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Effect of protein kinase C alpha, caspase-3, and survivin on apoptosis of oral cancer cells induced by staurosporine

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Acta Pharmacologica Sinica 2005年第11期26卷 1365-1372页

作者： Yu-xia ZHANG~(2,4), Shi-bin YU~(3,4), Jing-ping OU-YANG~(2,5), Dong XIA~2, Min WANG~2, Jin-rong LI~3 ~2 department of Pathology and Pathophysiology, School of Medicine ~3 The First department of oral and maxillofacial surgery, School of Stomatology, Wuhan University Wuhan 430071, China department of Pathology and Pathophysiology School of Medicine Wuhan University Wuhan China The First department of oral and maxillofacial surgery School of Stomatology Wuhan University Wuhan China

Aim: To elucidate inhibition of protein kinase C α （PKC α） activity by staurosporine on apoptosis of oral cancer cell line tongue squamous cell carcinoma （TSCCa） cells and to clarify the role of survivin and caspase-3 in mediating apoptosis. Methods: TSCCa cell viability was measured by MTT assay after 100 nmol/L staurosporine treatment. Apoptotic cells were identified by using phase contrast microscopy, acridine orange/ethidium bromide staining, and flow cytometry. Level of PKC α and its subcellular location were investigated using Western blot analysis. Expression of survivin and caspase-3 were evaluated using immunocytochemistry. Results: Staurosporine significantly inhibited the cell viability of TSCCa cells in a dose- and time-dependent manner. Marked cell accumulation in G2/M phase was observed after 100 nmol/L staurosporine exposure for 6 h and 12 h. In addition, the percentage of apoptosis increased in a time-dependent manner, from 2.9% in control cultures to approximately 27.4% at 100 nmol/L staurosporine treatment for 24 h. Staurosporine displayed difference in inhibitory efficacy between cytosolic and membrance-derived PKC α. The content of PKCα in membrane versus cyto-sol decreased quickly, from 0.45 in ethanol-treated control cultures to 0.18 after staurosporine exposure for 24 h （P<0.01）. After treatment with staurosporine, a time-dependent reduction of survivin and an activation of caspase-3 were observed in TSCCa cells. Conclusion: Staurosporine inhibited cell viability and promoted apoptosis in TSCCa cells. Inhibition of PKCα activity might be a potential mechanism for staurosporine to induce apoptosis in this cell line. The cleavage of survivin and activation of caspase-3 signaling pathway might contribute to PKC α inhibition-induced apoptosis.

关键词： protein kinase C alpha caspase-3 survivin protein apoptosis staurosporine carcinoma, squamous cell mouth

A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: superior delivery of curcumin and alleviation of diabetic osteoporosis

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Bone Research 2024年第1期12卷 227-239页

作者： Yong Li Zhengwen Cai Wenjuan Ma Long Bai En Luo Yunfeng Lin State Key Laboratory of oral Diseases&National Center for Stomatology&National Clinical Research Center for oral Diseases West China Hospital of StomatologySichuan UniversityChengduSichuan 610041PR China department of oral and maxillofacial surgery Affiliated Stomatological HospitalSouthwest Medical UniversityLuzhouSichuan 646000PR China Sichuan Provincial Engineering Research Center of oral Biomaterials ChengduSichuan 610041China

Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal changes.To address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of DOP.We synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with tFNA.Both in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone formation.These findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.

关键词： curcumin osteoporosis diabetic

Anatomical variation in the internal jugular vein:potential risk factors for central venous catheterization-a case report

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World Journal of Emergency Medicine 2024年第4期15卷 316-318页

作者： Yidan Shan Weijia Huang department of oral and maxillofacial surgery the Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310009China

Central venous catheterization(CVC)is an invasive medical procedure used to measure central venous pressure and provides a stable route for continuous drug administration.CVC is widely used in the emergency department and intensive care units.It is typically performed by inserting a catheter through the internal jugular vein(IJV)into the superior vena cava near the right atrium.[1,2]While catheterization is a fundamental skill proficiently performed by healthcare professionals,lethal complications may occasionally occur because of undesirable positioning,depth and diameter.

关键词： venous catheter jugular

Intracystic negative pressure may promote bone formation around jaw cysts

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上海口腔医学 2011年第2期20卷 217-218页

作者：赵熠刘冰 department of Prosthodontics School and Hospital of StomatologyWuhan University department of oral and maxillofacial surgery School and Hospital of StomatologyWuhan University

The growth and enlargement of jaw cysts are associated with raised intracystic pressure and bone resorption surrounding the cysts.The major bone-resorbing cells are the osteoclasts.They are acting under the influence of local bone-resorbing factors: prostaglandins,proteinases and cytokines.It was found that positive pressure enhanced the expression of IL-1αmRNA and protein in epithelial cells of odontogenic keratocyst,and increased the secretion of matrix metalloproteinase and PGE2 in a co-culture of odontogenic keratocyst fibroblasts and epithelial cells.However,the signal intensities for IL-1α mRNA and protein in the epithelium were significantly decreased after marsupialization which relived intracystic pressure.Experimental study indicated that intermittent negative pressure could promote osteogenesis in human bone marrow-derived stroma cells(BMSCs) in vitro.We propose a hypothesis that bone formation around the cyst of the jaws would be stimulated by intracystic negative pressure.

关键词： Jaw cysts Bone formation Negative pressure

Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma

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International Journal of oral Science 2024年第1期16卷 110-121页

作者： Zheqi Liu Zhen Zhang Yu Zhang Wenkai Zhou Xu Zhang Canbang Peng Tong Ji Xin Zou Zhiyuan Zhang Zhenhu Ren department of oral and maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyShanghaiChina department of oral and maxillofacial surgery Zhongshan HospitalFudan UniversityShanghaiChina School and Hospital of Stomatology Kunming Medical UniversityKunmingChina Center for Tumor Diagnosis&Therapy Jinshan HospitalFudan UniversityShanghaiChina department of Pathology Jinshan HospitalFudan UniversityShanghaiChina Hainan Western Central Hospital Academician Zhang Zhiyuan Team Innovation CenterDanzhouChina

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-βexpression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

关键词： CXCL12 microenvironment squamous

The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

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International Journal of oral Science 2024年第1期16卷 154-162页

作者： Yutaro Ando Masayuki Tsukasaki Nam Cong-Nhat Huynh Shizao Zang Minglu Yan Ryunosuke Muro Kazutaka Nakamura Masatsugu Komagamine Noriko Komatsu Kazuo Okamoto Kenta Nakano Tadashi Okamura Akira Yamaguchi Kazuyuki Ishihara Hiroshi Takayanagi department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan department of Microbiology Tokyo Dental College2-1-14 Kanda-Misaki-choChiyoda-kuTokyoJapan oral Health Science Center Tokyo Dental College2-9-18Kanda-Misaki-choChiyodakuTokyoJapan department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Unit of Prosthodontics Laboratory of Oral-Maxillofacial Biology Faculty of Odonto-StomatologyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam department of oral and maxillofacial surgery Department of Sensory and Motor System MedicineGraduate School of MedicineThe University of TokyoTokyoJapan Division of Rheumatology Department of Internal MedicineKeio University School of MedicineTokyoJapan department of Laboratory Animal Medicine Research InstituteNational Center for Global Health and MedicineTokyoJapan

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

关键词： period neutrophil destruction

Sema3A secreted by sensory nerve induces bone formation under mechanical loads

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International Journal of oral Science 2024年第1期16卷 62-72页

作者： Hongxiang Mei Zhengzheng Li Qinyi Lv Xingjian Li Yumeng Wu Qingchen Feng Zhishen Jiang Yimei Zhou Yule Zheng Ziqi Gao Jiawei Zhou Chen Jiang Shishu Huang Juan Li State Key Laboratory of oral Diseases&National Center for Stomatology&National Clinical Research Center for oral Diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina department of Orthopedic surgery and Orthopedic Research Institute West China HospitalSichuan UniversityChengduChina

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM) model. Firstly, bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs) within 24 hours.Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.

关键词： Sema3A formation overload

A Case Report of Kissing Molars Class II

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Open Journal of Stomatology 2024年第5期14卷 249-254页

作者： Toshiyuki Inou Keiichi Uchida Keiko Kaneko Anna Fuji Nina Wakimoto Tatsuo Takaya Hiroyuki Kitamura Hiroshi Mori Yuji Kurihara department of oral Diagnostics and Comprehensive Dentistry Matsumoto Dental University Hospital Shiojiri Japan department of oral and maxillofacial surgery School of Dentistry Matsumoto Dental University Shiojiri Japan

Kissing molars (KMs) is a condition of occlusal molar surfaces in a single follicular space with roots extending in opposite directions. Here, we have reported a case of KMs in a 58-year-old woman. The patient complained of pain in the right mandibular molar region and was diagnosed with KMs consisting of the right mandibular second and third molars. Because of the patient’s pain having subsided at the time of the visit and her unwillingness to undergo tooth extraction, the patient was followed up. KMs is classified into three classes (I-III) and is either true-KMs or pseudo-KMs and presents with or without cystic variants of dental follicles. The presents as true-KMs class II without a cystic variant. With reference to the literature and based on our analysis, the mean age of patients affected by this specific case of KMs is 31.7 years and unilateral KMs is relatively more common (85.7%). Histopathological findings of dentigerous cysts are more often indicated (42.9%). The treatment policy for KMs should therefore be based on the classification of KMs. Importantly, the focus should be on preserving the first and second molars as much as possible. The treatment approach, such as the employment of surgical removal or orthodontics, should be determined by considering the associated factors such as the crowns, tissues, and age of the patient.

关键词： Kissing Molars Mandibular Second Molar Mandibular Third Molar Cone-Beam Computed Tomography

Immediate reconstruction following resection of oral cancer with free rectus abdominis myocutaneous flap

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口腔医学研究 1999年第2期15卷 49-52页

作者： Xing Long, Linsheng Zhong, Hongli Li, Sangang He, Xiuli Wang, Takashi Fujibayashi *, Shoji Enomot *. department of oral and maxillofacial surgery,Hospital of Stomatology,Hubei Medical University,Wuhan,P.R.China. *The Second department of oral surgery department of oral and maxillofacial surgery Hospital of StomatologyHubei Medical UniversityWuhanP.R.China The Second department of oral surgery Faculty of DentistryTokyo Medical and Dental UniversityTokyoJapan

目的：研究游离腹直肌肌皮瓣即刻修复口腔颌面部恶性肿瘤切除术后缺损的方法并评价其作用。方法：６例患者在进行广泛的口腔癌切除术后，应用游离腹直肌肌皮瓣进行缺损即刻修复，３例颊癌患者分别切除唇，颊，下颌骨及上颌骨后造成大面... 详细信息

目的：研究游离腹直肌肌皮瓣即刻修复口腔颌面部恶性肿瘤切除术后缺损的方法并评价其作用。方法：６例患者在进行广泛的口腔癌切除术后，应用游离腹直肌肌皮瓣进行缺损即刻修复，３例颊癌患者分别切除唇，颊，下颌骨及上颌骨后造成大面积洞穿性缺损，２例舌癌及１例下颌骨恶性肿瘤患者在进行舌切除及下颌骨切除后造成大面积及复杂的缺损，缺损修复的转移皮瓣最大面积达１１０ｍｍ×２３０ｍｍ。结果：游离腹直肌肌皮瓣及供区无严重的手术并发症，６例游离腹直肌肌皮瓣有５例愈合无并发症，１例皮瓣出现部分坏死，供皮区腹壁无组织感染及裂开。结论：游离腹直肌肌皮瓣使口腔颌面部缺损修复在功能和美观上达到满意的效果，提高了口腔颌面部恶性肿瘤患者广泛切除术后的生存质量。

关键词：微血管外科腹直肌游离皮瓣头颈部