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1.
Kidney Blood Press Res ; : 1-11, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34788763

RESUMO

BACKGROUND: Trimethylamine-N-oxide (TMAO) is an intestinal metabolic toxin, which is produced by gut flora via metabolizing high-choline foods. TMAO is known to increase the risk of atherosclerosis and cardiovascular events in chronic kidney disease (CKD) patients. OBJECTIVES: The objective of this study was to explore the role and mechanism of TMAO aggravating kidney injury. METHOD: We used the five-sixths nephrectomy (5/6 Nx)-induced CKD rats to investigate whether TMAO could aggravate kidney damage and its possible mechanisms. Six weeks after the operation, the two groups of 5/6 Nx rats were subjected to intraperitoneal injection with 2.5% glucose peritoneal dialysis fluid (2.5% PDF) and 2.5% PDF plus TMAO 20 mg/kg/day. RESULTS: In this study, we provided evidence showing TMAO significantly aggravated renal failure as well as inflammatory cell infiltration and in five-sixths nephrectomy-induced CKD rats. We found that TMAO could upregulate inflammatory factors including MCP-1, TNF-α, IL-6, IL-1ß, and IL-18 by activating p38 phosphorylation and upregulation of human antigen R. TMAO could aggravate oxidative stress by upregulating NOX4 and downregulating SOD. The result also confirmed that TMAO promoted NLRP3 inflammasome formation as well as cleaved caspase-1 and IL-1ß activation in the kidney tissue. CONCLUSIONS: Taken together, the present study validates TMAO as a pro-inflammatory factor that causes renal inflammatory injury and renal function impairment. Inhibition of TMAO synthesis or promoting its clearance may be a potential therapeutic approach of CKD in the future.

2.
Cancer Cell Int ; 21(1): 616, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809621

RESUMO

BACKGROUND: UCA1 is frequently upregulated in a variety of cancers, including CRC, and it can play an oncogenic role by various mechanisms. However, how UCA1 is regulated in cancer is largely unknown. In this study, we aimed to determine whether RNA methylation at N6-methyladenosine (m6A) can impact UCA1 expression in colorectal cancer (CRC). METHODS: qRT-PCR was performed to detect the level of UCA1 and IGF2BP2 in CRC samples. CRISPR/Cas9 was employed to knockout (KO) UCA1, METTL3 and WTAP in DLD-1 and HCT-116 cells, while rescue experiments were carried out to re-express METTL3 and WTAP in KO cells. Immunoprecipitation using m6A antibody was performed to determine the m6A modification of UCA1. In vivo pulldown assays using S1m tagging combined with site-direct mutagenesis was carried out to confirm the recognition of m6A-modified UCA1 by IGF2BP2. Cell viability was measured by MTT and colony formation assays. The expression of UCA1 and IGF2BP2 in TCGA CRC database was obtained from GEPIA ( http://gepia.cancer-pku.cn ). RESULTS: Our results revealed that IGF2BP2 serves as a reader for m6A modified UCA1 and that adenosine at 1038 of UCA1 is critical to the recognition by IGF2BP2. Importantly, we showed that m6A writers, METTL3 and WTAP positively regulate UCA1 expression. Mechanically, IGF2BP2 increases the stability of m6A-modified UCA1. Clinically, IGF2BP2 is upregulated in CRC tissues compared with normal tissues. CONCLUSION: These results suggest that m6A modification is an important factor contributing to upregulation of UCA1 in CRC tissues.

3.
Opt Lett ; 46(21): 5461-5464, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724501

RESUMO

In this study, we introduce the phase correlation arc of an orbital angular momentum (OAM) beam to investigate the evolution of OAM entanglement. We reveal that the entanglement decay of all OAM states of Laguerre-Gaussian modes in atmospheric turbulence is universal via both numerical predictions and experimental data. A similar evolution law is also theoretically confirmed to exist in Bessel-Gaussian modes. Finally, by using the phase correlation arc, the precise formula of the decay distance dependence on the OAM number is derived, and it exhibits excellent agreement with previous experimental conclusions.

4.
Opt Lett ; 46(22): 5631-5634, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34780423

RESUMO

We propose a geometric optimization method combined with the Coulombic energy indicator that can uniformly distribute N polarization states on the Poincaré sphere. Based on this method, we investigate the optimal frames of a rotating polarizer and rotating quarter-wave plate (RPRQ)-based polarization state generator (PSG) at different numbers of modulations. We use the PSG on a dual DoFP polarimeter-based Mueller matrix microscope to measure standard samples and pathological sections for testing the performance of an optimized RPRQ. The experimental results show that this method can effectively restrain noise and improve measurement accuracy.

6.
J Asian Nat Prod Res ; : 1-7, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647840

RESUMO

A new megastimane sesquiterpenoid, cassianol A (1), and five known analogues (2-6) were isolated from the leaves extract of Cinnamomum cassia. Their structures were elucidated by extensive spectroscopic methods and single-crystal X-ray diffraction analyses. All the isolates were isolated from C. cassia for the first time. The anti-inflammatory activities of compounds 1-6 were evaluated against nitric oxide (NO) production in LPS-induced RAW 264.7 mouse macrophages.

7.
Free Radic Res ; : 1-14, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34670466

RESUMO

Sonodynamic therapy (SDT) represents a noninvasive therapeutic method via the activation of certain chemical sensitizers using low intensity ultrasound to generate various reactive oxygen species (ROS). In this work, we conducted systematic experiments to evaluate the production of hydrogen peroxide (H2O2) in sinoporphyrin sodium (DVDMS) mediated SDT (DVDMS-SDT). We found that the fluorescence intensities of H2O2 specific probe BES-H2O2 and Amplex Red increased significantly exposure to DVDMS-SDT while decreased with the introduction of catalase (H2O2 scavenger), indicating the production of H2O2. And the fluorescence intensity of H2O2 susceptible probes were positively correlated with DVDMS concentration, ultrasound intensity and irradiation time. Under the same molarity concentration, DVDMS has advantages over proto-porphyrin IX (PpIX) and hemoporrin monomethyl ether (HMME) in H2O2 production, indicating that the yield of H2O2 depends on the properties of sensitizer. More importantly, DVDMS-SDT is involved in the process of H2O2 even in the oxygen-free condition, showing its greater superiority for the treatment of tumor under hypoxia environment.

8.
BMC Surg ; 21(1): 360, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627202

RESUMO

BACKGROUND: To evaluate the survival rate of porous tantalum rod implantation in the treatment of osteonecrosis of the femoral head (ONFH), evaluate its clinical effect and imaging results. METHODS: From January 2008 to December 2013, porous tantalum rod implantation for ONFH was performed in two institutions. Statistical analysis of operation data, including operation time, blood loss and blood transfusion were recorded. RESULTS: 52 hips received complete follow-up, the average follow-up time was 85.7 months (60-132 months). 24 hips turned to THA at the end of follow-up (46.2%), the average time was 44.3 ± 32.8 months, and the average Harris hip score before THA was 57.1 ± 7.6. Cox proportional-hazards model revealed that Association Research Circulation Osseous (ARCO) stage (P = 0.017), bone marrow edema (P = 0.006) and age > 40 years (P = 0.043) were independent risk factors for conversion to THA. CONCLUSION: ARCO stage, age and bone marrow edema were risk factors for the failure of porous tantalum rod implantation to convert to THA.


Assuntos
Necrose da Cabeça do Fêmur , Cabeça do Fêmur , Adulto , Necrose da Cabeça do Fêmur/cirurgia , Seguimentos , Humanos , Porosidade , Tantálio
9.
Opt Express ; 29(16): 25270-25279, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34614860

RESUMO

Vortex beams are playing an increasingly crucial role in wireless optical communications. Traditional vortex beam generators based on spiral phase plates and metasurfaces have a geometric center in real space, which limit their convenience in practical applications. In this work, we propose that the creation of a vortex beam can be achieved by using the bound state in the continuum (BIC) supported by a photonic crystal slab structure. Theoretical analysis shows that the proposed structure can be used as a kind of "momentum-space resonators" and thus can generate vortex beams. Moreover, higher-order vortex beams can also be achieved by changing the symmetry of photonic crystal slab, thus paving the way for the application of vortex beams in the fields of quantum information processing and micro optical micromanipulation.

10.
Cell Mol Immunol ; 18(11): 2541-2553, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34635806

RESUMO

Allogeneic hematopoietic cell transplantation (allo-HCT) is a promising therapeutic option for hematological malignancies, but relapse resulting predominantly from residual disease in the bone marrow (BM) remains the major cause of treatment failure. Using immunodeficient mice grafted with laboratory-generated human B-ALL, our previous study suggested that leukemia cells within the BM are resistant to graft-versus-leukemia (GVL) effects and that mobilization with CXCR4 antagonists may dislodge leukemia cells from the BM, enabling them to be destroyed by GVL effects. In this study, we extended this approach to patient-derived xenograft (PDX) and murine T-ALL and AML models to determine its clinical relevance and effects on GVHD and donor hematopoietic engraftment. We found that posttransplant treatment with the CXCR4 antagonist AMD3100 significantly improved the eradication of leukemia cells in the BM in PDX mice grafted with B-ALL cells from multiple patients. AMD3100 also significantly improved GVL effects in murine T-ALL and AML models and promoted donor hematopoietic engraftment in mice following nonmyeloablative allo-HCT. Furthermore, posttransplant treatment with AMD3100 had no detectable deleterious effect related to acute or chronic GVHD. These findings provide important preclinical data supporting the initiation of clinical trials exploring combination therapy with CXCR4 antagonists and allo-HCT.

11.
Transl Res ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34673277

RESUMO

Trimethylamine-N-oxide (TMAO), a gut microbiota-produced metabolite, is accumulated in chronic kidney disease (CKD) patients. It is well known to contribute to CKD-related cardiovascular complications. However, the effect of TMAO on peritoneal dialysis (PD)-related peritonitis remains largely unknown. Here, we demonstrate that serum concentrations of TMAO were positively correlated with C-reactive protein levels, and the appearance rate of dialysate IL-6 and PAI-1, in PD patients. During the follow-up period of 28.3 ± 8.0 months, patients with higher TMAO levels (≥50 µM) had a higher risk of new-onset peritonitis (HR, 3.60; 95%CI, 1.18-10.99; P=0.025) after adjusting for sex, age, diabetes, PD duration, BUN, rGFR, C-reactive protein, BMI and ß2-M. In CKD rat models, TMAO significantly promoted peritoneal dialysate-induced inflammatory cell infiltration, inflammatory cytokines production in the peritoneum. In vitro study revealed that TMAO directly induced primary peritoneal mesothelial cell necrosis, together with increased production of pro-inflammatory cytokines including CCL2, TNF-α, IL-6, and IL-1ß. In addition, TMAO significantly increased TNF-α-induced P-selectin production in mesothelial cells, as well as high glucose-induced TNF-α and CCL2 expression in endothelial cells. In conclusion, our data demonstrate that higher levels of TMAO exacerbate peritoneal inflammation and might be a risk factor of incidence of peritonitis in PD patients.

12.
Small ; 17(47): e2103778, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34632702

RESUMO

Reducing SF6 (as gas cathode) in Li batteries is a promising concept for the double benefit of mildly converting greenhouse SF6 and providing a high theoretical energy density of 3922 Wh kg-1 . However, the reduction process is hampered by its sluggish kinetics. Here, cobalt phthalocyanine (CoPc) molecules immobilized on porous carbon matrix are, for the first time, introduced to the LiSF6 chemistry to deliver an enhanced energy density. It is revealed that the high redox potential of Co(II)Pc/[Co(I)Pc]- (≈2.85 V) facilitates the formation of Co(I)N4 sites to catalyze the SF6 electrochemical reduction. By using highly porous holey nitrogen-doped carbon nanocages as carbon matrix, the LiSF6 cells deliver a high discharge voltage of 2.82 V at 50 mA gC+CoPc -1 and an unprecedented areal capacity of 25 mAh cm-2 at 0.1 mA cm-2 , much superior to previous results. This work opens up new possibilities for high-efficiency conversion of SF6 in lithium batteries.

13.
Biomolecules ; 11(9)2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34572586

RESUMO

Metformin is a widely used antidiabetic drug for cancer prevention and treatment. However, the overproduction of lactic acid and its inefficiency in cancer therapy limit its application. Here, we demonstrate the synergistic effects of the lactate/GPR81 blockade (3-hydroxy-butyrate, 3-OBA) and metformin on inhibiting cancer cells growth in vitro. Simultaneously, this combination could inhibit glycolysis and OXPHOS metabolism, as well as inhibiting tumor growth and reducing serum lactate levels in tumor-bearing mice. Interestingly, we observed that this combination could enhance the functions of Jurkat cells in vitro and CD8+ T cells in vivo. In addition, considering that 3-OBA could recover the inhibitory effects of metformin on PD-1 expression, we further determined the dual blockade effects of PD-1/PD-L1 and lactate/GPR81 on the antitumor activity of metformin. Our results suggested that this dual blockade strategy could remarkably enhance the anti-tumor effects of metformin, or even lead to tumor regression. In conclusion, our study has proposed a novel and robust strategy for a future application of metformin in cancer treatment.

14.
Proteomics ; : e2100041, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545670

RESUMO

Posttranslational modifications (PTMs) affect protein function/dysfunction, playing important roles in the occurrence and development of tauopathies including Alzheimer's disease. PTM detection is significant and still challenging due to the requirements of high sensitivity to identify the subtle structural differences between modifications. Herein, in terms of the unique geometry of the aerolysin (AeL) nanopore, we elaborately engineered a T232K AeL nanopore to detect the acetylation and phosphorylation of Tau segment (Pep). By replacing neutral threonine (T) with positively charged lysine (K) at the 232 sites, the T232K and K238 rings of this engineered T232K AeL nanopore corporately work together to enhance electrostatic trapping of the acetylated and phosphorylated Tau peptides. Translocation speed of the monophosphorylated Pep-P was decelerated by up to 46 folds compared to the wild-type (WT) AeL nanopore. The prolonged residences within the T232K AeL nanopore enabled to simultaneously identify the monoacetylated Pep-Ac, monophosphorylated Pep-P, di-modified Pep-P-Ac and non-modified Pep. The tremendous potential is demonstrated for PTM sensing by manipulating non-covalent interactions between nanopores and single analytes.

15.
Funct Plant Biol ; 48(11): 1139-1147, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34585661

RESUMO

Long non-coding RNAs (lncRNAs) affect gene expressions via a wide range of mechanisms and are considered important regulators of numerous essential biological processes, including abiotic stress responses. However, the biological functions of most lncRNAs are yet to be determined. Moreover, to date, no effective methods have been developed to study the function of plant lncRNAs. We previously discovered a salt stress-related lncRNA, lncRNA77580 in soybean (Glycine max L.). In this study, we cloned the full-length lncRNA77580 and found that it shows nuclear-specific localisation. Furthermore, we employed CRISPR/Cas9 technology to induce large DNA fragment deletions in lncRNA77580 in soybean using a dual-single guide RNA/Cas9 design. As a result, we obtained deletion mutant soybean roots with targeted genomic fragment deletion in lncRNA77580. Deletion and overexpression of lncRNA77580 were found to alter the expression of several neighboring protein-coding genes associated with the response to salt stress. The longer the deleted DNA fragment in lncRNA77580, the greater the influence on the expression of lncRNA77580 itself and neighboring genes. Collectively, the findings of this study revealed that large DNA fragment deletion in lncRNAs using the CRISPR/Cas9 system is a powerful method to obtain functional mutations of soybean lncRNAs that could benefit future research on lncRNA function in soybean.


Assuntos
Estresse Salino , Soja , DNA , Expressão Gênica , Mutação , Soja/genética
16.
Sci Total Environ ; 801: 149785, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34467934

RESUMO

Nitrite-dependent anaerobic methane oxidation (n-damo) catalyzed by Candidatus Methylomirabilis oxyfera (M. oxyfera)-like bacteria is a new pathway for the regulation of methane emissions from paddy fields. Elevated atmospheric CO2 concentrations (e[CO2]) can indirectly affect the structure and function of microbial communities. However, the response of M. oxyfera-like bacteria to e[CO2] is currently unknown. Here, we investigated the effect of e[CO2] (ambient CO2 + 200 ppm) on community composition, abundance, and activity of M. oxyfera-like bacteria at different depths (0-5, 5-10, and 10-20 cm) in paddy fields across multiple rice growth stages (tillering, jointing, and flowering). High-throughput sequencing showed that e[CO2] had no significant effect on the community composition of M. oxyfera-like bacteria. However, quantitative PCR suggested that the 16S rRNA gene abundance of M. oxyfera-like bacteria increased significantly in soil under e[CO2], particularly at the tillering stage. Furthermore, 13CH4 tracer experiments showed potential n-damo activity of 0.31-8.91 nmol CO2 g-1 (dry soil) d-1. E[CO2] significantly stimulated n-damo activity, especially at the jointing and flowering stages. The n-damo activity and abundance of M. oxyfera-like bacteria increased by an average of 90.9% and 50.0%, respectively, under e[CO2]. Correlation analysis showed that the increase in soil dissolved organic carbon content caused by e[CO2] had significant effects on the activity and abundance of M. oxyfera-like bacteria. Overall, this study provides the first evidence for a positive response of M. oxyfera-like bacteria to e[CO2], which may help reduce methane emissions from paddy fields under future climate change conditions.


Assuntos
Dióxido de Carbono , Nitritos , Anaerobiose , Metano , Oxirredução , Filogenia , RNA Ribossômico 16S
17.
Epilepsy Behav ; 124: 108276, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34547687

RESUMO

OBJECTIVE: Rolandic epilepsy (RE) is one of the most common forms of epilepsy syndromes in children. The condition is usually accompanied with either unilateral or bilateral centrotemporal epileptic discharge. Despite the term "benign", many studies have reported that children with benign epilepsy with centrotemporal spikes (BECTS) display a range of pervasive cognitive difficulties. In addition, existing research suggests that unilateral and bilateral centrotemporal spikes may affect cognition through different mechanisms. Consequently, the present study aimed to investigate cognitive impairment and the resting-state network topology of children with benign epilepsy with unilateral centrotemporal spikes (U-BECTS) and with bilateral centrotemporal spikes (B-BECTS). METHODS: This study recruited 14 children with U-BECTS and 14 with B-BECTS. Thereafter, cognition was assessed in 28 children with BECTS and 14 healthy controls, using the fourth edition of the Wechsler Intelligence Scale (WISC-IV). Additionally, the functional network of the brain was constructed through magnetoencephalography (MEG) to record the resting-state brain magnetic signals of the brain and by computing virtual sensor waveforms at the source level. Moreover, graph theory (GT) analysis was used to assess the properties of the brain network. RESULTS: Children in the B-BECTS group had an earlier onset of epilepsy compared to those in the U-BECTS category. In addition, both the B-BECTS and U-BECTS groups had lower Full Scale Intelligence Quotient (FSIQ), Verbal Comprehension Index (VCI), and Working Memory Index (WMI) scores, compared to the healthy controls although only children in the B-BECTS category had lower Perceptual Reasoning Index (PRI) scores. The results also showed that both BECTS groups had increased frontal cortex connectivity in specific frequency bands. Notably, children with B-BECTS showed a more disorderly and randomized network in the 1-4-Hz and 80-250-Hz frequency bands. Moreover, GT analysis showed that children with B-BECTS had lower clustering coefficient and characteristic path length in the 80-250-Hz frequency bands and higher connection strength in the 4-8-Hz frequency bands. On the other hand, the U-BECTS group had a higher clustering coefficient in the 8-12-Hz frequency bands, compared to the healthy controls. Correlation analysis revealed that there were negative correlations between network parameters, clinical characteristics, and neuropsychological data in the U-BECTS category. CONCLUSION: The findings revealed that children with BECTS display a diffuse early cognitive deficit. In addition, resting-state suboptimal network topology may be the mechanism of cognitive impairment in children with BECTS. The study also showed that and children with B-BECTS may be at a higher risk of cognitive impairment.

18.
Brain Imaging Behav ; 2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34420145

RESUMO

To investigate the influence of epileptogenic cortex (Rolandic areas) with executive functions in Rolandic epilepsy using structural covariance analysis of structural magnetic resonance imaging (MRI). Structural MRI data of drug-naive patients with Rolandic epilepsy (n = 70) and typically developing children as healthy controls (n = 83) were analyzed using voxel-based morphometry. Gray matter volumes in the patients were compared with those of healthy controls, and were further correlated with epilepsy duration and cognitive score of executive function, respectively. By applying Granger causal analysis to the sequenced morphometric data according to disease progression information, causal network of structural covariance was constructed to assess the causal influence of structural changes from Rolandic cortices to the regions engaging executive function in the patients. Compared with healthy controls, epilepsy patients showed increased gray matter volume in the Rolandic regions, and also the regions engaging in executive function. Covariance network analyses showed that along with disease progression, the Rolandic regions imposed positive causal influence on the regions engaging in executive function. In the patients with Rolandic epilepsy, epileptogenic regions have causal influence on the structural changes in the regions of executive function, implicating damaging effects of Rolandic epilepsy on human brain.

19.
Front Plant Sci ; 12: 675121, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447399

RESUMO

Surface runoff is one of the predominant routes for agricultural nitrogen (N) and phosphorus (P) losses, yet their characteristics and corresponding control measures are not fully understood. In 2019 and 2020, field-scale plot experiments were performed at Dongjiang Basin in South China to investigate the characteristics of N and P runoff losses from paddy and maize cropping systems. The results showed that N and P losses from maize fields via surface runoff (27.85 and 1.24 kg ha-1 year-1) were significantly higher than those from paddy fields (15.37 and 0.8 kg ha-1 year-1). The main forms of N losses were nitrate ( NO 3 - -N) and ammonium ( NH 4 + -N) in paddy and maize fields, respectively, whereas particulate P form predominated in surface runoff losses from both the paddy and maize fields. Considerable proportions of agricultural N and P (71-83% of the total runoff loss) were lost during basal fertilization and first topdressing application. Moreover, frequent rainfall events following fertilizer application triggered N and P losses from the monitored fields. About 26.22 and 37.48% of N fertilizer was recovered from grains and straw of paddy and maize, respectively, whereas only 12.35 and 19.51% of P fertilizer were recovered during the crop harvesting stage. Surface runoff was one of the dominant liquid pathways in N loss, whereas most of P loss (introduced from fertilizers without crops utilization) was fixed in the soil. Principal component analysis (PCA) proved that the primary sources of N and P losses were fertilizers rather than N and P in the soil. The current results suggest controlled management relating to fertilization, irrigation, and tillage strategies are effective measures for reducing N and P losses, thereby controlling agricultural non-point source pollution. It is hoped that this study will provide comprehensive field-based inputs on characteristics of N and P runoff losses and formulate appropriate control strategies to protect aquatic environments from eutrophication.

20.
Cell Biosci ; 11(1): 163, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419144

RESUMO

BACKGROUND: Aberrant expression of Aldo-Keto reductase family 1 member B10 (AKR1B10) was associated with tumor size and metastasis of breast cancer in our published preliminary studies. However, little is known about the detailed function and underlying molecular mechanism of AKR1B10 in the pathological process of breast cancer. METHODS: The relationship between elevated AKR1B10 expression and the overall survival and disease-free survival of breast cancer patients was analyzed by Kaplan-Meier Plotter database. Breast cancer cell lines overexpressing AKR1B10 (MCF-7/AKR1B10) and breast cancer cell lines with knockdown of AKR1B10 (BT-20/shAKR1B10) were constructed to analyze the impact of AKR1B10 expression on cell proliferation and migration of breast cancer. The expression levels of AKR1B10 were detected and compared in the breast cancer cell lines and tissues by RT-qPCR, western blot and immunohistochemistry. The proliferation of breast cancer cells was monitored by CCK8 cell proliferation assay, and the migration and invasion of breast cancer cells was observed by cell scratch test and transwell assay. The proliferation- and EMT-related proteins including cyclinD1, c-myc, Survivin, Twist, SNAI1, SLUG, ZEB1, E-cadherin, PI3K, p-PI3K, AKT, p-AKT, IKBα, p-IKBα, NF-κB p65, p-NF-κB p65 were detected by western blot in breast cancer cells. MCF-7/AKR1B10 cells were treated with LY294002, a PI3K inhibitor, to consider the impact of AKR1B10 overexpression on the PI3K/AKT/NF-κB signal cascade and the presence of NF-κB p65 in nuclear. In vivo tumor xenograft experiments were used to observe the role of AKR1B10 in breast cancer growth in mice. RESULTS: AKR1B10 expression was significantly greater in breast cancer tissue compared to paired non-cancerous tissue. The expression of AKR1B10 positively correlated with lymph node metastasis, tumor size, Ki67 expression, and p53 expression, but inversely correlated with overall and disease-free survival rates. Gene Ontology analysis showed that AKR1B10 activity contributes to cell proliferation. Overexpression of AKR1B10 facilitated the proliferation of MCF-7 cells, and induced the migration and invasion of MCF-7 cells in vitro in association with induction of epithelial-mesenchymal transition (EMT). Conversely, knockdown of AKR1B10 inhibited these effects in BT-20 cells. Mechanistically, AKR1B10 activated PI3K, AKT, and NF-κB p65, and induced nuclear translocation of NF-κB p65, and expression of proliferation-related proteins including c-myc, cyclinD1, Survivin, and EMT-related proteins including ZEB1, SLUG, Twist, but downregulated E-cadherin expression in MCF-7 cells. AKR1B10 silencing reduced the phosphorylation of PI3K, AKT, and NF-κB p65, the nuclear translocation of NF-κB p65, and the expression of proliferation- and migration-related proteins in BT-20 cells. LY294002, a PI3K inhibitor, attenuated the phosphorylation of PI3K, AKT, and NF-κB p65, and the nuclear translocation of NF-κB p65. In vivo tumor xenograft experiments confirmed that AKR1B10 promoted breast cancer growth in mice. CONCLUSIONS: AKR1B10 promotes the proliferation, migration and invasion of breast cancer cells via the PI3K/AKT/NF-κB signaling pathway and represents a novel prognostic indicator as well as a potential therapeutic target in breast cancer.

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