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1.
Biol Direct ; 19(1): 52, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956667

RESUMO

BACKGROUND: Adiposity profoundly impacts reproductive health in both humans and animals. However, the precise subpopulations contributing to infertility under obese conditions remain elusive. RESULTS: In this study, we established an obese mouse model through an eighteen-week high-fat diet regimen in adult female mice. Employing single-cell RNA sequencing (scRNA-seq), we constructed a comprehensive single-cell atlas of ovarian tissues from these mice to scrutinize the impact of obesity on the ovarian microenvironment. ScRNA-seq revealed notable alterations in the microenvironment of ovarian tissues in obese mice. Granulosa cells, stromal cells, T cells, and macrophages exhibited functional imbalances compared to the control group. We observed heightened interaction strength in the SPP1-CD44 pairing within lgfbp7+ granulosa cell subtypes and Il1bhigh monocyte subtypes in the ovarian tissues of obese mice. Moreover, the interaction strength between Il1bhigh monocyte subtypes and Pdgfrb+ stromal cell subtypes in the form of TNF - TNFrsf1α interaction was also enhanced subsequently to obesity, potentially contributing to ovarian fibrosis pathogenesis. CONCLUSIONS: We propose a model wherein granulosa cells secrete SPP1 to activate monocytes, subsequently triggering TNF-α secretion by monocytes, thereby activating stromal cells and ultimately leading to the development of ovarian fibrosis. Intervening in this process may represent a promising avenue for improving clinical outcomes in fertility treatments for obese women.


Assuntos
Fibrose , Camundongos Obesos , Obesidade , Análise de Célula Única , Animais , Feminino , Camundongos , Fibrose/genética , Obesidade/genética , Obesidade/metabolismo , Perfilação da Expressão Gênica , Ovário/metabolismo , Transcriptoma , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos , Células da Granulosa/metabolismo
2.
Front Nutr ; 11: 1379982, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38798768

RESUMO

Zein is the main vegetable protein from maize. In recent years, Zein has been widely used in pharmaceutical, agriculture, food, environmental protection, and other fields because it has excellent biocompatibility and biosafety. However, there is still a lack of systematic review and research on Zein-based nano-delivery systems. This paper systematically reviews preparation and modification methods of Zein-based nano-delivery systems, based on the basic properties of Zein. It discusses the preparation of Zein nanoparticles and the influencing factors in detail, as well as analyzing the advantages and disadvantages of different preparation methods and summarizing modification methods of Zein nanoparticles. This study provides a new idea for the research of Zein-based nano-delivery system and promotes its application.

3.
Sci Rep ; 14(1): 8435, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600253

RESUMO

Ignition electrodes have an immense impact on the accurate measurement of the flame propagation spherical radius. In this study, a flame-radius calculation method is designed. The method is able to eliminate effects due to the ignition electrodes. The adaptability and optimization effects of the proposed method are analyzed. The results show that the ratio of the angle is affected by the ignition electrodes under the Han II method. There are three obvious divisions include a high-value area, a sharp-variation area, and a mild-variation area. The ratio of the angle affected by the ignition electrodes is only applicable to the mild-variation region when the flame presents respective convex and concave distributions. For these distributions, the increment rate of the mean radius is 0.4-0.85% and 0.42-3.19%. The reduced rate of the standard deviation of the radius extraction value is 11.91-22.1% and 5.13-17.99%, and the reduced rate of the radius extraction value range is 20.32-39.51% and 0.32-8.09%.

4.
Sci Rep ; 14(1): 1009, 2024 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200039

RESUMO

Patients with bladder cancer (BLCA) still show high recurrence after surgery and chemotherapy. Hesperetin (HE), as a natural compound, has attracted researchers' attention due to its low toxicity and easy access. However, the inhibitory effect of HE on BLCA remains unknown. The hub genes and enrichment pathways regulated by HE in the treatment of BLCA were predicted by network pharmacology. The molecular docking of HE and hub proteins was visualized. Colony and CCK8 assays were used to test cell proliferation, and BLCA migration was confirmed by transwell and wound healing assays. In addition, the occurrence of apoptosis and ferroptosis was demonstrated by Hoechst staining, transmission electron microscopy (TEM) and ROS (reactive oxygen species) assay. Western Blotting was performed to validate the hub proteins, target functions and pathways. SRC, PIK3R1 and MAPK1 were identified as hub targets for HE in BLCA, involving the PI3k/AKT pathway. Furthermore, HE inhibited the proliferation and migration of BLCA cells. The MMP2/MMP9 proteins were significantly inhibited by HE. The increased expression of Bax and cleaved caspase-3 indicated that HE could promote BLCA cell apoptosis. In addition, Hoechst staining revealed concentrated and illuminated apoptotic nuclei. The activation of ROS and the decline of GPX4 expression suggested that HE might induce ferroptosis as an anti-BLCA process. Shrunk mitochondria and apoptotic bodies were observed in BLCA cells treated with HE, with reduced or absent mitochondrial cristae. We propose for the first time that HE could inhibit the proliferation and migration of BLCA cells and promote apoptosis and ferroptosis. HE may act by targeting proteins such as SRC, PIK3R1 and MAPK1 and the PI3K/AKT pathway.


Assuntos
Hesperidina , Fosfatidilinositol 3-Quinases , Neoplasias da Bexiga Urinária , Humanos , Simulação de Acoplamento Molecular , Proteínas Proto-Oncogênicas c-akt , Farmacologia em Rede , Espécies Reativas de Oxigênio , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Fatores de Transcrição
5.
Viruses ; 15(12)2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-38140602

RESUMO

MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) serves as a pivotal mediator for NF-κB activation in response to a wide spectrum of transmembrane receptor stimuli. In the present study, a homolog of MALT1, named LvMALT1, is cloned from the Pacific white shrimp (Litopenaeus vannamei) and its potential function in shrimp innate immunity is explored. The open reading frame of LvMALT1 is 2364 bp that encodes 787 amino acids. The predicted LvMALT1 protein structure comprises a death domain, three immunoglobulin domains, and a caspase-like domain, exhibiting remarkable similarity to other homologs. LvMALT1 is a cytoplasmic-localized protein and could interact with LvTRAF6. Overexpression of LvMALT1 induces the activation of promoter elements governing the expression of several key antimicrobial peptides (AMPs), including penaeidins (PENs) and crustins (CRUs). Conversely, silencing of LvMALT1 leads to a reduction in the phosphorylation levels of Dorsal and Relish, along with a concomitant decline in the in vivo expression levels of multiple AMPs. Furthermore, LvMALT1 is prominently upregulated in response to a challenge by the white spot syndrome virus (WSSV), facilitating the NF-κB-mediated expression of AMPs as a defense against viral infection. Taken together, we identified a MALT1 homolog from the shrimp L. vannamei, which plays a positive role in the TRAF6/NF-κB/AMPs axis-mediated innate immunity.


Assuntos
Viroses , Vírus da Síndrome da Mancha Branca 1 , Humanos , NF-kappa B/metabolismo , Transdução de Sinais , Regiões Promotoras Genéticas , Regulação da Expressão Gênica , Vírus da Síndrome da Mancha Branca 1/genética , Imunidade Inata , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/genética , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/metabolismo
6.
Cell Mol Biol Lett ; 28(1): 89, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891494

RESUMO

BACKGROUND: The unique expression pattern endows oncofetal genes with great value in cancer diagnosis and treatment. However, only a few oncofetal genes are available for clinical use and the underlying mechanisms that drives the fetal-like reprogramming of cancer cells remain largely unknown. METHODS: Microarray assays and bioinformatic analyses were employed to screen for potential oncofetal long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC). The expression levels of MIR4435-2HG, NOP58 ribonucleoprotein (NOP58), insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) and stem markers were detected by quantitative polymerase chain reaction. The 2'-O-methylation (2'-O-Me) status of rRNA were detected through reverse transcription at low dNTP concentrations followed by PCR. The regulation of MIR4435-2HG by IGF2BP1 was explored by RNA immunoprecipitation (RIP), methylated RIP (MeRIP) and dual-luciferase assays. The interaction between MIR4435-2HG and NOP58 was investigated by RNA Pulldown, RIP and protein stability assays. In vitro and in vivo function assays were performed to detect the roles of MIR4435-2HG/NOP58 in HCC. RESULTS: MIR4435-2HG was an oncofetal lncRNA associated with poor prognosis in HCC. Functional experiments showed that overexpression of MIR4435-2HG remarkably enhanced the stem-cell properties of HCC cells, promoting tumorigenesis in vitro and in vivo. Mechanically, MIR4435-2HG directly bound NOP58 and IGF2BP1. IGF2BP1 upregulated MIR4435-2HG expression in HCC through N6-methyladenosine (m6A) modification. Moreover, MIR4435-2HG protected NOP58 from degradation, which raised rRNA 2'-O-Me levels and promoted internal ribosome entry site (IRES)-dependent translation of oncogenes. CONCLUSIONS: This study identified an oncofetal lncRNA MIR4435-2HG, characterized the role of MIR4435-2HG/NOP58 in stemness maintenance and proliferation of HCC cells, and confirmed m6A as a 'driver' that reactivated MR4435-2HG expression in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , RNA Longo não Codificante/genética , Metilação , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética
7.
Eur J Med Res ; 28(1): 264, 2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37537658

RESUMO

Premature ovarian failure (POF) is defined by amenorrhea, ovarian atrophy, hypoestrogenism, elevated gonadotropin level, and infertility under the age of 40. POF is frequently induced by chemotherapeutic agents. However, the underlying mechanisms regarding chemotherapy-mediated damage to ovarian function are unclear. In this study, enhanced apoptosis of granulosa cells (GCs) and aberrant activation of primordial follicles were observed in a POF mouse model induced by cisplatin. We subsequently observed significant downregulation of miR-144-3p and upregulation of mitogen-activated protein kinase kinase kinase 9 (MAP3K9) in primary ovarian GCs from POF mice, as revealed by microarrays. Furthermore, MAP3K9 expression was higher in human ovarian granulosa cells (COV434) treated with cisplatin and was identified as a novel target of miR-144-3p. Functional analysis revealed that miR-144-3p attenuated cisplatin induced apoptosis of GCs via silencing MAP3K9 expression, which suppressed the activity of the downstream p38 mitogen activated protein kinase (MAPK) pathway. Meanwhile, miR-144-3p prevented premature primordial follicle depletion in cisplatin-induced POF mice through targeting Map3k9, which led to a decline in the phosphorylation and activation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase b (AKT) pathway. Taken together, this study revealed the protective effects of miR-144-3p on ovarian function and shed light on the epigenetic regulatory mechanism in the development of POF, which might provide new biomarkers for the ovarian reserve.


Assuntos
Antineoplásicos , MicroRNAs , Insuficiência Ovariana Primária , Animais , Feminino , Humanos , Camundongos , Antineoplásicos/farmacologia , Apoptose , Cisplatino/efeitos adversos , Células da Granulosa/metabolismo , MAP Quinase Quinase Quinases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/prevenção & controle
8.
J Immunol ; 210(9): 1324-1337, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36883975

RESUMO

ß-Defensins are a family of cysteine-rich antimicrobial peptides that are generally monodomain. Interestingly, the avian ß-defensin 11 (AvBD11) is unique, with two ß-defensin motifs with a broad range of antimicrobial activities. However, a double-sized ß-defensin has not been identified and functionally characterized in invertebrates. In this study, we cloned and identified a double-ß-defensin in shrimp Litopenaeus vannamei (named LvDBD) and explored its potential roles during infection with shrimp pathogens Vibrio parahaemolyticus and white spot syndrome virus (WSSV). LvDBD is an atypical double-sized defensin, which is predicted to possess two motifs related to ß-defensin and six disulfide bridges. The RNA interference-mediated knockdown of LvDBD in vivo results in phenotypes with increased bacterial loads, rendering the shrimp more susceptible to V. parahaemolyticus infection, which could be rescued by the injection of recombinant LvDBD protein. In vitro, rLvDBD could destroy bacterial membranes and enhance hemocyte phagocytosis, possibly attributable to its affinity to the bacterial wall components LPS and peptidoglycan. In addition, LvDBD could interact with several viral envelope proteins to inhibit WSSV proliferation. Finally, the NF-κB transcription factors (Dorsal and Relish) participated in the regulation of LvDBD expression. Taken together, these results extend the functional understanding of a double-ß-defensin to an invertebrate and suggest that LvDBD may be an alternative agent for the prevention and treatment of diseases caused by V. parahaemolyticus and WSSV in shrimp.


Assuntos
Anti-Infecciosos , Penaeidae , Vibrio parahaemolyticus , Vírus da Síndrome da Mancha Branca 1 , beta-Defensinas , Animais , beta-Defensinas/genética , Invertebrados , Vibrio parahaemolyticus/metabolismo , Interferência de RNA , Penaeidae/microbiologia , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/farmacologia , Proteínas de Artrópodes/metabolismo
9.
Langmuir ; 38(50): 15506-15515, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36480753

RESUMO

In this study, the flame spray pyrolysis (FSP) technique was employed to produce WO3 nanoparticles, which were subsequently used as sensing materials for NO2 sensors. To enhance the sensing performance, the effects of flame parameters on the particle properties and sensing performances for 150-1200 ppb NO2 at 125 °C were investigated. The results indicate that WO3 particles with an average crystal size of about 10-20 nm and a standard deviation of about 3-7.5 nm were generated by controlling the precursor and dispersion oxygen flow rate of FSP. Based on the evaluation of NO2 sensing performance, WO3 sensing materials synthesized under the 3/5 flame condition exhibited better sensitivity than sensors made under other flame conditions. In summary, the FSP method and the optimization of flame synthesis parameters could be an effective strategy to prepare the sensing materials with high sensing performance.

10.
Front Pharmacol ; 13: 1053184, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36532756

RESUMO

Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system, which is highly invasive, metastatic, and insensitive to radiotherapy and chemotherapy. Chinese herbal medicine has always been an important source of anti-tumor drug development. Reineckia carnea Kunth is a traditional herb commonly used by the Miao nationality in southwest China. In this study, the extract of Reineckia carnea was isolated and purified by reverse phase preparative chromatography and other chromatographic techniques. According to the physicochemical properties and spectral data, the structure of the compound was identified, and a novel biflavone compound named Reineckia-biflavone A (RFA) was obtained. The result of antiproliferative activity showed that RFA had cytotoxicity on 786-O cells with an IC50 value of 19.34 µmol/L. The results of CCK-8 and hemolysis assays showed that RFA was not significantly cytotoxic to both red blood cells (RBC) and peripheral blood mononuclear cells (PBMC). By Hoechst 33258 apoptosis staining, typical apoptotic morphology was observed under fluorescence microscope. RFA could induce the apoptosis of 786-O cells with the increase of apoptosis rate. The cell cycle tests showed that the cell proportion was obviously arrested in the S phase. At the same time, RFA could decrease the mitochondrial membrane potential and increase the intracellular free Ca2+ concentration. Western blot showed that the expression levels of pro-apoptotic proteins (Bax, Caspase-3, Cleaved Caspase-3, and Cytochrome c) in cells rose, while the expression level of anti-apoptotic proteins (Bcl-2) declined significantly. In conclusion, this study suggests that the RFA is a new biflavone determined by SciFinder retrieval. The apoptosis may be triggered by RFA through the mitochondrial pathway, which is mediated by up-regulating the intracellular calcium ion, down-regulating the mitochondrial membrane potential, and changing the apoptosis-related proteins.

11.
J Immunol ; 209(10): 2022-2032, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36426947

RESUMO

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates immune modulation following exposure of animals to many environmental xenobiotics. However, its role in innate immune responses during viral infection is not fully understood, especially in invertebrates. In this study, a cDNA encoding an AhR homolog was cloned from an arthropod Litopenaeus vannamei (LvAhR). The expression of LvAhR was strongly upregulated in response to the challenge of white spot syndrome virus, a pathogen of highly contagious and fatal infectious disease of shrimp. The relevance of LvAhR to host defense was underlined by heightened susceptibility and elevated virus loads after AhR-silenced shrimp exposure to white spot syndrome virus. LvAhR could induce an apoptosis response through regulating the expression of L. vannamei caspase-1 (homologous to human caspase-3) by directly targeting its promoter that was required to couple with AhR nuclear translocator. Additionally, knockdown of L. vannamei caspase-1 resulted in elevated virus titers and a lower cell apoptotic rate. Thus, we demonstrate that an AhR-caspase axis restrains virus replication by promoting antiviral apoptosis, supporting a previously unidentified direct link between AhR signaling and caspase-mediated apoptosis signaling and, furthermore, suggests that the AhR-caspase axis could be a potential therapeutic target for enhancing antiviral responses in arthropods.


Assuntos
Artrópodes , Vírus da Síndrome da Mancha Branca 1 , Animais , Humanos , Receptores de Hidrocarboneto Arílico/genética , Caspases/genética , Antivirais , Apoptose/genética , Caspase 1
12.
Materials (Basel) ; 15(13)2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35806666

RESUMO

The effects of Al deoxidation and Zr deoxidation on the microstructure and properties of sulfide stress corrosion resistant high-strength steel have been investigated. The feasibility of the Zr deoxidation instead of Al deoxidation was confirmed by the thermodynamic analysis of the deoxidation of various elements. The experimental results indicate that the average diameters of the inclusions in Al-Steel and Zr-Steel were 2.45 µm and 1.65 µm, respectively. The Al-Steel and Zr-Steel contained 22.38% and 68.77% inclusions per unit area, respectively, and the fraction of inclusions in the Al-Steel and Zr-Steel with diameters less than 2 µm was about 73.46% and 89.63%, respectively, indicating that the Zr deoxidation process could effectively refine inclusions and promote dispersion. The average diameters of austenite grain for the Al-Steel and Zr-Steel were about 9.1 µm and 8 µm, respectively. The fine particles in Zr-Steel could pin the austenite grain boundaries and clearly refine the grains. The average grain size of tempered martensite was 8.2 µm and 3.8 µm, respectively. The yield strength of the Al-Steel and Zr-Steel was 922 MPa and 939 MPa, respectively; the impact energy was 60 ± 6 J and 132 ± 6 J, respectively. Moreover, the fracture time of the NACE-A was from 28 h (Al-Steel) to 720 h (Zr-Steel) without fracture. The experimental steel deoxidized by Zr achieved a simultaneous improvement in strength, toughness and sulfide stress corrosion resistance, and the effect of inclusions on the fracture of the sulfide stress corrosion resistant high-strength steel can be explained by the Griffith theory.

13.
Front Oncol ; 12: 851300, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35392243

RESUMO

The leading cause of cancer deaths is lung cancer, non-small cell lung cancer (NSCLC), the most common type of lung cancers, remains a difficult cancer to treat and cure. It is urgent to develop new products to treat NSCLS. Gracillin, extracted from Reineckia carnea, Dioscorea villosa, and other medicinal plants, has anti-tumor potential with toxic effect on a variety of tumor cells such as NSCLC. However, the anti-NSCLC mechanism of gracillin is not completely clear. In this study, A549 cells and athymic nude mice were used as models to evaluate the anti-NSCLC effects of gracillin. The antiproliferative activity of gracillin on A549 cells was conducted by CCK-8, and obvious autophagy was observed in gracillin-treated A549 through transmission electron microscopy. Furthermore, the expressions of Beclin-1, LC3-II, and WIPI1 were upregulated, while the expression of p62 was downregulated in gracillin-treated A549. The further mechanism study found that the mTOR signaling pathway was significantly inhibited by gracillin. Accordingly, the PI3K/Akt pathway positively regulating mTOR was inhibited, and AMPK negatively regulating mTOR was activated. Meanwhile, LC3-II transformation was found to be significantly reduced after WIPI1 was silenced in A549 cells but increased after gracillin treatment. It also proves that WIPI is involved in the process of gracillin regulating A549 autophagy. At last, the anti-tumor growth activity of gracillin in vivo was validated in A549-bearing athymic nude mice. In conclusion, gracillin has anti-NSCLC activity by inducing autophagy. The mechanism maybe that gracillin inhibited the mTOR signaling pathway. Gracillin has the potential to be a candidate product for the treatment of NSCLC in the future.

14.
Dev Comp Immunol ; 125: 104174, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34324899

RESUMO

Antimicrobial peptides (AMPs) play an important role in the host defense system of shrimps. In this study, an Arasin-like peptide, named as LvArasin-like, was identified from the hemocytes of the pacific white shrimp, Litopenaeus vannamei. The complete open reading frame (ORF) of LvArasin-like was 213 bp, encoding 70 amino acid residues with a predicted molecular mass of 5.68 kDa and a theoretical isoelectric point (pI) of 6.73. The predicted peptide consisted of a signal peptide, an N-terminal Pro/Arg-rich domain, and a C-terminal cysteine-rich domain. LvArasin-like expression was most abundant in the gills and was up-regulated in hemocytes after LPS or Poly I:C injection as well as challenges by Vibrio parahaemolyticus or Staphylococcus aureus infection. In the heterologous expression system, LvArasin-like protein (rLvArasin-like) was recombinantly expressed in the forms of a dimer or both a monomer and dimer. The rLvArasin-like could directly bind to gram-positive and gram-negative bacteria and exhibited broad-spectrum antimicrobial activity towards them, with 50 % of minimal inhibitory concentrations (MIC50) of 6.25-50 µM. Moreover, dsRNA-mediated knockdown of LvArasin-like enhanced the susceptibility of shrimp to V. parahaemolyticus. In addition, the transcriptional level of LvArasin-like was downregulated when silencing of the transcription factors LvDorsal and LvRelish using RNAi in vivo. All of these results suggest that LvArasin-like is involved in host defense against bacterial infection. Therefore, it is a potential therapeutic agent for disease control in shrimp aquaculture.


Assuntos
Peptídeos Antimicrobianos/metabolismo , Proteínas de Artrópodes/metabolismo , Brânquias/metabolismo , Hemócitos/metabolismo , Penaeidae/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/fisiologia , Vibrioses/imunologia , Vibrio parahaemolyticus/fisiologia , Viroses/imunologia , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Antimicrobianos/genética , Proteínas de Artrópodes/genética , Clonagem Molecular , Imunidade Inata , Poli I-C/imunologia
15.
Fish Shellfish Immunol Rep ; 2: 100034, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36420505

RESUMO

Penaeidins are members of an antimicrobial peptide (AMP) family that have broad anti-microbial activities only found in penaeid shrimps. The LvBigPEN, a member of penaeidins from shrimp Litopenaeus vannamei, has showed antiviral activity against white spot syndrome virus (WSSV) in our previous report. However, whether LvBigPEN possesses potential anti-bacterial activities is still unknown. Herein, we found that the LvBigPEN played an important role in restricting the infection of Vibrio parahaemolyticus, a natural and Gram-negative bacteria pathogen in shrimp. The transcription of LvBigPEN was strongly induced after V. parahaemolyticus challenge. RNA interference (RNAi) mediated knockdown of LvBigPEN showed that LvBigPEN had a potential antibacterial function against V. parahaemolyticus. Microorganism binding assays indicated that rLvBigPEN could bind to both Gram-negative bacteria and Gram-positive bacteria. Transmission electron microscopy (TEM) analysis showed its ability to destroy bacterial cells in vitro. Besides, in a gel retardation assay, rLvBigPEN could bind to plasmid DNA and bacteria (V. parahaemolyticus) genomic DNA in a concentration-dependent manner. Moreover, the AP-1 pathway could participate in the transcription of LvBigPEN by the dual luciferase reporter assays. Taken together, these results suggested that LvBigPEN possessed the antibacterial activity against V. parahaemolyticus and may be alternative agents for the prevention and treatment of diseases caused by V. parahaemolyticus.

16.
Int J Oncol ; 57(3): 767-779, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32705161

RESUMO

Circular RNAs (circRNAs) are non­coding RNAs that are connected at the 3' and 5' ends by an exon or intron. Studies increasingly show that circRNAs play an important role in tumorigenesis by acting as a 'sponge' for microRNAs (miRNAs), which abrogates the latter's effect on their target mRNAs. To identify a possible circRNA/miRNA/mRNA network in bladder cancer (BCa), we analyzed the circRNA and mRNA expression profiles of BCa and adjacent normal bladder tissues. A total of 127 circRNAs and 1,612 mRNAs were differentially expressed in the tumor tissues, and were primarily associated with cancer­related pathways. A competing endogenous RNAs (ceRNA) network was then constructed which predicted a regulatory axis of circRNA_0071196, miRNA­19b­3p and its target gene citron Rho­interacting serine/threonine kinase (CIT). Luciferase reporter assay validated the relationship between circRNA_0071196 and miRNA­19b­3p and of the latter with CIT. Furthermore, CIT was overexpressed in the BCa tissues, and was found to be correlated with metastasis and tumor histological grade. Knockdown of CIT in the human bladder cancer cell line 5367 significantly inhibited the proliferation, migration and colony formation capacity of the cells, and also upregulated the mediators of the p53 and RhoA­ROCK signaling cascades that regulate cell cycle and migration. Taken together, our findings indicate that circRNA­0071196 upregulates CIT levels in BCa by sponging off miRNA­19b­3p, and the circRNA_0071196/miRNA­19b­3p/CIT axis is a potential therapeutic target in BCa.


Assuntos
Carcinoma/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , MicroRNAs/metabolismo , Proteínas Serina-Treonina Quinases/genética , RNA Circular/metabolismo , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Carcinoma/cirurgia , Linhagem Celular Tumoral , Cistectomia , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Redes Reguladoras de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Regulação para Cima , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
17.
Emerg Microbes Infect ; 9(1): 390-412, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32397950

RESUMO

Emerging studies have indicated that some penaeidins restrict virus infection; however, the mechanism(s) involved are poorly understood. In the present study, we uncovered that penaeidins are a novel family of antiviral effectors against white spot syndrome virus (WSSV), which antagonize the envelope proteins to block viral entry. We found that the expression levels of four identified penaeidins from Litopenaeus vannamei, including BigPEN, PEN2, PEN3, and PEN4, were significantly induced in hemocytes during the early stage of WSSV infection. Knockdown of each penaeidin in vivo via RNA interference resulted in elevated viral loads and rendered shrimp more susceptible to WSSV, while the survival rate was rescued via the injection of recombinant penaeidins. All penaeidins, except PEN4, were shown to interact with several envelope proteins of WSSV, and all four penaeidins were observed to be located on the outer surface of the WSSV virion. Co-incubation of each recombinant penaeidin with WSSV inhibited virion internalization into hemocytes. More importantly, we found that PEN2 competitively bound to the envelope protein VP24 to release it from polymeric immunoglobulin receptor (pIgR), the cellular receptor required for WSSV infection. Moreover, we also demonstrated that BigPEN was able to bind to VP28 of WSSV, which disrupted the interaction between VP28 and Rab7 - the Rab GTPase that contributes to viral entry by binding with VP28. Taken together, our results demonstrated that penaeidins interact with the envelope proteins of WSSV to block multiple viral infection processes, thereby protecting the host against WSSV.


Assuntos
Antivirais/farmacologia , Penaeidae/virologia , Peptídeos , Vírus da Síndrome da Mancha Branca 1/efeitos dos fármacos , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/farmacologia , Expressão Gênica , Hemócitos/virologia , Peptídeos/genética , Peptídeos/farmacologia , Proteínas do Envelope Viral/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
18.
Biol Open ; 8(9)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31551242

RESUMO

Accumulating evidence suggests that circular RNAs (circRNAs) play important roles in various physiological and pathological processes. In the present study, we explored the role of circRNA PVT1 in hepatocellular carcinoma (HCC). qRT-PCR was performed to detect the relative expression of circPVT1 in HCC tissues and cell lines. The oncogenic roles of circPVT1 in HCC were evaluated by cell counting kit-8 (CCK-8) assay, ethynyl deoxyuridine (EdU) incorporation assays, transwell assays, flow cytometry and in vivo xenograft growth. Furthermore, bioinformatics, luciferase reporter assays and rescue experiments were conducted to determine the underlying mechanism of circPVT1 in HCC. Enhanced circPVT1 expression was detected in HCC tissues, which was closely associated with poor prognosis of patients with HCC. Knockdown of circPVT1 decreased the proliferation and migration ability of HCC cell lines in vitro Conversely, upregulation of circPVT1 improved the growth and migration in HCC cells. Mechanistically, we found that circPVT1 could bind directly to miR-203 and contributed to the initiation and progression of HCC by regulating miR-203/homebox D3 (HOXD3) pathway. In conclusion, our study reveals that circPVT1 participates in the progression of HCC through the miR-203/homeobox D3 (HOXD3) pathway and might represent a potential therapeutic target for HCC treatment.

19.
Biol Open ; 8(5)2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30890521

RESUMO

Bone marrow mesenchymal stem cells (BMSCs) have potential therapeutic benefits for the treatment of endometrial diseases and injury. BMSCs interact with uterus parenchymal cells by direct contact or indirect secretion of growth factors to promote functional recovery. In this study, we found that BMSC treatment in rats subjected to mechanical damage (MD) significantly increased microRNA-340 (miR-340) levels in the regenerated endometrium. Then we employed knockin and knockdown technologies to upregulate or downregulate the miR-340 level in BMSCs (miR-340+ BMSCs or miR-340- BMSCs) and their corresponding exosomes, respectively, to test whether exosomes from BMSCs mediate miR-340 transfer. We found that the exosomes released from the primitive BMSCs or miR-340+ BMSCs but not miR-340- BMSCs increased the miR-340 levels in primary cultured endometrial stromal cells (ESCs) compared with control. Further verification of this exosome-mediated intercellular communication was performed using exosomal inhibitor GW4869. Tagging exosomes with red fluorescent protein demonstrated that exosomes were released from BMSCs and transferred to adjacent ESCs. Compared with controls, rats receiving primitive BMSC treatment significantly improved functional recovery and downregulated collagen 1α1, α-SMA and transforming growth factor (TGF)-ß1 at day 14 after MD. The outcomes were significantly enhanced by miR-340+ BMSC treatment, and were significantly weakened by miR-340- BMSC treatment, compared with primitive BMSC treatment. In vitro studies reveal that miR-340 transferred from BMSCs suppresses the upregulated expression of fibrotic genes in ESCs induced by TGF-ß1. These data suggest that the effective antifibrotic function of BMSCs is able to transfer miR-340 to ESCs by exosomes, and that enhancing the transfer of BMSC-derived miR-340 is an alternative modality in preventing intrauterine adhesion.

20.
Adv Healthc Mater ; 8(5): e1801455, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30734535

RESUMO

Intrauterine adhesion (IUA) causing infertility and recurrent miscarriage of reproductive female mammals usually results from endometrium injury. Nevertheless, there is no efficient therapeutic method to avoid IUA. Bone marrow derived mesenchymal stem cells (BMSCs) are an important cell source for tissue regeneration. This study designs and explores the ability of BMSC-loaded elastic poly(glycerol sebacate) (PGS) scaffold to prevent IUA and compares the effect of PGS with poly(lactic-co-glycolic acid) (PLGA) and collagen scaffolds in resumption of damaged rat uteruses. The 3D architecture provided by PGS scaffolds favors the attachment and growth of rat BMSCs. In vivo bioluminescence imaging shows that compared with direct BMSC intrauterine injection, PLGA, and collagen scaffolds, the PGS scaffold significantly prolongs the retention time of BMSCs in a wounded rat uterus model. More importantly, BMSCs can directly differentiate into endometrial stromal cells after transplantation of PGS/BMSCs constructs, but not PLGA/BMSCs and collagen/BMSCs. It is found that the level of transforming growth factor ß1 (TGF-ß1), basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and insulin-like growth factors in the injured endometrium adjacent to PGS/BMSCs constructs is higher than those of rats receiving PLGA/BMSCs, collagen/BMSCs, or BMSCs intrauterine transplantation. Besides, transplantation of PGS/BMSCs leads to better morphology recovery of the damaged uterus than PLGA/BMSCs and collagen/BMSCs. The receptive fertility of PGS/BMSCs is 72.2 ± 6.4%, similar to the one of collagen/BMSCs, but significantly higher than 42.3 ± 3.9% in PLGA/BMSCs. Taken together, PGS/BMSCs may be a promising candidate for preventing IUA.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Decanoatos/química , Glicerol/análogos & derivados , Células-Tronco Mesenquimais/efeitos dos fármacos , Polímeros/química , Alicerces Teciduais/química , Útero/efeitos dos fármacos , Animais , Células da Medula Óssea/metabolismo , Células Cultivadas , Colágeno/metabolismo , Feminino , Glicerol/química , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos , Ratos Sprague-Dawley , Engenharia Tecidual/métodos , Fator de Crescimento Transformador beta1/metabolismo , Útero/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
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