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2.
ChemistryOpen ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33829677

RESUMO

During the last decades, there has been growing interest in using therapeutic messager RNA (mRNA) together with drug delivery systems. Naked, unformulated mRNA is, however, unable to cross the cell membrane and is susceptible to degradation. Here we use graphene quantum dots (GQDs) functionalized with polyethyleneimine (PEI) as a novel mRNA delivery system. Our results show that these modified GQDs can be used to deliver intact and functional mRNA to Huh-7 hepatocarcinoma cells at low doses and, that the GQDs are not toxic, although cellular toxicity is a problem for these first-generation modified particles. Functionalized GQDs represent a potentially interesting delivery system that is easy to manufacture, stable and effective.

3.
Int J Med Sci ; 18(9): 1999-2007, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33850470

RESUMO

Precartilaginous stem cells (PCSCs) are able to initiate chondrocyte and bone development. The present study aimed to investigate the role of miR-143 and the underlying mechanisms involved in PCSC proliferation. In a rat growth plate injury model, tissue from the injury site was collected and the expression of miR-143 and its potential targets was determined. PCSCs were isolated from the rabbits' distal epiphyseal growth plate. Cell viability, DNA synthesis, and apoptosis were determined with MTT, BrdU, and flow cytometric analysis, respectively. Real time PCR and western blot were performed to detect the mRNA and protein expression of the indicated genes. Indian hedgehog (IHH) was identified as a target gene for miR-143 with luciferase reporter assay. Decreased expression of miR-143 and increased expression of IHH gene were observed in the growth plate after injury. miR-143 mimics decreased cell viability and DNA synthesis and promoted apoptosis of PCSCs. Conversely, siRNA-mediated inhibition of miR-143 led to increased growth and suppressed apoptosis of PCSCs. Transfection of miR-143 decreased luciferase activity of wild-type IHH but had no effect when the 3'-UTR of IHH was mutated. Furthermore, the effect of miR-143 overexpression was neutralized by overexpression of IHH. Our study showed that miR-143 is involved in growth plate behavior and regulates PCSC growth by targeting IHH, suggesting that miR-143 may serve as a novel target for PCSC-related diseases.

4.
Materials (Basel) ; 14(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799829

RESUMO

An SiO2-TiO2 closed-surface antireflective coating was fabricated by the one-dipping method. TiO2 nanoparticles were mixed with a nanocomposited silica sol, which was composed of acid-catalyzed nanosilica networks and silica hollow nanospheres (HNs). The microstructure of the sol-gel was characterized by transmission electron microscopy. The silica HNs were approximately 40-50 nm in diameter with a shell thickness of approximately 8-10 nm. The branched-chain structure resulting from acidic hydrolysis grew on these silica HNs, and TiO2 was distributed inside this network. The surface morphology of the coating was measured by field emission scanning electron microscopy and atomic force microscopy. After optimization, transmittance of up to 94.03% was obtained on photovoltaic (PV) glass with a single side coated by this antireflective coating, whose refractive index was around 1.30. The short-circuit current gain of PV module was around 2.14-2.32%, as shown by the current-voltage (IV) curve measurements and external quantum efficiency (EQE) tests. This thin film also exhibited high photocatalytic activity. Due to the lack of voids on its surface, the antireflective coating in this study possessed excellent long-term reliability and robustness in both high-moisture and high-temperature environments. Combined with its self-cleaning function, this antireflective coating has great potential to be implemented in windows and photovoltaic modules.

5.
J Int Med Res ; 49(4): 3000605211002703, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33794677

RESUMO

Azoospermia is divided into two categories of obstructive azoospermia and non-obstructive azoospermia. Before 1995, couples with a male partner diagnosed with non-obstructive azoospermia had to choose sperm donation or adoption to have a child. Currently, testicular sperm aspiration or micro-dissection testicular sperm extraction combined with intracytoplasmic sperm injection allows patients with non-obstructive azoospermia to have biological offspring. The sperm retrieval rate is significantly higher in micro-dissection testicular sperm extraction compared with testicular sperm aspiration. Additionally, micro-dissection testicular sperm extraction has the advantages of minimal invasion, safety, limited disruption of testicular function, a low risk of postoperative intratesticular bleeding, and low serum testosterone concentrations. Failed micro-dissection testicular sperm extraction has significant emotional and financial implications on the involved couples. Testicular sperm aspiration and micro-dissection testicular sperm extraction have the possibility of failure. Therefore, predicting the sperm retrieval rate before surgery is important. This narrative review summarizes the existing data on testicular sperm aspiration and micro-dissection testicular sperm extraction to identify the possible factor(s) that can predict the presence of sperm to guide clinical practice. The predictors of surgical sperm retrieval in patients with non-obstructive azoospermia have been widely studied, but there is no consensus.

6.
Carbohydr Polym ; 261: 117878, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33766365

RESUMO

Hydrogels have gained great attentions as wound dressing. Binding to the tissue and preventing wound infection were the basic requirements for an "ideal dressing". We employed l-DOPA and ε-Poly-l-lysine to modify thermo-sensitive hydroxybutyl chitosan (HBC) to obtain (l-DOPA) - (ε-Poly-l-lysine)-HBC hydrogels (eLHBC). The eLHBC exhibited an almost 1.5 fold (P < 0.01) increase in wet adhesion strength compared to HBC. Upon the introduction of ε-Poly-l-lysine, eLHBC presented inherent antimicrobial property and prevented wound infection and inflammation response. Bone marrow mesenchymal stem cells (BMSCs) encapsulated in the eLHBC (BMSCs ⊂ eLHBC) could secret cytokins and growth factors via paracrine and promote the migration of fibroblast cells. BMSCs ⊂ eLHBC enhanced the complete skin-thickness wound healing via promoting collagen deposition and inhibiting infection and inflammation in vivo with wound closure rate being above 99 % after 15 days. The bioinspired, tissue-adhesive eLHBC could serve as advanced wound dressings for facilitating tissue repair and regeneration.

7.
Oncol Rep ; 45(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33760221

RESUMO

Hydrogen sulfide (H2S), the third gas signal molecule, is associated with the modulation of various physiological and pathological processes. Recent studies have reevealed that endogenous H2S may promote proliferation, induce angiogenesis and inhibit apoptosis, thereby stimulating oncogenesis. Conversely, decreased endogenous H2S release suppresses growth of various tumors including breast cancer. This observation suggests an alternative tumor therapy strategy by inhibiting H2S­producing enzymes to reduce the release of endogenous H2S. Breast cancer is the most common type of cancer in women. Due to the lack of approved targeted therapy, its recurrence and metastasis still affect its clinical treatment. In recent years, significant progress has been made in the control of breast cancer by using inhibitors on H2S­producing enzymes. This review summarized the roles of endogenous H2S­producing enzymes in breast cancer and the effects of the enzyme inhibitors on anticancer and anti­metastasis, with the aim of providing new insights for the treatment of breast cancer.

8.
Chem Biodivers ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33682992

RESUMO

4,21-Secovincanol (1), a novel C-21/N-4 cleavage monoterpenoid indole alkaloid, along with four analogs (2-5), were obtained from the aerial parts of Kopsia hainanensis. Structurally, compound 1 might be a derivative of epivincanol (2) via C-21/N-4 cleavage. Their structures were confirmed by means of comprehensive spectroscopic data analysis and comparison with the reported data. All isolates significantly inhibited Con A-stimulated mice splenocytes proliferation at 10-40 µM in a dose-dependent manner in vitro. Especially, compound 3 exhibited potent activities comparable to positive control (Dexamethasone, DXM).

9.
J Dig Dis ; 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33742780

RESUMO

BACKGROUND: COVID-19 has caused an ongoing worldwide pandemic. Much remains unknown about detailed symptomatic features of COVID-19 onset and rehabilitation. METHODS: In this retrospective cohort study, 932 hospitalized patients with COVID-19 in Wuhan were enrolled, including 52 severe cases and 880 non-severe cases. The symptomatic features were analyzed and compared between the severe and non-severe groups. All patients were followed up 3 months after discharge. RESULTS: Of the 932 patients, fever (60%), cough (50.8%), and fatigue (36.4%) were the most common symptoms, followed by anorexia (21.8%) and dyspnea (19.2%). The median duration of fever was 7 days, which was characterized by persistent low fever. The median duration of cough was 17 days, characterized by dry cough without sputum. Most dyspnea occurred on the fourth day after illness onset, with a median duration of 16 days. The incidences of taste loss and olfactory disturbance were only 6.2% and 3.1%, respectively. After adjusting age and gender, multivariate regression analysis showed that fever lasting for more than 5 days (OR 1.90, 95%CI 1.00-3.62, P = 0.0498), anorexia at onset (2.61, 1.26-5.40, P = 0.0096), and modified Medical Research Council level above grade 2 when dyspnea occurred (14.19, 7.01-28.71, P < 0.0001) were symptomatic risk factors for severe COVID-19. Through follow-up, cough (6.2%), dyspnea (7.2%), fatigue (1.8%), olfactory and taste disorders (1.5%) were the significant remaining symptoms. CONCLUSIONS: COVID-19 caused clusters of symptoms with multiple systems involved. Certain symptomatic characteristics have predictive value for severe COVID-19. Short-term follow-up showed that most patients had a good prognosis.

10.
Theriogenology ; 165: 92-98, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33647740

RESUMO

MicroRNAs (miRNAs) are key epigenomic regulators of proliferation, differentiation, and secretion in cells involved in follicular development. We here studied the functional role of one such molecule, miR-130a-3p, in goat ovarian granulosa cells (GCs). High expression of this miRNA was evident in goat GCs by fluorescence in situ hybridization and suppressed estradiol and progesterone secretion from these cells, as determined by ELISA. miR-130a-3p was predicted to have a binding site for the 3' UTR of the prostate transmembrane protein androgen induced 1 gene (PMEPA1), and this was verified by a dual-luciferase reporter assay. PMEPA1 mRNA and protein expression were both found to be regulated by miR-130a-3p in GCs. Moreover, the overexpression or knockdown of PMEPA1 enhanced or suppressed estradiol and progesterone secretion from these cells, respectively. Furthermore, the secretion of estradiol and progesterone did not change significantly after the offsetting of PMEPA1 overexpression in GCs by miR-130a-3p. In summary, our present data indicate that miR-130a-3p inhibits the secretion of estradiol and progesterone in GCs by targeting PMEPA1. Our study thus provides seminal data and important new insights into the regulation of reproductive mechanisms in the nanny goat and other female mammals.

11.
J Hazard Mater ; 415: 125599, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33765563

RESUMO

With a huge amount of waste liquid crystal displays (LCDs) generated annually, their proper recycling raises continuous concern to realize pollution control (heavy metal and liquid crystal) and resource recovery (indium). However, due to their multi-metal feature, traditional hydrometallurgy lacks of sufficient selectivity, which makes the recycling route lengthy, costly, and generate more waste. Electrodeposition acts as a promising technique for selective metal extraction from multi-metal system due to its high selectivity and electron as clean reagent. To fully develop its application in metal recovery, stepwise Cu/MoO2 and In electrodeposition from In-Cu-Mo-Fe waste LCD leachate is explored in depth. Electrochemical behavior analysis shows Cu and MoO2 can be first electrodeposited for their higher electroreduction potential. Cl- plays a key role in accelerating indium electroreduction kinetics, which largely shortens the extraction time without the sacrifice of current efficiency. This accelerating effect is attributed to the increased concentration of electroactive species or collision frequency. Under optimized condition, 99.41% of indium (> 99% purity) can be electrodeposited within 13 h with high current efficiency. This study provides a cleaner approach for waste LCDs recycling and gives implications for the potential application of electrochemical technique in e-waste recycling.

12.
J Diabetes Investig ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33655702

RESUMO

OBJECTIVE: The role of cell death-inducing DFF45-like effector C (CIDEC) in insulin resistance has been established, and it is considered to be an important trigger factor for the progression of diabetic nephropathy (DN). We intend to explore whether CIDEC plays an important role in the regulation of DN and its potential mechanism. METHODS: High fat diet and low dose streptozotocin were used to establish type 2 diabetic rat model. We investigate the role of CIDEC in the pathogenesis and process of DN through histopathological analysis, western blot and gene silencing. Meanwhile, the effect of CIDEC on renal tubular epithelial cells stimulated by high glucose was also verified. RESULTS: DM group exhibited glucose and lipid metabolic disturbance, with hypertrophy of kidneys, damaged renal function, increased apoptosis, decreased autophagy, glomerulosclerosis and interstitial fibrosis. CIDEC gene silencing improved metabolic disorder and insulin resistance, alleviated renal hypertrophy and renal function damage, decreased glomerular and tubular apoptosis, increased autophagy and inhibited renal fibrosis. At the cellular level, high glucose stimulation increased CIDEC expression in renal tubular epithelial cells, accompanied by increased apoptosis and decreased autophagy. CIDEC gene silencing can improve autophagy and reduce apoptosis. At the molecular level, CIDEC gene silencing also decreased the expression of early growth response factor (EGR)1 and increased the expression of adipose triglyceride lipase (ATGL). CONCLUSION: CIDEC gene silencing may delay the progression of DN by restoring autophagy activity and inhibiting apoptosis with the participation of EGR1and ATGL.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33674440

RESUMO

We investigated the prevalence and transmission of NDM-producing Enterobacteriaceae in fecal samples of geese and environmental samples from a goose farm in Southern China. The samples were cultivated on MacConkey agar plates supplemented with meropenem. Individual colonies were examined for bla NDM and bla NDM-positive bacteria were characterized based on WGS data from the Illumina and ONT platforms. Of 117 samples analyzed, the carriage rates for NDM-positive Enterobacteriaceae were 47.1, 18 and 50% in geese, inanimate environments (sewage, soil, fodder and dust) and mouse samples, respectively. Two variants (4 bla NDM-1 and 40 bla NDM-5) were found among 44 bla NDM-positive Enterobacteriaceae, which belonged to 8 species and Escherichia coli was the most prevalent (50%). WGS analysis revealed that bla NDM co-existed with diverse antibiotic resistance genes (ARGs). Population structure analysis showed that most E. coli and Enterobacter sp. isolates were highly heterogeneous while most Citrobacter sp. and P. stuartii isolates possessed extremely high genetic similarity. Additionally, bla NDM-5-positive ST4358/ST48 E. coli isolates were found to be clonally spread between the geese and environment and were highly genetically similar to those reported from ducks, farm environments and humans in China. Plasmid analysis indicated that IncX3 pHNYX644-1-like (n=40) and untypable pM2-1-like plasmids (n=4) mediated bla NDM spread. pM2-1-like plasmids possessed diverse ARGs including bla NDM-1, the arsenical and mercury resistance operons and the maltose operon. Our findings revealed that the goose farm is a reservoir for NDM-positive Enterobacteriaceae. The bla NDM contamination of wild mice and the novel pM2-1-like plasmid described in this study likely adds to the risk for dissemination of bla NDM and associated resistance genes.Importance: The carbapenem-resistant bacteria, in particular NDM-producing Enterobacteriaceae, has become a great threat to global public. These bacteria have been found not only in hospital and community environments, but also among food animal production chains, which are recognized as reservoirs for NDM-producing Enterobacteriaceae. However, the dissemination of NDM-producing bacteria in the waterfowl farm has been less well explored. Our study demonstrated that horizontal spread of bla NDM-carrying plasmids and the partial clonal spread of bla NDM-positive Enterobacteriaceae contributed to widespread contamination of bla NDM in the goose farm ecosystem, including mouse. Furthermore, we found a novel and transferable bla NDM-1-carrying MDR plasmid that possessed multiple environmental adaptation-related genes. The outcomes of this study contribute to a better understanding of the prevalence and transmission of bla NDM-producing Enterobacteriaceae among diverse niches in the farm ecosystem.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33686406

RESUMO

In this study, we isolated and characterized HSP70 cDNA from pufferfish (Takifugu rubripes). The 3053 bp full-length TrHSP70 sequence consisted of a 167 bp 5'-UTR (untranslated region), a 2535 bp open reading frame, and a 351 bp 3'-UTR. BLAST analysis revealed that the TrHSP70 shared high similarity with HSP70 sequences in other species. In our study, we set 3 experimental groups as H1 group (20 °C), H2 group (24 °C), and H3 group (28 °C) for checking the expression level of TrHSP70 in T. rubripes. Tissue-specific gene expression results showed that TrHSP70 had higher expression in the intestines than other tissues of the T. rubripes by RT-qPCR. In the experimental group, we found that the expression of TrHSP70 was upregulated in different tissues in the H3 group. The results show that TrHSP70 is a constitutively expressed gene, which plays an important role in maintaining normal physiological function and coping with stress.

15.
World J Pediatr ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33650030

RESUMO

BACKGROUND: Our goal was to evaluate the association between neonatal blood brain-derived neurotrophic factor (BDNF) level and autism spectrum disorder (ASD) diagnosis later in life. METHODS: MEDLINE and Web of Science databases were searched from inception until September 16, 2020. Reference lists of all relevant articles also were reviewed. Mean blood BDNF concentrations, standard deviations, sample sizes, and other data needed for calculation of effect sizes were extracted by two independent investigators. The quality of the included studies was appraised using the Newcastle-Ottawa Scale for case-control studies. Data were pooled using the random-effects model. RESULTS: Five case-control studies involving 1341 cases and 3395 controls were included in the meta-analysis. The meta-analysis of all included studies showed no significant difference in blood BDNF levels between neonates diagnosed with ASD later in life and healthy controls [standardized mean difference (SMD) = 0.261; 95% confidence interval (CI) - 0.052 to 0.573; P = 0.102], with high level of heterogeneity (Q = 64.346; I2 = 93.784; P < 0.001). A subgroup analysis by assay type showed decreased blood BDNF levels in ASDs compared to controls (SMD = - 0.070; 95% CI - 0.114 to - 0.026; P = 0.002), with high level of homogeneity (Q = 0.894; I2 = 0.000; P = 0.827). No evidence of publication bias was observed. CONCLUSIONS: Neonates diagnosed with ASD later in life have decreased blood levels of BDNF measured by double-antibody immunoassay. More studies are warranted to facilitate a more robust conclusion.

16.
Sports Biomech ; : 1-12, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663343

RESUMO

Bat-ball contacts are critical in the baseball hitting process. However, an effective training method for increasing the impact perception of a bat-ball contact is currently unavailable. Although not widely used, hitting a stationary weighted baseball can be an appropriate method for batters to simulate the perception of hitting a moving baseball. Therefore, swing velocity, wrist vibration, and forearm muscle activation for hitting stationary weighted, stationary regulation, and pitched baseballs were investigated in this study. Twelve position players hit a stationary weighted, stationary regulation, and pitched baseball at a speed of 70.28 ± 3.84 km/h in a random order. The swing velocity, wrist vibration, forearm muscle activation, and co-contraction ratio during hitting phases were analysed. The results indicated that the swing velocity during each specific phase demonstrated no significant differences between the different conditions. Hitting weighted and pitched baseballs caused higher wrist vibration, muscle activation, and co-contraction ratio during the contact phase than hitting regulation balls (p < 0.05). The conclusion was that hitting weighted baseballs could mimic the impact condition of hitting pitched baseballs without changing the pattern of swing velocity, which suggested that this method has potential as a hitting drill for improving hitting perception at bat-ball contact.

17.
Phytochemistry ; 184: 112673, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33556841

RESUMO

The Melodinus species have been proved to be good resources of bisindole alkaloids. Six bisindole alkaloids were isolated from the leaves and stems of Melodinus cochinchinensis (Lour.) Merr. guided by HRESIMS data analysis. Among them, melokhanines K-M, epi-scandomelonine, and epi-scandomeline possessed aspidosperma-scandine skeleton linked by a C-C bond while meloyine II had a scandine-scandine skeleton. The structures were established by extensive spectroscopic analysis of their HRESIMS and NMR data. Melokhanines K-M were undescribed compounds, while epi-scandomelonine, epi-scandomeline and meloyine II were known compounds, which were reported from Melodinus species for the first time. The anti-inflammatory and cytotoxic activities of the isolates were also evaluated in vitro. Melokhanine K and meloyine II showed potent inhibitory activity on the production of nitric oxide, interleukin-6, and tumor necrosis factor-α in LPS-induced RAW 264.7 macrophages, whereas epi-scandomelonine and epi-scandomeline exhibited certain cytotoxic activity against MOLT-4 cells with IC50 values 5.2 and 1.5 µM, respectively.


Assuntos
Alcaloides , Apocynaceae , Aspidosperma , Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Alcaloides Indólicos/farmacologia , Estrutura Molecular
18.
Mol Immunol ; 133: 110-121, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33640761

RESUMO

As a major feature of diabetes, inflammation is closely related to macrophage extracellular traps and the expression of hepcidin upregulated by diabetes is reportedly involved in chronic inflammation. Therefore, we aimed to explore whether hepcidin could be implicated in inflammation and macrophage extracellular traps (METs) formation. The diabetic db/db mouse model was established exhibiting insulin resistance (IR), inflammation, macrophages infiltration and higher expression of hepcidin, where samples were obtained from epididymal adipose tissue. We observed that inflammation and IR improved in adipose tissue of mice treated with hepcidin gene silencing. Furthermore, METs formation could be markedly inhibited via hepcidin gene silencing followed by attenuated inflammatory response due to METs, indicating hepcidin gene silencing played a key role in anti-inflammation by inhibiting METs formation. So, we concluded that hepcidin gene silencing has a potential for treatment of diabetes due to its ability to ameliorate inflammation via inhibiting METs formation.

19.
Appl Environ Microbiol ; 87(9)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33608292

RESUMO

Bacterial proline-alanine-alanine-arginine (PAAR) proteins are located at the top of the type VI secretion system (T6SS) nanomachine and carry and deliver effectors into neighboring cells. Many PAAR proteins are fused with a variable C-terminal extended domain (CTD). Here, we report that two paar-ctd genes (MXAN_RS08765 and MXAN_RS36995) located in two homologous operons are involved in different ecological functions of Myxococcus xanthus MXAN_RS08765 inhibited the growth of plant-pathogenic fungi, while MXAN_RS36995 was associated with the colony-merger incompatibility of M. xanthus cells. These two PAAR-CTD proteins were both toxic to Escherichia coli cells, while MXAN_RS08765, but not MXAN_RS36995, was also toxic to Saccharomyces cerevisiae cells. Their downstream adjacent genes, i.e., MXAN_RS08760 and MXAN_RS24590, protected against the toxicities. The MXAN_RS36995 protein was demonstrated to have nuclease activity, and the activity was inhibited by the presence of MXAN_RS24590. Our results highlight that the PAAR proteins diversify the CTDs to play divergent roles in M. xanthus IMPORTANCE The type VI secretion system (T6SS) is a bacterial cell contact-dependent weapon capable of delivering protein effectors into neighboring cells. The PAAR protein is located at the top of the nanomachine and carries an effector for delivery. Many PAAR proteins are extended with a diverse C-terminal sequence with an unknown structure and function. Here, we report two paar-ctd genes located in two homologous operons involved in different ecological functions of Myxococcus xanthus; one has antifungal activity, and the other is associated with the kin discrimination phenotype. The PAAR-CTD proteins and the proteins encoded by their downstream genes form two toxin-immunity protein pairs. We demonstrated that the C-terminal diversification of the PAAR-CTD proteins enriches the ecological functions of bacterial cells.

20.
Histol Histopathol ; : 18310, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33570156

RESUMO

OBJECTIVE: To investigate the effect of the downregulation of FXYD domain-containing ion transport regulator 5 (FXYD5) on the cisplatin resistance (CisR) of epithelial ovarian cancer (EOC) cells. METHODS: A2780-CisR and SKOV3-CisR cells were obtained through repeated administrations of different cisplatin concentrations, and the half-maximal inhibition concentration (IC50) was calculated by MTT assays. After transfection with FXYD5 siRNA-1 and FXYD5 siRNA-2, the IC50 values of the A2780-CisR and SKOV3-CisR cells were also detected by the MTT method. Cell proliferation, migration, invasion and apoptosis were evaluated through 5-ethynyl-2'-deoxyuridine (EdU) DNA synthesis, wound healing, Transwell invasion and Annexin-V-FITC/PI dual-staining assays, respectively. qRT-PCR and Western blotting were conducted to detect mRNA and protein expression. RESULTS: Compared with the sensitive parental cells, the A2780-CisR and SKOV3-CisR cells had increased IC50 and FXYD5 expression. FXYD5 siRNA reduced the IC50 value of cisplatin in the A2780-CisR and SKOV3-CisR cells and decreased the expression of ABCG2 (BCRP) and ABCB1 (MDR1). In addition, FXYD5 inhibition reduced the invasion and migration of the A2780-CisR and SKOV3-CisR cells, with upregulation of E-cadherin and downregulation of Snail and Vimentin. Both FXYD5 siRNA-1 and FXYD5 siRNA-2 inhibited the proliferation and promoted the apoptosis of the A2780-CisR and SKOV3-CisR cells with reduced Ki-67 and increased caspase-3. CONCLUSION: FXYD5 downregulation may reduce the invasion, migration and EMT formation of EOC cells to increase their sensitivity to cisplatin chemotherapy by inhibiting cell proliferation and promoting cell apoptosis.

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