OBJECTIVES: To investigate CEACAM6 expression in nasopharyngeal carcinoma (NPC) and its regulatory effects on tumor cell proliferation, migration, and epithelial-mesenchymal transition (EMT). METHODS: CEACAM6 expression in NPC was analyzed using GEO datasets and validated by immunohistochemistry in NPC tissues and by Western blotting and RT-qPCR in NPC cell lines (HNE1, C666-1, HK1, 5-8F and CNE2Z) and normal nasopharyngeal epithelial NP69 cells. In the NPC cell lines, the effects of lentivirus-mediated CEACAM6 overexpression and knockdown on cell proliferation, migration, invasion and cytoskeletal structures were evaluated using CCK-8 assay, Edu staining, wound healing assay, Transwell assay, and phalloidin staining. Western blotting was performed to determine the expressions of EMT-related proteins (FN1, ITGA5, ITGB1, E-cadherin, N-cadherin and vimentin) in the NPC cells and the effect of FN1 overexpression on ITGA5 and ITGB1 protein expressions. RESULTS: Analysis of the data from the GEO datasets suggested that CEACAM6 was significantly downregulated in NPC, which was associated with poor patient prognosis. Immunohistochemistry also showed low expressions of CEACAM6 in clinical NPC tissues (P<0.05). In NPC cells, CEACAM6 overexpression significantly suppressed cell proliferation, migration and invasion and reduced the fluorescence intensity of actin. CEACAM6 overexpression also resulted in significant downregulation of FN1, ITGA5, ITGB1, N-cadherin and vimentin expressions and upregulation of E-cadherin expression, and FN1 overexpression obviously attenuated the inhibitory effect of CEACAM6 overexpression on ITGA5 and ITGB1 expressions. CONCLUSIONS CEACAM6 inhibits NPC cell migration and invasion by inhibiting EMT via regulating FN1, ITGA5 and ITGB1 expressions.
Humans ; Epithelial-Mesenchymal Transition ; Cell Movement ; Cell Proliferation ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/metabolism* ; Cell Line, Tumor ; Cell Adhesion Molecules/genetics* ; Antigens, CD/metabolism* ; GPI-Linked Proteins ; Integrin alpha5/metabolism* ; Integrin beta1/metabolism* ; Cadherins/metabolism* ; Fibronectins ; Integrins

Early-life stress (ES) leads to cognitive dysfunction in female adolescents, but the underlying neural mechanisms remain elusive. Recent evidence suggests that the cell adhesion molecules NECTIN1 and NECTIN3 play a role in cognition and ES-related cognitive deficits in male rodents. In this study, we aimed to investigate whether and how nectins contribute to ES-induced cognitive dysfunction in female adolescents. Applying the well-established limited bedding and nesting material paradigm, we found that ES impairs recognition memory, suppresses prefrontal NECTIN1 and hippocampal NECTIN3 expression, and upregulates corticotropin-releasing hormone (Crh) and its receptor 1 (Crhr1) mRNA levels in the hippocampus of adolescent female mice. Genetic experiments revealed that the reduction of dorsal CA1 (dCA1) NECTIN3 mediates ES-induced object recognition memory deficits, as knocking down dCA1 NECTIN3 impaired animals' performance in the novel object recognition task, while overexpression of dCA1 NECTIN3 successfully reversed the ES-induced deficits. Notably, prefrontal NECTIN1 knockdown did not result in significant cognitive impairments. Furthermore, acute systemic administration of antalarmin, a CRHR1 antagonist, upregulated hippocampal NECTIN3 levels and rescued object and spatial memory deficits in stressed mice. Our findings underscore the critical role of dCA1 NECTIN3 in mediating ES-induced object recognition memory deficits in adolescent female mice, highlighting it as a potential therapeutic target for stress-related psychiatric disorders in women.
Animals ; Female ; Mice ; CA1 Region, Hippocampal/metabolism* ; Cell Adhesion Molecules/metabolism* ; CRF Receptor, Type 1/metabolism* ; Memory Disorders/etiology* ; Mice, Inbred C57BL ; Nectins/genetics* ; Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors* ; Recognition, Psychology/physiology* ; Stress, Psychological/complications*

Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration, especially in orthodontic tooth movement. Abaloparatide (ABL), a synthetic analog of human PTHrP (1-34) and a clinical medication for treating osteoporosis, has recently demonstrated its potential in enhancing craniofacial bone formation. Herein, we show that intraoral submucosal injection of ABL, when combined with mechanical force, promotes in situ alveolar bone thickening. The newly formed bone is primarily located outside the original compact bone, implying its origin from the periosteum. RNA sequencing of the alveolar bone tissue revealed that the focal adhesion (FA) pathway potentially mediates this bioprocess. Local injection of ABL alone enhances cell proliferation, collagen synthesis, and phosphorylation of focal adhesion kinase (FAK) in the alveolar periosteum; when ABL is combined with mechanical force, the FAK expression is upregulated, in line with the accomplishment of the ossification. In vitro, ABL enhances proliferation, migration, and FAK phosphorylation in periosteal stem cells. Furthermore, the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor. In summary, abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis. Thus, we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation, which may prevent or repair the detrimental periodontal dehiscence, holding significant potential in dentistry.
Osteogenesis/drug effects* ; Periosteum/cytology* ; Parathyroid Hormone-Related Protein/administration & dosage* ; Animals ; Focal Adhesion Protein-Tyrosine Kinases/metabolism* ; Alveolar Process/drug effects* ; Cell Proliferation/drug effects* ; Phosphorylation ; Rats ; Male ; Humans ; Focal Adhesion Kinase 1/metabolism* ; Cell Movement/drug effects*

OBJECTIVES: This study aimed to compare the osteogenic performance differences of titanium surface coatings modified by dopamine or silanized graphene oxide, and to provide a more suitable modification scheme for titanium surface graphene oxide coatings. METHODS: Titanium was subjected to alkali-heat treatment and then modified with dopamine and silanization, respectively, followed by coating with graphene oxide. Control and experimental groups were designed as follows: pure titanium (Ti) group; titanium after alkali-heat treatment (Ti-NaOH) group; titanium after alkali-heat treatment and silanization modification (Ti-APTES) group; titanium after alkali-heat treatment and dopamine modification (Ti-DOPA) group; titanium with silanization-modified surface decorated with graphene oxide (Ti-APTES/GO) group; titanium with dopamine-modified surface decorated with graphene oxide (Ti-DOPA/GO) group. The physical and chemical properties of the material surfaces were analyzed using scanning electron microscopy (SEM), contact angle goniometer, X-ray photoelectron spectroscopy (XPS), and Raman spectrometer. The proliferation and adhesion morphology of mouse embryonic osteoblast precursor cells MC3T3-E1 on the material surfaces were observed by cell viability detection and immunofluorescence staining followed by laser confocal microscopy. The effects on the osteogenic differentiation of MC3T3-E1 cells were studied by alkaline phosphatase (ALP) staining, alizarin red staining and quantification, and real-time quantitative polymerase chain reaction. RESULTS: After modification with graphene oxide coating, a thin-film-like structure was observed on the surface under SEM. The hydrophilicity of all experimental groups was improved, among which the Ti-DOPA/GO group had the best hydrophilicity. XPS and Raman spectroscopy analysis showed that the modified materials exhibited typical D and G peaks, and XPS revealed the presence of a large number of oxygen-containing functional groups on the surface. CCK8 assay showed that all groups of materials had no cytotoxicity, and the proliferation level of the Ti-APTES/GO group was higher than that of the Ti-DOPA/GO group. Under the laser confocal microscope, the cells in the Ti-DOPA/GO and Ti-APTES/GO groups spread more fully. The Ti-DOPA/GO and Ti-APTES/GO groups had the deepest ALP staining, and the Ti-APTES/GO group had the most alizarin red-stained mineralized nodules and the highest quantitative result of alizarin red staining. In the Ti-DOPA/GO and Ti-APTES/GO groups, the expression of the early osteogenic-related gene RUNX2 reached a relatively high level, while in the expression of the late osteogenic-related genes OPN and OCN, the Ti-APTES/GO group performed better than the Ti-DOPA/GO group. CONCLUSIONS Ti-APTES/GO significantly outperformed Ti-DOPA/GO in promoting the adhesion, proliferation, and in vitro osteogenic differentiation of MC3T3-E1 cells.
Titanium/chemistry* ; Graphite/chemistry* ; Dopamine/chemistry* ; Animals ; Mice ; Osteogenesis ; Osteoblasts/cytology* ; Surface Properties ; Cell Proliferation ; Silanes/chemistry* ; Cell Adhesion ; Coated Materials, Biocompatible/chemistry* ; Cell Differentiation ; Alkaline Phosphatase/metabolism* ; Microscopy, Electron, Scanning

OBJECTIVES: This study investigated the effects of a polycaprolactone (PCL)-polyethylene glycol (PEG) scaffold incorporated with concentrated growth factor (CGF) on the adhesion, proliferation, and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). METHODS: The PCL-PEG-CGF composite scaffold was fabricated using an immersion and freeze-drying technique. Its microstructure, mechanical properties, and biocompatibility were systematically characterized. The hPDLSCs were isolated through enzymatic digestion, and the hPDLSCs were identified through flow cytometry. Third-passage hPDLSCs were seeded onto the composite scaffolds, and their adhesion, proliferation and osteogenic differentiation were assessed using CCK-8 assays, 4',6-diamidino-2-phenylindole (DAPI) staining, alkaline phosphatase (ALP) staining, alizarin red staining, and Western blot analysis of osteogenesis-related proteins [Runt-related transcription factor 2 (Runx2), ALP, and morphogenetic protein 2 (BMP2)]. RESULTS: Scanning electron microscopy revealed that the PCL-PEG-CGF composite scaffold exhibited a honeycomb-like structure with heterogeneous pore sizes. The composite scaffold exhibited excellent hydrophilicity, as evidenced by a contact angle (θ) approaching 0° within 6 s. Its elastic modulus was measured at (4.590 0±0.149 3) MPa, with comparable hydrophilicity, fracture tensile strength, and fracture elongation to PCL-PEG scaffold. The hPDLSCs exhibited significantly improved adhesion to the PCL-PEG-CGF composite scaffold compared with the PCL-PEG scaffold (P<0.01). Additionally, cell proliferation was markedly improved in all the experimental groups on days 3, 5, and 7 (P<0.01), and statistically significant differences were found between the PCL-PEG-CGF group and other groups (P<0.01). The PCL-PEG-CGF group showed significantly elevated ALP activity (P<0.05), increased mineralization nodule formation, and upregulated expression of osteogenic-related proteins (Runx2, BMP2 and ALP; P<0.05). CONCLUSIONS The PCL-PEG-CGF composite scaffold exhibited excellent mechanical properties and biocompatibility, enhancing the adhesion and proliferation of hPDLSCs and promoting their osteogenic differentiation by upregulating osteogenic-related proteins.
Humans ; Polyesters/chemistry* ; Periodontal Ligament/cytology* ; Polyethylene Glycols/chemistry* ; Stem Cells/cytology* ; Tissue Scaffolds ; Cell Proliferation ; Osteogenesis ; Cell Differentiation ; Cell Adhesion ; Bone Morphogenetic Protein 2/metabolism* ; Cells, Cultured ; Alkaline Phosphatase/metabolism* ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Intercellular Signaling Peptides and Proteins/pharmacology* ; Tissue Engineering/methods*

Cancer ranks as the second leading cause of death globally and has surpassed cardiovascular diseases to become the primary cause of mortality in developed countries. Cancer stem cells (CSCs), which play crucial roles in cancer recurrence, metastasis, and drug resistance, have attracted significant attention in targeted therapeutic strategies. Aptamers, with unique three-dimensional structures capable of specifically recognizing the surface markers of CSCs, show promising potential in targeted drug delivery systems. Compared with conventional antibodies, aptamers are praised for small molecular weights, low production costs, and easy chemical modification. This review systematically summarizes recent advances in aptamer research targeting the surface markers of CSCs, with particular emphasis on aptamer-drug conjugate systems targeting the markers including EpCAM, CD133, CD44, and ABCG2. Both in vitro cellular studies and in vivo animal models have demonstrated the definite anti-cancer efficacy of aptamer-based drug delivery systems, which are of great significance to develop novel therapeutic strategies and improving the therapeutic effects of CSC-targeted treatment. Thus, aptamer-based drug delivery system has broad application prospects in the field of precise cancer treatment.
Humans ; Neoplastic Stem Cells/metabolism* ; Aptamers, Nucleotide/therapeutic use* ; Drug Delivery Systems/methods* ; Neoplasms/drug therapy* ; Biomarkers, Tumor/metabolism* ; Animals ; Epithelial Cell Adhesion Molecule ; AC133 Antigen ; Hyaluronan Receptors

This paper aims to explore the effect of electrical stimulation of triboelectric nanogenerators (TENGs) on the osteogenic and other biological behaviors of mouse embryonic osteoblast precursor cells (MC3T3-E1 cells) on titanium surfaces. First, an origami-type TENG was fabricated, and its electrical output performance was tested. The optimal current of the generator and the feasibility of the experiment were verified by the CCK-8 assay and scratch assay. At the optimal current, the osteogenic conditions of the cells in each group were determined by quantitative analysis of the total protein content, alkaline phosphatase (ALP) activity, and alizarin red staining (ARS) on the titanium surface. Finally, the adhesion and spreading of cells on the titanium surface after electrical stimulation were observed. The results showed that the TENG had good electrical output performance, with an open-circuit voltage of 65 V and a short-circuit current of 42 μA. Compared with the rest of the current, a current strength of 30 μA significantly improved cell proliferation and migration, osteogenesis, and adhesion and spreading capabilities. The above results confirm the safety and operability of TENG in biomedical applications, laying the foundation for future TENG applications in reducing the time of bone integration around titanium implants after surgery.
Titanium/chemistry* ; Osteogenesis ; Animals ; Mice ; Osteoblasts/cytology* ; Electric Stimulation/instrumentation* ; Cell Adhesion ; Cell Proliferation ; Surface Properties ; Cell Differentiation ; Nanotechnology

Extramedullary disease (EMD) is an independent prognostic factor for multiple myeloma (MM). Compared with MM without EMD, MM with EMD has different genetic characteristics, with a higher incidence of high-risk chromosomal abnormalities, more complex genomic profile, and immunophenotypic features related to adhesion molecule and chemokine expression. The mutual regulation between myeloma cells and tumor microenvironment, including changes in immune environment, deposition of extracellular matrix, abnormal expression of adhesion molecules, and autocrine secretion of myeloma cells, is involved in the extramedullary migration of myeloma cells. Various immune-targeted therapies have improved the prognosis of extramedullary MM (EMM). This article reviews the genetic characteristics of EMM, important role of tumor microenvironment, and progress of treatment.
Multiple Myeloma/therapy* ; Prognosis ; Incidence ; Gene Expression Regulation, Neoplastic ; Tumor Microenvironment ; Extracellular Matrix/metabolism* ; Cell Adhesion ; Humans ; Immunophenotyping

OBJECTIVE: To prepare clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSC) with high expression of hematopoietic supporting factors and evaluate their stem cell characteristics. METHODS: Fetal umbilical cord tissues were collected from healthy postpartum women during full-term cesarean section. Wharton's jelly was mechanically separated and hUC-MSCs were obtained by explant culture method and enzyme digestion method in an animal serum-free culture system with addition of human platelet lysate. The phenotypic characteristics of hUC-MSCs obtained by two methods were detected by flow cytometry. The differences in proliferation ability between the two groups of hUC-MSCs were identified through CCK-8 assay and colony forming unit-fibroblast (CFU-F) assay. The differences in multilineage differentiation potential between the two groups of hUC-MSCs were identified through induction of adipogenic, osteogenic, and chondrogenic differentiation. The mRNA expression levels of hematopoietic supporting factors such as SCF, IL-3, CXCL12, VCAM1 and ANGPT1 in the two groups of hUC-MSCs were identified by real-time fluorescence quantiative PCR(RT-qPCR). RESULTS: The results of flow cytometry showed that hUC-MSCs obtained by the two methods both expressed high levels of CD73, CD90 and CD105, while lowly expressed CD31, CD45 and HLA-DR. The results of CCK-8 and CFU-F assay showed that the proliferation ability of hUC-MSCs obtained by explant culture method was better than those obtained by enzyme digestion method. The results of the triple lineage differentiation experiment showed that there was no significant difference in multilineage differentiation potential between the two grous of hUC-MSCs. The results of RT-qPCR showed that the mRNA expression levels of hematopoietic supporting factors SCF, IL-3, CXCL12, VCAM1 and ANGPT1 in hUC-MSCs obtained by explant cultrue method were higher than those obtained by enzyme digestion method. CONCLUSION Clinical-grade hUC-MSCs with high expression levels of hematopoietic supporting factors were successfully cultured in an animal serum-free culture system.
Humans ; Mesenchymal Stem Cells/metabolism* ; Umbilical Cord/cytology* ; Cell Differentiation ; Female ; Cell Proliferation ; Cells, Cultured ; Chemokine CXCL12/metabolism* ; Angiopoietin-1/metabolism* ; Vascular Cell Adhesion Molecule-1/metabolism* ; Stem Cell Factor/metabolism* ; Flow Cytometry ; Pregnancy

OBJECTIVE: To investigate the biological effect of medical recombinant human-derived collagen functional dressings in wound healing. METHODS: MTT assay and RTCA assay were used to detect cell toxicity and proliferation. Scratch assay and Transwell cell migration assay were used to detect cell motility and migration ability. Enzyme-linked immunosorbent assay was used to detect the contents of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-endothelial cell adhesion molecule (CD31) in the supernatant of four types of cells. After animal surgery, the surgical wound was taken at 1 week, 4 weeks and 13 weeks, respectively, for hematoxylin eosin (HE) staining and immunohistochemistry to observe the inflammatory response and CD31 expression of the wound. RESULTS: Medical recombinant human-derived collagen functional dressing promotes cell proliferation and migration, enhances wound angiogenesis by upregulating the expression of VEGF, FGF, and CD31 in human dermal vascular endothelial cells (HDVEC) and human vascular endothelial cells (HVEC), thereby improving local blood supply to the wound, regulating the inflammatory response of the wound, and accelerating wound healing. CONCLUSION Recombinant type Ⅲ humanized collagen plays an important role in wound healing.
Humans ; Wound Healing/drug effects* ; Recombinant Proteins/pharmacology* ; Animals ; Cell Proliferation ; Cell Movement ; Collagen/pharmacology* ; Vascular Endothelial Growth Factor A/metabolism* ; Bandages ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism* ; Endothelial Cells ; Fibroblast Growth Factors/metabolism*