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As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE-DTX) as an anti-metastasis agent to treat breast cancer. CTCE-DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE-DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.
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Natural extracellular vesicles (EVs) play important roles in many life processes such as in the intermolecular transfer of substances and genetic information exchanges. Investigating the origins and working mechanisms of natural EVs may provide an understanding of life activities, especially regarding the occurrence and development of diseases. Additionally, due to their vesicular structure, EVs (in small molecules, nucleic acids, proteins, etc.) could act as efficient drug-delivery carriers. Herein, we describe the sources and biological functions of various EVs, summarize the roles of EVs in disease diagnosis and treatment, and review the application of EVs as drug-delivery carriers. We also assess the challenges and perspectives of EVs in biomedical applications.
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Objective@#To investigate the genetic characteristics of enterovirus A group 71 type (EV-A71) and etiological features of hand, foot and mouth disease (HFMD) in Xining city in 2017.@*Methods@#The pharyngeal swab specimens were collected from HFMD patients, and detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). For EV-A71 positive samples, virus isolation was performed. Then RNA of EV-A71 strains was extracted, and then VP1 coding region was amplified by RT-PCR. The phylogenetic tree was constructed by comparing with other genotypes and sub-genotypes strains of EV-A71.@*Results@#Total 57 strains of EV-A71 were isolated in Xining city in 2017, which all belonged to genotype C4a, and could be divided into two different lineages by phylogenetic analysis. The epidemic strains of EV-A71 in Xining City was closely related to other provinces of China in 2017.@*Conclusions@#C4a was the dominant genotype of EV-A71 in Xining city in 2017, and no other genotype was detected. In addition, EV-A71 isolated from Xining city was co-evolved with EV-A71 in other provinces of China.
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Objective@#To understand the pathogenic composition of hand, foot and mouth disease (HFMD) in Ningxia Hui Autonomous Region (Ningxia) from 2016 to 2017, and analyze the genetic characteristics of the main pathogens enterovirus (EV)-A71 and coxsackievirus (CV)-A16.@*Methods@#Analysis of the result of nucleic acid testing of HFMD in Ningxia from 2016 to 2017 to determine the pathogenic composition of HFMD. The complete VP1 coding region was amplified by RT-PCR and the gene sequence was determined for the enterovirus strains sent to the National HFMD Network Monitoring Laboratory in Ningxia from 2016 to 2017. BLAST analysis confirmed the serotype of the strain, and the phylogenetic tree was constructed respectively by selecting EV-A71 and CV-A16 isolates.@*Results@#The leading pathogens of HFMD in Ningxia of 2016 and 2017 were other EV (397, 43.72%) and EV-A71 (918, 56.18%) respectively, and the dominant pathogens in different months may differ. The pathogenic composition causing HFMD in the past two years has changed from CV-A16 and other EV to EV-A71 and other EV. The isolated EV-A71 strains were C4a evolutionary branch and the isolated CV-A16 strains were B1b evolutionary branch.@*Conclusions@#Compared to 2016, in 2017 EV-A71, CV-A16 and other EV changed dynamically. Dynamic monitoring of EV-A71 in Ningxia is of great significance to guide the strategy of using EV-A71 vaccine, concentrating medical resources to strengthen the treatment and reduce the mortality rate of severe HFMD cases.
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Objective@#To evaluate the epidemiologic characteristics of hand, foot and mouth disease in Zhejiang province between 2009 and 2017, so that scientific evidence could be provided for prevention and control of hand, foot and mouth disease.@*Methods@#Spatial, temporal and population distribution of HFMD was analyzed. Real-time reverse transcription polymerase cain reaction was used to test Enterovirus A71 and Coxsackievirus A16 in samples.@*Results@#Between 2009 and 2017, 1 108 093 HFMD cases were reported in Zhejiang with the prevalence of 226.24/100000; 2010, 2012, 2014 and 2016 had a higher prevalence than other years. Prevalence of HFMD peaked in April-July and September-October. Wenzhou, Taizhou and Ningbo had a higher prevalence than other cities. In total, 69.27% cases were children who were not enrolled in nursery school, and 65.67% were 1-3 years old. Pathogen surveillance showed that EV-A71 decreased in mild cases, whereas other enterovirus increased. However EV-A71 was still predominant in severe and fatal cases (56.0%).@*Conclusions@#Temporal and spatial distribution of HFMD is characteristic in Zhejiang province. EV-A71 predominated in severe cases and fatal cases, while other enterovirus (non-EV-A71, non CV-A16) were the main pathogen for mild cases.
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Objective@#To investigate the genetic characteristics of enterovirus A 71 (EV-A71) and etiological features of hand, foot and mouth disease (HFMD) in Qinghai province from 2016 to 2017.@*Methods@#Specimens were collected from HFMD patients in Qinghai province, and detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). For EV-A71 positive samples, virus was isolated and RNA was extracted, and then VP1 coding region was amplified by RT-PCR. The phylogenetic tree was constructed by comparing with other genotypes and sub-genotypes strains of EV-A71.@*Results@#It was shown that 114 strains of EV-A71 were isolated in Qinghai province from 2016 to 2017, which all belonged to genotype C4a, and could be divided to two different lineages by phylogenetic analysis. From 2016 to 2017, the epidemic strains of EV-A71 in the different transmission chains of Qinghai province was closely related to other provinces of China.@*Conclusions@#C4a was the dominant genotype of EV-A71 in Qinghai province from 2016 to 2017, and no other genotype was detected. In addition, EV-A71 isolated from Qinghai province co-evolved with EV-A71 in other provinces of China.
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Objective@#To evaluate the running status of Qinghai provincial hand foot and mouth disease (HFMD) laboratory network in 2017.@*Methods@#The surveillance database developed in Qinghai provincial HFMD laboratory network in 2017 were analyzed, and the indicators for the running status of HFMD laboratory network in Qinghai province were evaluated.@*Results@#It was shown that 574 samples of suspected HFMD cases were detected by real time RT-PCR in 2017, and 368 were positive, the positive rate was 64.11%. Then 121 virus strains were isolated, the results of sequencing and analysis showed that 100 strains were EV71 with C4a genotype, 16 strains were CA16 with B1b genotype, and 5 strains belonged to the other enterovirus. In addition, Qinghai provincial HFMD network labs passed all the confirmatory test and proficiency test, and on-site review held by national HFMD laboratory in 2017, respectively.@*Conclusions@#Qinghai provincial HFMD laboratory network has been established and running well. It provided important scientific basis for HFMD surveillance in Qinghai province.
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We analyzed the genetic characteristics of coxsackievirus A4 (CV-A4) based on the entire VP1 coding region. Samples were isolated from patients with acute flaccid paralysis (AFP) in Shaanxi, China from 2006 to 2010. We wished to ascertain the predominant genotype and the relationship between CV-A4 infection and AFP. Sixty-eight non-polio enteroviruses were inoculated onto RD cells (to increase the virus titer) and molecular typing was undertaken. The entire VP1 coding region was amplified. Percentage of CV-A4 was 10.3% (7/68). Analyses of genetic identify and creation of phylogenetic trees revealed that CV-A4 could be classified into A, B and C genotypes. Seven CV-A4 strains from Shaanxi and other CV-A4 strains from China formed an independent evolution lineage located in group 4 and belonged to the C2 sub-genotype. These data suggested that CV-A4 strains of sub-genotype C2 were the predominant genotypes in China. These strains co-evolved and co-circulated with those from other provinces in China, so continued monitoring of CV-A4 (by clinical and genetic surveillance) should be enhanced.
Subject(s)
Humans , China , Enterovirus A, Human , Classification , Genetics , Enterovirus Infections , Virology , Genotype , Paralysis , Virology , Phylogeny , Viral Proteins , GeneticsABSTRACT
We wished to understand the genetic characteristics of enteric cytopathic human orphan (ECHO) virus type 6 (ECHO6) circulating in China. First, the partial VP1 coding region of six strains of the ECH-O6 virus isolated from cases of hand, foot and mouth diseases during routine surveillance in Hunan Province (China) from 2009 to 2014 were sequenced. Those sequences were analyzed along with 138 sequences of ECHO viruses covering five provinces of China and countries outside China retrieved from the GenBank database. A phylogenetic tree based on partial VPI was constructed, and it indicated that Chinese strains of the ECHO virus could form two distinct evolutionary branches: branch 1 and branch 2. All isolates of the ECHO virus from Hunan Province belonged to the 2c subranch, which revealed that they may share a common evolutionary origin. ECHO strains in branch 2 may be the predominant strains in China due to their wide geographic distribution and long period of circulation. We used nucleotide differences of >30%o as the basis of cluster division. ECHO, viruses could be divided into four clusters (A-D). Cluster D could be divided further into ten subclusters on the basis of nucleotide differences of 15%-30%. All ECHO6 isolates from Hunan Province belonged to the D7 subcluster. These data showed that the ECHO6 strains that circulated in Hunan Province in 2009-2014 were closely related to each other, and probably shared a common evolutionary origin. In addition, at least four distinct lineages of ECHO viruses have circulated in China.