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1.
ACS Synth Biol ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396719

##### RESUMO

The production of the aglycosylated immunoglobulin G (IgG) in Escherichia coli has received wide interest for its analytical and therapeutic applications. To enhance the production titer of IgG, we firstly used synthetic sRNAs to perform a systematical analysis of the genes expression in the translational level in the glycolytic pathway (Module 1) and the tricarboxylic acid (TCA) cycle (Module 2) to reveal the critical genes for the efficient IgG production. Secondly, to provide sufficient amino acid precursors for the protein biosynthesis, amino acid biosynthesis pathways (Module 3) were enhanced to facilitate the IgG production. Upon integrated engineering of these genes in the three Modules (Module 1: aceF; Module 2: gltA and acnA; and Module 3: serB) and optimization of fermentation conditions, the recombinant E. coli enabled a titer of the full-length IgG 4.5±0.6 mg/L in the shake flask culture, and 184±9.2 mg/L in the 5-L high cell-density fed-batch fermenter, which is, to the best of our knowledge, the highest reported IgG production titer by recombinant E. coli.

2.
Curr Biol ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32416074

##### RESUMO

The unprecedented pandemic of pneumonia caused by a novel coronavirus, SARS-CoV-2, in China and beyond has had major public health impacts on a global scale [1, 2]. Although bats are regarded as the most likely natural hosts for SARS-CoV-2 [3], the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomic analysis of samples from 227 bats collected from Yunnan Province in China between May and October 2019. Notably, RmYN02 shares 93.3% nucleotide identity with SARS-CoV-2 at the scale of the complete virus genome and 97.2% identity in the 1ab gene, in which it is the closest relative of SARS-CoV-2 reported to date. In contrast, RmYN02 showed low sequence identity (61.3%) to SARS-CoV-2 in the receptor-binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, and in a similar manner to SARS-CoV-2, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the spike (S) protein. This provides strong evidence that such insertion events can occur naturally in animal betacoronaviruses.

3.
Clin Infect Dis ; 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32357209

##### RESUMO

BACKGROUND: Thousands of medical staff had been infected with SARS-CoV-2 virus with hundreds of deaths reported. Such loss could be prevented if there is a serologic assay for SARS-CoV-2-specific antibodies for serological surveillance of its infection at the early stage of disease. METHODS: Using CHO cell expressed full length SARS-CoV-2 S1 protein as capturing antigen, a COVID-19/SARS-CoV-2 S1 serology ELISA kit was developed and validated with negative samples collected prior to the outbreaks or during the outbreak, and positive samples from patients confirmed with COVID-19. RESULTS: The specificity of the ELISA kit was 97.5%, as examined against total 412 normal human samples. The sensitivity was 97.1% by testing against 69 samples from hospitalized and/or recovered COVID-19 patients. The overall accuracy rate reached 97.3%. The assay was able to detect SARS-CoV-2 antibody on day one after the onset of COVID-19 disease. The average antibody levels increased during the hospitalization and after been discharged for two weeks. SARS-CoV-2 antibodies were detected in 28 out of 276 asymptomatic medical staff and one out of five nucleic acid test-negative "Close contacts" of COVID-19 patient. CONCLUSION: With the assays developed here, we can screen medical staff, in-coming patients, passengers and people who are in close contact with the confirmed patients to identify the "innocent viral spreaders", protect the medical staff and stop the further spreading of the virus.

4.
J Mater Chem B ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32391536

##### RESUMO

Polyethylenimine (PEI) functionalization onto nanoparticles is a widely used strategy for constructing particulate vectors for gene delivery. However, how to control the conformation of PEI chains and the resultant impact on gene transfection efficiency remains largely unexplored. Herein, we report that drying methods dramatically affect the conformation of PEI chains modified on the surface of silica nanoparticles and consequently the plasmid DNA transfection performance. Specifically, lyophilization renders less entangled PEI compared to commonly used vacuum drying as evidenced by an elevated glass transition temperature. The lyophilization induced disentangled conformation is likely associated with the solid-to-gas phase transition drying mechanism, which removes the bound crystal water content and thus reduces hydrogen bonding between amines. Moreover, we find that the stretched PEI chains on the surface of rambutan-like silica nanoparticles promote their binding capacity towards plasmid DNA molecules and thereby enhanced gene delivery and transfection efficiency. Our findings have provided new understanding about amine based polymers modified on nanoparticles, and have significant implications on the design of efficient particulate vectors for gene delivery.

5.
Genomics ; 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32353476

##### RESUMO

Color plays a vital function in camouflage, sexual selection, immunity, and evolution. Mollusca possess vivid shell colors and pigmentation starts at the juvenile stage. The hard clam Mercenaria mercenaria is a widely cultivated bivalve of high economic value. To explore the molecular mechanism of pigmentation in juvenile clams, here, we performed RNA-Seq analysis on non-pigmented, white, and red M. mercenaria specimens. Clean reads were assembled into 358,285 transcripts and 149,234 unigenes, whose N50 lengths were 2107 bp and 1567 bp, respectively. Differentially expressed genes were identified and analyzed for KEGG enrichment. "Melanoma/Melanogenesis", "ABC transporters", and "Porphyrin and chlorophyll metabolism" pathways appeared to be associated with pigmentation. Pathways related to carotenoid metabolism seemed to also play a vital role in pigmentation in juveniles. Our results provide new insights into the formation of shell color in juvenile hard clams.

6.
Gene ; 748: 144678, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32305633

##### RESUMO

Previous reports have revealed that circRNA_100876 was extremely important in the progression of triple-negative breast cancer. Nevertheless, the mechanism towards the role of circRNA_100876 in Gastric cancer (GC) remains unknown. Here, we determined circRNA_100876 expression by quantitative real-time PCR (qRT-PCR) in twenty pairs of GC tissues and adjacent tissues. Our data indicated that the expression of circRNA_100876 was raised in GC tissues. In vitro, functional experiments confirmed that cell proliferation, invasion along with migration was promoted by circRNA_100876 in GC tissues. Simultaneously, relative luciferase assay uncovered that circRNA_100876 functioned as a sponge for miR-136, followed by retarding miR-136-induced inhibited effects on the corresponding target, MIEN1. Moreover, we revealed that the expression of MIEN1 was up-regulated and correlated to much worse prognosis of GC. Collectively, our data identified that the promotion of GC growth and metastasis induced by circRNA_100876 interacted with miR-136 and MIEN1, indicating an emerging announcement for uncovering the potential mechanism of GC progression.

7.
Opt Express ; 28(1): 753-759, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-32118997

##### RESUMO

A magnetic mirror operating in the terahertz band is designed based on the functional reflective metasurface, which is simply constructed by a one-dimensional periodic lithium tantalate micro cylindrical rod array on a Teflon substrate coated with a metal layer at the bottom and reflects the incoming electric field with a zero-phase change. Magnetic dipole resonance of the micro cylindrical rods excited in the metasurface is attributed to the perfect magnetic mirror at the frequency of 0.286 THz with the reflectivity of R = 0.98 for a normal incident electromagnetic wave. By real-time varying the direction from normal (0) to 28.45 degrees and the frequency from 0.286 to 0.382 THz of the incident wave, the metasurface can still behave as a perfect magnetic mirror with the reflectivity as high as 0.99. Most interestingly, in this case, the metasurface possesses the property of a retroreflector that the reflected wave returns along the direction of the incident wave, which is consistent with the grating equation. The tunable perfect magnetic mirror effect and the retroreflector property may provide ways in novel photonic devices and sensing applications.

8.
Chem Biol Drug Des ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32167672

##### RESUMO

Vascular endothelial growth factor (VEGF) had neuroprotective effects on dopaminergic (DA) neurons. In order to overcome the gastrointestinal digestion and bioaccessibility, VEGF was encapsulated with poly-lactic-co-glycolic acid nanospheres (NS) in order to prevent the VEGF degradation until its release. The caudal administration of VEGF and NS encapsulated VEGF at different doses (1.0, 10.0, and 100.0 ng/ml) on the rats with Parkinson's disease lesion was evaluated. Intravenous injected VEGF at the dose of 1 ng/ml displayed the strongest neuroprotective effect than other groups as well as the stereotaxic group. The NS encapsulated with VEGF can pass through blood-brain barrier and protect the DA neurons. There was no significant difference between intravenous injection method and stereotaxic method, while the first method is simpler and convenient. Injection of NS encapsulated with VEGF may become a valuable neurorescuing therapeutic approach for Parkinson's disease.

9.
Biotechnol J ; 15(5): e1900363, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32034883

##### RESUMO

Production of monoclonal antibodies (mAbs) receives considerable attention in the pharmaceutical industry. There has been an increasing interest in the expression of mAbs in Escherichia coli for analytical and therapeutic applications in recent years. Here, a modular synthetic biology approach is developed to rationally engineer E. coli by designing three functional modules to facilitate high-titer production of immunoglobulin G (IgG). First, a bicistronic expression system is constructed and the expression of the key genes in the pyruvate metabolism is tuned by the technologies of synthetic sRNA translational repression and gene overexpression, thus enhancing the cellular material and energy metabolism of E. coli for IgG biosynthesis (module 1). Second, to prevent the IgG biodegradation by proteases, the expression of a number of key proteases is identified and inhibited via synthetic sRNAs (module 2). Third, molecular chaperones are co-expressed to promote the secretion and folding of IgG (module 3). Synergistic integration of the three modules into the resulting recombinant E. coli results in a yield of the full-length IgG ≈150 mg L-1 in a 5L fed-batch bioreactor. The modular synthetic biology approach could be of general use in the production of recombinant mAbs.

10.
Opt Lett ; 45(3): 702-705, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32004289

##### RESUMO

We experimentally demonstrate simultaneous turbulence mitigation and channel demultiplexing in a 200 Gbit/s orbital-angular-momentum (OAM) multiplexed link by adaptive wavefront shaping and diffusing (WSD) the light beams. Different realizations of two emulated turbulence strengths (the Fried parameter ${r_0} = 0.4,\,1.0\;{\rm mm}$r0=0.4,1.0mm) are mitigated. The experimental results show the following. (1) Crosstalk between OAM $l = + 1$l=+1 and $l = - 1$l=-1 modes can be reduced by ${\gt} {10.0}$>10.0 and ${\gt} {5.8}\;{\rm dB}$>5.8dB, respectively, under the weaker turbulence (${r_0} = 1.0\;{\rm mm}$r0=1.0mm); crosstalk is further improved by ${\gt} {17.7}$>17.7 and ${\gt} {19.4}\;{\rm dB}$>19.4dB, respectively, under most realizations in the stronger turbulence (${r_0} = 0.4\;{\rm mm}$r0=0.4mm). (2) The optical signal-to-noise ratio penalties for the bit error rate performance are measured to be ${\sim}{0.7}$â¼0.7 and ${\sim}{1.6}\;{\rm dB}$â¼1.6dB under weaker turbulence, while measured to be ${\sim}{3.2}$â¼3.2 and ${\sim}{1.8}\;{\rm dB}$â¼1.8dB under stronger turbulence for OAM $l = + 1$l=+1 and $l = - 1$l=-1 mode, respectively.

11.
Lancet ; 395(10224): 565-574, 2020 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-32007145

##### RESUMO

BACKGROUND: In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. METHODS: We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. FINDINGS: The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. INTERPRETATION: 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. FUNDING: National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.

##### Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Genoma Viral , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Receptores Virais/metabolismo , Betacoronavirus/metabolismo , Líquido da Lavagem Broncoalveolar/virologia , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/transmissão , DNA Viral/genética , Reservatórios de Doenças/virologia , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Filogenia , Pneumonia Viral/diagnóstico , Pneumonia Viral/transmissão , Alinhamento de Sequência
12.
Sci Rep ; 10(1): 3626, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32107399

##### RESUMO

In this paper, analytical pyrolyzer coupled with a gas chromatography-mass spectrometry set-up (Py-GC/MS) and density functional theory(DFT) theory was used to reveal the initial pyrolysis mechanism and product formation mechanism of cellulose pyrolysis. We demonstrated an experimentally benchmarked molecular simulation approach that delineates pyrolysis process of cellulose. Experimental results indicated that the cellulose pyrolysis products mostly incorporate levoglucosan (LG), glycolaldehyde (HAA), 5-hydroxyfurfural (5-HMF), and the like. The constituents of fast pyrolysis products of cellulose and cellobiose demonstrated the identical trend, although the contents of certain products are different. Laying the foundation of experimental analysis, the reaction pathways of four categories of cellulose pyrolysis were outlined using DFT theory; the pathways are those of generating LG, HAA, and 5-HMF and the dehydration reaction in the process of cellulose pyrolysis. Also, by comparing the energy barriers of various reactions, the optimal pathway of different reactions were summarized. The deduced cellulose pyrolysis reaction pathway opened up new ideas for studying the pyrolysis behavior of cellulose.

13.
J Coll Physicians Surg Pak ; 30(1): 37-40, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31931930

##### RESUMO

OBJECTIVE: To determine the expression levels and clinical significance of serum N-terminal pro-brain natriuretic peptide (NT-proBNP), hydrogen sulfide (H2S) and interleukin-6 (IL-6) in children with Kawasaki disease (KD). STUDY DESIGN: Descriptive comparative study. PLACE AND DURATION OF STUDY: Department of Pediatric Medicine, Baoding Children's Hospital, from July 2017 to July 2018. METHODOLOGY: Ninety-five KD children were chosen as the case group, and were classified into CAL group (23 patients) and NCAL group (72 patients, according to the presence of a coronary artery lesion (CAL). Forty-six non-KD children with an upper respiratory infection in the same time period were chosen as the control group. Electrochemiluminescence method was used to detect serum NT-proBNP levels. The spectrophotometer method was used to test H2S levels, and an enzyme-linked immunosorbent assay was used to test serum IL-6 levels and to analyse the correlation. RESULTS: In the acute phase and recovery phase, serum NT-proBNP and IL-6 levels were higher in the case group than the control group, while H2S levels were lower than those in the control group (p<0.001). In both the acute and recovery phases, serum NT-proBNP and IL-6 levels were higher in the CAL group than in the NCAL group, while H2S levels were lower than those in the NCAL group (p<0.001). CONCLUSION: NT-proBNP and IL-6 levels rise and the H2S level decreases in the blood of KD children, indicating that these indicators may participate in the pathogenesis of KD and that their levels are related to CAL occurrence and the vascular inflammatory response.

14.
J Phys Chem Lett ; 11(3): 646-651, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31903761

##### RESUMO

Highly compressed hydrides have been at the forefront of the search for high-Tc superconductivity. The recent discovery of record-high Tc's in H3S and LaH10±x under high pressure fuels the enthusiasm for finding good superconductors in similar hydride groups. Guided by first-principles structure prediction, we successfully synthesized ZrH3 and Zr4H15 at modest pressures (30-50 GPa) in diamond anvil cells by two different reaction routes: ZrH2 + H2 at room temperature and Zr + H2 at â¼1500 K by laser heating. From the synchrotron X-ray diffraction patterns, ZrH3 is found to have a Pm3Ìn structure corresponding to the familiar A15 structure, and Zr4H15 has an I4Ì3d structure isostructural to Th4H15. Electrical resistance measurement and the dependence of Tc on the applied magnetic field of the sample showed the emergence of two superconducting transitions at 6.4 and 4.0 K at 40 GPa, which correspond to the two Tc's for ZrH3 and Zr4H15.

15.
Angew Chem Int Ed Engl ; 59(7): 2695-2699, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31820548

##### RESUMO

Effective messenger RNA (mRNA) transfection in hard-to-transfect cells delivered by vectors is a long-standing challenge. Now it is hypothesized that the high intracellular glutathione level is associated with suppressed mRNA translation. This theory leads to a new design principle of next-generation mRNA vectors: nanoparticles with glutathione depletion chemistry upregulate mRNA translation and enhance transfection, which is beneficial for mRNA delivery in hard-to-transfect cells inâvitro and inâvivo.

16.
Behav Brain Res ; 379: 112385, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31778736

##### RESUMO

BACKGROUND: Chronic cerebral hypoperfusion (CCH) is a common pathophysiological basis for Alzheimer's Disease and vascular dementia in the early stages. It has been confirmed that blood-brain barrier (BBB) destruction is a key factor in CCH-related cognitive impairment. Here we explored the effects of an enriched environment (EE) intervention on CCH-induced BBB destruction and cognitive impairment, and the underlying mechanism. METHODS: Rats in the EE group were exposed to an EE, while the standard environment (SE) group was maintained in a standard cage with bedding but no other objects. On day 14, CCH was induced via permanent bilateral common carotid artery occlusion (2VO). Next, Evans blue (EB) leakage in the hippocampus was measured by chemical colorimetry to dynamically evaluate BBB permeability. On day 28, the BBB ultrastructure was observed using transmission electron microscopy. The expression levels of BBB integrity-related proteins, matrix metalloproteinases-2/-9 (MMP-2/-9), and the classical Wnt/ß-catenin signaling pathway-related proteins were detected using western-blotting techniques. On day 43, cognitive function was assessed using the Morris water maze. RESULTS: After 2VO, CCH rats exposed to the SE developed obvious cognitive impairment and BBB destruction. BBB damage was manifested through increased EB leakage, ultrastructural destruction, degradation of BBB integrity-related proteins, and up-regulation of MMP-2/-9. These changes were significantly alleviated after the EE intervention. In addition, EEs activated the Wnt/ß-catenin signaling pathway in the hippocampus of rats. CONCLUSIONS: These results suggest that protection of the BBB may be a novel mechanism by which EEs ameliorate CCH-induced cognitive impairment, and this effect may be related to the activation of the Wnt/ß-catenin pathway.

17.
Cell Host Microbe ; 26(6): 836-843.e3, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31787524

##### RESUMO

African swine fever virus (ASFV) is a large double-stranded DNA virus with an icosahedral multilayered structure. ASFV causes a lethal swine hemorrhagic disease and is currently responsible for widespread damage to the pork industry in Asia. Neither vaccines nor antivirals are available and the molecular characterization of the ASFV particle is outstanding. Here, we describe the cryogenic electron microscopy (cryo-EM) structure of the icosahedral capsid of ASFV at 4.6-Å. The ASFV particle consists of 8,280 copies of the major capsid protein p72, 60 copies of the penton protein, and at least 8,340 minor capsid proteins, of which there might be 3 different types. Like other nucleocytoplasmic large DNA viruses, the minor capsid proteins form a hexagonal network below the outer capsid shell, functioning as stabilizers by "gluing" neighboring capsomers together. Our findings provide a comprehensive molecular model of the ASFV capsid architecture that will contribute to the future development of countermeasures, including vaccines.

18.
Adv Mater ; : e1904106, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31799752

##### RESUMO

Bacterial infection is one of the top ten leading causes of death globally and the worst killer in low-income countries. The overuse of antibiotics leads to ever-increasing antibiotic resistance, posing a severe threat to human health. Recent advances in nanotechnology provide new opportunities to address the challenges in bacterial infection by killing germs without using antibiotics. Antibiotic-free antibacterial strategies enabled by advanced nanomaterials are presented. Nanomaterials are classified on the basis of their mode of action: nanomaterials with intrinsic or light-mediated bactericidal properties and others that serve as vehicles for the delivery of natural antibacterial compounds. Specific attention is given to antibacterial mechanisms and the structure-performance relationship. Practical antibacterial applications employing these antibiotic-free strategies are also introduced. Current challenges in this field and future perspectives are presented to stimulate new technologies and their translation to fight against bacterial infection.

19.
Cell Rep ; 29(8): 2217-2228.e5, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31747596

##### RESUMO

Since 2013, H7N9 avian influenza viruses (AIVs) have caused more than 1,600 human infections, posing a threat to public health. An emerging concern is whether H7N9 AIVs will cause pandemics among humans. Molecular analysis of hemagglutinin (HA), which is a critical determinant of interspecies transmission, shows that the current H7N9 AIVs are still dual-receptor tropic, indicating limited human-to-human transmission potency. Mutagenesis and structural studies reveal that a G186V substitution is sufficient for H7N9 AIVs to acquire human receptor-binding capacity, and a Q226L substitution would favor binding to both avian and human receptors only when paired with A138/V186/P221 hydrophobic residues. These data suggest a different evolutionary route of H7N9 viruses compared to other AIV-subtype HAs.

20.
Int J Med Sci ; 16(11): 1510-1516, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31673243

##### RESUMO

Introduction: We aimed to explore small interfering (si)RNA silencing of ribonucleotide reductase M2 (RRM2) gene combined with cisplatin for the treatment of human ovarian cancer in nude mice models of subcutaneous transplantation of tumor cells. Methods: After conventional cultivation of human ovarian cancer cell line SKOV3 in vitro, SKOV3 cells were injected into the right back of nude mice by subcutaneous injection to establish the subcutaneous tumor models. Twenty-four tumor-burdened rats were randomly divided into four groups (n=6): siRNA group, siRNA in combination with cisplatin group, cisplatin group, and control group. Intraperitoneal injection of cisplatin and subcutaneous injection of siRNA were performed weekly. Tumor volume was measured, and tumor growth inhibition rate was calculated. RRM2 expression at the mRNA and protein levels was detected by reverse transcription-polymerase chain reaction and immunohistochemistry. Results: In the siRNA group, the tumor volume and tumor growth inhibition rate were 249.60±20.46 mm³ and 36.39%, respectively. The tumor growth inhibition rate and tumor volume were significantly different between the siRNA and control groups (p<0.05). In the cisplatin group, the tumor volume and tumor growth inhibition rate were 249.86±12.46 mm³ and 41.10%, respectively. The tumor growth inhibition rate and tumor volume were significantly different between the cisplatin and control groups (p<0.05). In the siRNA + cisplatin group, the tumor volume reduced to 180.84±16.25 mm³ and the tumor growth inhibition rate was increased to 64.33%, which were significantly different compared with the control group (p<0.01). Significant downregulation of RRM2 mRNA and protein expression in the tumor tissues was detected by reverse transcription polymerase chain reaction and immunohistochemistry assay (p<0.05). Discussion: siRNA alone or combined with cisplatin can effectively inhibit the growth of human ovarian cancer in nude mice models of subcutaneous transplantation of tumor cells. RRM2 gene silencing may be a potential treatment regimen for ovarian cancer in future.