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1.
Environ Res ; : 118924, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38631473

RESUMO

Nitrite, as an electron acceptor, plays a good role in denitrifying phosphorus removal (DPR); however, high nitrite concentration has adverse affects on sludge performance. We investigated the precise mechanisms of responses of sludge to high nitrite stress, including surface characteristics, intracellular and extracellular components, microbial and metabolic responses. When the nitrite stress reached 90 mg/L, the sludge settling performance was improved, but the activated sludge was aging. FTIR and XPS analysis revealed a significant increase in the hydrophobicity of the sludge, resulting in improve settling performance. However, the intracellular carbon sources synthesis was inhibited. In addition, the components in the tightly bound extracellular polymeric substances (TB-EPS) of sludge were significantly reduced and indicated the disturb of metabolism. Notably, Exiguobacterium emerged as a new genus when face high nitrite stress that could maintaining survival in hostile environments. Moreover, metabolomic analysis demonstrated strong biological response to nitrite stress further supported above results that include the inhibited of carbohydrate and amino acid metabolism. More importantly, some lipids (PS, PA, LysoPA, LysoPC and LysoPE) were significantly upregulated that related enhanced membrane lipid remodeling. The comprehensive analyses provide novel insights into the high nitrite stress responses mechanisms in activated sludge systems.

2.
J Hazard Mater ; 470: 134235, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38608585

RESUMO

The misuse of aromatic amines like 4-chloroaniline (4-CA) has led to severe environmental and health issues. However, it's difficult to be utilized by microorganisms for degradation. Nano-zero-valent iron (nZVI) is a promising material for the remediation of chloroaniline pollution, however, the synergistic effect and mechanism of nZVI with microorganisms for the degradation of 4-CA are still unclear. This study investigated the potential of 4-CA removal by the synergistic system involving nZVI and 4-CA degrading microbial flora. The results indicate that the addition of nZVI significantly enhanced the bio-degradation rate of 4-CA from 43.13 % to 62.26 %. Under conditions involving 0.1 % nZVI addition at a 24-hour interval, pH maintained at 7, and glucose as an external carbon source, the microbial biomass, antioxidant enzymes, and dehydrogenase were significantly increased, and the optimal 4-CA degradation rate achieved 68.79 %. Additionally, gas chromatography-mass spectrometry (GC-MS) analysis of intermediates indicated that the addition of nZVI reduced compounds containing benzene rings and enhanced the dechlorination efficiency. The microbial community remained stable during the 4-CA degradation process. This study illustrates the potential of nZVI in co-microbial remediation of 4-CA compounds in the environment.

3.
Food Chem ; 450: 139276, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38626711

RESUMO

This study presents a new method combining cold plasma-activated oxygen (CPAO) and microwave (MW) to decontaminate milkshake powder, exploring its effectiveness, mechanisms, and quality impact. CPAO (6 min) alone reduced bacterial load by 0.419 log CFU/g, and MW (3 min) by 0.030 log CFU/g. However, their co-application significantly amplified decontamination, achieving a 1.265 log CFU/g reduction. CPAO-MW co-treatment inflicted more oxidative damage on bacterial cell membranes and intracellular antioxidant defense system, leading to higher mortality. It also raised protein and lipid oxidation, while decreasing vitamin C and A levels in the powder. Specifically, CPAO (6 min)-MW (3 min) co-treatment increased the carbonyl content from 0.438 to 0.891 nmol/mg protein, malondialdehyde from 0.824 to 0.996 mg/kg, and lowered vitamin C from 162.151 to 137.640 mg/kg, and vitamin A from 2.05 to 1.38 mg/kg. This study shows CPAO-MW is effective for decontaminating powdered foods but highlights a need to reduce negative effects.

4.
IEEE Trans Med Imaging ; PP2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607706

RESUMO

Multimodal neuroimaging provides complementary information critical for accurate early diagnosis of Alzheimer's disease (AD). However, the inherent variability between multimodal neuroimages hinders the effective fusion of multimodal features. Moreover, achieving reliable and interpretable diagnoses in the field of multimodal fusion remains challenging. To address them, we propose a novel multimodal diagnosis network based on multi-fusion and disease-induced learning (MDL-Net) to enhance early AD diagnosis by efficiently fusing multimodal data. Specifically, MDL-Net proposes a multi-fusion joint learning (MJL) module, which effectively fuses multimodal features and enhances the feature representation from global, local, and latent learning perspectives. MJL consists of three modules, global-aware learning (GAL), local-aware learning (LAL), and outer latent-space learning (LSL) modules. GAL via a self-adaptive Transformer (SAT) learns the global relationships among the modalities. LAL constructs local-aware convolution to learn the local associations. LSL module introduces latent information through outer product operation to further enhance feature representation. MDL-Net integrates the disease-induced region-aware learning (DRL) module via gradient weight to enhance interpretability, which iteratively learns weight matrices to identify AD-related brain regions. We conduct the extensive experiments on public datasets and the results confirm the superiority of our proposed method. Our code will be available at: https://github.com/qzf0320/MDL-Net.

5.
J Chem Phys ; 160(13)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38577980

RESUMO

PtS2, a member of the group 10 transition metal dichalcogenides (TMDs), has received extensive attention because of its excellent electrical properties and air stability. However, there are few reports on the preparation of single-crystal PtS2 in the literature, and the growth mechanism of single crystal PtS2 is not well elucidated. In this work, we proposed a method of preparation that combines magnetron sputtering and chemical vapor transport to obtain monocrystalline PtS2 on a SiO2/Si substrate. By controlling the growth temperature and time, we have synthesized a single crystalline PtS2 of hexagonal shape and size of 1-2 µm on a silicon substrate. Combining the molecular dynamics simulation, the growth mechanism of single crystal PtS2 was investigated both experimentally and theoretically. The synthesis method has a short production cycle and low cost, which opens the door for the fabrication of other TMDs single crystals.

6.
Cancer Sci ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558246

RESUMO

Chemoresistance is a major cause of high mortality and poor survival in patients with ovarian cancer (OVCA). Understanding the mechanisms of chemoresistance is urgently required to develop effective therapeutic approaches to OVCA. Here, we show that expression of the long noncoding RNA, taurine upregulated gene 1 (TUG1), is markedly upregulated in samples from OVCA patients who developed resistance to primary platinum-based therapy. Depletion of TUG1 increased sensitivity to cisplatin in the OVCA cell lines, SKOV3 and KURAMOCHI. Combination therapy of cisplatin with antisense oligonucleotides targeting TUG1 coupled with a drug delivery system effectively relieved the tumor burden in xenograft mouse models. Mechanistically, TUG1 acts as a competing endogenous RNA by downregulating miR-4687-3p and miR-6088, both of which target DNA polymerase eta (POLH), an enzyme required for translesion DNA synthesis. Overexpression of POLH reversed the effect of TUG1 depletion on cisplatin-induced cytotoxicity. Our data suggest that TUG1 upregulation allows OVCA to tolerate DNA damage via upregulation of POLH; this provides a strong rationale for targeting TUG1 to overcome cisplatin resistance in OVCA.

8.
Opt Express ; 32(6): 8959-8973, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571141

RESUMO

In current optical systems, defocus blur is inevitable due to the constrained depth of field. However, it is difficult to accurately identify the defocus amount at each pixel position as the point spread function changes spatially. In this paper, we introduce a histogram-invariant spatial aliasing sampling method for reconstructing all-in-focus images, which addresses the challenge of insufficient pixel-level annotated samples, and subsequently introduces a high-resolution network for estimating spatially varying defocus maps from a single image. The accuracy of the proposed method is evaluated on various synthetic and real data. The experimental results demonstrate that our proposed model outperforms state-of-the-art methods for defocus map estimation significantly.

9.
Bioorg Chem ; 147: 107315, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38604017

RESUMO

Seven new meroterpenoids, paraphaeones A-G (1-7), and two new polyketides, paraphaeones H-I (8-9), along with eight known compounds (10-17), were isolated from the endophytic fungus Paraphaeosphaeria sp. C-XB-J-1. The structures of 1-9 were identified through the analysis of 1H, 13C, and 2D NMR spectra, assisted by HR-ESI-MS data. Compounds 1 and 7 exhibited a dose-dependent decrease in lactate dehydrogenase levels, with IC50 values of 1.78 µM and 1.54 µM, respectively. Moreover, they inhibited the secretion of IL-1ß and CASP-1, resulting in a reduction in the activity levels of NLRP3 inflammasomes. Fluorescence microscopy results indicated that compound 7 concentration-dependently attenuated cell pyroptosis. Additionally, compounds 4 and 7 showed potential inhibitory effects on the severe acute respiratory syndrome coronavirus-2 main protease (SARS-CoV-2 Mpro), with IC50 values of 10.8 ± 0.9 µM and 12.9 ± 0.7 µM, respectively.

10.
Angew Chem Int Ed Engl ; : e202405763, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607321

RESUMO

Photocatalytic oxygen reduction reactions and water oxidation reactions are extremely promising green approaches for massive H2O2 production. Nonetheless, constructing effective photocatalysts for H2O2 generation is critical and still challenging. Since the network topology has significant impacts on the electronic properties of two dimensional (2D) polymers, herein, for the first time, we regulated the H2O2 photosynthetic activity of 2D covalent organic frameworks (COFs) by topology. Through designing the linking sites of the monomers, we synthesized a pair of novel COFs with similar chemical components on the backbones but distinct topologies. Without sacrificial agents, TBD-COF with cpt topology exhibited superior H2O2 photoproduction performance (6085 and 5448 µmol g-1 h-1 in O2 and air) than TBC-COF with hcb topology through the O2-O2•--H2O2, O2-O2•--O21-H2O2, and H2O-H2O2 three paths. Further experimental and theoretical investigations confirmed that during the H2O2 photosynthetic process, the charge carrier separation efficiency, O2•- generation and conversion, and the energy barrier of the rate determination steps in the three channels, related to the formation of *OOH, *O21, and *OH, can be well tuned by the topology of COFs. The current study enlightens the fabrication of high-performance photocatalysts for H2O2 production by topological structure modulation.

11.
Plant Biotechnol J ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593377

RESUMO

Fusarium head blight (FHB) and the presence of mycotoxin deoxynivalenol (DON) pose serious threats to wheat production and food safety worldwide. DON, as a virulence factor, is crucial for the spread of FHB pathogens on plants. However, germplasm resources that are naturally resistant to DON and DON-producing FHB pathogens are inadequate in plants. Here, detoxifying bacteria genes responsible for DON epimerization were used to enhance the resistance of wheat to mycotoxin DON and FHB pathogens. We characterized the complete pathway and molecular basis leading to the thorough detoxification of DON via epimerization through two sequential reactions in the detoxifying bacterium Devosia sp. D6-9. Epimerization efficiently eliminates the phytotoxicity of DON and neutralizes the effects of DON as a virulence factor. Notably, co-expressing of the genes encoding quinoprotein dehydrogenase (QDDH) for DON oxidation in the first reaction step, and aldo-keto reductase AKR13B2 for 3-keto-DON reduction in the second reaction step significantly reduced the accumulation of DON as virulence factor in wheat after the infection of pathogenic Fusarium, and accordingly conferred increased disease resistance to FHB by restricting the spread of pathogenic Fusarium in the transgenic plants. Stable and improved resistance was observed in greenhouse and field conditions over multiple generations. This successful approach presents a promising avenue for enhancing FHB resistance in crops and reducing mycotoxin contents in grains through detoxification of the virulence factor DON by exogenous resistance genes from microbes.

12.
Int J Surg ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38597396

RESUMO

OBJECTIVE: Negative remodeling of the distal aorta following proximal repair for acute aortic dissection has garnered growing attention. This clinical scenario has spurred the development of techniques and devices. A multicenter, prospective, and randomized controlled study was conducted with the aim of confirming the safety and effectiveness of a newly-designed flowdynamics dense mesh stent for the treatment of residual dissection after proximal repair. METHODS: Patients with nonchronic residual dissection affecting visceral branches were prospectively enrolled at three centers and randomly allocated to either the FDMS group or the control group. Primary endpoints encompassed all-cause and aortic-related mortality, while the patency of branch arteries is indeed a key focal metric. Morphological changes (diameter, area, and volume) were analyzed to demonstrate the therapeutic effect. RESULTS: 112 patients were recruited in the clinical trial, and 103 patients completed the 12-month follow-up. The rate of freedom from all-cause and aortic-related death in the FDMS group was 94.64% and 100%, respectively. All visceral branches remained patent. The FDMS group exhibited a substantial expansion in TL and a notable shrinkage in FL at the planes below renal arteries (ΔArea TL: FDMS vs. Control, 0.74±0.46 vs. 0.34±0.66 cm2, P<0.001; ΔArea FL: FDMS vs. Control, -0.72±1.26 vs. -0.12±0.86 cm, P = 0.01) and 5 cm below renal arteries (ΔArea TL: FDMS vs. Control, 1.06±0.75 vs. 0.16±0.63 cm2, P<0.001; ΔArea FL: FDMS vs. Control, -0.53±1.43 vs. -0.25±1.00 cm, P = 0.27). Meanwhile, the FDMS group demonstrated an increase of 22.55±11.14 cm3 in TL (P<0.001) and a corresponding reduction of 21.94±11.77 cm3 in FL (P=0.08). CONCLUSIONS: This newly-designed FDMS for endovascular repair of residual dissection following the proximal repair is demonstrated to be safe and effective at 12 months.

13.
Int Wound J ; 21(4): e14870, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38629599

RESUMO

To analyse the risk factors affecting wound healing and infection after spinal meningioma resection surgery. The surgical incision healing of 137 patients who underwent spinal meningioma resection at our hospital from January 2021 to January 2024 was analysed. The data collected included physical examination findings, haematological and biochemical measurements, and various scales assessed upon admission and after surgery. These data were then analysed. The surgical wound healing, infection and postoperative complications were statistically analysed. Multiple logistic regression analysis method was used to conduct risk factor analysis on corresponding indicators; the odds ratio and p value of 95% confidence interval were calculated. Factors such as age and smoking history were significantly negatively correlated with wound healing after meningioma resection (odds ratio < 1.000, p < 0.05), while preoperative albumin and platelet count were significantly positively correlated with wound healing (odds ratio > 1.000, p < 0.05). Age, WHO Meningioma Grading, preoperative albumin and preoperative platelet were significantly negatively correlated with wound infection after meningioma resection (odds ratio < 1.000, p < 0.05). The history of virus infection and history of neurological disorders were significantly positively correlated with wound infection (odds ratio > 1.000, p < 0.05). The influence of each factor is different. Age, smoking history, WHO Meningioma Grading, preoperative albumin, preoperative platelets, history of virus infection and history of neurological disorders had the greatest influence on wound healing and infection after meningioma resection.


Assuntos
Neoplasias Meníngeas , Meningioma , Ferida Cirúrgica , Viroses , Infecção dos Ferimentos , Humanos , Meningioma/cirurgia , Estudos Retrospectivos , Fatores de Risco , Cicatrização , Neoplasias Meníngeas/cirurgia , Albuminas
14.
Molecules ; 29(7)2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38611728

RESUMO

The epidermal growth factor receptor (EGFR) plays a pivotal role in cancer therapeutics, with small-molecule EGFR inhibitors emerging as significant agents in combating this disease. This review explores the synthesis and clinical utilization of EGFR inhibitors, starting with the indispensable role of EGFR in oncogenesis and emphasizing the intricate molecular aspects of the EGFR-signaling pathway. It subsequently provides information on the structural characteristics of representative small-molecule EGFR inhibitors in the clinic. The synthetic methods and associated challenges pertaining to these compounds are thoroughly examined, along with innovative strategies to overcome these obstacles. Furthermore, the review discusses the clinical applications of FDA-approved EGFR inhibitors such as erlotinib, gefitinib, afatinib, and osimertinib across various cancer types and their corresponding clinical outcomes. Additionally, it addresses the emergence of resistance mechanisms and potential counterstrategies. Taken together, this review aims to provide valuable insights for researchers, clinicians, and pharmaceutical scientists interested in comprehending the current landscape of small-molecule EGFR inhibitors.


Assuntos
Carcinogênese , Transformação Celular Neoplásica , Humanos , Afatinib , Receptores ErbB , Cloridrato de Erlotinib
15.
Artigo em Inglês | MEDLINE | ID: mdl-38635211

RESUMO

Improving the efficiency of platinum group metals (Pt, Pd, Rh, etc.) in catalytic oxidation reactions remains an urgent topic. The conflict between the low-temperature activity and high-temperature stability of noble metals can hardly reach a consensus. For instance, Pt cluster catalysts supported on CeO2 with high low-temperature activity will suffer from deactivation due to the redispersion under high-temperature lean-burn reaction conditions. Herein, two Pt1/CeO2 prepared by the incipient wetness impregnation method using different Pt precursors possessed varied Pt-O and Pt-O-Ce coordination numbers (CNs). They showed various priorities in CO oxidation versus NH3 selective catalytic oxidation, materials with higher CNPt-O-Ce selectively catalyzing NH3 oxidation to N2 more superior, conversely materials with lower CNPt-O-Ce performing better in CO oxidation. After activation by H2 reduction, both formed massive Pt clusters on the CeO2 surface but showed drastically distinct stability in lean-burn CO oxidation reactions. By summarizing the experimental results of high-angle annular dark-field scanning transmission electron microscopy, X-ray absorption spectroscopy, Raman spectroscopy, in situ diffuse reflectance infrared Fourier transform spectroscopy, etc., it is beyond doubt that the difference in the initial states of Pt1 due to distinct precursors indeed determine the redispersion behavior of the reduced Pt clusters on CeO2. Materials with lower CNPt-O-Ce and higher CNPt-O are more likely to form robust Pt clusters, as they are not conducive to Pt anchoring, thus restricting the reversible structural evolution occurring under lean-burn CO oxidation and reductive conditions. This approach serves as a guide for the convenient and efficient construction and exploration of robust Pt cluster catalysts.

16.
Nat Prod Res ; : 1-5, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501743

RESUMO

Two new megastigmane glycosides, (6 R,7E,9R)-3-oxo-α-ionyl-9-O-α-L-rhamnopyranosyl-(1''→4')-ß-D-glucopyranoside (1) and (6 R,7E,9R)-3-oxo-α-ionyl-9-O-ß-D-glucopyranosyl-(1''→6')-ß-D-glucopyranoside (2), together with six known analogues (3-8) were isolated from the leaves of Nicotiana tabacum. The structures of all metabolites were determined by comprehensive analysis of NMR and MS spectroscopic data as well as by comparison with those of previously reported. The in vitro anti-inflammatory activity of all isolates was evaluated using a lipopolysaccharide (LPS)-induced RAW264.7 cell inflammatory model, and the compounds 1, 3, 7, and 8 exhibited inhibition of LPS-induced NO production in RAW264.7 macrophage cells with IC50 values of 42.3-61.7 µM (positive control, dexamethasone, IC50 = 21.3 ± 1.2 µM).

17.
Neurocrit Care ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480608

RESUMO

BACKGROUND: In this study, we aimed to investigate the risk factors and impact of poststroke pneumonia (PSP) on mortality and functional outcome in patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT). METHODS: This was a post hoc analysis of a prospective randomized trial (Direct intraarterial thrombectomy in order to revascularize AIS patients with large-vessel occlusion efficiently in Chinese tertiary hospitals: a multicenter randomized clinical trial). Patients with AIS who completed EVT were evaluated for the occurrence of PSP during the hospitalization period and their modified Rankin Scale (mRS) scores at 90 days after AIS. Logistic regression analysis was conducted to investigate the independent predictors of PSP. Propensity score matching was conducted for the PSP and non-PSP groups by using the covariates resulting from the logistic regression analysis. The associations between PSP and outcomes were analyzed. The outcomes included 90-day poor functional outcome (mRS scores > 2), 90-day mortality, and early 2-week mortality. RESULTS: A total of 639 patients were enrolled, of whom 29.58% (189) developed PSP. Logistic regression analysis revealed that history of chronic heart failure (unadjusted odds ratio [OR] 2.011, 95% confidence interval [CI] 1.026-3.941; P = 0.042), prethrombectomy reperfusion on initial digital subtraction angiography (OR 0.394, 95% CI 0.161-0.964; P = 0.041), creatinine levels at admission (OR 1.008, 95% CI 1.000-1.016; P = 0.049), and National Institutes of Health Stroke Scale at 24 h (OR 1.023, 95% CI 1.007-1.039; P = 0.004) were independent risk factors for PSP. With propensity scoring matching, poor functional outcome (mRS > 2) was more common in patients with PSP than in patients without PSP (81.03% vs. 71.83%, P = 0.043) at 90 days after EVT. The early 2-week mortality of patients with PSP was lower (5.74% vs. 12.07%, P = 0.038). But there was no statistically significant difference in 90-day mortality between the PSP group and non-PSP group (22.41% vs. 14.94%, P = 0.074). The survivorship curve also shows no statistical significance (P = 0.088) between the two groups. CONCLUSIONS: Nearly one third of patients with AIS and EVT developed PSP. Heart failure, higher creatinine levels, prethrombectomy reperfusion, and National Institutes of Health Stroke Scale at 24 h were associated with PSP in these patients. PSP was associated with poor 90-day functional outcomes in patients with AIS treated with EVT.

18.
Phys Chem Chem Phys ; 26(15): 11570-11581, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38533820

RESUMO

The capture and separation of CF4 from CF4/N2 mixture gas is a crucial issue in the electronics industry, as CF4 is a commonly used etching gas and the ratio of CF4 to N2 directly affects process efficiency. Utilizing high-throughput computational screening techniques and grand canonical Monte Carlo (GCMC) simulations, we comprehensively screened and assessed 247 types of pure silicon zeolite materials to determine their adsorption and separation performance for CF4/N2 mixtures. Based on screening, the relationships between the structural parameters and adsorption and separation properties were meticulously investigated. Four indicators including adsorption selectivity, working capacity, adsorbent performance score (APS), and regenerability (R%) were used to evaluate the performance of adsorbents. Based on the evaluation, we selected the top three best-performing zeolite structures for vacuum swing adsorption (LEV, AWW and ESV) and pressure swing adsorption (AVL, ZON, and ERI) processes respectively. Also, we studied the preferable adsorption sites of CF4 and N2 in the selected zeolite structures through centroid density distributions at the molecule level. We expect the study may provide some valuable guidance for subsequent experimental investigations on adsorption and separation of CF4/N2.

19.
Cancer Res ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38451249

RESUMO

Longitudinal monitoring of patients with advanced cancers is crucial to evaluate both disease burden and treatment response. Current liquid biopsy approaches mostly rely on the detection of DNA-based biomarkers. However, plasma RNA analysis can unleash tremendous opportunities for tumor state interrogation and molecular subtyping. Through the application of deep learning algorithms to the deconvolved transcriptomes of RNA within plasma extracellular vesicles (evRNA), we successfully predict consensus molecular subtypes in metastatic colorectal cancer patients. We further demonstrate the ability to monitor changes in transcriptomic subtype under treatment selection pressure and identify molecular pathways in evRNA associated with recurrence. Our approach also identified expressed gene fusions and neoepitopes from evRNA. These results demonstrate the feasibility of transcriptomic-based liquid biopsy platforms for precision oncology approaches, spanning from the longitudinal monitoring of tumor subtype changes to identification of expressed fusions and neoantigens as cancer-specific therapeutic targets, sans the need for tissue-based sampling.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38551020

RESUMO

Benign prostatic hyperplasia (BPH) is the expansion of the prostate gland that results in urinary symptoms. Both the epithelial-to-mesenchymal transition (EMT) and the Wnt signaling pathway are associated with BPH pathology. In this study, we find that miR-1202 is increased in BPH samples. Overexpression of miR-1202 in TGF-ß-treated BPH-1 cells enhances cell survival and DNA synthesis and inhibits cell apoptosis, whereas miR-1202 inhibition partially abolishes the effects of TGF-ß on BPH-1 cells. miR-1202 overexpression reduces E-cadherin level but elevates vimentin, N-cadherin, and snail levels, whereas miR-1202 inhibition partially attenuates the effects of TGF-ß on EMT markers. Regarding the Wnt/ß-catenin pathway, miR-1202 overexpression significantly enhances, whereas miR-1202 inhibition partially decreases, the promotive effects of TGF-ß on Wnt1, c-Myc, and cyclin D1 proteins. 3-Hydroxy-3-methylglutaryl-CoA lyase (HMGCL) is a direct downstream target of miR-1202, and miR-1202 inhibits HMGCL expression through binding to its 3'UTR. Overexpression of HMGCL significantly reduces the effect of miR-1202 overexpression on the phenotypes of BPH-1 cells by inhibiting cell survival and promoting apoptosis. Similarly, HMGCL overexpression has the opposite effects on EMT markers and the Wnt/ß-catenin signaling, and markedly alleviates the effects of miR-1202 overexpression. Finally, in the BPH rat model, Ki67 and vimentin levels are elevated, but E-cadherin and HMGCL levels are reduced. In conclusion, miR-1202 is upregulated in benign prostatic hyperplasia; miR-1202 enhances epithelial cell proliferation, suppresses cell apoptosis, and promotes EMT by targeting HMGCL. The Wnt/ß-catenin pathway may participate in the miR-1202/HMGCL axis-mediated regulation of BPH-1 cell phenotypes.

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