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2.
Drug Discov Today ; 28(4): 103514, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36736580

RESUMO

Small interfering RNA (siRNA) therapeutics for cancer are a focus of increasing research interest. However, the major obstacle to their clinical application is the targeted delivery of siRNA to cancer cells at desirable levels. Cell membrane-coated nanocarriers have the advantage of combining the properties of both cell membranes and nanoparticles (NPs). In this review, we highlight the most common RNAi therapeutics and the extracellular and intracellular barriers to siRNA delivery. Moreover, we discuss clinical applications of different cell membrane-coated nanocarriers for targeted siRNA delivery, including cancer cell membranes (CCMs), platelet membranes, erythrocyte membranes, stem cell membranes, exosome membranes, and hybrid membranes. Taken together, biomimetic cell membrane-coated nanotechnology is a promising strategy for targeted siRNA delivery for cancer treatment.


Assuntos
Exossomos , Nanopartículas , Neoplasias , Humanos , RNA Interferente Pequeno , Biomimética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Membrana Celular/metabolismo , Sistemas de Liberação de Medicamentos
3.
J Orthop Surg Res ; 18(1): 40, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36642708

RESUMO

BACKGROUND: Accumulated evidence indicates that cholesterol is offensive to bone metabolism. Therefore, we examined the real-world study among total cholesterol and total bone mineral density (BMD). We investigated the relationship between total cholesterol and total BMD among 10,039 US participants aged 20-59 years old over the period 2011-2018 from the NHANES. METHODS: To analyze the relationship among total cholesterol and total BMD, multivariate linear regression models were used. Fitted smoothing curves, generalized additive models, and threshold effect analysis were also conducted. RESULTS: After adjusting for additional covariates, weighted multivariable linear regression models indicated total cholesterol concentration levels exhibited a negative relationship with total BMD, particularly among participants aged 20-29 years. Concerning subgroup analysis, stratified by gender, race/ethnicity and age group, the negative correlation of total cholesterol with total BMD dwelled in both female and male as well as in whites and other races (including Hispanic and Multi-Racial), but not in non-Hispanic blacks and Mexican American. In other races, this relationship presented a nonlinear association (inflection point: 6.7 mmol/L) with a U-shaped curve. Among participants aged 40 to 49 years, this relationship also followed a nonlinear association (inflection point: 5.84 mmol/L), indicating a saturation effect. Moreover, the three types of diabetes status were found to have negative, U-shaped, and positive relationships. In participants with borderline diabetes status, the relationship of total cholesterol with total BMD was a U-shaped curve (inflection point: 4.65 mmol/L). CONCLUSIONS: For US young adults (20-29 years old), our study revealed a negative relationship between total cholesterol and total BMD. This association followed a U-shaped curve (inflection point: 4.65 mmol/L) in borderline diabetes status participants, a saturation curve (inflection point: 5.84 mmol/L) in participants aged 40-49 years and a nonlinear curve (inflection point: 6.7 mmol/L) in other races (including Hispanic and Multi-Racial). Therefore, keeping total cholesterol concentration at a reasonable level for young adults and diabetic population might be an approach to prevent osteoporosis or osteopenia.


Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Absorciometria de Fóton , Densidade Óssea , Inquéritos Nutricionais , Grupos Populacionais , Estados Unidos
4.
ACS Sens ; 8(3): 1076-1084, 2023 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-36651835

RESUMO

Next-generation biosensing tools based on CRISPR/Cas have revolutionized the molecular detection. A number of CRISPR/Cas-based biosensors have been reported for the detection of nucleic acid targets. The establishment of efficient methods for non-nucleic acid target detection would further broaden the scope of this technique, but up to now, the concerning research is limited. In the current study, we reported a versatile biosensing platform for non-nucleic acid small-molecule detection called SMART-Cas12a (small-molecule aptamer regulated test using CRISPR/Cas12a). Simply, hybridization chain reaction cascade signal amplification was first trigged by functional nucleic acid (aptamer) through target binding. Then, the CRISPR/Cas system was integrated to recognize the amplified products followed by activation of the trans-cleavage. As such, the target can be ingeniously converted to nucleic acid signals and then fluorescent signals that can be readily visualized and analyzed by a customized 3D-printed visualizer with the help of a home-made App-enabled smartphone. Adenosine triphosphate was selected as a model target, and under the optimized conditions, we achieved fine analytical performance with a linear range from 0.1 to 750 µM and a detection limit of 1.0 nM. The satisfactory selectivity and recoveries that we have obtained further demonstrated this method to be suitable for a complex sample environment. The sample-to-answer time was less than 100 min. Our work not only expanded the reach of the CRISPR-Cas system in biosensing but also provided a prototype method that can be generalized for detecting a wider range of analytes with desirable adaptability, sensitivity, specificity, and on-site capability.


Assuntos
Sistemas CRISPR-Cas , Ácidos Nucleicos , Sistemas CRISPR-Cas/genética , Hibridização de Ácido Nucleico , Trifosfato de Adenosina , Corantes , Oligonucleotídeos , Impressão Tridimensional
5.
Bioact Mater ; 23: 69-79, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36406251

RESUMO

Background: Immunosuppressive M2 macrophages in the tumor microenvironment (TME) can mediate the therapeutic resistance of tumors, and seriously affect the clinical efficacy and prognosis of tumor patients. This study aims to develop a novel drug delivery system for dual-targeting tumor and macrophages to inhibit tumor and induce macrophage polarization. Methods: The anti-tumor effects of methyltransferase like 14 (METTL14) were investigated both in vitro and in vivo. The underlying mechanisms of METTL14 regulating macrophages were also explored in this study. We further constructed the cyclic (Arg-Gly-Asp) (cRGD) peptide modified macrophage membrane-coated nanovesicles to co-deliver METTL14 and the TLR4 agonist. Results: We found that METTL14 significantly inhibits the growth of tumor in vitro. METTL14 might downregulate TICAM2 and inhibit the Toll-like receptor 4 (TLR4) pathway of macrophages, meanwhile, the combination of METTL14 and the TLR4 agonist could induce M1 polarization of macrophages. Macrophage membrane-coated nanovesicles are characterized by easy modification, drug loading, and dual-targeting tumor and macrophages, and cRGD modification can further enhance its targeting ability. It showed that the nanovesicles could improve the in vivo stability of METTL14, and dual-target tumor and macrophages to inhibit tumor and induce M1 polarization of macrophages. Conclusions: This study anticipates achieving the dual purposes of tumor inhibition and macrophage polarization, and providing a new therapeutic strategy for tumors.

6.
Adv Healthc Mater ; 12(7): e2202751, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36442997

RESUMO

Angiogenesis plays a critical role in diabetic wound healing. However, no effective strategies have been developed to target endothelial cells (ECs) to facilitate diabetic wound healing. Dapagliflozin (DA) as a sodium-glucose linked transporter 2 (SGLT2) inhibitor, may promote neovascularization in diabetic mice via HIF-1α-mediated enhancement of angiogenesis. Here, the bioinspired nanovesicles (NVs) prepared from induced pluripotent stem cells-derived ECs through an extrusion approach are reported, which can function as exosome mimetics to achieve targeted deliver of DA. Abundant membrane C-X-C motif chemokine receptor 4 conferred the EC-targeting ability of these NVs and the endothelial homology facilitated the accumulation in ECs. Furthermore, these DA-loaded induced pluripotent stem cells (iPSC)-EC NVs can facilitate angiogenesis and diabetic wound healing by HIF-1α/VEGFA pathway. Taken together, this study indicated that targeting ECs and regulating angiogenesis may be a promising strategy for the treatment of diabetic wound healing.


Assuntos
Diabetes Mellitus Experimental , Exossomos , Camundongos , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Células Endoteliais/metabolismo , Exossomos/metabolismo , Neovascularização Fisiológica/fisiologia , Cicatrização , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
7.
Front Genet ; 13: 1000515, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386816

RESUMO

In several tumors, Nicotinamide N-Methyltransferase (NNMT) was identified as a bridge between methylation metabolism and tumorigenesis and was associated with a poor prognosis. This research aims is to study the prognostic value of NNMT in cancer, its relationship with DNA methylation, and the immune microenvironment. On the basis of the Cancer Genome Atlas and the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, Cellminer, Gene Expression Profiling Interactive Analysis, Human Protein Atlas and Clinical Proteomic Tumor Analysis Consortium, we used a series of bioinformatics strategies to investigate the potential carcinogenicity of NNMT, including the relationship between NNMT expression and prognosis, tumor mutational burden, microsatellite instability, and sensitivity analysis of anticancer drugs. The GeneMANIA, STRING, and BioGRID databases were examined for protein-protein interactions, and Gene Ontology and the Kyoto Encyclopedia of Genes were used to infer the signal pathway. The results indicated that NNMT was significantly expressed in several tumor tissues compared to the matching non-tumor tissues. Increased NNMT expression was linked to reduced OS, DSS, and DFI. In addition, there was a link between NNMT expression and TMB and MSI in 18 cancer types, and between NNMT expression and DNA methylation in 23 cancer types. Further study of NNMT gene alteration data revealed that deletion was the most prevalent form of NNMT mutation, and that there was a significant negative association between NNMT expression and mismatch repair genes. In addition, there was a strong positive connection between NNMT and immune infiltration in 28 types of tumors, and the immune cells that infiltrated the tumors displayed a characteristic NNMT pattern. According to the enrichment study, cell migration, cell motility, and cell adhesion were highly enriched in biological processes, and NNMT may be associated with the PI3K-Akt signaling pathway. By downregulating gene methylation or impacting the immunological microenvironment widely, NNMT may drive carcinogenesis and cause a poor prognosis. Our research showed that NNMT could be used as a biomarker of tumor immune infiltration and poor prognosis, thus providing a unique strategy for cancer therapy.

8.
Biomaterials ; 290: 121821, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36201949

RESUMO

Hypoxia is a common feature within many types of solid tumors, which is closely associated with limited efficacy for tumor therapies. Moreover, the inability to reach hypoxic tumor cells that are distant from blood vessels results in tumor-targeting and penetrating drug delivery systems in urgent need. Here, glucose oxidase (GOX) and hypoxia-activated prodrug tirapazamine (TPZ) are loaded into photothermal conversion agent polydopamine (PDA) as the glucose/oxygen-exhausting nanoreactor named PGT. We further construct a tumor cell membrane-coated nanovesicle for the targeted delivery of PGT. This biomimetic nanovesicle exhibits significantly improved tumor-targeting and tumor-penetrating abilities. After internalization by the tumor cells, the loaded drug is quickly released in response to near-infrared (NIR) laser. The PGT nanoreactor can exhaust glucose and oxygen, and further enhance hypoxia within tumor, which efficiently inhibits hypoxic tumor by combining starvation therapy and hypoxia-activated chemotherapy. Mechanically, it is revealed that the nanoreactor significantly increases hypoxia level and downregulates the expression of hypoxia-inhibitory factor-1α (HIF-1α), thereby promoting T cell activation and macrophage polarization to remodel tumor immunosuppressive microenvironment. Therefore, this tumor microenvironment-regulable nanoreactor with sustainable and cascade targeted starvation-chemotherapy provides a novel insight into the treatment of hypoxic tumor.


Assuntos
Nanopartículas , Neoplasias , Humanos , Biomimética , Oxigênio/uso terapêutico , Microambiente Tumoral , Glucose , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Hipóxia , Membrana Celular/metabolismo , Nanotecnologia , Linhagem Celular Tumoral
9.
Biofouling ; 38(8): 747-763, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36224109

RESUMO

Biofouling is a problem affecting the operation of nanofiltration systems due to the complexity of the carbon matrix affecting bacteria and biofilm growth. This study used membrane fouling simulators to investigate the effects of five different carbon sources on the biofouling of nanofiltration membranes. For all the carbon sources analyzed, the increase in pressure drop was most accelerated for acetate. The use of acetate as the single carbon source produced less adenosine triphosphate but more extracellular polymers than glucose. The microbial community was analyzed using 16 s rRNA. The use of more than a single carbon source produced an increase in bacteria diversity even at similar concentrations. The relative abundance of proteobacteria was the highest at the phylum level (95%) when a single carbon source was added. Additionally, it was found that the use of different carbon sources produced a shift in the microbial community, affecting the biofouling and pressure drop on membranes.


Assuntos
Incrustação Biológica , Microbiota , Purificação da Água , Carbono , Membranas Artificiais , Biofilmes , Bactérias/genética , Acetatos
10.
Adv Healthc Mater ; 11(23): e2200955, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36123781

RESUMO

Osteosarcoma is a rare malignant bone-originating tumor that usually occurs in young people. Programmed cell death 1 ligand 1 (PD-L1), an immune checkpoint protein, is highly expressed in osteosarcoma tissues. Several recent studies have indicated that the tumor-related role of PD-L1 in tumors, especially non-plasma membrane (NPM)-localized PD-L1, is not limited to immune regulation in osteosarcoma. Here, mass spectrometry analysis is combined with RNA-seq examination to identify the intracellular binding partners of PD-L1 and elucidate the underlying mechanism of its action. It is found that the NPM-localized PD-L1 interacted with Insulin-like growth factor binding protein-3 (IGFBP3) to promote osteosarcoma tumor growth by activating mTOR signaling. This interaction is enforced after phosphoglyceratekinase1 (PGK1)-mediated PD-L1 phosphorylation. Based on these findings, a phosphorylation-mimicking peptide is designed from PD-L1 and it is encapsulated with a Cyclic RGD (cRGD)-modified red blood cell membrane (RBCM) vesicle (Peptide@cRGD-M). The Peptide@cRGD-M precisely delivers the PD-L1-derived phosphorylation-mimicking peptide into osteosarcoma lesions and significantly promotes its therapeutic effect on the tumor. Therefore, this investigation not only highlights the function of NPM-localized PD-L1, but also uses an engineering approach to synthesize a small molecular peptide capable of inhibiting osteosarcoma growth.


Assuntos
Antígeno B7-H1 , Osteossarcoma , Humanos , Biomimética , Osteossarcoma/tratamento farmacológico , Peptídeos
11.
J Control Release ; 351: 151-163, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36122895

RESUMO

Photodynamic therapy (PDT) can produce a large amount of reactive oxygen species (ROS) in the radiation field to kill tumor cells. However, the sustainable anti-tumor efficacy of PDT is limited due to the hypoxic microenvironment of tumor. In this study, classic PDT agent indocyanine green (ICG) and hypoxia-activated chemotherapeutic drug tirapazamine (TPZ) were loaded on mesoporous polydopamine (PDA) to construct PDA@ICG-TPZ nanoparticles (PIT). Then, PIT was camouflaged with cyclic arginine-glycine-aspartate (cRGD) modified tumor cell membranes to obtain the engineered membrane-coated nanoreactor (cRGD-mPIT). The nanoreactor cRGD-mPIT could achieve the dual-targeting ability via tumor cell membrane mediated homologous targeting and cRGD mediated active targeting. With the enhanced tumor-targeting and penetrating delivery system, PIT could efficiently accumulate in hypoxic tumor cells and the loaded drugs were quickly released in response to near-infrared (NIR) laser. The nanoreactor might produce cytotoxic ROS under NIR and further enhance hypoxia within tumor to activate TPZ, which efficiently inhibited hypoxic tumor by synergistic photodynamic-chemotherapy. Mechanically, hypoxia-inhibitory factor-1α (HIF-1α) was down-regulated by the synergistic therapy. Accordingly, the cRGD-mPIT nanoreactor with sustainable and cascade anti-tumor effects and satisfied biosafety might be a promising strategy in hypoxic tumor therapy.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Espécies Reativas de Oxigênio/metabolismo , Biomimética , Tirapazamina , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Verde de Indocianina/uso terapêutico , Hipóxia , Nanotecnologia , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes , Microambiente Tumoral
12.
Theranostics ; 12(13): 5877-5887, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966586

RESUMO

Rationale: Osteosarcoma (OS) is the most common primary bone tumor with a poor prognosis, but the detailed mechanism is still unclear. A comprehensive investigation of tumor microenvironment (TME) of OS might help find effective anti-tumor strategies. Single-cell transcriptomics is a powerful new tool to explore TME. Therefore, this study is designed to investigate the TME and gene expression pattern of primary and recurrent OS at the single-cell level. Methods: The single-cell RNA sequencing and bioinformatic analysis were conducted to investigate the cellular constitution of primary, recurrent, and lung metastatic OS lesions according to the datasets of GSE152048 and GSE162454. TIMER database was used to investigate the role of LOX in the prognosis of sarcoma. The functions of related cells and markers were further confirmed by in vitro and in vivo experiments. Results: Cancer associated fibroblasts (CAFs) were found with a higher infiltrating level in recurrent OS, and were enriched in the epithelial-mesenchymal transition (EMT) pathway. CAFs showed remarkably increased expression of LOX, which might lead to EMT and poor prognosis of OS. Mechanically, LOX regulated the function of CAFs and macrophage polarization to remodel the tumor immune microenvironment. Moreover, LOX inhibitor could inhibit migration and promote apoptosis of OS both in vitro and in vivo. Conclusions: This study revealed the heterogeneity of recurrent OS and highlighted an innovative mechanism that CAFs regulate EMT of OS via LOX. Targeting LOX of CAFs showed promising efficacy in remodeling TME and treating recurrent OS.


Assuntos
Neoplasias Ósseas , Fibroblastos Associados a Câncer , Osteossarcoma , Neoplasias Ósseas/patologia , Fibroblastos Associados a Câncer/metabolismo , Humanos , Recidiva Local de Neoplasia/metabolismo , Osteossarcoma/patologia , Transcriptoma , Microambiente Tumoral
13.
BMC Musculoskelet Disord ; 23(1): 295, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35346154

RESUMO

PURPOSE: To assess the preoperative planning of visualized simulative surgery (VSS) and clinical outcomes based on computer-aided design (CAD) and 3D reconstruction for proximal femoral varus osteotomy of DDH. METHODS: A total of 31 consecutive patients (23 females and 8 males) with DDH who underwent proximal femoral varus osteotomy were retrospectively reviewed between June 2014 and July 2018. Patients were divided into conventional group (n = 15) and VSS group (n = 16) according to different surgical methods. In VSS group, 16 consecutive patients who underwent proximal femoral varus osteotomy were evaluated preoperatively with the aid of VSS. The VSS steps included morphological evaluation of DDH, simulated reconstruction of proximal femoral varus osteotomy, and the implantation of locking compression pediatric hip plate (LCP-PHP). Meanwhile, the osteotomy degrees, surgery time, and radiation exposure were compared between the two groups. RESULTS: The average follow-up time was 33.5 months (range, 24 to 46 months). The varus angle for proximal femoral varus osteotomy was 24.2 ± 1.1° in VSS group and 25.1 ± 1.0° in conventional group (P = 0.4974). The surgery time was 31.0 ± 4.5 mins in VSS group and 48.2 ± 7.3 mins in conventional group, while radiography was 5.0 ± 1.5 times in VSS group and 8.3 ± 2.4 times in conventional group. There was a statistical significance in surgery time and radiography (P <  0.0001) when compared with the conventional group. CONCLUSION: The VSS can greatly decrease surgery time and radiation exposure for proximal femoral varus osteotomy, which could also be a tool to train young doctors to improve surgical skills and academic communication.


Assuntos
Fêmur , Osteotomia , Criança , Simulação por Computador , Feminino , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Humanos , Masculino , Osteotomia/métodos , Radiografia , Estudos Retrospectivos
14.
Mol Ther Nucleic Acids ; 27: 947-955, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35211355

RESUMO

N6-methyladenosine (m6A), as the most common RNA modification, plays a vital role in the development of cancers. Circular RNAs (circRNAs) are a class of single-stranded covalently closed RNA molecules. Recently, m6A modification has been identified as performing biological functions for regulating circRNAs. Increasing evidence also shows that circRNAs are involved in cancer progression by targeting m6A regulators. In this review, we describe the functional crosstalk between m6A and circRNAs, and illustrate their roles in cancer development. m6A methylation mediates the biogenesis, stability, and cytoplasmic export of circRNAs in different cancer types. Moreover, circRNAs regulate the expression of m6A regulators, participate in the degradation of m6A regulators, and regulate the m6A modification of target mRNAs. Finally, we discuss the potential applications and future research directions of m6A modification and circRNAs in cancer. Further understanding of the biological roles of m6A and circRNAs will provide new insight into the diagnosis and treatment of cancer patients.

15.
J Control Release ; 343: 107-117, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35077741

RESUMO

Exosomes as nanosized membrane vesicles, could targeted deliver therapeutic agents by modification with target ligands. Exosome-derived non-coding RNAs play a vital role in the development of tumors. Previous evidences reveal that long non-coding RNA maternally expressed gene 3 (lncRNA MEG3) has anti-tumor properties. Whereas, the inhibitory effects of exosome-derived lncRNA MEG3 in osteosarcoma (OS) remain largely unknown. In this study, we utilize the engineering technology to combine exosome and lncRNA for tumor-targeting therapy of OS. We elucidated the anti-OS effects of lncRNA MEG3, and then prepared the c(RGDyK)-modified and MEG3-loaded exosomes (cRGD-Exo-MEG3). The engineered exosomes cRGD-Exo-MEG3 could deliver more efficiently to OS cells both in vitro and in vivo. In this way, cRGD-Exo-MEG3 facilitate the anti-OS effects of MEG3 significantly, with the help of enhanced tumor-targeting therapy. This study elucidates that engineered exosomes as targeted lncRNA MEG3 delivery vehicles have potentially therapeutic effects for OS.


Assuntos
Neoplasias Ósseas , Exossomos , Osteossarcoma , RNA Longo não Codificante , Neoplasias Ósseas/genética , Neoplasias Ósseas/terapia , Exossomos/genética , Exossomos/patologia , Humanos , Osteossarcoma/genética , Osteossarcoma/terapia , RNA Longo não Codificante/genética
16.
Biomater Transl ; 3(3): 201-212, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36654778

RESUMO

Microorganisms with innate and artificial advantages have been regarded as intelligent drug delivery systems for cancer therapy with the help of engineering technology. Although numerous studies have confirmed the promising prospects of microorganisms in cancer, several problems such as immunogenicity and toxicity should be addressed before further clinical applications. This review aims to investigate the development of engineered microorganism-based delivery systems for targeted cancer therapy. The main types of microorganisms such as bacteria, viruses, fungi, microalgae, and their components and characteristics are introduced in detail. Moreover, the engineering strategies and biomaterials design of microorganisms are further discussed. Most importantly, we discuss the innovative attempts and therapeutic effects of engineered microorganisms in cancer. Taken together, engineered microorganism-based delivery systems hold tremendous promise for biomedical applications in targeted cancer therapy.

17.
Front Cell Dev Biol ; 9: 737314, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712664

RESUMO

Osteosarcoma is the most common bone tumor affecting both adolescents and children. Although localized osteosarcoma has an overall survival of >70% in the clinic, metastatic, refractory, and recurrent osteosarcoma have poorer survival rates. Exosomes are extracellular vesicles released by cells and originally thought to be a way for cells to discard unwanted products. Currently, exosomes have been reported to be involved in intercellular cross-talk and induce changes in cellular behavior by transferring cargoes (proteins, DNA, RNA, and lipids) between cells. Exosomes regulate osteosarcoma progression, and processes such as tumorigenesis, proliferation, metastasis, angiogenesis, immune evasion, and drug resistance. Increasing evidences shows that exosomes have significant potential in promoting osteosarcoma progression and development. In this review, we describe the current research status of exosomes in osteosarcoma, focusing on the biological functions of osteosarcoma exosomes as well as their application in osteosarcoma as diagnostic biomarkers and therapeutic targets.

18.
Pest Manag Sci ; 76(2): 758-768, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31392798

RESUMO

BACKGROUND: Metarhizium acridum, is a specific acridid pathogen developed for use against the migratory locust (Locusta migratoria manilensis). Adenylate-forming reductases (AFRs) include enzymes that are involved in natural product biosynthesis. Here, we genetically characterize the functions of a class IV AFR in M. acridum (MaAfrIV ) on fungal development and virulence. RESULTS: Gene expression analyses indicated MaAfrIV was induced on locust wings early during the infection process. Surprisingly, loss of MaAfrIV increased virulence (25.20% decrease in the median lethal time) against the locust in topical bioassays but was no different than the wild type when the cuticle was bypassed by direct infection of conidia into the insect hemocoel. Virulence markers including protease (Pr1) expression and appressorial turgor pressure were higher in the mutant than the parent strain. No difference was seen in the expression of host immune genes (Toll pathway) or in polyphenol oxidase (PPO) activity in locusts infected by the ΔMaAfrIV or wild type strains. However, the ΔMaAfrIV strain was unable to successfully sporulate on dead cadavers. CONCLUSION: Disruption of MaAfrIV increased fungal virulence by promoting insect cuticle invasion without altering host immune response or fungal immune evasion. Although loss of MaAfrIV conferred an apparent benefit to the fungus in terms of enhanced virulence, a significant trade-off was seen in the inability of the fungus to sporulate on the cadaver. As conidiation on the cadaver is essential for subsequent propagation in the environment, loss of MaAfrIV can reduce the engineering strains survivability in the field and improve the safety. © 2019 Society of Chemical Industry.


Assuntos
Metarhizium , Animais , Locusta migratoria , Oxirredutases , Esporos Fúngicos , Virulência
19.
BMC Genomics ; 20(1): 1032, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31888472

RESUMO

BACKGROUND: MYC transcriptional factors are members of the bHLH (basic helix-loop-helix) superfamily, and play important roles in plant growth and development. Recent studies have revealed that some MYCs are involved in the crosstalk between Jasmonic acid regulatory pathway and light signaling in Arabidopsis, but such kinds of studies are rare in wheat, especially in photo-thermo-sensitive genic male sterile (PTGMS) wheat line. RESULTS: 27 non-redundant MYC gene copies, which belonged to 11 TaMYC genes, were identified in the whole genome of wheat (Chinese Spring). These gene copies were distributed on 13 different chromosomes, respectively. Based on the results of phylogenetic analysis, 27 TaMYC gene copies were clustered into group I, group III, and group IV. The identified TaMYC genes copies contained different numbers of light, stress, and hormone-responsive regulatory elements in their 1500 base pair promoter regions. Besides, we found that TaMYC3 was expressed highly in stem, TaMYC5 and TaMYC9 were expressed specially in glume, and the rest of TaMYC genes were expressed in all tissues (root, stem, leaf, pistil, stamen, and glume) of the PTGMS line BS366. Moreover, we found that TaMYC3, TaMYC7, TaMYC9, and TaMYC10 were highly sensitive to methyl jasmonate (MeJA), and other TaMYC genes responded at different levels. Furthermore, we confirmed the expression profiles of TaMYC family members under different light quality and plant hormone stimuli, and abiotic stresses. Finally, we predicted the wheat microRNAs that could interact with TaMYC family members, and built up a network to show their integrative relationships. CONCLUSIONS: This study analyzed the size and composition of the MYC gene family in wheat, and investigated stress-responsive and light quality induced expression profiles of each TaMYC gene in the PTGMS wheat line BS366. In conclusion, we obtained lots of important information of TaMYC family, and the results of this study was supposed to contribute novel insights and gene and microRNA resources for wheat breeding, especially for the improvement of PTGMS wheat lines.


Assuntos
Genes myc , Genoma de Planta , Genômica , Família Multigênica , Triticum/genética , Alelos , Mapeamento Cromossômico , Regulação da Expressão Gênica de Plantas , Genômica/métodos , Especificidade de Órgãos , Filogenia , Proteínas de Plantas/genética , Sequências Reguladoras de Ácido Nucleico , Estresse Fisiológico/genética , Triticum/classificação
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