Recently,magnesium(Mg)alloys have attracted extensive attention as biodegradable implant materials.However,cyclic loading and the corrosive environment of the body are significant challenges for the practical use of a...Recently,magnesium(Mg)alloys have attracted extensive attention as biodegradable implant materials.However,cyclic loading and the corrosive environment of the body are significant challenges for the practical use of alloys,and there are few studies on this topic.In this study,we conducted a four-point bending fatigue test for 86,400 cycles(12 h)in simulated body fluid(SBF),plasma,and whole blood with an AZ series alloy Mg-9Al-0.5Zn-0.27Mn-0.12Ag,to examine the effects of inorganic ions,organic particles,blood cells,and cyclic loading on Mg alloy corrosion.The Mg^(2+)concentration and solution pH were measured before and after experimentation,and the sample surfaces were characterized by 3D digital microscopy,scanning electron microscopy(SEM),energy-dispersive X-ray spectroscopy(EDS),Fourier-transform infrared(FTIR)spectroscopy,Raman spectroscopy,and X-ray photoelectron spectroscopy(XPS).Our results showed that in the non-loading condition,a porous and weak inorganic product layer(mainly Mg/Ca phosphate and carbonate)formed on the surface of the Mg alloy sample immersed in SBF,which hardly had a protective effect on Mg alloy corrosion.For the samples immersed in plasma,the organic particles promoted the formation of an organic and more compact product layer,which protected the Mg alloy from severe corrosion.For the sample immersed in whole blood,the blood cells affected organic particle deposition on the product layer and thus interfered with the formation of an organic compact product layer,which slightly accelerated the corrosion process.Furthermore,cyclic loading damaged the layer integrity and significantly increased the corrosion rates of all the studied materials compared to the samples not subjected to cyclic loading.Nonetheless,under cyclic loading,blood cells adsorbed on the Mg alloy surfaces,and formed films,which protected the Mg alloy substrate and delayed Mg alloy corrosion.展开更多
The correlation between microbiota plays a vital role in the progression of periodontal disease.This study investigated the in situ interaction networks between periodontal pathogens in periodontal and peri-implant di...The correlation between microbiota plays a vital role in the progression of periodontal disease.This study investigated the in situ interaction networks between periodontal pathogens in periodontal and peri-implant disease.We used quantitative real-time polymerase chain reaction and Pearson’s correlation coefficients to quantify the copy numbers and correlations of four oral core species—Fusobacterium nucleatum,Porphyromonas gingivalis,Prevotella intermedia,and Streptococcus gordonii—from 80 subgingival sites(healthy and with periodontitis or gingivitis)in patients with periodontitis,and 68 subgingival sites(healthy and with periodontitis,gingivitis,peri-implantitis,or peri-implant mucositis)in patients with implants.The highest bacterial counts were observed for Porphyromonas gingivalis and Prevotella intermedia at all the sites.Within the same cohorts,the bacterial loads were greater at diseased sites than at healthy sites.Bacterial counts did not differ among clinical sites in the same group(P>0.05)but differed between periodontitis and peri-implant mucositis sites in the two groups.Porphyromonas gingivalis,F.nucleatum,and Prevotella intermedia had strong correlations at gingivitis and healthy sites and moderate correlations at periodontitis sites in patients with periodontitis.In patients with implants,Prevotella intermedia,F.nucleatum,and S.gordonii had strong correlations only at peri-implantitis sites.Also,based on metagenomic analysis,F.nucleatum and Prevotella intermedia were significantly correlated at the subgingival plaque in peri-implantitis and periodontitis samples.Our results suggest that variations in microbe-microbe interactions in subgingival plaque reflect changes in the progression of periodontal disease,providing a new perspective for understanding the mechanisms of periodontitis and peri-implantitis.展开更多
BACKGROUND Malignant peripheral nerve sheath tumor(MPNST)is a rare and aggressive soft tissue sarcoma that poses a major diagnostic and therapeutic challenge.CASE SUMMARY We retrospectively reviewed patients with head...BACKGROUND Malignant peripheral nerve sheath tumor(MPNST)is a rare and aggressive soft tissue sarcoma that poses a major diagnostic and therapeutic challenge.CASE SUMMARY We retrospectively reviewed patients with head and neck MPNSTs treated in our hospital from 2000 to 2021.The clinical features,pathological manifestations,treatments,and prognoses were summarized.We also reviewed the literature,focusing on MPNST in the mandible and maxilla.The study population consisted of five women and five men aged 22–75 years(mean age,49 years).Of the 10 patients,7 were initial cases and 3 were recurrent cases.All lesions were sporadic.The most common site was the mandible.The most frequently encountered symptoms were a progressive mass and local swelling.Complete or partial loss of trimethylation at lysine 27 of histone H3(H3K27me3)was evident on staining in four of nine cases(one case was excluded due to lack of tissue for evaluation of loss of H3K27me3).The 2-and 5-year disease-specific survival rates were 86%a nd 43%,respectively.The average survival time was 64 mo.CONCLUSION MPNST is a highly malignant tumor with a poor prognosis,prone to a high risk of recurrence and distant metastasis.Complete surgical resection is the main treatment.展开更多
BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or to...BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root resorption.Low-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture healing.It is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.AIM To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying mechanisms.METHODS A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections.In vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red staining.The expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via immunofluorescence.RESULTS The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),decreased.LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force.Mechanically,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by LIPUS.Moreover,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment.Consistently,LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo.The decreased expression of COL1,OCN,and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS.CONCLUSION LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis,which may be a promising strategy to reduce the orthodontic treatment process.展开更多
In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we dev...In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porous scaffolds can significantly promote the regeneration of bone defects.展开更多
Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy pre...Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.展开更多
Natural bone is a mineralized biological material, which serves a supportive and protective framework for the body, stores minerals for metabolism, and produces blood cells nourishing the body. Normally, bone has an i...Natural bone is a mineralized biological material, which serves a supportive and protective framework for the body, stores minerals for metabolism, and produces blood cells nourishing the body. Normally, bone has an innate capacity to heal from damage.However, massive bone defects due to traumatic injury, tumor resection, or congenital diseases pose a great challenge to reconstructive surgery. Scaffold-based tissue engineering(TE) is a promising strategy for bone regenerative medicine, because biomaterial scaffolds show advanced mechanical properties and a good degradation profile, as well as the feasibility of controlled release of growth and differentiation factors or immobilizing them on the material surface. Additionally, the defined structure of biomaterial scaffolds, as a kind of mechanical cue, can influence cell behaviors, modulate local microenvironment and control key features at the molecular and cellular levels. Recently, nano/micro-assisted regenerative medicine becomes a promising application of TE for the reconstruction of bone defects. For this reason, it is necessary for us to have in-depth knowledge of the development of novel nano/micro-based biomaterial scaffolds. Thus, we herein review the hierarchical structure of bone, and the potential application of nano/micro technologies to guide the design of novel biomaterial structures for bone repair and regeneration.展开更多
Anterior repositioning splint(ARS)therapy is considered one of the most effective therapies for treating disc displacement-related temporomandibular disorders(TMDs),which account for a large proportion of TMD cases.Ow...Anterior repositioning splint(ARS)therapy is considered one of the most effective therapies for treating disc displacement-related temporomandibular disorders(TMDs),which account for a large proportion of TMD cases.Owing to the wide application of this therapy,the exact mechanism of remission has increasingly drawn attention.Given that practitioners have different views on ARS therapy,its indications are broadened,and operating methods diverged.This review attempts to provide an overview of ARS therapy and helps practitioners establish indications and suitable operating methods.Representative views in the past 10 years were summarised,and conclusions were drawn as follows:The mechanism of ARS therapy is mainly attributed to internal derangement correction,improvement of stress distribution and recently reported joint remodeling.It has an evident effect in the short term,and the most prevalent operating methods are protruding the mandible to the edge-to-edge position and wearing the ARS for 24 hours daily for 3-6 months.However,long-term stability is not optimal,and thus indications should be selected carefully.Notably,most of the clinical studies in this field are case analyses with low-quality evidence.Well-designed RCTs are required to further validate relevant theories.展开更多
Mesenchymal stem cells(MSCs)are a heterogeneous population that can be isolated from various tissues,including bone marrow,adipose tissue,umbilical cord blood,and craniofacial tissue.MSCs have attracted increasingly m...Mesenchymal stem cells(MSCs)are a heterogeneous population that can be isolated from various tissues,including bone marrow,adipose tissue,umbilical cord blood,and craniofacial tissue.MSCs have attracted increasingly more attention over the years due to their regenerative capacity and function in immunomodulation.The foundation of tissue regeneration is the potential of cells to differentiate into multiple cell lineages and give rise to multiple tissue types.In addition,the immunoregulatory function of MSCs has provided insights into therapeutic treatments for immune-mediated diseases.DNA methylation and demethylation are important epigenetic mechanisms that have been shown to modulate embryonic stem cell maintenance,proliferation,differentiation and apoptosis by activating or suppressing a number of genes.In most studies,DNA hypermethylation is associated with gene suppression,while hypomethylation or demethylation is associated with gene activation.The dynamic balance of DNA methylation and demethylation is required for normal mammalian development and inhibits the onset of abnormal phenotypes.However,the exact role of DNA methylation and demethylation in MSC-based tissue regeneration and immunomodulation requires further investigation.In this review,we discuss how DNA methylation and demethylation function in multi-lineage cell differentiation and immunomodulation of MSCs based on previously published work.Furthermore,we discuss the implications of the role of DNA methylation and demethylation in MSCs for the treatment of metabolic or immune-related diseases.展开更多
The interplay between mechanoresponses and a broad range of fundamental biological processes, such as cell cycle progression,growth and differentiation, has been extensively investigated. However, metabolic regulation...The interplay between mechanoresponses and a broad range of fundamental biological processes, such as cell cycle progression,growth and differentiation, has been extensively investigated. However, metabolic regulation in mechanobiology remains largely unexplored. Here, we identified glucose transporter 1(GLUT1)—the primary glucose transporter in various cells—as a novel mechanosensitive gene in orthodontic tooth movement(OTM). Using an in vivo rat OTM model, we demonstrated the specific induction of Glut1 proteins on the compressive side of a physically strained periodontal ligament. This transcriptional activation could be recapitulated in in vitro cultured human periodontal ligament cells(PDLCs), showing a time-and dose-dependent mechanoresponse. Importantly, application of GLUT1 specific inhibitor WZB117 greatly suppressed the efficiency of orthodontic tooth movement in a mouse OTM model, and this reduction was associated with a decline in osteoclastic activities. A mechanistic study suggested that GLUT1 inhibition affected the receptor activator for nuclear factor-κ B Ligand(RANKL)/osteoprotegerin(OPG)system by impairing compressive force-mediated RANKL upregulation. Consistently, pretreatment of PDLCs with WZB117 severely impeded the osteoclastic differentiation of co-cultured RAW264.7 cells. Further biochemical analysis indicated mutual regulation between GLUT1 and the MEK/ERK cascade to relay potential communication between glucose uptake and mechanical stress response. Together, these cross-species experiments revealed the transcriptional activation of GLUT1 as a novel and conserved linkage between metabolism and bone remodelling.展开更多
BACKGROUND Palatal expansion treatment has been used to expand the constricted maxillary arch and has become a routine procedure in orthodontic practice over the past decades.However,the long-term stability of expansi...BACKGROUND Palatal expansion treatment has been used to expand the constricted maxillary arch and has become a routine procedure in orthodontic practice over the past decades.However,the long-term stability of expansion in the permanent dentition without a surgical approach is uncertain.CASE SUMMARY We present the case of a 15-year-old boy with Class II malocclusion and constricted arches.The patient was treated with rapid palatal expansion(RPE)followed by a fixed orthodontic appliance.A 7-year follow-up evaluation was performed by analyzing cephalometric radiographs,plaster models,and photographs.The patient’s constricted maxillary and mandibular arches were relived after the expansion treatment.A Class I occlusion and normal arch form were established and maintained in the long-term.CONCLUSION RPE treatment is successful in solving constricted dental arch in the permanent dentition without a surgical approach.Permanent retention and even occlusal contact help prevent long-term relapse.展开更多
Objective:To understand the oral health status of urban and rural residents in China,the Fourth National Oral Health Epidemiological Survey (FNOHES) was conducted in 2015.Materials and methods:Based on the principles ...Objective:To understand the oral health status of urban and rural residents in China,the Fourth National Oral Health Epidemiological Survey (FNOHES) was conducted in 2015.Materials and methods:Based on the principles of multi-stage,stratified,equal capacity,and random sampling,the subjects included five groups of residents aged 3-5,12-15,35-44,55-64,and 65-74 years in all 31 provinces,municipalities,and autonomous regions except Hong Kong,Macao,and Taiwan.The total sample size was 172,425.The survey covered two areas,namely oral health status and knowledge,attitude and oral health behavior.Results:Residents in China had serious caries and poor periodontal condition.The prevalence of caries was above 50% in all age groups,subjects without periodontal disease accounted for <50%,and fewer than 50% of subjects brushed their teeth twice a day.Based on the results of the FNOHES,the following suggestions were proposed for improving the oral health in China in the future:to establish and improve the comprehensive prevention and control system for oral diseases,implement a comprehensive prevention and control strategy for priority groups,strengthen the oral health education for all people to improve oral health literacy,enhance dynamic monitoring to scientifically evaluate oral health status,and coordinate multi-party resources to establish and improve the oral health service security system.Conclusion:The oral health status of Chinese residents and their oral health behavior habits need to be improved.With the support of the administrative departments of the government and unremitting efforts of the oral health staff,all sectors of society must be coordinated to strengthen oral health education for the whole population.Furthermore,comprehensive prevention and control measures must be implemented for priority groups.展开更多
Background:The effect of platelet factor 4(PF4)on bone marrow mesenchymal stem cells(BMMSCs)and osteoporosis is poorly understood.Therefore,this study aimed to evaluate the effects of PF4-triggered bone destruction in...Background:The effect of platelet factor 4(PF4)on bone marrow mesenchymal stem cells(BMMSCs)and osteoporosis is poorly understood.Therefore,this study aimed to evaluate the effects of PF4-triggered bone destruction in mice and determine the underlying mechanism.Methods:First,in vitro cell proliferation and cell cycle of BMMSCs were assessed using a CCK8 assay and flow cytometry,respectively.Osteogenic differentiation was confirmed using staining and quantification of alkaline phosphatase and Alizarin Red S.Next,an osteoporotic mouse model was established by performing bilateral ovariectomy(OVX).Furthermore,the PF4 concentrations were obtained using enzymelinked immunosorbent assay.The bone microarchitecture of the femur was evaluated using microCT and histological analyses.Finally,the key regulators of osteogenesis and pathways were investigated using quantitative real-time polymerase chain reaction and Western blotting.Results:Human PF4 widely and moderately decreased the cell proliferation and osteogenic differentiation ability of BMMSCs.Furthermore,the levels of PF4 in the serum and bone marrow were generally increased,whereas bone microarchitecture deteriorated due to OVX.Moreover,in vivo mouse PF4 supplementation triggered bone deterioration of the femur.In addition,several key regulators of osteogenesis were downregulated,and the integrinα5-focal adhesion kinase-extracellular signalregulated kinase(ITGA5-FAK-ERK)pathway was inhibited due to PF4 supplementation.Conclusions:PF4 may be attributed to OVX-i nduced bone loss triggered by the suppression of bone formation in vivo and alleviate BMMSC osteogenic differentiation by inhibiting the ITGA5-FAK-ERK pathway.展开更多
Cancer is a major threat to human life worldwide. Traditional cancer treatments, such as chemotherapy and surgery, have major limitations and can cause irreversible damage to normal tissues while killing the cancer ce...Cancer is a major threat to human life worldwide. Traditional cancer treatments, such as chemotherapy and surgery, have major limitations and can cause irreversible damage to normal tissues while killing the cancer cells. Magnesium(Mg) alloys are widely reported novel potential biomedical materials with acceptable mechanical properties and good osteogenic and angiogenic properties. In this review, we summarize the Mg alloys for antitumor applications, including pure Mg and Mg alloys(Mg-Ag, Mg-Gd, Mg-Li-Zn, Mg-Ca-Sr-Zn, et al.) fabricated by casting and extruding, selective laser melting methods. Mg alloys can exhibit antitumor effect on bone tumor, breast cancer, and liver tumor,etal. What's more, after tumor tissue is eliminated, Mg alloys prevent tumor recurrence, fill tissue defects and promote tissue regeneration.The antitumor effects of Mg alloys are mainly due to their degradation products. Overall, Mg alloys show great potential in tumor treatments due to the dual function of antitumor and tissue regeneration.展开更多
Macrophages play an important role in material-related immune responses and bone formation,but the functionality of macrophage-derived extracellular vesicles(EVs)in material-mediated bone regeneration is still unclear...Macrophages play an important role in material-related immune responses and bone formation,but the functionality of macrophage-derived extracellular vesicles(EVs)in material-mediated bone regeneration is still unclear.Here,we evaluated intracellular communication through small extracellular vesicles(sEVs)and its effects on endogenous bone regeneration mediated by biomimetic intrafibrillarly mineralized collagen(IMC).After implantation in the bone defect area,IMC generated more neobone and recruited more mesenchymal stem cells(MSCs)than did extrafibrillarly mineralized collagen(EMC).More CD63+CD90+and CD63+CD163+cells were detected in the defect area in the IMC group than in the EMC group.To determine the functional roles of sEVs,extracellular vesicles from macrophages cultured on different mineralized collagen were isolated,and they showed no morphological differences.However,macrophage-derived sEVs in the IMC group showed an enhanced Young’s modulus and exerted beneficial effects on the osteogenic differentiation of bone marrow MSCs by increasing the expression of the osteoblastic differentiation markers BMP2,BGLAP,COL1,and OSX and calcium nodule formation.Mechanistically,sEVs from IMC-treated macrophages facilitated MSC osteogenesis through the BMP2/Smad5 pathway,and blocking sEV secretion with GW4869 significantly impaired MSC proliferative,immunomodulative and osteogenic potential.Taken together,these findings show that macrophage-derived sEVs may serve as an emerging functional tool in biomaterial-mediated endogenous bone regeneration.展开更多
BACKGROUND Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide,which emphasizes the urgent need to identify novel treatments.Stem cells from human exfoliated deciduous teet...BACKGROUND Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide,which emphasizes the urgent need to identify novel treatments.Stem cells from human exfoliated deciduous teeth(SHED),which are easy to obtain in a non-invasive manner,show pronounced proliferative and immunomodulatory capacities.AIM To investigate the protective effects of SHED on concanavalin A(ConA)-induced hepatitis in mice,and to elucidate the associated regulatory mechanisms.METHODS We used a ConA-induced acute hepatitis mouse model and an in vitro co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis,as well as the associated underlying mechanisms.RESULTS SHED infusion could prevent aberrant histopathological liver architecture caused by ConA-induced infiltration of CD3+,CD4+,tumor necrosis-alpha+,and interferon-gamma+inflammatory cells.Alanine aminotransferase and aspartate aminotransferase were significantly elevated in hepatitis mice.SHED infusion could therefore block ConA-induced alanine aminotransferase and aspartate aminotransferase elevations.Mechanistically,ConA upregulated tumor necrosisalpha and interferon-gamma expression,which was activated by the nuclear factor-kappa B pathway to induce hepatocyte apoptosis,resulting in acute liver injury.SHED administration protected hepatocytes from ConA-induced apoptosis.CONCLUSION SHED alleviates ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the nuclear factor-kappa B pathway.Our findings could provide a potential treatment strategy for hepatitis.展开更多
Early childhood caries （ECC） is a considerable pediatric and public health problem worldwide. Preceding studies have focused primarily on bacterial diversity at the taxonomic level. Although these studies have provi...Early childhood caries （ECC） is a considerable pediatric and public health problem worldwide. Preceding studies have focused primarily on bacterial diversity at the taxonomic level. Although these studies have provided significant information regarding the connection between dental caries and oral micmbiomes, further comprehension of this microbial community＇s ecological relevance is limited. This study identified the carbon source metabolic differences in dental plaque between children with and without ECC. We compared the microbial community functional diversity in 18 caries-free subjects with 18 severe ECC patients based on sole carbon source usage using a Biolog assay. The anaerobic microbial community in the ECC patients displayed greater metabolic activity than that of the control group. Specific carbon source metabolism differed significantly between the two groups. Subjects from the two groups were well distinguished by cluster and principal component analyses based on discriminative carbon sources. Our results implied that the microbial functional diversity between the ECC patients and healthy subjects differed significantly. In addition, the Biolog assay furthered our understanding of oral microbiomes as a composite of functional abilities, thus enabling us to identify the ecologically relevant functional differences among oral microbial communities.展开更多
Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures.Biodegradable Zn metals are revolutionary materials for orthopedic implants.In this...Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures.Biodegradable Zn metals are revolutionary materials for orthopedic implants.In this study,pure Zn porous scaffolds with diamond structures were fabricated using customized laser powder bed fusion(L-PBF)technology.First,the mechanical properties,corrosion behavior,and biocompatibility of the pure Zn porous scaffolds were characterized in vitro.The scaffolds were then implanted into the rabbit femur critical-size bone defect model for 24 weeks.The results showed that the pure Zn porous scaffolds had compressive strength and rigidity comparable to those of cancellous bone,as well as relatively suitable degradation rates for bone regeneration.A benign host response was observed using hematoxylin and eosin(HE)staining of the heart,liver,spleen,lungs,and kidneys.Moreover,the pure Zn porous scaffold showed good biocompatibility and osteogenic promotion ability in vivo.This study showed that pure Zn porous scaffolds with customized structures fabricated using L-PBF represent a promising biodegradable solution for treating large bone defects.展开更多
The primary treatment modality for tumors affecting the oral and maxillofacial region is surgery.Surgical treatment of tumors affecting this region is a challenge and poses relatively high surgical risk,especially in ...The primary treatment modality for tumors affecting the oral and maxillofacial region is surgery.Surgical treatment of tumors affecting this region is a challenge and poses relatively high surgical risk,especially in lesions affecting the deep regions of the head and the neck due to the complex anatomy of this region including structures of great importance such as the internal carotid artery,the internal jugular vein,and the cavernous sinus at the skull base,the cranial nerves and the orbital contents with the eye globes,extraocular muscles,and the lacrimal gland.Oncologic resection often results in devastating defects in the oral and maxillofacial region,which adversely affect patients’facial appearance and important functions such as speech,chewing,deglutition,or vision and significantly impact patients’quality of life.In order to obtain a good result concerning tumor excision in the oral and cranio-maxillofacial region as well as a correct aesthetic and functional reconstruction,an adequate presurgical evaluation of the patient and accurate planning of the surgical resection and the reconstructive approach must be carefully designed.展开更多
Skin wounds are a major medical challenge that threaten human health.Functional hydrogel dressings demonstrate great potential to promote wound healing.In this study,magnesium(Mg)and zinc(Zn)are introduced into methac...Skin wounds are a major medical challenge that threaten human health.Functional hydrogel dressings demonstrate great potential to promote wound healing.In this study,magnesium(Mg)and zinc(Zn)are introduced into methacrylate gelatin(GelMA)hydrogel via low-temperature magnetic stirring and photocuring,and their effects on skin wounds and the underlying mechanisms are investigated.Degradation testing confirmed that the GelMA/Mg/Zn hydrogel released magnesium ions(Mg^(2+))and zinc ions(Zn^(2+))in a sustained manner.The Mg^(2+) and Zn^(2+)not only enhanced the migration of human skin fibroblasts(HSFs)and human immortalized keratinocytes(HaCats),but also promoted the transformation of HSFs into myofibroblasts and accelerated the production and remodeling of extracellular matrix.Moreover,the GelMA/Mg/Zn hydrogel enhanced the healing of full-thickness skin defects in rats via accelerated collagen deposition,angiogenesis and skin wound re-epithelialization.We also identified the mechanisms through which GelMA/Mg/Zn hydrogel promoted wound healing:the Mg^(2+) promoted Zn^(2+)entry into HSFs and increased the concentration of Zn^(2+)in HSFs,which effectively induced HSFs to differentiate into myofibroblasts by activating the STAT3 signaling pathway.The synergistic effect of Mg^(2+) and Zn^(2+)promoted wound healing.In conclusion,our study provides a promising strategy for skin wounds regeneration.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.81771119)the National Key Research and Development Project(Governmental International S&T Innovation Cooperation Projects,Grant No.2019YFE0101100).
文摘Recently,magnesium(Mg)alloys have attracted extensive attention as biodegradable implant materials.However,cyclic loading and the corrosive environment of the body are significant challenges for the practical use of alloys,and there are few studies on this topic.In this study,we conducted a four-point bending fatigue test for 86,400 cycles(12 h)in simulated body fluid(SBF),plasma,and whole blood with an AZ series alloy Mg-9Al-0.5Zn-0.27Mn-0.12Ag,to examine the effects of inorganic ions,organic particles,blood cells,and cyclic loading on Mg alloy corrosion.The Mg^(2+)concentration and solution pH were measured before and after experimentation,and the sample surfaces were characterized by 3D digital microscopy,scanning electron microscopy(SEM),energy-dispersive X-ray spectroscopy(EDS),Fourier-transform infrared(FTIR)spectroscopy,Raman spectroscopy,and X-ray photoelectron spectroscopy(XPS).Our results showed that in the non-loading condition,a porous and weak inorganic product layer(mainly Mg/Ca phosphate and carbonate)formed on the surface of the Mg alloy sample immersed in SBF,which hardly had a protective effect on Mg alloy corrosion.For the samples immersed in plasma,the organic particles promoted the formation of an organic and more compact product layer,which protected the Mg alloy from severe corrosion.For the sample immersed in whole blood,the blood cells affected organic particle deposition on the product layer and thus interfered with the formation of an organic compact product layer,which slightly accelerated the corrosion process.Furthermore,cyclic loading damaged the layer integrity and significantly increased the corrosion rates of all the studied materials compared to the samples not subjected to cyclic loading.Nonetheless,under cyclic loading,blood cells adsorbed on the Mg alloy surfaces,and formed films,which protected the Mg alloy substrate and delayed Mg alloy corrosion.
基金supported by grants from the Peking University School of Stomatology(PKUSS20170112).
文摘The correlation between microbiota plays a vital role in the progression of periodontal disease.This study investigated the in situ interaction networks between periodontal pathogens in periodontal and peri-implant disease.We used quantitative real-time polymerase chain reaction and Pearson’s correlation coefficients to quantify the copy numbers and correlations of four oral core species—Fusobacterium nucleatum,Porphyromonas gingivalis,Prevotella intermedia,and Streptococcus gordonii—from 80 subgingival sites(healthy and with periodontitis or gingivitis)in patients with periodontitis,and 68 subgingival sites(healthy and with periodontitis,gingivitis,peri-implantitis,or peri-implant mucositis)in patients with implants.The highest bacterial counts were observed for Porphyromonas gingivalis and Prevotella intermedia at all the sites.Within the same cohorts,the bacterial loads were greater at diseased sites than at healthy sites.Bacterial counts did not differ among clinical sites in the same group(P>0.05)but differed between periodontitis and peri-implant mucositis sites in the two groups.Porphyromonas gingivalis,F.nucleatum,and Prevotella intermedia had strong correlations at gingivitis and healthy sites and moderate correlations at periodontitis sites in patients with periodontitis.In patients with implants,Prevotella intermedia,F.nucleatum,and S.gordonii had strong correlations only at peri-implantitis sites.Also,based on metagenomic analysis,F.nucleatum and Prevotella intermedia were significantly correlated at the subgingival plaque in peri-implantitis and periodontitis samples.Our results suggest that variations in microbe-microbe interactions in subgingival plaque reflect changes in the progression of periodontal disease,providing a new perspective for understanding the mechanisms of periodontitis and peri-implantitis.
文摘BACKGROUND Malignant peripheral nerve sheath tumor(MPNST)is a rare and aggressive soft tissue sarcoma that poses a major diagnostic and therapeutic challenge.CASE SUMMARY We retrospectively reviewed patients with head and neck MPNSTs treated in our hospital from 2000 to 2021.The clinical features,pathological manifestations,treatments,and prognoses were summarized.We also reviewed the literature,focusing on MPNST in the mandible and maxilla.The study population consisted of five women and five men aged 22–75 years(mean age,49 years).Of the 10 patients,7 were initial cases and 3 were recurrent cases.All lesions were sporadic.The most common site was the mandible.The most frequently encountered symptoms were a progressive mass and local swelling.Complete or partial loss of trimethylation at lysine 27 of histone H3(H3K27me3)was evident on staining in four of nine cases(one case was excluded due to lack of tissue for evaluation of loss of H3K27me3).The 2-and 5-year disease-specific survival rates were 86%a nd 43%,respectively.The average survival time was 64 mo.CONCLUSION MPNST is a highly malignant tumor with a poor prognosis,prone to a high risk of recurrence and distant metastasis.Complete surgical resection is the main treatment.
基金Supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China,No.2022YFA1105800the National Natural Science Foundation of China,No.81970940.
文摘BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root resorption.Low-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture healing.It is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.AIM To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying mechanisms.METHODS A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections.In vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red staining.The expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via immunofluorescence.RESULTS The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),decreased.LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force.Mechanically,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by LIPUS.Moreover,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment.Consistently,LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo.The decreased expression of COL1,OCN,and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS.CONCLUSION LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis,which may be a promising strategy to reduce the orthodontic treatment process.
基金supported by the National Key R&D Program of China[grant number 2021YFC2400700]the National Natural Science Foundation of China[grant numbers 82170929,81970908 and 81771039].
文摘In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porous scaffolds can significantly promote the regeneration of bone defects.
基金Beijing Natural Science Foundation,Grant/Award Number:L222145 and L222030Emerging Engineering Interdisciplinary Project and the Fundamental Research Funds for the Central Universities,Grant/Award Number:PKU2022XGK008Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological Innovation,Grant/Award Number:BMU2022PY010。
文摘Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.
基金The authors acknowledge the financial support from the Beijing Municipal Natural Science Foundation No.2184119(D.L.)and No.L182005(Y.L.)the Projects of Beijing Nova Programme No.Z171100001117018(Y.L.)+2 种基金Beijing Nova Programme Interdisciplinary Cooperation Project No.Z181100006218135(Y.L.and D.L.)the National Natural Science Foundations of China No.81571815(Y.L.),No.81871492(Y.L.)and No.51902344(D.L.)the Science Foundation of China University of Petroleum No.2462018BJB002(D.L.).
文摘Natural bone is a mineralized biological material, which serves a supportive and protective framework for the body, stores minerals for metabolism, and produces blood cells nourishing the body. Normally, bone has an innate capacity to heal from damage.However, massive bone defects due to traumatic injury, tumor resection, or congenital diseases pose a great challenge to reconstructive surgery. Scaffold-based tissue engineering(TE) is a promising strategy for bone regenerative medicine, because biomaterial scaffolds show advanced mechanical properties and a good degradation profile, as well as the feasibility of controlled release of growth and differentiation factors or immobilizing them on the material surface. Additionally, the defined structure of biomaterial scaffolds, as a kind of mechanical cue, can influence cell behaviors, modulate local microenvironment and control key features at the molecular and cellular levels. Recently, nano/micro-assisted regenerative medicine becomes a promising application of TE for the reconstruction of bone defects. For this reason, it is necessary for us to have in-depth knowledge of the development of novel nano/micro-based biomaterial scaffolds. Thus, we herein review the hierarchical structure of bone, and the potential application of nano/micro technologies to guide the design of novel biomaterial structures for bone repair and regeneration.
文摘Anterior repositioning splint(ARS)therapy is considered one of the most effective therapies for treating disc displacement-related temporomandibular disorders(TMDs),which account for a large proportion of TMD cases.Owing to the wide application of this therapy,the exact mechanism of remission has increasingly drawn attention.Given that practitioners have different views on ARS therapy,its indications are broadened,and operating methods diverged.This review attempts to provide an overview of ARS therapy and helps practitioners establish indications and suitable operating methods.Representative views in the past 10 years were summarised,and conclusions were drawn as follows:The mechanism of ARS therapy is mainly attributed to internal derangement correction,improvement of stress distribution and recently reported joint remodeling.It has an evident effect in the short term,and the most prevalent operating methods are protruding the mandible to the edge-to-edge position and wearing the ARS for 24 hours daily for 3-6 months.However,long-term stability is not optimal,and thus indications should be selected carefully.Notably,most of the clinical studies in this field are case analyses with low-quality evidence.Well-designed RCTs are required to further validate relevant theories.
基金Supported by Beijing Natural Science Foundation,No.7182182the Young Elite Scientist Sponsorship Program by Cast,No.YESS20170089+1 种基金the National Natural Science Foundation of China,No.81600865 and No.81970940the National Science and Technology Major Project of the Ministry of Science and Technology of China,No.2018ZX10302207。
文摘Mesenchymal stem cells(MSCs)are a heterogeneous population that can be isolated from various tissues,including bone marrow,adipose tissue,umbilical cord blood,and craniofacial tissue.MSCs have attracted increasingly more attention over the years due to their regenerative capacity and function in immunomodulation.The foundation of tissue regeneration is the potential of cells to differentiate into multiple cell lineages and give rise to multiple tissue types.In addition,the immunoregulatory function of MSCs has provided insights into therapeutic treatments for immune-mediated diseases.DNA methylation and demethylation are important epigenetic mechanisms that have been shown to modulate embryonic stem cell maintenance,proliferation,differentiation and apoptosis by activating or suppressing a number of genes.In most studies,DNA hypermethylation is associated with gene suppression,while hypomethylation or demethylation is associated with gene activation.The dynamic balance of DNA methylation and demethylation is required for normal mammalian development and inhibits the onset of abnormal phenotypes.However,the exact role of DNA methylation and demethylation in MSC-based tissue regeneration and immunomodulation requires further investigation.In this review,we discuss how DNA methylation and demethylation function in multi-lineage cell differentiation and immunomodulation of MSCs based on previously published work.Furthermore,we discuss the implications of the role of DNA methylation and demethylation in MSCs for the treatment of metabolic or immune-related diseases.
基金supported by the National Natural Science Foundation of China (# 81502345 to Qian Li and #81470717 to Yanheng Zhou)the International Science & Technology Cooperation Program of China (#2015DFB30040 to Yanheng Zhou)
文摘The interplay between mechanoresponses and a broad range of fundamental biological processes, such as cell cycle progression,growth and differentiation, has been extensively investigated. However, metabolic regulation in mechanobiology remains largely unexplored. Here, we identified glucose transporter 1(GLUT1)—the primary glucose transporter in various cells—as a novel mechanosensitive gene in orthodontic tooth movement(OTM). Using an in vivo rat OTM model, we demonstrated the specific induction of Glut1 proteins on the compressive side of a physically strained periodontal ligament. This transcriptional activation could be recapitulated in in vitro cultured human periodontal ligament cells(PDLCs), showing a time-and dose-dependent mechanoresponse. Importantly, application of GLUT1 specific inhibitor WZB117 greatly suppressed the efficiency of orthodontic tooth movement in a mouse OTM model, and this reduction was associated with a decline in osteoclastic activities. A mechanistic study suggested that GLUT1 inhibition affected the receptor activator for nuclear factor-κ B Ligand(RANKL)/osteoprotegerin(OPG)system by impairing compressive force-mediated RANKL upregulation. Consistently, pretreatment of PDLCs with WZB117 severely impeded the osteoclastic differentiation of co-cultured RAW264.7 cells. Further biochemical analysis indicated mutual regulation between GLUT1 and the MEK/ERK cascade to relay potential communication between glucose uptake and mechanical stress response. Together, these cross-species experiments revealed the transcriptional activation of GLUT1 as a novel and conserved linkage between metabolism and bone remodelling.
基金Supported by the National Natural Science Foundation of China No.81970909(to Liu DW),No.51903003(to Yu TT)the New Clinical Technology Fund of PKUSS,No.PKUSSNCT-11A07(to Liu DW)Peking University Medicine Seed Fund for Interdisciplinary Research,No.BMU2018MX007(to Liu DW).
文摘BACKGROUND Palatal expansion treatment has been used to expand the constricted maxillary arch and has become a routine procedure in orthodontic practice over the past decades.However,the long-term stability of expansion in the permanent dentition without a surgical approach is uncertain.CASE SUMMARY We present the case of a 15-year-old boy with Class II malocclusion and constricted arches.The patient was treated with rapid palatal expansion(RPE)followed by a fixed orthodontic appliance.A 7-year follow-up evaluation was performed by analyzing cephalometric radiographs,plaster models,and photographs.The patient’s constricted maxillary and mandibular arches were relived after the expansion treatment.A Class I occlusion and normal arch form were established and maintained in the long-term.CONCLUSION RPE treatment is successful in solving constricted dental arch in the permanent dentition without a surgical approach.Permanent retention and even occlusal contact help prevent long-term relapse.
文摘Objective:To understand the oral health status of urban and rural residents in China,the Fourth National Oral Health Epidemiological Survey (FNOHES) was conducted in 2015.Materials and methods:Based on the principles of multi-stage,stratified,equal capacity,and random sampling,the subjects included five groups of residents aged 3-5,12-15,35-44,55-64,and 65-74 years in all 31 provinces,municipalities,and autonomous regions except Hong Kong,Macao,and Taiwan.The total sample size was 172,425.The survey covered two areas,namely oral health status and knowledge,attitude and oral health behavior.Results:Residents in China had serious caries and poor periodontal condition.The prevalence of caries was above 50% in all age groups,subjects without periodontal disease accounted for <50%,and fewer than 50% of subjects brushed their teeth twice a day.Based on the results of the FNOHES,the following suggestions were proposed for improving the oral health in China in the future:to establish and improve the comprehensive prevention and control system for oral diseases,implement a comprehensive prevention and control strategy for priority groups,strengthen the oral health education for all people to improve oral health literacy,enhance dynamic monitoring to scientifically evaluate oral health status,and coordinate multi-party resources to establish and improve the oral health service security system.Conclusion:The oral health status of Chinese residents and their oral health behavior habits need to be improved.With the support of the administrative departments of the government and unremitting efforts of the oral health staff,all sectors of society must be coordinated to strengthen oral health education for the whole population.Furthermore,comprehensive prevention and control measures must be implemented for priority groups.
基金Beijing Natural Science Foundation,Grant/Award Number:L222145CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2019-I2M-5-038+2 种基金Clinical Medicine Plus X-Young Scholars Project,Peking Universitythe Fundamental Research Funds for the Central Universities,Grant/Award Number:PKU2023LCXQ017National Natural Science Foundation of China,Grant/Award Number:81700935。
文摘Background:The effect of platelet factor 4(PF4)on bone marrow mesenchymal stem cells(BMMSCs)and osteoporosis is poorly understood.Therefore,this study aimed to evaluate the effects of PF4-triggered bone destruction in mice and determine the underlying mechanism.Methods:First,in vitro cell proliferation and cell cycle of BMMSCs were assessed using a CCK8 assay and flow cytometry,respectively.Osteogenic differentiation was confirmed using staining and quantification of alkaline phosphatase and Alizarin Red S.Next,an osteoporotic mouse model was established by performing bilateral ovariectomy(OVX).Furthermore,the PF4 concentrations were obtained using enzymelinked immunosorbent assay.The bone microarchitecture of the femur was evaluated using microCT and histological analyses.Finally,the key regulators of osteogenesis and pathways were investigated using quantitative real-time polymerase chain reaction and Western blotting.Results:Human PF4 widely and moderately decreased the cell proliferation and osteogenic differentiation ability of BMMSCs.Furthermore,the levels of PF4 in the serum and bone marrow were generally increased,whereas bone microarchitecture deteriorated due to OVX.Moreover,in vivo mouse PF4 supplementation triggered bone deterioration of the femur.In addition,several key regulators of osteogenesis were downregulated,and the integrinα5-focal adhesion kinase-extracellular signalregulated kinase(ITGA5-FAK-ERK)pathway was inhibited due to PF4 supplementation.Conclusions:PF4 may be attributed to OVX-i nduced bone loss triggered by the suppression of bone formation in vivo and alleviate BMMSC osteogenic differentiation by inhibiting the ITGA5-FAK-ERK pathway.
基金supported by the National Key R&D Program of China [grant number 2021YFC2400700]the National Natural Science Foundation of China [grant numbers 82170929,81970908]the Beijing Natural Science Foundation [L222090,L222030]。
文摘Cancer is a major threat to human life worldwide. Traditional cancer treatments, such as chemotherapy and surgery, have major limitations and can cause irreversible damage to normal tissues while killing the cancer cells. Magnesium(Mg) alloys are widely reported novel potential biomedical materials with acceptable mechanical properties and good osteogenic and angiogenic properties. In this review, we summarize the Mg alloys for antitumor applications, including pure Mg and Mg alloys(Mg-Ag, Mg-Gd, Mg-Li-Zn, Mg-Ca-Sr-Zn, et al.) fabricated by casting and extruding, selective laser melting methods. Mg alloys can exhibit antitumor effect on bone tumor, breast cancer, and liver tumor,etal. What's more, after tumor tissue is eliminated, Mg alloys prevent tumor recurrence, fill tissue defects and promote tissue regeneration.The antitumor effects of Mg alloys are mainly due to their degradation products. Overall, Mg alloys show great potential in tumor treatments due to the dual function of antitumor and tissue regeneration.
基金This work was supported by the Projects of the National Natural Science Foundations of China(No.81970901 to N.J.and No.81871492 to Y.L.)the Ten Thousand Talents Program(Y.L.)the Beijing Municipal Natural Science Foundation(No.L182005 to Y.L.).
文摘Macrophages play an important role in material-related immune responses and bone formation,but the functionality of macrophage-derived extracellular vesicles(EVs)in material-mediated bone regeneration is still unclear.Here,we evaluated intracellular communication through small extracellular vesicles(sEVs)and its effects on endogenous bone regeneration mediated by biomimetic intrafibrillarly mineralized collagen(IMC).After implantation in the bone defect area,IMC generated more neobone and recruited more mesenchymal stem cells(MSCs)than did extrafibrillarly mineralized collagen(EMC).More CD63+CD90+and CD63+CD163+cells were detected in the defect area in the IMC group than in the EMC group.To determine the functional roles of sEVs,extracellular vesicles from macrophages cultured on different mineralized collagen were isolated,and they showed no morphological differences.However,macrophage-derived sEVs in the IMC group showed an enhanced Young’s modulus and exerted beneficial effects on the osteogenic differentiation of bone marrow MSCs by increasing the expression of the osteoblastic differentiation markers BMP2,BGLAP,COL1,and OSX and calcium nodule formation.Mechanistically,sEVs from IMC-treated macrophages facilitated MSC osteogenesis through the BMP2/Smad5 pathway,and blocking sEV secretion with GW4869 significantly impaired MSC proliferative,immunomodulative and osteogenic potential.Taken together,these findings show that macrophage-derived sEVs may serve as an emerging functional tool in biomaterial-mediated endogenous bone regeneration.
基金Supported by The National Natural Science Foundation of China,No.81970940 and No.81600865Beijing Natural Science Foundation,No.7182182and the National Science and Technology Major Project of the Ministry of Science and Technology of China,No.2018ZX10302207.
文摘BACKGROUND Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide,which emphasizes the urgent need to identify novel treatments.Stem cells from human exfoliated deciduous teeth(SHED),which are easy to obtain in a non-invasive manner,show pronounced proliferative and immunomodulatory capacities.AIM To investigate the protective effects of SHED on concanavalin A(ConA)-induced hepatitis in mice,and to elucidate the associated regulatory mechanisms.METHODS We used a ConA-induced acute hepatitis mouse model and an in vitro co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis,as well as the associated underlying mechanisms.RESULTS SHED infusion could prevent aberrant histopathological liver architecture caused by ConA-induced infiltration of CD3+,CD4+,tumor necrosis-alpha+,and interferon-gamma+inflammatory cells.Alanine aminotransferase and aspartate aminotransferase were significantly elevated in hepatitis mice.SHED infusion could therefore block ConA-induced alanine aminotransferase and aspartate aminotransferase elevations.Mechanistically,ConA upregulated tumor necrosisalpha and interferon-gamma expression,which was activated by the nuclear factor-kappa B pathway to induce hepatocyte apoptosis,resulting in acute liver injury.SHED administration protected hepatocytes from ConA-induced apoptosis.CONCLUSION SHED alleviates ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the nuclear factor-kappa B pathway.Our findings could provide a potential treatment strategy for hepatitis.
基金The National Natural Science Foundation of China(81200762 and 81470769)supported this work
文摘Early childhood caries （ECC） is a considerable pediatric and public health problem worldwide. Preceding studies have focused primarily on bacterial diversity at the taxonomic level. Although these studies have provided significant information regarding the connection between dental caries and oral micmbiomes, further comprehension of this microbial community＇s ecological relevance is limited. This study identified the carbon source metabolic differences in dental plaque between children with and without ECC. We compared the microbial community functional diversity in 18 caries-free subjects with 18 severe ECC patients based on sole carbon source usage using a Biolog assay. The anaerobic microbial community in the ECC patients displayed greater metabolic activity than that of the control group. Specific carbon source metabolism differed significantly between the two groups. Subjects from the two groups were well distinguished by cluster and principal component analyses based on discriminative carbon sources. Our results implied that the microbial functional diversity between the ECC patients and healthy subjects differed significantly. In addition, the Biolog assay furthered our understanding of oral microbiomes as a composite of functional abilities, thus enabling us to identify the ecologically relevant functional differences among oral microbial communities.
基金supported by the National Key R&D Program of China[grant number 2018YFE0104200]the National Natural Science Foundation of China[grant numbers 51901003,51931001,52171233,51875310]+1 种基金the Beijing Natural Science Foundation[grant number L212014]the Open Project of NMPA Key Laboratory for Dental Materials[grant number PKUSS20200401].
文摘Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures.Biodegradable Zn metals are revolutionary materials for orthopedic implants.In this study,pure Zn porous scaffolds with diamond structures were fabricated using customized laser powder bed fusion(L-PBF)technology.First,the mechanical properties,corrosion behavior,and biocompatibility of the pure Zn porous scaffolds were characterized in vitro.The scaffolds were then implanted into the rabbit femur critical-size bone defect model for 24 weeks.The results showed that the pure Zn porous scaffolds had compressive strength and rigidity comparable to those of cancellous bone,as well as relatively suitable degradation rates for bone regeneration.A benign host response was observed using hematoxylin and eosin(HE)staining of the heart,liver,spleen,lungs,and kidneys.Moreover,the pure Zn porous scaffold showed good biocompatibility and osteogenic promotion ability in vivo.This study showed that pure Zn porous scaffolds with customized structures fabricated using L-PBF represent a promising biodegradable solution for treating large bone defects.
基金supported by the National Natural Science Foundation of China(81974151).
文摘The primary treatment modality for tumors affecting the oral and maxillofacial region is surgery.Surgical treatment of tumors affecting this region is a challenge and poses relatively high surgical risk,especially in lesions affecting the deep regions of the head and the neck due to the complex anatomy of this region including structures of great importance such as the internal carotid artery,the internal jugular vein,and the cavernous sinus at the skull base,the cranial nerves and the orbital contents with the eye globes,extraocular muscles,and the lacrimal gland.Oncologic resection often results in devastating defects in the oral and maxillofacial region,which adversely affect patients’facial appearance and important functions such as speech,chewing,deglutition,or vision and significantly impact patients’quality of life.In order to obtain a good result concerning tumor excision in the oral and cranio-maxillofacial region as well as a correct aesthetic and functional reconstruction,an adequate presurgical evaluation of the patient and accurate planning of the surgical resection and the reconstructive approach must be carefully designed.
基金supported by the National Key R&D Program of China[grant number 2021YFC2400700]the National Natural Science Foundation of China[grant numbers 82170929,81970908]+1 种基金Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund Project[grant numbers L222090,L212014]the Beijing Nova Program.
文摘Skin wounds are a major medical challenge that threaten human health.Functional hydrogel dressings demonstrate great potential to promote wound healing.In this study,magnesium(Mg)and zinc(Zn)are introduced into methacrylate gelatin(GelMA)hydrogel via low-temperature magnetic stirring and photocuring,and their effects on skin wounds and the underlying mechanisms are investigated.Degradation testing confirmed that the GelMA/Mg/Zn hydrogel released magnesium ions(Mg^(2+))and zinc ions(Zn^(2+))in a sustained manner.The Mg^(2+) and Zn^(2+)not only enhanced the migration of human skin fibroblasts(HSFs)and human immortalized keratinocytes(HaCats),but also promoted the transformation of HSFs into myofibroblasts and accelerated the production and remodeling of extracellular matrix.Moreover,the GelMA/Mg/Zn hydrogel enhanced the healing of full-thickness skin defects in rats via accelerated collagen deposition,angiogenesis and skin wound re-epithelialization.We also identified the mechanisms through which GelMA/Mg/Zn hydrogel promoted wound healing:the Mg^(2+) promoted Zn^(2+)entry into HSFs and increased the concentration of Zn^(2+)in HSFs,which effectively induced HSFs to differentiate into myofibroblasts by activating the STAT3 signaling pathway.The synergistic effect of Mg^(2+) and Zn^(2+)promoted wound healing.In conclusion,our study provides a promising strategy for skin wounds regeneration.
