Latest Issue
Issue 5 ， 2021
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Exosomes in bladder cancer: novel biomarkers and targets
Abstract：Exosomes are nanometer-sized vesicles that contain various types of biologically active components, including proteins, nucleic acids, carbohydrates, and lipids, which vary with the type and physiological state of the cell. In recent years, several studies have showed that exosomes can provide new non-invasive diagnostic and prognostic biomarkers in patients affected by cancers, including bladder cancer (BC), and the lipid bilayer membrane structure makes exosomes as promising delivery vehicles for therapeutic applications. Exosomes have the characteristics of high abundance, high stability, tissue specificity, and wide distribution in body fluids, and are secreted as various types by cells in different states, thereby possessing great potential as biomarkers for BC. Herein, we briefly summarize the functions and roles of exosomes in the occurrence and development of BC and the current progress of research on exosomes in BC, while focusing on potential clinical applications of the diagnosis, treatment, and prognosis of BC.Keywords：Exosome;Bladder cancer;Function;Clinical application;Biomarker- 195
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Published：2021-05-12
Review
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Protective effect of recombinant
Lactobacillus plantarum against H2O2-induced oxidative stress in HUVEC cellsAbstract：This study probed the protective effect of recombinant Lactobacillus plantarum against hydrogen peroxide (H2O2)-induced oxidative stress in human umbilical vein endothelial cells (HUVECs). We constructed a new functional L. plantarum (NC8-pSIP409-alr-angiotensin-converting enzyme inhibitory peptide (ACEIP)) with a double-gene-labeled non-resistant screen as an expression vector. A 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) colorimetric assay was carried out to determine the cell viability of HUVEC cells following pretreatment with NC8-pSIP409-alr-ACEIP. Flow cytometry (FCM) was used to determine the apoptosis rate of HUVEC cells. Cysteinyl aspartate specific proteinase (caspase)-3/8/9 activity was also assayed and western blotting was used to determine protein expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), inducible nitric oxide synthase (iNOS), nicotinamide adenine dinucleotide phosphate oxidase 2 (gp91phox), angiotensin II (AngII), and angiotensin-converting enzyme 2 (ACE2), as well as corresponding indicators of oxidative stress, such as reactive oxygen species (ROS), mitochondrial membrane potential (MMP), malondialdehyde (MDA), and superoxide dismutase (SOD). NC8-pSIP409-alr-ACEIP attenuated H2O2-induced cell death, as determined by the MTT assay. NC8-pSIP409-alr-ACEIP reduced apoptosis of HUVEC cells by FCM. In addition, compared to the positive control, the oxidative stress index of the H2O2-induced HUVEC (Hy-HUVEC), which was pretreated by NC8-pSIP409-alr-ACEIP, iNOS, gp91phox, MDA, and ROS, was decreased obviously; SOD expression level was increased; caspase-3 or -9 was decreased, but caspase-8 did not change; Bcl-2/Bax ratio was increased; permeability changes of mitochondria were inhibited; and loss of transmembrane potential was prevented. Expression of the hypertension-related protein (AngII protein) in HUVEC cells protected by NC8-pSIP409-alr-ACEIP decreased and expression of ACE2 protein increased. These plantarum results suggested that NC8-pSIP409-alr-ACEIP protects against H2O2-induced injury in HUVEC cells. The mechanism for this effect is related to enhancement of antioxidant capacity and apoptosis.Keywords：Oxidative stress;Apoptosis;Human umbilical vein endothelial cell (HUVEC);Hydrogen peroxide (H2O2)- 114
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Published：2021-05-12 -
Genome-wide analysis of microRNA156 and its targets, the genes encoding SQUAMOSA promoter-binding protein-like (SPL) transcription factors, in the grass family Poaceae
Abstract：MicroRNAs (miRNAs) are endogenous small non-coding RNAs that play an important role in post-transcriptional gene regulation in plants and animals by targeting messenger RNAs (mRNAs) for cleavage or repressing translation of specific mRNAs. The first miRNA identified in plants, miRNA156 (miR156), targets the SQUAMOSA promoter-binding protein-like (SPL) transcription factors, which play critical roles in plant phase transition, flower and plant architecture, and fruit development. We identified multiple copies of MIR156 and SPL in the rice, Brachypodium, sorghum, maize, and foxtail millet genomes. Sequence and chromosomal synteny analysis showed that both MIR156s and SPLs are conserved across species in the grass family. Analysis of expression data of the SPLs in eleven juvenile and adult rice tissues revealed that four non-miR156-targeted genes were highly expressed and three miR156-targeted genes were only slightly expressed in all tissues/developmental stages. The remaining SPLs were highly expressed in the juvenile stage, but their expression was lower in the adult stage. It has been proposed that under strong selective pressure, non-miR156-targeted mRNA may be able to re-structure to form a miRNA-responsive element. In our analysis, some non-miR156-targeted SPLs (SPL5/8/10) had gene structure and gene expression patterns similar to those of miR156-targeted genes, suggesting that they could diversify into miR156-targeted genes. DNA methylation profiles of SPLs and MIR156s in different rice tissues showed diverse methylation patterns, and hypomethylation of non-CG sites was observed in rice endosperm. Our findings suggested that MIR156s and SPLs had different origination and evolutionary mechanisms: the SPLs appear to have resulted from vertical evolution, whereas MIR156s appear to have resulted from strong evolutionary selection on mature sequences.Keywords：MicroRNA156 (miR156);SQUAMOSA promoter-binding protein-like (SPL) gene;DNA methylation;Gene expression;Grass genome- 119
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Published：2021-05-12 -
Development of a
pyrF -based counterselectable system for targeted gene deletion inStreptomyces rimosus Abstract：Streptomyces produces many valuable and important biomolecules with clinical and pharmaceutical applications. The development of simple and highly efficient gene editing tools for genetic modification of Streptomyces is highly desirable. In this study, we developed a screening system for targeted gene knockout using a uracil auxotrophic host (ΔpyrF) resistant to the highly toxic uracil analog of 5-fluoroorotic acid (5-FOA) converted by PyrF, and a non-replicative vector pKC1132-pyrF carrying the complemented pyrF gene coding for orotidine-5'-phosphate decarboxylase. The pyrF gene acts as a positive selection and counterselection marker for recombinants during genetic modifications. Single-crossover homologous integration mutants were selected on minimal medium without uracil by reintroducing pyrF along with pKC1132-pyrF into the genome of the mutant ΔpyrF at the targeted locus. Double-crossover recombinants were generated, from which the pyrF gene, plasmid backbone, and targeted gene were excised through homologous recombination exchange. These recombinants were rapidly screened by the counterselection agent, 5-FOA. We demonstrated the feasibility and advantage of using this pyrF-based screening system through deleting the otcR gene, which encodes the cluster-situated regulator that directly activates oxytetracycline biosynthesis in Streptomyces rimosus M4018. This system provides a new genetic tool for investigating the genetic characteristics of Streptomyces species.Keywords：Counterselectable system;pyrF;5-Fluoroorotic acid (5-FOA);Gene deletion;Streptomyces rimosus- 163
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Phenolic profile of jujube fruit subjected to gut microbiota fermentation and its antioxidant potential against ethyl carbamate-induced oxidative damage
Abstract：ObjectiveTo evaluate the composition of bioactive substances and the antioxidant effects of jujube fruit under gut microbiota fermentation (GMF), and the inhibitory effect on cytotoxicity caused by ethyl carbamate (EC).MethodsChanges in the contents of flavonoids, polyphenols, total sugars, and reducing sugars of jujube fruit after GMF (0, 2, 6, 12, 24, and 48 h) were determined. The oxidation resistance of fermented jujube fruits (from 0 to 48 h fermentation) was evaluated using in vitro 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) and ferric reducing antioxidant power (FRAP) assays. Inhibitory effects of 48 h-fermented jujube fruit at various concentrations (0.25, 0.50, 1.00, and 2.00 mg/mL) on EC-treated toxicity and DNA damage of Caco-2 cells were estimated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and nuclear staining assays, respectively. Effects of different concentrations of jujube fruit on EC-treated Caco-2 cells’ intracellular reactive oxygen species (ROS), glutathione (GSH) levels, and mitochondrial membrane potential (MMP) were also evaluated.ResultsJujube fruit has rich bioactive components after GMF and shows strong antioxidant capacity. Fermented jujube fruit can inhibit the cytotoxicity and DNA damage of Caco-2 cells caused by EC and reduce intracellular ROS generation, as well as restoring GSH and MMP.ConclusionsFermented jujube fruit extracts produced by GMF still contain biologically active substances which retain biological activity and antioxidation capabilities.Keywords：Jujube;Gut microbiota fermentation;Polyphenols;Ethyl carbamate;Antioxidant activity- 19
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Osteogenic effects of antihypertensive drug benidipine on mouse MC3T3-E1 cells in vitro
Abstract：Hypertension is a prevalent systemic disease in the elderly, who can suffer from several pathological skeletal conditions simultaneously, including osteoporosis. Benidipine (BD), which is widely used to treat hypertension, has been proved to have a beneficial effect on bone metabolism. In order to confirm the osteogenic effects of BD, we investigated its osteogenic function using mouse MC3T3-E1 preosteoblast cells in vitro. The proliferative ability of MC3T3-E1 cells was significantly associated with the concentration of BD, as measured by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cell cycle assay. With BD treatment, the osteogenic differentiation and maturation of MC3T3-E1 cells were increased, as established by the alkaline phosphatase (ALP) activity test, matrix mineralized nodules formation, osteogenic genetic test, and protein expression analyses. Moreover, our data showed that the BMP2/Smad pathway could be the partial mechanism for the promotion of osteogenesis by BD, while BD might suppress the possible function of osteoclasts through the OPG/RANKL/RANK (receptor activator of nuclear factor-κB (NF-κB)) pathway. The hypothesis that BD bears a considerable potential in further research on its dual therapeutic effect on hypertensive patients with poor skeletal conditions was proved within the limitations of the present study.Keywords：Benidipine;Osteoblast;Osteogenesis;MC3T3-E1- 17
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Cornuside alleviates experimental autoimmune encephalomyelitis by inhibiting Th17 cell infiltration into the central nervous system
Abstract：The present study was conducted to clarify the therapeutic effect of cornuside on experimental autoimmune encephalomyelitis (EAE) and its influence on T helper 17 (Th17) cell and regulatory T (Treg) cell infiltration into the central nervous system. Rats were randomly placed into four treatment groups: control, EAE, EAE+cornuside, and EAE+prednisolone. The neurological function scores of rats were assessed daily. On the second day after EAE rats began to show neurological deficit symptoms, the four groups were treated with normal saline, normal saline, cornuside (150 mg/kg), and prednisolone (5 mg/kg), respectively. The treatment was discontinued after two weeks, and the spinal cord was obtained for hematoxylin and eosin (H&E) and luxol fast blue staining, as well as retinoic acid receptor-related orphan receptor γ (RORγ) and forkhead box protein P3 (Foxp3) immunohistochemical staining. Blood was collected for Th17 and Treg cell flow cytometry testing, and the serum levels of interleukin (IL)-17A, IL-10, transforming growth factor-β (TGF-β), IL-6, IL-23, and IL-2 were measured via enzyme-linked immunosorbent assay (ELISA). Compared with rats in the EAE group, rats in the EAE+cornuside and EAE+prednisolone groups began to recover from neurological deficits earlier, and had a greater degree of improvement of symptoms. Focal inflammation, demyelination, and RORγ-positive cell infiltration were reduced by cornuside or prednisolone treatment, whereas the Foxp3-positive cell numbers were not significantly different. Meanwhile, the number of Th17 cells and the IL-17A, IL-6, and IL-23 levels were lower in the blood after cornuside or prednisolone treatment, whereas the number of Treg cells or the levels of IL-10, TGF-β, and IL-2 were not markedly different. Cornuside can alleviate symptoms of EAE neurological deficits through its anti-inflammatory and immunosuppressive effects, and Th17 cells may be one of its therapeutic targets.Keywords：Cornuside;Experimental autoimmune encephalomyelitis;Multiple sclerosis;Inflammation- 17
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Published：2021-05-12
Research Article
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