BACKGROUND:Autologous or artificial bone grafts have been widely used to repair maxillofacial bone defects clinically,but these methods still suffer from insufficient osteogenesis.Bone marrow mesenchymal stem cells play a key role in the bone formation.Notably,ectoderm-derived jaw bone marrow mesenchymal stem cells have stronger proliferation and osteogenic differentiation capacity compared with mesoderm-derived iliac bone marrow mesenchymal stem cells,elucidating the key mechanisms involved.It is expected to provide a new strategy for the repair of craniomaxillofacial bone defects.OBJECTIVE:To compare the biological differences between human jaw bone marrow mesenchymal stem cells and iliac bone marrow mesenchymal stem cells and identify the key regulatory genes.METHODS:(1)Jaw bone and iliac bone were collected from three patients with alveolar cleft.Primary bone marrow mesenchymal stem cells were isolated and cultured.Cell proliferation ability was detected by colony formation assay.Cell senescence was detected by β-galactosidase staining assay.Senescence and osteogenesis-related protein expression levels were detected by western blot assay.Osteogenic ability was detected by alizarin red staining after osteogenic induction solution treatment.(2)Jaw bone marrow mesenchymal stem cells and iliac bone marrow mesenchymal stem cells were subjected to transcriptome and differential gene expression analysis to find the 20 genes with the largest differential expression and identify the key regulatory factors.(3)The gene in iliac bone marrow mesenchymal stem cells were knocked down to comparatively analyze the changes in self-renewal,anti-aging and osteogenic capacity of iliac bone marrow mesenchymal stem cells.(4)The gene-edited iliac bone marrow mesenchymal stem cells were loaded into β-tricalcium phosphate scaffolds and implant into nude mice for 8 weeks.The scaffolds were stained with Masson staining and immunofluorescence staining to observe the difference in osteogenic capacity.RESULTS AND CONCLUSION:(1)Jaw bone marrow mesenchymal stem cells have stronger proliferation,anti-aging and osteogenic differentiation abilities compared to iliac bone marrow mesenchymal stem cells.(2)By transcriptome analysis,we identified HOXA10 as a highly up-regulated core transcription factor in iliac bone marrow mesenchymal stem cells.(3)After knocking down HOXA10 in iliac bone marrow mesenchymal stem cells,we observed a significant increase in proliferation,anti-aging,and osteogenic differentiation abilities.(4)After HOXA10 knocked-down iliac bone marrow mesenchymal stem cells/β-tricalcium phosphate was implanted subcutaneously on the back of nude mice,and their bone formation ability was stronger.(5)The above results suggest that HOXA10 is a key regulatory gene that determines the proliferative,anti-aging and osteogenic differentiation abilities of bone marrow mesenchymal stem cells.HOXA10 gene-modified iliac bone marrow mesenchymal stem cell transplantation can be used as a potential application strategy for repairing maxillofacial bone defects.

OBJECTIVES: This study aims to compare the effects of two orthodontic treatment modalities for skeletal class Ⅲ malocclusion on specific changes in airway volume, morphology, palatal angle, mandibular rotation, and bone displacement. Results provide scientific evidence for the selection of orthodontic treatment plans and reduce the risk of developing obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Thirty-six patients diagnosed with skeletal class Ⅲ malocclusion at the Department of Orthodontics, the Affiliated Stomatological Hospital of Nanjing Medical University from September 2018 to December 2023 were divided into two groups: orthodontic-orthognathic treatment group (18 patients) and camouflage orthodontic treatment group (18 patients). Changes in airway volume, cross-sectional area, palatal angle, mandibular, and tongue positions were observed through pre- and post-operative cone beam computed tomography and 3D cephalometric measurements. RESULTS: In the camouflage orthodontic treatment group, nasopharyngeal volume and oropharyngeal volume statistically increased after treatment (P<0.05). In the orthodontic-orthognathic treatment group, changes in nasopharyngeal volume, nasopharyngeal airway, distance from posterior tongue to pharyngeal wall, palatal angle, mandibular rotation, and hyoid bone displacement were statistically significant after surgery (P<0.05). In the comparison between the two groups after treatment, changes in the distance from posterior tongue to pharyngeal wall, palatal angle, and distance from hyoid bone to sella turcica point were statistically significant (P<0.05). CONCLUSIONS Patients in the orthodontic-orthognathic treatment group showed significantly greater changes in oropharyngeal cross-sectional area, palate angle, and tongue position compared with patients in the camouflage orthodontic treatment group. As individuals susceptible to OSAHS often exhibit mandibular retrusion and decreased minimum airway cross-sectional area, special attention should be paid to airway morphology changes when adopting orthodontic-orthognathic treatment to avoid adverse consequences.
Humans ; Hyoid Bone/diagnostic imaging* ; Malocclusion, Angle Class III/therapy* ; Male ; Female ; Cone-Beam Computed Tomography ; Cephalometry ; Orthodontics, Corrective/methods* ; Adult ; Mandible ; Pharynx/diagnostic imaging* ; Sleep Apnea, Obstructive/etiology* ; Orthognathic Surgical Procedures

BACKGROUND:Autologous or artificial bone grafts have been widely used to repair maxillofacial bone defects clinically,but these methods still suffer from insufficient osteogenesis.Bone marrow mesenchymal stem cells play a key role in the bone formation.Notably,ectoderm-derived jaw bone marrow mesenchymal stem cells have stronger proliferation and osteogenic differentiation capacity compared with mesoderm-derived iliac bone marrow mesenchymal stem cells,elucidating the key mechanisms involved.It is expected to provide a new strategy for the repair of craniomaxillofacial bone defects.OBJECTIVE:To compare the biological differences between human jaw bone marrow mesenchymal stem cells and iliac bone marrow mesenchymal stem cells and identify the key regulatory genes.METHODS:(1)Jaw bone and iliac bone were collected from three patients with alveolar cleft.Primary bone marrow mesenchymal stem cells were isolated and cultured.Cell proliferation ability was detected by colony formation assay.Cell senescence was detected by β-galactosidase staining assay.Senescence and osteogenesis-related protein expression levels were detected by western blot assay.Osteogenic ability was detected by alizarin red staining after osteogenic induction solution treatment.(2)Jaw bone marrow mesenchymal stem cells and iliac bone marrow mesenchymal stem cells were subjected to transcriptome and differential gene expression analysis to find the 20 genes with the largest differential expression and identify the key regulatory factors.(3)The gene in iliac bone marrow mesenchymal stem cells were knocked down to comparatively analyze the changes in self-renewal,anti-aging and osteogenic capacity of iliac bone marrow mesenchymal stem cells.(4)The gene-edited iliac bone marrow mesenchymal stem cells were loaded into β-tricalcium phosphate scaffolds and implant into nude mice for 8 weeks.The scaffolds were stained with Masson staining and immunofluorescence staining to observe the difference in osteogenic capacity.RESULTS AND CONCLUSION:(1)Jaw bone marrow mesenchymal stem cells have stronger proliferation,anti-aging and osteogenic differentiation abilities compared to iliac bone marrow mesenchymal stem cells.(2)By transcriptome analysis,we identified HOXA10 as a highly up-regulated core transcription factor in iliac bone marrow mesenchymal stem cells.(3)After knocking down HOXA10 in iliac bone marrow mesenchymal stem cells,we observed a significant increase in proliferation,anti-aging,and osteogenic differentiation abilities.(4)After HOXA10 knocked-down iliac bone marrow mesenchymal stem cells/β-tricalcium phosphate was implanted subcutaneously on the back of nude mice,and their bone formation ability was stronger.(5)The above results suggest that HOXA10 is a key regulatory gene that determines the proliferative,anti-aging and osteogenic differentiation abilities of bone marrow mesenchymal stem cells.HOXA10 gene-modified iliac bone marrow mesenchymal stem cell transplantation can be used as a potential application strategy for repairing maxillofacial bone defects.

Melanoma is a malignant skin tumor characterized by a propensity for early metastasis and high mortality rates. Immune checkpoint inhibitors have significantly improved the prognosis for melanoma patients, however, some individuals remain unresponsive to immunotherapy, primarily due to the immunosuppressive characteristics of the tumor microenvironment. This review summarizes recent research on the melanoma tumor microenvironment and analyzes how dynamic changes in its components influence melanoma development and the efficacy of immunotherapy. Additionally, it outlines immunotherapy strategies focused on immune checkpoint inhibitors, examines their mechanisms of action and limitations, and further investigates the effects of combining immune checkpoint inhibitors with various therapeutic modalities, including radiotherapy, chemotherapy, and targeted therapies. This study aims to provide new insights into the melanoma tumor microenvironment and the advancement of personalized precision immunotherapy.

Melanoma is a malignant skin tumor characterized by a propensity for early metastasis and high mortality rates. Immune checkpoint inhibitors have significantly improved the prognosis for melanoma patients, however, some individuals remain unresponsive to immunotherapy, primarily due to the immunosuppressive characteristics of the tumor microenvironment. This review summarizes recent research on the melanoma tumor microenvironment and analyzes how dynamic changes in its components influence melanoma development and the efficacy of immunotherapy. Additionally, it outlines immunotherapy strategies focused on immune checkpoint inhibitors, examines their mechanisms of action and limitations, and further investigates the effects of combining immune checkpoint inhibitors with various therapeutic modalities, including radiotherapy, chemotherapy, and targeted therapies. This study aims to provide new insights into the melanoma tumor microenvironment and the advancement of personalized precision immunotherapy.

Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen, particularly the Porphyromonas gingivalis (P. gingivalis), by inducing apoptosis. However, it remains obscure whether accumulated apoptotic cells in P. gingivalis-accelerated plaque formation are associated with impaired macrophage clearance. Here, we show that smooth muscle cells (SMCs) have a greater susceptibility to P. gingivalis-induced apoptosis than endothelial cells through TLR2 pathway activation. Meanwhile, large amounts of miR-143/145 in P.gingivalis-infected SMCs are extracellularly released and captured by macrophages. Then, these miR-143/145 are translocated into the nucleus to promote Siglec-G transcription, which represses macrophage efferocytosis. By constructing three genetic mouse models, we further confirm the in vivo roles of TLR2 and miR-143/145 in P. gingivalis-accelerated atherosclerosis. Therapeutically, we develop P.gingivalis-pretreated macrophage membranes to coat metronidazole and anti-Siglec-G antibodies for treating atherosclerosis and periodontitis simultaneously. Our findings extend the knowledge of the mechanism and therapeutic strategy in oral pathogen-associated systemic diseases.
Animals ; Mice ; Endothelial Cells ; Toll-Like Receptor 2 ; Macrophages ; Apoptosis ; Atherosclerosis ; Myocytes, Smooth Muscle ; MicroRNAs

Objective To investigate the correlation between ATP-binding cassette transporter A1 (ABCA1) R219K polymorphism and ischemic stroke in Chinese populations.Methods The case control studies of the correlation between Chinese ABCA1 R219K polymorphism and ischemic stroke published before May 2013 were collected using comprehensive literature search.The Stata 11.0 software was used to conduct metaanalysis.Odds ratio (OR) and its 95％ confidence interval (CI) was used to evaluate the strength of association between the gene polymorphism and ischemic stroke.Results A total of 10 studies met the criteria and were included in the analysis,including 1 619 patients in the patient group and 1907 in the control group.The selected literature had no obvious bias.Meta-analysis showed that the risk of ischemic stroke in patients carrying RK + KK genotype significantly decreased 8％ (OR 0.92,95％ CI 0.88-0.96; P =0.000)compared to those carrying RR genotype.The risk of ischemic stroke in patients carrying KK genotype significantly decreased 36％ compared to those carrying RR genotype (OR 0.64,95％ CI 0.44-0.94; P =0.02).The risk of ischemic stroke in patients carrying RK genotype significantly decreased 19％ compared to those carrying RR genotype (OR 0.81,95％ CI 0.69-0.95; P =0.009).The risk of ischemic stroke in patients carrying K allele significantly decreased 17％ compared to those carrying R allele (0R 0.83,95％ CI 0.69-0.99; P =0.036).Conclusions ABCA1 R219K polymorphism is associated with the susceptibility of ischemic stroke in Chinese.K allele may be a genetic protective factor for ischemic stroke in Chinese populations.

Objective To explore the relationship between lecithin cholesterol acy ltransferase (LCAT) gene 608C/T and 511C/T polymorphisms and stroke in Chinese Han population in Hunan province. Methods One hundred fifty patients with cerebral infarction, 150patients with cerebral hemorrhage, and 122 age- and sex-matched healthy controls were selected.LCAT gene 608C/T and 511C/T polymorphisms were detected by using polyrnerase chain reaction, single strand conformation polymorphism, and restriction fragment length polymorphisms. Results The CT genotype frequency (14. 0% ) and T allele frequency (7. 0% )of the LCAT gene 608C/T in the cerebral infarction group were significantly higher than those in the control group (all P ＜0. 05), while there were no significant differences in the CT genotype frequency (7. 3% ) and T allele frequency (3.7%) between the cerebral hemorrhage group and the control group (P ＞ 0. 05). The CT genotype frequency (10. 0% ) and T allele frequency (5. 0% ) of the LCAT gene 511C/T in the cerebral infarction group were significantly higher than those in the control group (all P ＜0. 01), while there were no significant differences in the CT genotype frequency (3.3%) and T allele frequency (1.7%) between the cerebral hemorrhage group and the control group (P ＞0. 05). Conclusions The 608C/T and 511C/T polymorphisms may be associated with the occurrence of atherosclerotic cerebral infarction in Chinese Han population in Hunan province. They may be the predisposing factors for atherosclerotic cerebral infarction in this population; however, they are not associated with cerebral hemorrhage.