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Cdc42 deletion yielded enamel defects by disrupting mitochondria and producing reactive oxygen species in dental epithelium

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Genes & Diseases 2024年第5期11卷 335-349页

作者： Jinxuan Zheng Rongcheng Yu Yiqi Tang Sihui Su Sainan Wang Chenxi Liao Xuecong Li Jiabin Liao Dongsheng Yu Tingting Ai Wei Zhao Vicky Yau Chufeng Liu Liping Wu Yang Cao Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong 510055China Guangdong Provincial Key Laboratory of oral Diseases GuangzhouGuangdong 510055China department of Cariology and Endodontology Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China department of oral and maxillofacial surgery University at BuffaloBuffaloNY 14214USA department of Orthodontics Stomatological HospitalSouthern Medical UniversityGuangzhouGuangdong 510280China

Developmental defects of enamel are common due to genetic and environmental factors before and after ***42,a Rho family small GTPase,regulates prenatal tooth development in ***,its role in postnatal tooth development,especially enamel formation,remains ***,we investigated Cdc42 functions in mouse enamel development and tooth repair after ***42 showed highly dynamic temporospatial patterns in the developing incisors,with robust expression in ameloblast and odontoblast ***,epithelium-specific Cdc42 deletion resulted in enamel defects in *** differentiation was inhibited,and hypomineralization of enamel was observed upon epithelial Cdc42 *** analysis showed that abnormal mitochondrial components,phosphotransferase activity,and ion channel regulator activity occurred in the Cdc42 mutant dental *** oxygen species accumulation was detected in the mutant mice,suggesting that abnormal oxidative stress occurred after Cdc42 ***,Cdc42 mutant mice showed delayed tooth repair and generated less calcified *** dysfunction and abnormal oxygen consumption were evidenced by reduced Apool and Timm8a1 expression,increased Atp5j2 levels,and reactive oxygen species overproduction in the mutant repair ***-specific Cdc42 deletion attenuated ERK1/2 signaling in the labial cervical *** Sox2 expression in the mutant labial cervical loop after clipping might lead to delayed tooth *** findings suggested that mitochondrial dysfunction,up-regulated oxidative stress,and abnormal ion channel activity may be among multiple factors responsible for the observed enamel defects in Cdc42 mutant ***,Cdc42 exerts multidimensional and pivotal roles in enamel development and is particularly required for ameloblast differentiation and enamel matrix formation.

关键词： Cdc42 Enamel defects Mitochondrial dysfunction Rho GTPase Tooth repair

Prospective cohort study on facial profile changes in infants with Robin sequence and healthy controls

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World Journal of Pediatrics 2024年第6期20卷 581-589页

作者： Cornelia Wiechers Julian Sowula Karen Kreutzer Christoph E.Schwarz Christina Weismann Michael Krimmel Christian F.Poets Bernd Koos department of Neonatology Tuebingen University HospitalCalwerstrasse 772076 TuebingenGermany Center for Cleft Lip Palate and Craniofacial MalformationsTuebingen University HospitalTuebingenGermany department of Orthodontics Tuebingen University HospitalTuebingenGermany department of oral and maxillofacial surgery Tuebingen University HospitalTuebingenGermany

Background Various conservative and surgical approaches exist to treat Robin sequence(RS),but their effects on facial profile and mandibular catch-up growth are unclear.A functional treatment concept,used in our centre for 25 years,includes an individualized palatal plate with a velo-pharyngeal extension and intensive feeding *** We performed a prospective study to objectively describe facial profiles in infants with RS treated with the above *** with isolated RS were admitted to our tertiary perinatal and national referral centre for craniofacial malformations between May 2018 and Nov *** with RS received 3D-photographs during clinically indicated *** controls were recruited from Dec 2018 to Sep 2019 and received 3D-photographs every 3 *** digitally measured jaw index(JI),defined as alveolar overjet(O)x maxillary arch(U)/mandibular arch(L),and the soft tissue reference points A’-point,Nasion’,B’-point angle(ANB’),describing the relative position of maxilla to mandible,were *** mixed models were used to examine time trajectories in JI and ANB’.Results A total of 2073D images,obtained in 19 infants with RS and 32 controls,were *** and ANB’decreased over time in both groups[for JI−0.18(95%CI−0.25 to−0.10);for ANB’:−0.40°per month[(95%CI−0.48 to−0.32)]]but remained lower in controls[for JI−2.5(95%CI−3.2 to−1.8);for ANB’-1.7°(95%CI−2.4 to−1.0)].Also,the ANB’model showed a significant effect of the interaction term diagnosis x *** Based on longitudinal 3D images,we describe changes in objective parameters of facial profile in infants with and without RS during the first year of *** findings indicate catch-up growth in infants treated for RS.

关键词： Infant Mandibular catch-up growth Pre-epiglottic Baton Plate Robin sequence Three-dimensional photography

Expect the unexpected:Brown tumor of the mandible as the first manifestation of primary hyperparathyroidism

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World Journal of Clinical Cases 2024年第7期12卷 1200-1204页

作者： Ana Majic Tengg Maja Cigrovski Berkovic Ivan Zajc Ivan Salaric Danko Müller Iva Markota department of Endocrinology DiabetesMetabolic Diseases and Clinical PharmacologyClinical Hospital DubravaZagreb 10000Croatia department for Sport and Exercise Medicine Faculty of Kinesiology University of ZagrebZagreb 10000Croatia department of oral surgery Clinical Hospital DubravaZagreb 10000Croatia University of Zagreb School of Dental Medicine Zagreb 10000Croatia Clinical department of Pathology and Cytology Clinical Hospital DubravaZagreb 10000Croatia

Hyperparathyroidism(HPT)is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone(PTH),causing disturbances in calcium *** commonly HPT presents with asymptomatic hypercalcemia but the clinical spectrum may include disturbances reflecting the combined effects of increased PTH secretion and *** tumors are rare,benign,tumor-like bone lesions,occurring in 1.5%to 4.5%of patients with HPT,as a complication of an uncontrolled disease pathway,and are nowadays rarely seen in clinical *** tumor can appear either as a solitary or multifocal lesion and usually presents as an asymptomatic swelling or a painful exophytic ***,it can cause a pathological fracture or skeletal pain and be radiologically described as a lytic bone *** diagnosis of a brown tumor in HPT is typically confirmed by assessing the levels of serum calcium,phosphorus,and *** when present,brown tumor is quite pathognomonic for HPT,the histologic finding often suggests a giant cell tumor,while clinical presentation might suggest other more frequent pathologies such as metastatic *** of brown tumors frequently focuses on managing the underlying HPT,which can often lead to regression and resolution of the lesion,without the need for surgical ***,in refractory cases or when dealing with large symptomatic lesions,surgical treatment may be necessary.

关键词： Brown tumor Hyperparathyroidism Lytic bone lesions Giant cell tumor

Role of oncogenic long noncoding RNA KCNQ1OT1 in colon cancer

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Oncology Research 2024年第3期32卷 585-596页

作者： GANG LIU LEI SHI BIN WANG ZEHUI WU HAIYUAN ZHAO TIANYU ZHAO LIANGHUI SHI department of Gastrointestinal surgery First ffiliated Hospital of Wannan Medical CollegeWuhu241001China Chongqing Key Laboratory of oral Diseases and Biomedical Sciences Stomatological Hospital of Chongqing Medical UniversityChongqing401147China

The role of lncRNA KCNQ1 opposite strand/antisense transcript 1(KCNQ1OT1)in colon cancer involves various tumorigenic processes and has been studed ***,the mechanism by which it promotes colon cancer remains *** vector pSEB61 was retroftted in established HCT116 siKCN and SW480-siKCN cells to silence KCNQ1 *** proliferation was measured using CCK8 assay,and flow cytometry(FCM)detected cell cydle *** sequencing(RNA Seq)analysis showed differentially expressed genes(DEGs).Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were carried out to analyze enriched functions and signaling ***-qPCR,immunofluorescence,and western blotting were carried out to validate downstream gene *** effects of tumorigenesis were evaluated in BALB/c nude mice by tumor *** data revealed that the silencing of KONQ1OT1 in HCT116 and SW480 cells slowed cell growth and decreased the number of cells in the G2/M ***-Seq analysis showed the data of DEGs enriched in various GO and KEGG pathways such as DNA replication and cell *** qPCR,immunofluorescence,and western blotting confirmed downstream CCNE2 and PCNA gene ***116 siKCN cells signifcantly suppressed tumorigenesis in BALB/c nude *** study suggests that lncRNA KCNQ1OT1 may provide a promising therapeutic strategy for colon cancer.

关键词： lncRNA KCNQ1OT1 Colon cancer HCT116 cells Tumorigenesis

ExosomalmicroRNA let-7c-5p enhances cell malignant characteristics by inhibiting TAGLN in oral cancer

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Oncology Research 2024年第10期32卷 1623-1635页

作者： YI LI TIANYI WANG HAORAN DING SHIYONG ZHUANG XIAOBO DAI BING YAN State Key Laboratory of oral Diseases&National Center for Stomatology&National Clinical Research Center for oral Diseases&department of Head and Neck Oncology surgery West China Hospital of StomatologySichuan UniversityChengdu610041China Frontier Innovation Center for Dental Medicine Plus Chengdu610041China

Background:oral cancer,a malignancy that is prevalent worldwide,is often diagnosed at an advanced ***(miRNAs)in circulating exosomes have emerged as promising cancer *** role of miRNA let-7c-5p in oral cancer remains underexplored,and its potential involvement in tumorigenesis warrants comprehensive ***:Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA *** of the exosomes was confirmed through transmission electron *** PCR was used to assess the miRNA *** effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability,migration,and invasion were analyzed via CCK-8 and Transwell ***,we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target ***:let-7c-5p was upregulated in serumderived exosomes of patients with oral *** of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative,migratory,and invasive capacities,and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell *** mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived *** further identified TAGLN as a direct target of let-7c-5p,which has been implicated in modulating the oncogenic potential of oral cancer *** of TAGLN reverses the promoting role of let-7c-5p on oral cancer ***:Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression,highlighting its potential as a diagnostic and therapeutic strategy.

关键词： oral cancer Exosomal microRNA let-7c-5p Tumorigenesis biomarkers Gene expression profiling TAGLN

Sulfation of chondroitin and bile acids converges to antagonize Wnt/β-catenin signaling and inhibit APC deficiency-induced gut tumorigenesis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1241-1256页

作者： Pengfei Xu Yue Xi Jong-Won Kim Junjie Zhu Min Zhang Meishu Xu Songrong Ren Da Yang Xiaochao Ma Wen Xie Center for Pharmacogenetics and department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261USA department of Hepatobiliary and Pancreatic surgery Zhongnan Hospital of Wuhan UniversitySchool of Pharmaceutical SciencesWuhan UniversityWuhan 430071China department of pharmacology&Chemical Biology University of PittsburghPittsburghPA 15261USA

Sulfation is a crucial and prevalent conjugation reaction involved in cellular processes and mammalian physiology.3’-Phosphoadenosine 5’-phosphosulfate(PAPS)synthase 2(PAPSS2)is the primary enzyme to generate the universal sulfonate donor *** involvement of PAPSS2-mediated sulfation in adenomatous polyposis coli(APC)mutation-promoted colonic carcinogenesis has not been ***,we showed that the expression of PAPSS2 was decreased in human colon tumors along with cancer stages,and the lower expression of PAPSS2 was correlated with poor prognosis in advanced colon *** epithelial-specific heterozygous Apc deficient and Papss2-knockout(Apc^(Δgut-Het)Papss2^(Δgut))mice were created,and the phenotypes were compared to the spontaneous intestinal tumorigenesis of Apc^(Δgut-Het)***^(Δgut-Het)Papss2^(Δgutmice) were more sensitive to gut tumorigenesis,which was mechanistically accounted for by the activation of Wnt/β-catenin signaling pathway due to the suppression of chondroitin sulfation and inhibition of the farnesoid X receptor(FXR)-transducin-like enhancer of split 3(TLE3)gene regulatory *** sulfate supplementation in Apc^(Δgut-Het)Papss2^(Δgutmice) alleviated intestinal *** summary,we have uncovered the protective role of PAPSS2-mediated chondroitin sulfation and bile acids-FXR-TLE3 activation in the prevention of gut carcinogenesis via the antagonization of Wnt/β-catenin *** sulfate may be explored as a therapeutic agent for Papss2 deficiency-associated colonic carcinogenesis.

关键词： Colon cancer APC Wnt/b-catenin PAPSS2 Chondroitin sulfate Sulfation Bile acids FXR

Paeoniflorin,the Main Monomer Component of Paeonia lactiflora,Exhibits Anti-inflammatory Properties in Osteoarthritis Synovial Inflammation

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Chinese Journal of Integrative Medicine 2024年第5期30卷 433-442页

作者： CHEN Pu ZHOU Jun RUAN An-min MA Yu-feng WANG Qing-fu department of Orthopaedic surgery Beijing University of Chinese Medicine Third Affiliated HospitalBeijing 100029China department of Orthopaedic surgery Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510120China department of Orthopaedic surgery Beijing Longfu HospitalBeijing 100010China

Objective:To explore the mechanism of paeoniflorin(PF)on osteoarthritis(OA)synovial inflammation from network pharmacology to experimental ***:Targets of OA were constructed by detecting the database of network database platforms(Therapeutic Target database,Drug Bank and Gene Cards),and the targets of PF were constructed by Pub Chem and Herbal Ingredients'Targets *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of these co-targeted genes were conducted via Database for Annotation,Visualization,and Integrated Discovery(DAVID)database,and protein-protein interaction(PPI)networks were conducted via the search tool for the retrieval of interacting genes(STRING)*** counting kit-8(CCK-8)assay was performed to assess the potential toxicity of PF on human OA fibroblast-like synoviocytes(FLS),quantitative real-time polymerase chain reaction(q PCR),enzyme-linked immunosorbent assay(ELISA)and Western blot were used to verify the potential mechanism of PF in synovial ***:Twenty-six co-targeted genes were *** enrichment results showed that these co-targeted genes were most likely localized in the cytoplasm,and the biological processes mainly involved'cellular response to hypoxia''lipopolysaccharide(LPS)-mediated signaling pathway'and'positive regulation of gene expression'.KEGG pathway analysis indicated that these co-targeted genes may function through pathways associated with'hypoxia-inducible factor-1(HIF-1)signaling pathway'and'tumornecrosis factor(TNF)signaling pathway'.The PPI network showed that the top 3 hub genes were TP53,TNF,and *** docking results showed that PF was well docking with ***-8 showed no potential toxicity of 10,20 and 50μmol/L PF on human OA *** PF significantly decreased the expression levels of interleukin-1β,interleukin-6,TNF-αmatrix metalloproteinase 13(MMP13),and a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5)and TNF

关键词： paeoniflorin osteoarthritis synovial inflammation tumor necrosis factor-α network pharmacology Paeonia lactiflora

A Comparative Study of Mandibular Fractures in Senegal: Children vs. Adults

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Open Journal of Stomatology 2024年第2期14卷 72-76页

作者： Paul Niang department of oral surgery Cheikh Anta Diop University Dakar Senegal

Introduction: The commonest maxillofacial fractures involve the mandible. Age can be considered among influential factors. Aim of the Study: To compare mandibular fractures between children and adults from the beginning up to the treatment in Senegal. Patients and Method: A three-year retrospective study was conducted in a university hospital. The medical records of patients admitted for maxillofacial injuries were reviewed. Patient and injury-related variables including age, gender, etiology, average consultation delay, anatomic location of fracture and treatment were compared up to age of 15 and beyond that. Results: Considering 272 casualties, maxillofacial fractures were less frequent among children than adults (36.7% and 59.7%) and were mainly mandibular (90.1% and 91.4%). Male predilection (sex ratio of 2.4 and 4.9) was twice (2) as pronounced from the age of 16. The average consultation delay was two (2) times shorter for children. Road traffic accidents which predominated among children (33.9%) had comparable frequency (32.3%) although they were outnumbered by assault (37.6%) among adults. Fractures occurred mainly on the corpus (90.1% and 90.4%), particularly on parasymphysis (40.1%) up to the age of 15, whereas angle fractures increased (8.5% to 19.6%) and joint damage decreased afterwards. Intra-oral orthopedic procedures (91.2% and 92.6%) in which mandibular retention splints were more common (37.3%) up to the age of 15 then arch ligatures (49%) were then widely favored. Conclusion: Differences relating to the distribution of causes but also to the anatomic location on the corpus and to the choice of intra-oral orthopedic procedures within overall similarities between children and adults regarding the male predilection, the frequency of road traffic accidents, the mandibular injuries, but also the school therapeutic attitude consisting of favoring the orthopedic option.

关键词： Fracture Mandible Child Adult

Self-adaptive hydrogel for breast cancer therapy via accurate tumor elimination and on-demand adipose tissue regeneration

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Chinese Chemical Letters 2024年第1期35卷 371-378页

作者： Ran Tian Xinyu Qiu Wenyun Mu Bolei Cai Zhongning Liu Shiyu Liu Xin Chen School of Chemical Engineering and Technology Department of Chemical EngineeringShaanxi Key Laboratory of Energy Chemical Process IntensificationXi'an Jiao Tong UniversityXi'an 710049China School of Stomatology State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Clinical Research Center for Oral DiseasesDepartment of Preventive DentistryThe Fourth Military Medical UniversityXi'an 710032China School of Stomatology State Key Laboratory of Military StomatologyDepartment of Oral and Maxillofacial SurgeryThe Fourth Military Medical UniversityXi'an 710032China department of Prosthodontics Peking University School and Hospital of StomatologyNational Clinical Research Center for Oral DiseasesNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyBeijing 100081China School of Stomatology State Key Laboratory of Military StomatologyNational Clinical Research Center for Oral DiseasesShaanxi International Joint Research Center for Oral DiseasesCenter for Tissue EngineeringThe Fourth Military Medical UniversityXi'an 710032China

The irregular defects and residual tumor tissue after surgery are challenges for effective breast cancer ***,a smart hydrogel with self-adaptable size and dual responsive cargos release was fabricated to treat breast cancer via accurate tumor elimination,on-demand adipose tissue regeneration and effective infection *** hydrogel consisted of thiol groups ended polyethylene glycol(SH-PEG-SH)and doxorubicin encapsulated mesoporous silica nanocarriers(DOX@MSNs)double crosslinked hyaluronic acid(HA)after loading of antibacterial peptides(AP)and adipose-derived stem cells(ADSCs).A pH-cleavable unsaturated amide bond was pre-introduced between MSNs and HA frame to perform the tumor-specific acidic environment dependent DOX@MSNs release,meanwhile an esterase degradable glyceryl dimethacrylate cap was grafted on MSNs,which contributed to the selective chemotherapy in tumor cells with over-expressed *** bond cleavage between MSNs and HA would also cause the swelling of the hydrogel,which not only provide sufficient space for the growth of ADSCs,but allows the hydrogel to fully fill the irregular defects generated by surgery and residual tumor atrophy,resulting in the on-demand regeneration of adipose ***,the sustained release of AP could be simultaneously triggered along with the size change of hydrogel,which further avoided bacterial infection to promote tissue regeneration.

关键词： Smart hydrogel with self-adaptable size Breast cancer therapy Dual responsive cargoes release Selective tumor elimination On-demand adipose tissue regeneration Effective bacteria inhibition