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1.
Acta Biomater ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35032718

RESUMO

Given that there is lack of effective therapies for castration-resistant prostate cancer (CRPC), the combination of photothermal (PTT), photodynamic (PDT), and chemical therapy (CT) has emerged as a prominent strategy. Tumor-targeted delivery and controlled release of antitumor drug are key-elements of any combined therapy. Considering these important elements, we designed and constructed tumor microenvironment (TME)-activated nanoprobes (PGP/CaCO3@IR820/DTX-HA). The CaCO3 shell could efficiently entrap the photosensitizer IR820 and the chemotherapeutic docetaxel (DTX) on the surface of pentagonal gold prisms (PGPs) to prevent elimination from the circulation, and it could act as a TME-trigger to achieve TME-responsive drug release. After modification with hyaluronic acid, PGP/CaCO3@IR820/DTX-HA was capable of synergistic TME-triggered PTT/PDT/CT and tumor-targeted delivery. Our in vitro and in vivo studies demonstrate that PGP/CaCO3@IR820/DTX-HA could achieve synergistic antitumor effects following near-infrared (NIR)-light irradiation. In addition, using the NIR fluorescence signal from IR820 and the photoacoustic (PA) signal from PGPs, i.e., through multimodal fluorescence/photoacoustic imaging, we could monitor the in vivo distribution and excretion of PGP/CaCO3@IR820/DTX-HA. Therefore, it can be concluded that PGP/CaCO3@IR820/DTX-HA shows promising clinical translational potential as a treatment for CRPC. STATEMENT OF SIGNIFICANCE: Utilizing pentagonal gold prisms (PGPs), we constructed a multifunctional nanoplatform (PGP/CaCO3@IR820/DTX-HA) for effectively delivering agents into the tumor microenvironment (TME) for the diagnosis and therapy of castration-resistant prostate cancer (CRPC). The synthetic nanoplatform can satisfy TME-activated synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/chemical therapy (CT) and NIR fluorescence imaging/photoacoustic (PA) imaging. Hyaluronic acid (HA) on the surface of nanoplatform allowed the specific tumor-targeting capacity and biocompatibility. In conclusion, PGP/CaCO3@IR820/DTX-HA could be a promising integrated nanoplatform for CRPC diagnosis and treatment.

2.
Mol Phylogenet Evol ; 166: 107330, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34687844

RESUMO

Catalpa Scop. (Bignoniaceae) is a small genus (8 spp.) of trees that is disjunctly distributed among eastern Asia, eastern United States, and the West Indies. Catalpa bears beautiful inflorescences and have been cultivated as important ornamental trees for landscaping, gardening, and timber. However, the phylogenetic relationships and biogeographic history of the genus have remained unresolved. In this study, we used a large genomic dataset that includes data from the chloroplast (plastomes), and nuclear genomes (ITS and 5,759 single-copy nuclear genes) to reconstruct phylogenetic relationship within Catalpa, test interspecific gene flow events within the genus, and infer its biogeographic history. Our phylogenetic results indicate that Catalpa is monophyletic containing two main clades, section Catalpa and section Macrocatalpa. Section Catalpa is further divided into three subclades. While most relationships are congruent between the chloroplast and nuclear datasets, the position of C. ovata differs, likely due to incomplete lineage sorting. Interspecific gene flow events include C. bungei s.s. with vectors of inheritance from C. duclouxii and C. fargesii, supporting a combination of these three species and recognizing a broadly circumscribed C. bungei s.l. Our biogeographic study suggests three main dispersal events, two of which occurred during the Oligocene. The first dispersal event occurred from southwestern North America and Mexico into the Greater Antilles giving rise to the ancestor of the section of Macrocatalpa. The second dispersal event also occurred from southwestern North America and Mexico, but led to central and northern North America, subsequently reaching China through the Bering land bridge, and also reaching Europe through the North Atlantic land bridge. The third dispersal event took place in the Miocene from China to North America and gave rise to a clade composed of C. bignonioides and C. speciosa. This study uses a phylogenomic approach and biogeographical methods to infer the evolutionary history of Catalpa, highlighting issues associated with gene tree discordance, and suggesting that incomplete lineage sorting likely played an important role in the evolutionary history of Catalpa.

3.
Adv Healthc Mater ; : e2102439, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34859964

RESUMO

The boosting exploitation of graphene oxide (GO) increases exposure risk to human beings. However, as primary defender in the first immune line, neutrophils' mechanism of defensive behavior toward GO remains unclear. Herein, we discovered that neutrophils recognize and defensively degrade GO in a lateral dimension dependent manner. The micrometer-sized GO (mGO) induces NETosis by releasing neutrophil extracellular traps (NETs), while nanometer-sized GO (nGO) elicits neutrophil degranulation. The two neutrophils' defensive behaviors are accompanied with generation of reactive oxygen species and activation of p-ERK and p-Akt kinases. However, mGO-induced NETosis is NADPH oxidase (NOX)-independent while nGO-triggered degranulation is NOX-dependent. Furthermore, myeloperoxidase (MPO) is determinant mediator despite distinct neutrophil phenotypes. Neutrophils release NETs comprising of MPO upon activated with mGO, while MPO is secreted via nGO-induced degranulation. Moreover, the binding energy between MPO and GO is calculated to be 69.8728 kJ mol-1 , indicating that electrostatic interactions mainly cause the spontaneous binding process. Meanwhile, the central enzymatic biodegradation occurs at oxygenic active sites and defects on GO. Mass spectrometry analysis deciphers the degradation products are biocompatible molecules like flavonoids and polyphenols. This study provides fundamental evidence and practical guidance for nanotechnology based on GO, including vaccine adjuvant, implantable devices, and energy storage.

4.
Cell Prolif ; : e13145, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34668606

RESUMO

OBJECTIVES: Success in pregnancy in mammals predominantly depends on a well-developed placenta. The differentiation of invasive trophoblasts is a fundamental process of placentation, the abnormalities of which are tightly associated with pregnancy disorders including preeclampsia (PE). Monoclonal nonspecific suppressor factor beta (MNSFß) is an immunosuppressive factor. Its conventional knockout in mice induced embryonic lethality, whereas the underlying mechanism of MNSFß in regulating placentation and pregnancy maintenance remains to be elucidated. METHODS: Trophoblast-specific knockout of MNSFß was generated using Cyp19-Cre mice. In situ hybridization (ISH), haematoxylin and eosin (HE), immunohistochemistry (IHC) and immunofluorescence (IF) were performed to examine the distribution of MNSFß and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) at the foeto-maternal interface. The interaction and expression of MNSFß, IGF2BP2 and invasion-related molecules were detected by immunoprecipitation (IP), immunoblotting and quantitative real-time polymerase chain reaction (qRT-PCR). The cell invasion ability was measured by the Transwell insert assay. RESULTS: We found that deficiency of MNSFß in trophoblasts led to embryonic growth retardation by mid-gestation and subsequent foetal loss, primarily shown as apparently limited trophoblast invasion. In vitro experiments in human trophoblasts demonstrated that the conjugation of MNSFß with IGF2BP2 and thus the stabilization of IGF2BP2 essentially mediated the invasion-promoting effect of MNSFß. In the placentas from MNSFß-deficient mice and severe preeclamptic (PE) patients, downregulation of MNSFß was evidently associated with the repressed IGF2BP2 expression. CONCLUSIONS: The findings reveal the crucial role of MNSFß in governing the trophoblast invasion and therefore foetal development, and add novel hints to reveal the placental pathology of PE.

5.
Nanoscale ; 13(37): 15569-15575, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34519326

RESUMO

Near-infrared two-zone (NIR-II) fluorescence imaging has attracted attention as a non-invasive imaging technology that provides centimeter-level depth and micron-level resolution. However, producing a NIR-II fluorescent nanoprobe with uniform size, high bio-identical capacity, and fluorescence intensity, while being metabolizable in vivo, remains a challenge. We first produce a hydrophobic NIR-II fluorescent molecule with AIE properties, and subject it to ultrasonic and extrusion treatments to generate a DSPE-PEG-encapsulated NIR-II nanoprobe with an ultra-homogeneous particle size. The current study based on in vitro and mouse tumor-bearing model-based experiments indicate that cancer cells could efficiently take up this nanoprobe, which aggregates in tumor tissues, is susceptible to metabolization, and enables ideal photothermal therapeutic effects. Thus, this NIR-II nanoprobe with AIE properties shows great potential for precise clinical diagnosis and treatment of cancer.


Assuntos
Terapia Fototérmica , Neoplasias da Próstata , Animais , Corantes , Fluorescência , Corantes Fluorescentes , Humanos , Masculino , Camundongos , Imagem Óptica , Tamanho da Partícula , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia
6.
Ecol Evol ; 11(17): 11627-11638, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34522329

RESUMO

DNA barcoding has become one of the most important techniques in plant species identification. Successful application of this technology is dependent on the availability of reference database of high species coverage. Unfortunately, there are experimental and data processing challenges to construct such a library within a short time. Here, we present our solutions to these challenges. We sequenced six conventional DNA barcode fragments (ITS1, ITS2, matK1, matK2, rbcL1, and rbcL2) of 380 flowering plants on next-generation sequencing (NGS) platforms (Illumina Hiseq 2500 and Ion Torrent S5) and the Sanger sequencing platform. After comparing the sequencing depths, read lengths, base qualities, and base accuracies, we conclude that Illumina Hiseq2500 PE250 run is suitable for conventional DNA barcoding. We developed a new "Cotu" method to create consensus sequences from NGS reads for longer output sequences and more reliable bases than the other three methods. Step-by-step instructions to our method are provided. By using high-throughput machines (PCR and NGS), labeling PCR, and the Cotu method, it is possible to significantly reduce the cost and labor investments for DNA barcoding. A regional or even global DNA barcoding reference library with high species coverage is likely to be constructed in a few years.

7.
Biosens Bioelectron ; 194: 113594, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34474280

RESUMO

Gastric cancer cell-derived exosomes as biomarkers have a very high application potential to the non-invasive detection of early-stage gastric cancer. However, the small size of exosomes (30-150 nm) results in huge challenges in separating and detecting them from complex media (e.g., plasma, urine, saliva, and cell culture supernatant). Here we proposed a highly integrated exosome separation and detection (ExoSD) chip to immunomagnetic separate exosomes from cell culture supernatant in a manner of continuous flow, and to immunofluorescence detect gastric cancer cell-derived exosomes with high sensitivity. The ExoSD chip has achieved a high exosome recovery (>80%) and purity (>83%) at the injection rate of 4.8 mL/h. Furthermore, experimental results based on clinical serum samples of patients with gastric cancer (stages I and II) show that the detection rate of the ExoSD chip is as high as 70%. The proposed ExoSD chip has been successfully demonstrated as a cutting-edge platform for exosomes separation and detection. It can be served as a versatile platform to extend to the applications of separation and detection of the other cell-derived exosomes or cells.


Assuntos
Técnicas Biossensoriais , Exossomos , Neoplasias Gástricas , Detecção Precoce de Câncer , Humanos , Separação Imunomagnética , Neoplasias Gástricas/diagnóstico
8.
Cancer Biol Med ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34427999

RESUMO

OBJECTIVE: Although great progress has been made in the field of siRNA gene therapy, safe, efficient, and targeted delivery of siRNA are still major challenges in siRNA therapeutics. METHODS: We developed an up-conversion nanoparticle-based nanocage system. This system protected the siRNA from being degraded by nucleases in organisms and selectively delivered the siRNAs to the tumor sites, due to modifications of targeted molecules on the surfaces of nanocages and local inhalation. RESULTS: The siRNAs delivered by the up-conversion nanoparticle nanocages were protected from degradation in transit to the tumor sites, where they accumulated. Compared with the passive target and control groups, the up-conversion nanoparticles based on the nanocage system showed a tumor suppressive effect after approximately 3 weeks of treatment. CONCLUSIONS: The up-conversion nanoparticle nanocages efficiently delivered vascular endothelial growth factor siRNAs to tumor sites. Mice with lung tumors treated with tumors targeting up-conversion nanoparticle nanocages showed steady body weight changes, high tumor inhibition ratios, and longer survival times.

9.
Research (Wash D C) ; 2021: 9873545, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34327332

RESUMO

Central nervous system diseases commonly occur with the destruction of the blood-brain barrier. As a primary cause of morbidity and mortality, stroke remains unpredictable and lacks cellular biomarkers that accurately quantify its occurrence and development. Here, we identify NeuN+/CD45-/DAPI+ phenotype nonblood cells in the peripheral blood of mice subjected to middle cerebral artery occlusion (MCAO) and stroke patients. Since NeuN is a specific marker of neural cells, we term these newly identified cells as circulating neural cells (CNCs). We find that the enumeration of CNCs in the blood is significantly associated with the severity of brain damage in MCAO mice (p < 0.05). Meanwhile, the number of CNCs is significantly higher in stroke patients than in negative subjects (p < 0.0001). These findings suggest that the amount of CNCs in circulation may serve as a clinical indicator for the real-time prognosis and progression monitor of the occurrence and development of ischemic stroke and other nervous system disease.

10.
BMC Genomics ; 22(1): 434, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34107868

RESUMO

BACKGROUND: Crape myrtles, belonging to the genus Lagerstroemia L., have beautiful paniculate inflorescences and are cultivated as important ornamental tree species for landscaping and gardening. However, the phylogenetic relationships within Lagerstroemia have remained unresolved likely caused by limited sampling and the insufficient number of informative sites used in previous studies. RESULTS: In this study, we sequenced 20 Lagerstroemia chloroplast genomes and combined with 15 existing chloroplast genomes from the genus to investigate the phylogenetic relationships and divergence times within Lagerstroemia. The phylogenetic results indicated that this genus is a monophyletic group containing four clades. Our dating analysis suggested that Lagerstroemia originated in the late Paleocene (~ 60 Ma) and started to diversify in the middle Miocene. The diversification of most species occurred during the Pleistocene. Four variable loci, trnD-trnY-trnE, rrn16-trnI, ndhF-rpl32-trnL and ycf1, were discovered in the Lagerstroemia chloroplast genomes. CONCLUSIONS: The chloroplast genome information was successfully utilized for molecular characterization of diverse crape myrtle samples. Our results are valuable for the global genetic diversity assessment, conservation and utilization of Lagerstroemia.


Assuntos
Genoma de Cloroplastos , Lagerstroemia , Lythraceae , Cloroplastos/genética , Lagerstroemia/genética , Lythraceae/genética , Filogenia
11.
Forensic Sci Int ; 324: 110828, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34000616

RESUMO

There are criminal cases that no frequently used evidence, for example, human DNAs from the criminal, is available. Such cases usually are unresolvable. With the advent of DNA metabarcoding, evidences are mined from environmental DNA and such cases become resolvable. This study reports how a criminal suspect was determined by environmental plant DNA metabarcoding technology. A girl was killed in a rural wet area in China without a witness or video record. Pants with dried mud was found from one of her classmate's house. The mud was removed from the pants and 11 more mud or soil samples surrounding murder scene were collected. DNA was extracted from the soil. Chloroplast rbcL gene were amplified and sequenced on a next generation sequencing platform. After bioinformatics analysis, ZOTU composition of 12 samples demonstrated that the mud on the suspect's pants was from the criminal scene. The suspect finally made a clean breast of his crime. This case implies that plant DNA in the environment soil is a new source of evidence in determination of suspects using DNA metabarcoding technology and has high potentials of extensive applications in criminal cases.


Assuntos
Código de Barras de DNA Taxonômico , DNA de Plantas/genética , Genética Forense/métodos , Solo/química , Cloroplastos/genética , Criminosos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Homicídio , Humanos , Ribulose-Bifosfato Carboxilase/genética
12.
BMC Genomics ; 22(1): 293, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888057

RESUMO

BACKGROUND: Most Distylium species are endangered. Distylium species mostly display homoplasy in their flowers and fruits, and are classified primarily based on leaf morphology. However, leaf size, shape, and serration vary tremendously making it difficult to use those characters to identify most species and a significant challenge to address the taxonomy of Distylium. To infer robust relationships and develop variable markers to identify Distylium species, we sequenced most of the Distylium species chloroplast genomes. RESULTS: The Distylium chloroplast genome size was 159,041-159,127 bp and encoded 80 protein-coding, 30 transfer RNAs, and 4 ribosomal RNA genes. There was a conserved gene order and a typical quadripartite structure. Phylogenomic analysis based on whole chloroplast genome sequences yielded a highly resolved phylogenetic tree and formed a monophyletic group containing four Distylium clades. A dating analysis suggested that Distylium originated in the Oligocene (34.39 Ma) and diversified within approximately 1 Ma. The evidence shows that Distylium is a rapidly radiating group. Four highly variable markers, matK-trnK, ndhC-trnV, ycf1, and trnT-trnL, and 74 polymorphic simple sequence repeats were discovered in the Distylium plastomes. CONCLUSIONS: The plastome sequences had sufficient polymorphic information to resolve phylogenetic relationships and identify Distylium species accurately.


Assuntos
Genoma de Cloroplastos , Hamamelidaceae , Cloroplastos/genética , Evolução Molecular , Filogenia
13.
Nanoscale ; 13(10): 5383-5399, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33666213

RESUMO

Early diagnosis of tumors is crucial in selecting appropriate treatment options to achieve the desired therapeutic effect, but it is difficult to accurately diagnose cancer by a single imaging modality due to technical constraints. Therefore, we synthesized a type of Fe3O4 nanoparticle with manganese dioxide grown on the surface and then prepared it by loading photosensitive drugs and traditional Chinese medicine monomers to create an integrated diagnosis/treatment multifunctional nanoplatform: Fe3O4@MnO2-celastrol (CSL)/Ce6. This nanoplatform can have full advantage of the tumor microenvironment (TME) characteristics of hypoxia (hypoxia), acidic pH (acidosis), and increased levels of reactive oxygen species (e.g., H2O2), even outside the TME. Specific imaging and drug release can also enhance tumor therapy by adjusting the hypoxic state of the TME to achieve the combined effect of chemotherapy (CT) and photodynamic therapy (PDT). Moreover, the obtained Fe3O4@MnO2-CSL/Ce6 has H2O2- and pH-sensitive biodegradation and can release the anticancer drug celastrol (CSL) and photosensitizer Ce6 in TME and simultaneously generate O2 and Mn2+. Therefore, the "dual response" synergistic strategy also confers specific drug release on nanomaterials, relieves tumor hypoxia and antioxidant capacity, and achieves significant optimization of CT and PDT. Furthermore, the resulting Mn2+ ions and Fe3O4 nanoparticles can be used for T1/T2 magnetic resonance imaging on tumor-bearing mice, and the released Ce6 can simultaneously provide fluorescence imaging functions. Therefore, Fe3O4@MnO2-CSL/Ce6 realized the synergistic treatment of PDT and CT under multimodal near-infrared fluorescence/photoacoustic (photoacoustic) imaging monitoring, showing its great potential in the accurate medical treatment of tumors.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Porfirinas , Animais , Linhagem Celular Tumoral , Peróxido de Hidrogênio/uso terapêutico , Ferro/uso terapêutico , Manganês , Compostos de Manganês , Camundongos , Imagem Multimodal , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Óxidos/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Microambiente Tumoral
14.
Cell J ; 23(1): 75-84, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33650823

RESUMO

Objective: We aimed to identify the differentially expressed proteins (DEPs) and functional differences between exosomes derived from mesenchymal stem cells (MSCs) derived from umbilical cord (UC) or adipose tissue (AD). Materials and Methods: In this experimental study, the UC and AD were isolated from healthy volunteers. Then, exosomes from UC-MSCs and AD-MSCs were isolated and characterized. Next, the protein compositions of the exosomes were examined via liquid chromatography tandem mass spectrometry (LC-MS/MS), followed by evaluation of the DEPs between UC-MSC and AD-MSC-derived exosomes. Finally, functional enrichment analysis was performed. Results: One hundred and ninety-eight key DEPs were identified, among which, albumin (ALB), alpha-II-spectrin (SPTAN1), and Ras-related C3 botulinum toxin substrate 2 (RAC2) were the three hub proteins present at the highest levels in the protein-protein interaction network that was generated based on the shared DEPs. The DEPs were mainly enriched in gene ontology (GO) items associated with immunity, complement activation, and protein activation cascade regulation corresponding to 24 pathways, of which complement and coagulation cascades as well as platelet activation pathways were the most significant. Conclusion: The different functions of AD- and UC-MSC exosomes in clinical applications may be related to the differences in their immunomodulatory activities.

15.
Appl Opt ; 60(7): 1916-1923, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33690281

RESUMO

Multi-wavelength radiometric thermometry has a wide application prospect in many fields. However, due to unknown emissivity, the data processing algorithm remains a difficult problem. The Broyden-Fletcher-Goldfarb-Shanno (BFGS) algorithm is proposed to inverse true temperature and spectral emissivity without assuming the emissivity model. The BFGS algorithm can automatically identify the emissivity models of different trends. These simulation results show that given different initial emissivity has no significant influence on the inverse temperature and emissivity. Then, we select 0.5 as the initial emissivity and carry out the simulation experiments at 800 and 900 K, respectively. The maximum absolute error of temperature is less than 3.5 K and the computation time is less than 0.2 s. Thus, the algorithm has high precision and efficiency. Finally, the verification experiment indicates that the BFGS algorithm is effective and reliable. The proposed method can be applied to real-time temperature measurement in many industrial processes.

16.
BMC Genomics ; 22(1): 103, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541261

RESUMO

BACKGROUND: Atractylodes DC is the basic original plant of the widely used herbal medicines "Baizhu" and "Cangzhu" and an endemic genus in East Asia. Species within the genus have minor morphological differences, and the universal DNA barcodes cannot clearly distinguish the systemic relationship or identify the species of the genus. In order to solve these question, we sequenced the chloroplast genomes of all species of Atractylodes using high-throughput sequencing. RESULTS: The results indicate that the chloroplast genome of Atractylodes has a typical quadripartite structure and ranges from 152,294 bp (A. carlinoides) to 153,261 bp (A. macrocephala) in size. The genome of all species contains 113 genes, including 79 protein-coding genes, 30 transfer RNA genes and four ribosomal RNA genes. Four hotspots, rpl22-rps19-rpl2, psbM-trnD, trnR-trnT(GGU), and trnT(UGU)-trnL, and a total of 42-47 simple sequence repeats (SSR) were identified as the most promising potentially variable makers for species delimitation and population genetic studies. Phylogenetic analyses of the whole chloroplast genomes indicate that Atractylodes is a clade within the tribe Cynareae; Atractylodes species form a monophyly that clearly reflects the relationship within the genus. CONCLUSIONS: Our study included investigations of the sequences and structural genomic variations, phylogenetics and mutation dynamics of Atractylodes chloroplast genomes and will facilitate future studies in population genetics, taxonomy and species identification.


Assuntos
Atractylodes , Genoma de Cloroplastos , Atractylodes/genética , Cloroplastos , Repetições de Microssatélites , Filogenia
17.
J Nanobiotechnology ; 19(1): 54, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627152

RESUMO

BACKGROUND: Gene and chemical therapy has become one of the rising stars in the field of molecular medicine during the last two decades. However, there are still numerous challenges in the development of efficient, targeted, and safe delivery systems that can avoid siRNA degradation and reduce the toxicity and adverse effects of chemotherapy medicine. RESULTS: In this paper, a highly efficient AS1411 aptamer modified, dsDNA and MMP-2 cleavable peptide-fabricated gold nanocage vehicle, which could load doxorubicin hydrochloride (DOX) and siRNAs to achieve a combination of tumor responsive genetic therapy, chemotherapy, and photothermal treatment is presented. Our results show that this combined treatment achieved targeted gene silencing and tumor inhibition. After nearly one month of treatment with DOX-loaded Au-siRNA-PAA-AS1411 nanoparticles with one dose every three days in mice, a synergistic effect promoting the eradication of long-lived tumors was observed along with an increased survival rate of mice. The combined genetic, chemotherapeutic, and photothermal treatment group exhibited more than 90% tumor inhibition ratio (tumor signal) and a ~ 67% survival rate compared with a 30% tumor inhibition ratio and a 0% survival rate in the passive genetic treatment group. CONCLUSIONS: The development of nanocarriers with double-stranded DNA and MMP-2 cleavable peptides provides a new strategy for the combined delivery of gene and chemotherapy medicine. Au-siRNA-PAA-AS1411 exerts high anticancer activities on lung cancer, indicating immense potentials for clinical application.


Assuntos
Técnicas de Transferência de Genes , Ouro/química , Ouro/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas Metálicas/química , RNA Interferente Pequeno/farmacologia , Animais , Aptâmeros de Nucleotídeos , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Portadores de Fármacos , Sistemas de Liberação de Medicamentos/métodos , Pulmão , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Oligodesoxirribonucleotídeos , Tamanho da Partícula , Taxa de Sobrevida
18.
Asian J Androl ; 23(6): 562-571, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33533735

RESUMO

Repairing DNA double-strand breaks (DSBs) with homologous chromosomes as templates is the hallmark of meiosis. The critical outcome of meiotic homologous recombination is crossovers, which ensure faithful chromosome segregation and promote genetic diversity of progenies. Crossover patterns are tightly controlled and exhibit three characteristics: obligatory crossover, crossover interference, and crossover homeostasis. Aberrant crossover patterns are the leading cause of infertility, miscarriage, and congenital disease. Crossover recombination occurs in the context of meiotic chromosomes, and it is tightly integrated with and regulated by meiotic chromosome structure both locally and globally. Meiotic chromosomes are organized in a loop-axis architecture. Diverse evidence shows that chromosome axis length determines crossover frequency. Interestingly, short chromosomes show different crossover patterns compared to long chromosomes. A high frequency of human embryos are aneuploid, primarily derived from female meiosis errors. Dramatically increased aneuploidy in older women is the well-known "maternal age effect." However, a high frequency of aneuploidy also occurs in young women, derived from crossover maturation inefficiency in human females. In addition, frequency of human aneuploidy also shows other age-dependent alterations. Here, current advances in the understanding of these issues are reviewed, regulation of crossover patterns by meiotic chromosomes are discussed, and issues that remain to be investigated are suggested.

19.
Biol Reprod ; 104(2): 418-429, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33074310

RESUMO

MicroRNA (miR)-210 is a well-known hypoxia-inducible small RNA. Increasing in vitro evidence demonstrates its involvement in regulating multiple behaviors of placental trophoblasts. However, direct in vivo evidence remains lacking. In the present study, we generated a miR-210-deficient mouse strain using CRISPR/Cas9 technology, in which miR-210 expression was markedly deficient in various tissues. Little influence on fertility rate and litter size was observed after the deletion of miR-210 in mice. Continuous exposure of pregnant mice to hypoxia (10.5% O2) from E6.5 to E10.5 or to E18.5 led to reduction in fetal weight, and such fetal weight loss was markedly worsened in miR-210-knockout dams. Analysis of the placental structure demonstrated the reduced expansion of placental spongiotrophoblast layer and hampered development of labyrinth fetal blood vessels in knockout mice compared to the wild-type controls upon hypoxia stimulation. The findings indicate that miR-210 participates in regulating placental adaptation to hypoxic stress during pregnancy.


Assuntos
Hipóxia/metabolismo , MicroRNAs/metabolismo , Oxigênio/administração & dosagem , Placenta/fisiologia , Adaptação Fisiológica , Animais , Sequência de Bases , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Tamanho da Ninhada de Vivíparos , Masculino , Troca Materno-Fetal , Camundongos , Camundongos Knockout , MicroRNAs/genética , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Distribuição Aleatória , Distribuição Tecidual
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