Correction: MicroRNA-329-3p inhibits the Wnt/β-catenin pathway and proliferation of osteosarcoma cells by targeting transcription factor 7-like 1

In the article‘MicroRNA-329-3p inhibits the Wnt/β-catenin pathway and proliferation of osteosarcoma cells by targeting transcription factor 7-like 1’(Oncology Research,2024,Vol.32,No.3,pp.463−476.doi:10.32604/or.2023.044085),there was an error in the compilation of Fig.8D.We have revised Fig.8D to correct this error.A corrected version of Fig.8 is provided.This correction does not change any results or conclusions of the article.We apologize for any inconvenience caused.

Alterations in Serum Lipids and Lipoproteins Induced by Neoadjuvant Chemotherapy in Patients with Osteosarcoma around the Knee Joint:A Retrospective Analysis

Objective To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy.Methods After retrospectively screening the data of 742 patients between January 2007 and July 2020,50 patients aged 13 to 39 years with Enneking stage II disease were included in the study.Serum lipid levels,including total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),lipoprotein-α[Lp(a)],and apolipoprotein A1,B,and E(ApoA1,ApoB,and ApoE),and clinicopathological characteristics were collected before and after neoadjuvant chemotherapy.Results The mean levels of TC,TG,and ApoB were significantly increased following neoadjuvant chemotherapy(16%,38%,and 20%,respectively,vs.pretreatment values;P<0.01).The mean levels of LDL-C and ApoE were also 19%and 16%higher,respectively(P<0.05).No correlation was found between the pretreatment lipid profile and the histologic response to chemotherapy.An increase in Lp(a)was strongly correlated with the Ki-67 index(R=0.31,P=0.023).Moreover,a trend toward longer disease-free survival(DFS)was observed in patients with decreased TG and increased LDL-C following chemotherapy,although this difference was not statistically significant(P=0.23 and P=0.24,respectively).Conclusion Significant elevations in serum lipids were observed after neoadjuvant chemotherapy in patients with localized osteosarcoma.There was no prognostic significance of pretreatment serum lipid levels on histologic response to neoadjuvant chemotherapy.The scale of increase in serum Lp(a)might have a potential prognostic role in osteosarcoma.Patients with increased LDL-C or reduced TG after chemotherapy seem to exhibit a trend toward favorable DFS.

Prognositic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma

Objective:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor prognosis.Anchorage-dependent cell death(anoikis)has been proven to be indispensable in tumor metastasis,regulating the migration and adhesion of tumor cells at the primary site.However,as a type of programmed cell death,anoikis is rarely studied in osteosarcoma,especially in the tumor immune microenvironment.This study aims to clarify prognostic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma.Methods:Anoikis-related genes(ANRGs)were obtained from GeneCards.Clinical information and ANRGs expression profiles of osteosarcoma patients were sourced from the therapeutically applicable research to generate effective therapies and Gene Expression Omnibus(GEO)databases.ANRGs highly associated with tumor immune microenvironment were identified by the estimate package and the weighted gene coexpression network analysis(WGCNA)algorithm.Machine learning algorithms were performed to construct long-term survival predictive strategy,each sample was divided into high-risk and low-risk subgroups,which was further verified in the GEO cohort.Finally,based on single-cell RNA-seq from the GEO database,analysis was done on the function of signature genes in the osteosarcoma tumor microenvironment.Results:A total of 51 hub ANRGs closely associated with the tumor microenvironment were identified,from which 3 genes(MERTK,BNIP3,S100A8)were selected to construct the prognostic model.Significant differences in immune cell activation and immune-related signaling pathways were observed between the high-risk and low-risk groups based on tumor microenvironment analysis(all P<0.05).Additionally,characteristic genes within the osteosarcoma microenvironment were identified in regulation of intercellular crosstalk through the GAS6-MERTK signaling pathway.Conclusion:The prognostic model based on ANRGs and tumor microenvironment demonstrate good predictive power and provide more personalized treatment options for patients with osteosarcoma.

Hydroxysafflor yellow A induced ferroptosis of Osteosarcoma cancer cells by HIF-1α/HK2 and SLC7A11 pathway

Osteosarcoma is a very serious primary bone cancer with a high death rate and a dismal prognosis.Since there is no permanent therapy for this condition,it is necessary to develop a cure.Therefore,this investigation was carried out to assess the impacts and biological functions of hydroxysafflor yellow A(HYSA)in osteosarcoma cell lines(MG63).In this investigational study,MG63 cells were utilized.Microarray experiments,quantitative polymerase chain reaction(qPCR),immunofluorescent staining,extracellular acidification rate(ECAR),oxygen consumption rate(OCR),glucose consumption,lactate production,and ATP levels,proliferation assay,5-Ethynyl-2′-deoxyuridine(EDU)staining,and Western blot were performed.In MG63 cells,HYSA lowered cell proliferation and metastasis rates,suppressed EDU cell number,and enhanced caspase-3/9 activity levels.HYSA reduced the Warburg effect and induced ferroptosis(FPT)in MG63 cells.Inhibiting ferroptosis diminished HYSA’s anti-cancer activities in MG63 cells.The stimulation of the HIF-1α/SLC7A11 pathway decreased HYSA’s anti-cancer activities in MG63 cells.HIF-1αis one target spot for HYSA in a model of osteosarcoma cancer(OC).HYSA altered HIF-1α’s thermophoretic activity;following binding with HYSA,HIF-1α’s melting point increased from~55°C to~60°C.HYSA significantly enhanced the thermal stability of exogenous WT HIF-1αwhile not affecting Mut HIF-1α,suggesting that ARG-311,GLY-312,GLN-347,and GLN-387 may be involved in the interaction between HIF-1αand HYSA.Conclusively,our study revealed that HYSA induced FPT and reduced the Warburg effect of OC through mitochondrial damage by HIF-1α/HK2/SLC7A11 pathway.HYSA is a possible therapeutic option for OC or other cancers.

Large Conventional Osteosarcoma of the Proximal Humerus in a 13-Year-Old Child: Case Report

Introduction: Osteosarcoma is the most common primary malignant bone tumor in children. It is highly aggressive and has a poor prognosis. A late presentation modifies and makes difficult the management affecting the survival of children. We report the case of a large conventional osteosarcoma in a 13-year-old girl. Case Presentation: Adolescent girl admitted for painful swelling of the left shoulder with absolute functional impotence of the thoracic limb and severe anemia. The painful swelling was thought to have been caused by a minor trauma that had occurred six months previously. The patient’s general condition was poor, and she presented with a large, shiny, painful mass over the shoulder and upper 2/3 of the left arm, measuring 28 cm long by 28 cm wide and 57 cm in circumference, and a large fistulous axillary adenopathy. CT scan showed a tumour lesion of the left humerus with liver and lung metastases, raising suspicion of osteogenic osteosarcoma. The tumor was classified according to TNM staging: T2N1M1(a + b). Management was modified when uncontrolled bleeding developed. It consisted of an extended amputation of the left thoracic limb. Pathological analysis showed a high-grade conventional osteosarcoma. Quality improvement was obtained for thirty days, followed by the onset of dyspnea. The evolution was towards death at forty days post-operatively. Conclusion: Osteosarcoma is a highly aggressive cancer. Delayed treatment leads to a fatal outcome. Early diagnosis is one of the challenges to be met in order to improve survival.

Exploring the effects of taurolidine on tumor weight and microvessel density in a murine model of osteosarcoma

Background:Osteosarcoma is the most common malignant primary bone tumor.The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy.Moreover,current treatment regimens bear a significant risk of serious side effects.Thus,there is an unmet clinical need for effective therapies with improved safety profiles.Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines.Methods:In this study,we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma.K7M2 murine osteosarcoma cells were injected,both intramuscular and intraperitoneal,into 60 BALB/c mice on day zero.Animals were then randomized to receive treatment with taurolidine 2%(800 mg/kg),taurolidine 1%(400 mg/kg),or NaCl 0.9%control for seven days by intravenous or intraperitoneal administration.Results:After 35 days,mice were euthanized,and the tumors were harvested for analysis.Eighteen mice were excluded from the analysis due to complications.Body weight was significantly lower in the 2%taurolidine intraperitoneal treatment group from day 9 to 21,consistent with elevated mortality in this group.Intraperitoneal tumor weight was significantly lower in the 1%(p=0.003)and 2%(p=0.006)intraperitoneal taurolidine treatment groups compared to the control.No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine.There were no significant differences in microvessel density or mitotic rate between treatment groups.Reduced body weight and elevated mortality in the 2%taurolidine intraperitoneal group suggest that the lower 1%dose is preferable.Conclusions:In conclusion,there is no evidence of antiangiogenic activity,and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited.Moreover,its toxic profile grants further evaluation.Given these observations,further research is necessary to refine the use of taurolidine in osteosarcoma treatment.

Codelivery of anti-CD47 antibody and chlorin e6 using a dual pH-sensitive nanodrug for photodynamic immunotherapy of osteosarcoma

Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.

MicroRNA-329-3p inhibits the Wnt/β-catenin pathway and proliferation of osteosarcoma cells by targeting transcription factor 7-like 1

An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein.This study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 on.the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches.MiR329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell lines.Additionally,a clinical comparison study was performed using the TCGA database.Subsequently,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments.When miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic bodies.The expression of proteins that indicate apoptosis increased simultaneously.The cell cycle was arrested in the G0/G1 phase,and the G1/S transition was blocked.The introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt pathway.Xenograf experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues decreased.MiR 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo.Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR 3293p.Summarizing these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcoma by inhibiting TCF7L1.

MiR-150-5p inhibits cell proliferation and metastasis by targeting FTO in osteosarcoma

Background:Osteosarcoma(OS),recognized as the predominant malignant tumor originating from bones,necessitates an in-depth comprehension of its intrinsic mechanisms to pinpoint novel therapeutic targets and enhance treatment methodologies.The role of fat mass and obesity-associated(FTO)in OS,particularly its correlation with malignant traits,and the fundamental mechanism,remains to be elucidated.Materials and Methods:1.The FTO expression and survival rate in tumors were analyzed.2.FTO in OS cell lines was quantified utilizing western blot and PCR.3.FTO was upregulated and downregulated separately in MG63.4.The impact of FTO on the proliferation and migration of OS cells was evaluated using CCK-8,colony formation,wound healing,and Transwell assays.5.The expression of miR-150-5p in OS cells-derived exosomes was identified.6.The binding of miR-150-5p to FTO was predicted by TargetScan and confirmed by luciferase reporter assay.7.The impact of exosome miR-150-5p on the proliferation and migration of OS cells was investigated.Results:The expression of FTO was higher in OS tissues compared to normal tissues correlating with a worse survival rate.Furthermore,the downregulation of FTO significantly impeded the growth and metastasis of OS cells.Additionally,miR-150-5p,which was downregulated in both OS cells and their derived exosomes,was found to bind to the 3′-UTR of FTO through dual luciferase experiments.Exosomal miR-150-5p was found to decrease the expression of FTO and inhibit cell viability.Conclusions:We identified elevated levels of FTO in OS,which may be attributed to insufficient miR-150-5p levels in both the cells and exosomes.It suggests that the dysregulation of miR-150-5p and its interaction with FTO could potentially promote the development of OS.

青海东昆仑三通沟北锰矿成矿时代与物质来源:来自Re-Os同位素年代学与地球化学的约束

东昆仑三通沟北锰矿床是近年来青海省发现的规模最大的海相沉积型锰矿。该矿床位于东昆南构造带的北缘,成矿地质背景与原特提斯洋的演化密切相关。但目前该矿床研究程度较低,尤其是成矿时代存在中-新元古代与奥陶-志留纪的争议,成矿物质来源存在海底热液为主还是海底热液与陆源风化共同来源的不同认识。为了解决这些问题,本文在对三通沟北锰矿进行详细野外地质调查和钻孔岩芯编录的基础上,选择11件锰矿石进行Re-Os同位素分析,获得了442±15Ma的Re-Os等时线年龄,说明三通沟北锰矿带形成于晚奥陶世,不是前人认为的中-新元古代,这一成矿年龄与区域上的奥陶纪纳赤台群沉积岩的形成时代一致。同时Re-Os同位素分析获得的^(187)Os/^(188)Os初始值为0.67±0.02,该值明显低于同期海水的Os同位素组成(0.72),初步表明三通沟北锰矿的锰质来源以海底热液为主。矿石在SiO_(2)-Al_(2)O_(3)、Al/(Al+Fe+Mn)-Fe/Ti、Fe-Mn-(Ni+Cu+Co)×10和lgU-lgTh等图解上主要位于热水沉积区,矿石稀土元素配分型式也具有海底热液来源的特征。可见三通沟北锰矿的成矿物质来源主要与海底热液活动有关。

新疆东天山黄滩金铜锌矿成矿时代——来自白云母^(40)Ar-^(39)Ar年龄和黄铁矿Re-Os年龄约束

卡拉塔格是东天山十分重要的铜矿集区,发育5个不同时代和成矿类型的成矿系统。近年来新发现了黄滩(包括金岭)金铜锌矿床,赋存于火山岩系中,发育层状矿化、脉状矿化和黄铁绢英岩化,但层状矿化和黄铁绢英岩化形成时代不清楚,制约了进一步找矿勘查工作。本文基于野外调查和室内研究,开展白云母^(40)Ar-^(39)Ar年龄和黄铁矿Re-Os年代学研究,获得黄铁绢英岩中白云母^(40)Ar-^(39)Ar坪年龄为429.46±3.91 Ma,7件层状矿化中黄铁矿Re-Os等时线年龄为436.5±4.2 Ma。层状矿化年龄与前人获得含矿岩系英安岩和英安质凝灰岩年龄(434~438 Ma)、脉状矿化年龄(432~438 Ma)一致,表明层状矿化、脉状矿化和黄铁绢英岩化是同一成矿事件的产物,黄滩为富金火山成因块状硫化物(VMS)型矿床。因此,尽管黄滩和红海‒黄土坡为VMS型矿床,红石为火山热液脉状矿床,但它们均为同一VMS成矿系统,形成于430~439 Ma,受控矿因素的差异,造成了成因类型、矿化类型和成矿元素组合的多样性。

Managing the immune microenvironment of osteosarcoma:the outlook for osteosarcoma treatment

Osteosarcoma,with poor survival after metastasis,is considered the most common primary bone cancer in adolescents.Notwithstanding the efforts of researchers,its five-year survival rate has only shown limited improvement,suggesting that existing therapeutic strategies are insufficient to meet clinical needs.Notably,immunotherapy has shown certain advantages over traditional tumor treatments in inhibiting metastasis.Therefore,managing the immune microenvironment in osteosarcoma can provide novel and valuable insight into the multifaceted mechanisms underlying the heterogeneity and progression of the disease.Additionally,given the advances in nanomedicine,there exist many advanced nanoplatforms for enhanced osteosarcoma immunotherapy with satisfactory physiochemical characteristics.Here,we review the classification,characteristics,and functions of the key components of the immune microenvironment in osteosarcoma.This review also emphasizes the application,progress,and prospects of osteosarcoma immunotherapy and discusses several nanomedicine-based options to enhance the efficiency of osteosarcoma treatment.Furthermore,we examine the disadvantages of standard treatments and present future perspectives for osteosarcoma immunotherapy.

没食子酸对人骨肉瘤HOS细胞增殖、迁移和侵袭能力及上皮-间充质转化的影响

目的探讨没食子酸(GA)对人骨肉瘤HOS细胞增殖、迁移和侵袭能力以及上皮-间充质转化(EMT)的影响。方法CCK-8试剂盒检测没食子酸对人骨肉瘤HOS细胞存活率的影响。细胞划痕愈合实验和Transwell小室检测没食子酸对HOS细胞迁移和侵袭能力的影响。Western blot检测HOS细胞E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)和Snail蛋白表达水平。结果没食子酸能显著抑制人骨肉瘤HOS细胞的增殖、迁移与侵袭;没食子酸显著上调E-cadherin蛋白表达,下调N-cadherin、Vimentin、Snail蛋白表达。结论没食子酸可以抑制人骨肉瘤HOS细胞的增殖、迁移、侵袭及EMT。

Characterizing the tumor microenvironment at the single-cell level reveals a novel immune evasion mechanism in osteosarcoma

The immune microenvironment extensively participates in tumorigenesis as well as progression in osteosarcoma(OS).However,the landscape and dynamics of immune cells in OS are poorly characterized.By analyzing single-cell RNA sequencing(sc RNA-seq)data,which characterize the transcription state at single-cell resolution,we produced an atlas of the immune microenvironment in OS.The results suggested that a cluster of regulatory dendritic cells(DCs)might shape the immunosuppressive microenvironment in OS by recruiting regulatory T cells.We also found that major histocompatibility complex class I(MHC-I)molecules were downregulated in cancer cells.The findings indicated a reduction in tumor immunogenicity in OS,which can be a potential mechanism of tumor immune escape.Of note,CD24 was identified as a novel“don’t eat me”signal that contributed to the immune evasion of OS cells.Altogether,our findings provide insights into the immune landscape of OS,suggesting that myeloid-targeted immunotherapy could be a promising approach to treat OS.

A novel molecular classification method for osteosarcoma based on tumor cell differentiation trajectories

Subclassification of tumors based on molecular features may facilitate therapeutic choice and increase the response rate of cancer patients.However,the highly complex cell origin involved in osteosarcoma(OS)limits the utility of traditional bulk RNA sequencing for OS subclassification.Single-cell RNA sequencing(sc RNA-seq)holds great promise for identifying cell heterogeneity.However,this technique has rarely been used in the study of tumor subclassification.By analyzing sc RNA-seq data for six conventional OS and nine cancellous bone(CB)samples,we identified 29 clusters in OS and CB samples and discovered three differentiation trajectories from the cancer stem cell(CSC)-like subset,which allowed us to classify OS samples into three groups.The classification model was further examined using the TARGET dataset.Each subgroup of OS had different prognoses and possible drug sensitivities,and OS cells in the three differentiation branches showed distinct interactions with other clusters in the OS microenvironment.In addition,we verified the classification model through IHC staining in 138 OS samples,revealing a worse prognosis for Group B patients.Furthermore,we describe the novel transcriptional program of CSCs and highlight the activation of EZH2 in CSCs of OS.These findings provide a novel subclassification method based on sc RNA-seq and shed new light on the molecular features of CSCs in OS and may serve as valuable references for precision treatment for and therapeutic development in OS.

雷公藤甲素通过miR-34b-5p/Notch1轴抑制骨肉瘤U2OS细胞增殖并诱导其铁死亡

目的:探究雷公藤甲素(TPL)通过miR-34b-5p调控Notch1表达对骨肉瘤U2OS细胞铁死亡影响的机制。方法:常规培养U2OS细胞,将其分为对照组、TPL(10μmol/L)组、TPL(10μmol/L)+Fer-1(铁死亡抑制剂,20μmol/L)组、miR-NC组、miR-34b-5p组、miR-34b-5p+Fer-1(20μmol/L)组、TPL(10μmol/L)+anti-miR-34b-5p组、anti-miR-34b-5p+Fer-1(20μmol/L)组。qPCR法、CCK-8法、铁离子检测试剂、DHE-荧光探针和WB法分别检测各组U2OS细胞中miR-34b-5p的表达、增殖能力、Fe2+水平、ROS水平以及铁死亡相关蛋白(GPX4、SLC7A11及Notch1蛋白)的表达,双萤光素酶报告基因实验验证miR-34b-5p与Notch1的靶向结合关系。结果:TPL可促进U2OS细胞中miR-34b-5p表达,Fer-1和anti-miR-34b-5p则抑制miR-34b-5p的表达(均P<0.05)。TPL明显抑制U2OS细胞的增殖、GPX4、SLC7A11、Notch1蛋白的表达、增加细胞中Fe2+和ROS的含量,Fer-1可逆转TPL对U2OS细胞的作用(均P<0.05)。过表达miR-34b-5p与TPL对U2OS细胞的作用相似(均P<0.05)。miR-34b-5p可靶向结合Notch1(均P<0.05)。miR-34b-5p抑制剂可明显抑制TPL对U2OS细胞的影响,Fer-1可增强miR-34b-5p抑制剂的作用(均P<0.05)。结论:TPL可抑制U2OS细胞的增殖能力并促进其铁死亡,其作用机制可能与miR-34a-5p靶向调节Notch1表达有关。

雷公藤甲素调控lncRNA BE503655影响骨肉瘤细胞SaOS-2增殖、侵袭和凋亡

目的研究雷公藤甲素对骨肉瘤细胞SaOS-2增殖、侵袭和凋亡的影响和机制.方法骨肉瘤细胞SaOS-2分成Control组、Triptolide组(40、80、160 nmol·L^(-1)雷公藤甲素)、阳性对照组(15 mg·L^(-1)5-氟尿嘧啶)、Triptolide+si-NC组(转染siRNA control,160 nmol·L^(-1)雷公藤甲素)、Triptolide+si-BE503655组(转染BE503655 siRNA,160 nmol·L^(-1)雷公藤甲素),以CCK-8实验分析细胞变化,用流式细胞术分析细胞凋亡变化,以Transwell小室分析细胞迁移和侵袭变化,West-ern blot分析神经性钙黏附素(neural cadherin,N-cadherin)、上皮性钙黏附素(epithelical cadherin,E-cadherin)、Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)、Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)、基质金属蛋白酶-2(matrix metalloprotease 2,MMP-2)蛋白表达变化,qRT-PCR方法分析BE503655表达.结果与Control组比较,Triptolide组(40、80、160 nmol·L^(-1)雷公藤甲素)、阳性对照组骨肉瘤细胞存活率降低,细胞凋亡率升高,侵袭数目和迁移数目减少,细胞中Bax、E-cadherin蛋白表达水平增加,Bcl-2、MMP-2、N-cadherin蛋白表达水平降低,BE503655表达水平升高.与Triptolide+si-NC组比较,Triptolide+si-BE503655组骨肉瘤细胞存活率升高,细胞凋亡率降低,迁移和侵袭数目均增加,MMP-2、N-cadherin、Bcl-2蛋白表达水平均升高,E-cadherin、Bax蛋白表达水平均降低,BE503655水平降低.结论雷公藤甲素通过上调BE503655发挥抑制骨肉瘤细胞SaOS-2增殖、迁移、侵袭、EMT和促凋亡作用.

原油组分Re-Os放射性同位素体系特征及其定年机理与应用启示

Re-Os放射性同位素体系可用于含油气系统关键地质过程的定年与示踪研究。不过,Re-Os定年的精度仍受到有关科学问题的制约,如原油组分的Re-Os体系特征、沥青质渐进散失对原油Re-Os体系特征与定年应用的影响等。本研究通过二元溶液直接分离原油次组分的实验,揭示了原油组分的Re-Os体系特征,模拟了实际地质情况中沥青质渐进散失对原油Re-Os体系特征与定年应用的影响,并通过重复实验验证相关实验流程对所取得的结果和认识的影响。研究发现,根据沉淀的先后顺序,原油次组分的Re和Os元素丰度总体上呈下降趋势,但有起伏变化,Re-Os同位素比值则单调下降。因此,沥青质的渐进散失将导致原油Re和Os元素丰度以及Re-Os同位素比值降低,进而对原油和低成熟度沥青Re-Os定年与示踪的应用产生影响。重复实验表明,实验室分离次组分的操作结果具有一定的随机性,但不影响Re-Os体系的总体性质。

豫西小秦岭地区大湖金(钼)矿床Re–Os和Ar–Ar同位素定年:对成矿期次的限定

【研究目的】位于华北克拉通南缘的东秦岭钼矿带是全球第二大钼矿带,其北缘蕴含有著名的小秦岭造山型金矿田。近年来通过地质调查工程的实施,在小秦岭大湖金(钼)矿区深部发现具有工业意义的钼矿化,并已开始开采钼矿,限定其成矿期次,有助于研究金钼成矿规律。【研究方法】本文基于小秦岭地区危机矿山深部找矿工作,研究了金钼深部成矿模式,分析了辉钼矿Re–Os和钾长石^(40)Ar/^(39)Ar同位素定年在划分成矿期次中的作用。【研究结果】来自S35矿脉的6件辉钼矿样品Re–Os模式年龄介于(192.3±2.9)~(223.4±3.2)Ma,等时线年龄为(214.9±5.2)Ma(MSWD=0.77),来自F5矿脉中钾长石晶体^(40)Ar/^(39)Ar坪年龄为(95.22±1.16)Ma,其等时线年龄为(95.10±4.57)Ma。【结论】辉钼矿年龄代表了印支期钼矿化事件,钾长石年龄反映存在燕山中期新的构造-岩浆-热事件,这期热事件对于金钼矿床的成矿活动可能有积极意义,叠加改造了印支期的钼矿化事件。结合手标本和BSE图像分析结果,认为大湖金(钼)矿区与金钼矿化相关的热事件应不低于两期。

The anti-oncogenic effect of 17-DMAG via the inactivation of HSP90 and MET pathway in osteosarcoma cells

Heat shock protein(HSP)90 plays a crucial role in correcting the misfolded three-dimensional structure of proteins,assisting them in folding into proper conformations.HSP90 is critical in maintaining the normal functions of various proteins within cells,as essential factors for cellular homeostasis.Contrastingly,HSP90 simultaneously supports the maturation of cancer-related proteins,including mesenchymal epithelial transition factor(MET)within tumor cells.All osteosarcoma cell lines had elevated MET expression in the cDNA array in our possession.MET,a tyrosine kinase receptor,promotes proliferation and an anti-apoptotic state through the activation of the MET pathway constructed by HSP90.In this study,we treated osteosarcoma cells with an HSP90 inhibitor,17-demethoxygeldanamycin hydrochloride(17-DMAG),and assessed the changes in the MET signaling pathway and also the antitumor effect of the drug.The cell cycle in osteosarcoma cells administered 17-DMAG was found to be halted at the G2/M phase.Additionally,treatment with 17-DMAG inhibited cell proliferation and induced apoptosis.Inhibition of tumor cell proliferation was also observed in an in vivo model system,mice that were treated with 17-DMAG.Based on the results of this study,we were able to confirm that 17-DMAG promotes inhibition of osteosarcoma cell proliferation and induction of apoptosis by inhibition of MET,a protein highly expressed in osteosarcoma cells.This approach may be useful for the establishment of a new treatment strategy for patients resistant to the standard treatment for osteosarcoma.