查看更多>>摘要:Inflammatory jaw bone diseases are common in stomatology,including periodontitis,peri-implantitis,medication-related osteonecrosis of the jaw,radiation osteomyelitis of the jaw,age-related osteoporosis,and other specific infections.These diseases may lead to tooth loss and maxillofacial deformities,severely affecting patients'quality of life.Over the years,the reconstruction of jaw bone deficiency caused by inflammatory diseases has emerged as a medical and socioeconomic challenge.Therefore,exploring the pathogenesis of inflammatory diseases associated with jaw bones is crucial for improving prognosis and developing new targeted therapies.Accumulating evidence indicates that the integrated bone formation and dysfunction arise from complex interactions among a network of multiple cell types,including osteoblast-associated cells,immune cells,blood vessels,and lymphatic vessels.However,the role of these different cells in the inflammatory process and the'rules'with which they interact are still not fully understood.Although many investigations have focused on specific pathological processes and molecular events in inflammatory jaw diseases,few articles offer a perspective of integration.Here,we review the changes and mechanisms of various cell types in inflammatory jaw diseases,with the hope of providing insights to drive future research in this field.
查看更多>>摘要:Ionizing radiation is a popular and effective treatment option for glioblastoma(GBM).However,resistance to radiation therapy inevitably occurs during treatment.It is urgent to investigate the mechanisms of radioresistance in GBM and to find ways to improve radiosensitivity.Here,we found that heat shock protein 90 beta family member 1(HSP90B1)was significantly upregulated in radioresistant GBM cell lines.More importantly,HSP90B1 promoted the localization of glucose transporter type 1,a key rate-limiting factor of glycolysis,on the plasma membrane,which in turn enhanced glycolytic activity and subsequently tumor growth and radioresistance of GBM cells.These findings imply that targeting HSP90B1 may effectively improve the efficacy of radiotherapy for GBM patients,a potential new approach to the treatment of glioblastoma.
查看更多>>摘要:Hepatoblastoma is the most frequent liver malignancy in children.HepG2 has been discovered as a hepatoblastoma-derived cell line and tends to form clumps in culture.Intriguingly,we observed that the addition of calcium ions reduced cell clumping and disassociated HepG2 cells.The calcium signal is in connection with a series of processes critical in the tumorigenesis.Here,we demonstrated that extracellular calcium ions induced morphological changes and enhanced the epithelial-mesenchymal transition in HepG2 cells.Mechanistically,calcium ions promoted HepG2 proliferation and migration by up-regulating the phosphorylation levels of focal adhesion kinase(FAK),protein kinase B,and p38 mitogen-activated protein kinase.The inhibitor of FAK or Ca2+/calmodulin-dependent kinase Ⅱ(CaMK Ⅱ)reversed the Ca2+-induced effects on HepG2 cells,including cell proliferation and migration,epithelial-mesenchymal transition protein expression levels,and phosphorylation levels of FAK and protein kinase B.Moreover,calcium ions decreased HepG2 cells'sensitivity to cisplatin.Furthermore,we found that the expression levels of FAK and CaMK Ⅱ were increased in hepatoblastoma.The group with high expression levels of FAK and CaMK Ⅱ exhibited significantly lower ImmunoScore as well as CD8+T and NK cells.The expression of CaMK Ⅱ was positively correlated with that of PDCD1 and LAG3.Correspondingly,the expression of FAK was negatively correlated with that of TNFSF9,TNFRSF4,and TNFRSF18.Collectively,extracellular calcium accelerates HepG2 cell proliferation and migration via FAK and CaMK Ⅱ and enhances cisplatin resistance.FAK and CaMK Ⅱ shape immune cell infiltration and responses in tumor microenvironments,thereby serving as potential targets for hepatoblastoma.
查看更多>>摘要:In the present study,we introduced the H2O2-sensitive thiazolidinone moiety at the 4th amino group of gemcitabine(GEM)to synthesize a new target compound named GEM-ZZQ,and then we confirmed its chemical structure by nuclear magnetic resonance spectroscopy.We further confirmed that GEM-ZZQ had a good chemical stability in different pH solutions in vitro and that it could be activated by H2O2 to release GEM.Pharmacodynamic studies revealed that the growth inhibition of human normal epithelial cells was weaker by GEM-ZZQ than by GEM treatment and that the inhibition of various lung cancer cell lines by GEM-ZZQ was similar to that of GEM.For the lung cancer cell lines that are resistant to the epidermal growth factor receptor(EGFR)-targeting inhibitor osimertinib,GEM-ZZQ showed less growth inhibition than GEM;however,GEM-ZZQ in combination with cisplatin showed better synergistic effects than GEM in the low-dose groups.In summary,we provided a new anti-cancer compound GEM-ZZQ for treating lung cancer by modifying the GEM structure.
查看更多>>摘要:Age-related macular degeneration(AMD)causes irreversible blindness in people aged over 50 worldwide.The dysfunction of the retinal pigment epithelium is the primary cause of atrophic AMD.In the current study,we used the ComBat and Training Distribution Matching method to integrate data obtained from the Gene Expression Omnibus database.We analyzed the integrated sequencing data by the Gene Set Enrichment Analysis.Peroxisome and tumor necrosis factor-α(TNF-α)signaling and nuclear factor kappa B(NF-κB)were among the top 10 pathways,and thus we selected them to construct AMD cell models to identify differentially expressed circular RNAs(circRNAs).We then constructed a competing endogenous RNA network,which is related to differentially expressed circRNAs.This network included seven circRNAs,15 microRNAs,and 82 mRNAs.The Kyoto Encyclopedia of Genes and Genomes analysis of mRNAs in this network showed that the hypoxia-inducible factor-1(HIF-1)signaling pathway was a common downstream event.The results of the current study may provide insights into the pathological processes of atrophic AMD.
查看更多>>摘要:Anti-cancer therapy often causes premature ovarian insufficiency and infertility as the ovarian follicle reserve is extremely sensitive to chemotherapy drugs,such as cisplatin.Various fertility preservation methods have been explored for women,especially prepubertal girls undergoing radiotherapy and chemotherapy due to cancer.In recent years,mesenchymal stem cell-derived exosomes(MSC-exos)have been reported to play an important role in tissue repair and the treatment of various diseases.In the current study,we observed that human umbilical cord-derived MSC-exos(hucMSC-exos)after short-term culture improved follicular survival and development while receiving cisplatin treatment.Moreover,intravenous injection of hucMSC-exos improved ovarian function and ameliorated inflammatory environment within the ovary.The underlying mechanism of hucMSC-exos on fertility preservation was associated with the down-regulation of p53-related apoptosis and their anti-inflammatory function.Based on these findings,we propose that hucMSC-exos may be a potential approach to improve fertility in women diagnosed with cancer.
查看更多>>摘要:The current study aims to ascertain the anatomical feasibility of transferring the contralateral S1 ventral root(VR)to the ipsilateral L5 VR for treating unilateral spastic lower limb paralysis.Six formalin-fixed(three males and three females)cadavers were used.The VR of the contralateral S1 was transferred to the VR of the ipsilateral L5.The sural nerve was selected as a bridge between the donor and recipient nerve.The number of axons,the cross-sectional areas and the pertinent distances between the donor and recipient nerves were measured.The extradural S1 VR and L5 VR could be separated based on anatomical markers of the dorsal root ganglion.The gross distance between the S1 nerve root and L5 nerve root was 31.31(±3.23)mm in the six cadavers,while that on the diffusion tensor imaging was 47.51(±3.23)mm in 60 patients without spinal diseases,and both distances were seperately greater than that between the outlet of S1 from the spinal cord and the ganglion.The numbers of axons in the S1 VRs and L5 VRs were 13 414.20(±2 890.30)and 10 613.20(±2 135.58),respectively.The cross-sectional areas of the S1 VR and L5 VR were 1.68(±0.26)mm2 and 1.08(±0.26)mm2,respectively.1n conclusion,transfer of the contralateral S1 VR to the ipsilateral L5 VR may be an anatomically feasible treatment option for unilateral spastic lower limb paralysis.
查看更多>>摘要:Scapular surgery has mainly been studied in the setting of fractures;regional anesthesia can be utilized as part of a multimodal analgesia regimen for postoperative pain relief.Previous studies are limited to scapular fracture pain.The available literature supports the use of various types of nerve blocks and even combinations of different blocks,of which the paravertebral nerve block is one such block that has been effective.We present a case of a patient undergoing excision of a scapular osteochondroma who received a single-shot paravertebral nerve block after surgery with an effective analgesia.