing rapidly， attracting international attention and covering a wide range of areas.

Objective:To evaluate the effect of laryngopharyngeal reflux on sedation-related adverse events in the patients undergoing painless gastroscopy.Methods:Two hundred and eighty-nine American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients of both sexes, aged 18-75 yr, with body mass index 18.5-28.0 kg/m 2, scheduled for elective painless gastrocopy, were selected.Specimens of glottic secretions before and after gastroscopy were collected, and the concentration of human pepsin was measured by enzyme-linked immunosorbent assay.The patients in whom the concentration of pepsin was positive before the examination were excluded (the concentration ≥ 31.34 pg/ml was considered as positive). The patients were divided into laryngopharyngeal reflux group (R group, the concentration of pepsin was positive after gastroscopy) and non-laryngopharyngeal reflux group (N group, the concentration of pepsin was negative after gastroscopy) according to the concentration of pepsin in the secretion samples before and after gastroscopy.The occurrence of hypoxemia, hypotension, bradycardia, bucking and body movement during operation was recorded.The patients were followed up by telephone on the 1st, 3rd and 7th days after operation.The sore throat, hoarseness, nausea and vomiting, cough and expectoration and use of antibiotics were recorded. Results:Compared with group N, the incidence of bucking and hypoxemia was significantly increased, the incidence of sore throat and hoarseness was increased on the 1st day after operation, and the incidence of cough and expectoration was increased on the 1st and 3rd days after gastroscopy in group R ( P<0.05). Conclusion:Laryngopharyngeal reflux can increase the development of intraoperative and postoperative sedation-related adverse events in the patients undergoing painless gastroscopy.

Objective To investigate the effect of miR-15b and miR-16 on the expression of vascular endothelial growth factor (VEGF) protein in human embryonic lung fibroblast (HLF) cells under hyperoxia.Methods The expression level of miR-15b and miR-16 was up-regulated and down-regulated in HLF cells by transfection technology, respectively.The expression of VEGF protein in HLF cells was assessed by Western blot.Furthermore, under hyperoxia exposure in vitro, the expression of miR-15b, miR-16 and VEGF protein in HLF cells was analyzed.Results Up-regulation of miR-15b and miR-16 suppressed VEGF protein expression, while down-regulated miR-15b and miR-16 promoted VEGF protein expression.In addition, hyperoxia exposure induced up-regulation of miR-15b and miR-16, but down-regulation of VEGF protein in HLF cells.Conclusions Hyperoxia exposure may up-regulate the expression level of miR-15b and miR-16, but suppress VEGF protein expression.These may contribute to the development of bronchopulmonary dysplasia.