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1.
Materials (Basel) ; 17(10)2024 May 13.
Article En | MEDLINE | ID: mdl-38793377

Hot-rolled backup rolls are widely used in steel rolling and usually need to be repaired by arc hardfacing after becoming worn. However, a corrugated-groove defect commonly occurs on the roll surface due to the uneven hardness distribution in the hardfacing layers, affecting the proper usage of the roll. Accordingly, a new swing-arc submerged arc welding (SA-SAW) process is proposed to attempt to solve this drawback. The microstructure and hardness are then investigated experimentally for both SAW and SA-SAW hardfacing layers. It is revealed that a self-tempering effect occurs in the welding pass bottom and the welding pass side neighboring the former pass for both processes, refining the grain in the two areas. In all the zones, including the self-tempering zone (STZ), heat-affected zone (HAZ), and not-heat-affected zone in the welding pass, both SAW and SA-SAW passes crystallize in a type of columnar grain, where the grains are the finest in STZ and the coarsest in HAZ. In addition, the arc swing improves the microstructure homogeneity of the hardfacing layers by obviously lowering the tempering degree in HAZ while promoting the even distribution of the arc heat. Accordingly, the hardness of the SA-SAW bead overall increases and distributes more uniformly with a maximum difference of < 80 HV0.5 along the horizontal direction of the bead. This hardness difference in SA-SAW is accordingly decreased by ~38.5% compared to that of the SAW bead, further indicating the practicability of the new process.

2.
PLoS One ; 19(5): e0299731, 2024.
Article En | MEDLINE | ID: mdl-38768191

The government's environmental protection policy can significantly contribute to alleviating resource shortages and curbing environmental pollution, but the impact of various policy instruments implemented by the government on energy efficiency is unclear. Based on the panel data of 30 provinces in China from 2005 to 2021, this paper analyses the impact of environmental regulation and the industrial structure on energy efficiency from the perspective of resource taxes. The U-shaped relationship between environmental regulation and energy efficiency and between the optimization of industrial structure can significantly improve energy efficiency, and the optimization of industrial structure is conducive to weakening the initial inhibitory effect of environmental regulation. In addition, the analysis of regional heterogeneity showed that the impact of environmental regulation was stronger in the central and western regions, while the impact of industrial structure was stronger in the eastern and western regions. The conclusions of this study can help to expand the understanding of the relationship between environmental regulation and industrial structure on energy efficiency, provide policy enlightenment for the realization of green development and high-quality development, and provide Chinese examples and experiences for developing countries to improve energy efficiency.


Industry , China , Environmental Pollution/prevention & control , Environmental Policy/legislation & jurisprudence , Conservation of Energy Resources , Conservation of Natural Resources/methods
3.
Microbiol Resour Announc ; 13(1): e0080223, 2024 Jan 17.
Article En | MEDLINE | ID: mdl-38084995

We isolated a strain of Staphylococcus nepalensis from Nasonia vitripennis and presented the draft genome sequence of this strain. This research was conducted at the Institute of Zoology, Chinese Academy of Sciences (Beijing, China). The genome spans 2,910,033 bp, distributed over 144 contigs, with a G+C content of 33.33%.

4.
Sci Total Environ ; 912: 168952, 2024 Feb 20.
Article En | MEDLINE | ID: mdl-38043807

Enhanced biological phosphorus removal (EBPR) is an effective process for phosphorus removal from wastewater. In this study, two lab-scale sequencing batch reactors (SBR) were used to perform EBPR process, in which genus Propioniciclava was unexpectedly accumulated and its relative abundance was over 70 %. A series of tests were conducted to explore the role of Propioniciclava in the two EBPR systems. The two systems performed steadily throughout the study, and the phosphorus removal efficiencies were 96.6 % and 93.5 % for SBR1 and SBR2, respectively. The stoichiometric analysis related to polyphosphate accumulating organisms (PAOs) indicated that polyphosphate accumulating metabolism (PAM) was achieved in the anaerobic phase. It appeared that the Propioniciclava-dominated systems could not perform denitrifying phosphorus removal. Instead, phosphorus was released under anoxic conditions without carbon sources. According to the genomic information from Integrated Microbial Genomes (IMG) database, Propioniciclava owns ppk1, ppk2 and ppx genes that are associated with phosphorus release and uptake functions. By phylogenetic investigation of communities by reconstruction of unobserved states 2 (PICRUSt2) analysis, the abundance of genes related to phosphorus metabolism was much higher than that of genes related to denitrification. Therefore, Propioniciclava was presumed to be a potential PAO without denitrifying phosphorus uptake function. In addition to Propioniciclava, Tessaracoccus and Thiothrix were also enriched in both systems. Overall, this study proposes a novel potential PAO and broadens the understanding of EBPR microbial communities.


Phosphorus , Polyphosphates , Polyphosphates/metabolism , Phosphorus/metabolism , Phylogeny , Wastewater , Biological Transport , Bioreactors , Sewage
5.
Article En | MEDLINE | ID: mdl-38127595

The incredible potentiality of reconfigurable intelligent surface (RIS) in addressing power supply and obstacle environment of Internet of Medical Things (IoMT) has been capturing our interest. Considering the nettlesome "double-fading" effect introduced by passive RIS, we investigate an active RIS-enhanced IoMT system in this paper, where the wireless power transfer (WPT) from power station (PS) to IoMT devices and the wireless information transfer (WIT) from IoMT devices to the access point (AP) are both implemented with the assistance of active RIS. Aiming to maximize the sum throughput of the considered IoMT system, a joint design of time schedules and reflecting coefficient matrices of the active RIS is proposed. Trapped by the non-convex and obstinate optimization problem, we explore the semi-definite programming (SDP) relaxation and successive convex approximation (SCA) techniques based on alternating optimization (AO) algorithm. Simulation results verify our solution approach to the intractable optimization problem and showcase the boosted spectrum and energy efficiency of the active RIS-enhanced IoMT system.

6.
Microbiol Resour Announc ; 12(11): e0043023, 2023 Nov 16.
Article En | MEDLINE | ID: mdl-37902323

Providencia stuartii prov-sta1 is a prevalent Gram-negative bacterium and dominant in the wasp Nasonia vitripennis. In this study, we present the draft genome sequence of P. stuartii prov-sta1, and the genome size is 4,380,152 bp in 183 contigs with a G+C content of 41.34%.

7.
J Vis Exp ; (197)2023 07 21.
Article En | MEDLINE | ID: mdl-37548461

Aseptic rearing technology is a method of culturing insects under sterile or almost sterile conditions, which can effectively eliminate the influence of external microorganisms on insect microbiota and thus promote the rapid development of insect microbiota research. Nasonia (wasp genus) is a parasitic wasp insect that has many advantages, such as a short lifespan, high genetic variation, easy operation, etc., and is widely used as an insect model system. Unlike antibiotic treatment, which can only reduce the number of microorganisms in animals, aseptic rearing techniques can control both the composition and quantity of microorganisms in animals, further facilitating the study of host-microbe interactions. However, previous versions of Nasonia rearing medium (NRM) have some defects and problems, such as a complex and time-consuming preparation process, easy contamination by bacteria or fungi, and short storage time. Therefore, this study solves these problems by optimizing the tools used in the NRM preparation process, storage conditions, and component ratios. The optimized medium could allow storage at -20 °C for at least 3 months and eliminate the possibility of NRM contamination during feeding sterile wasps. This further improves the survival rate and health level of aseptic Nasonia, which is important for using Nasonia as a model for microbial research.


Microbiota , Wasps , Animals , Wasps/genetics , Insecta , Models, Biological , Anti-Bacterial Agents
8.
J Innate Immun ; 15(1): 647-664, 2023.
Article En | MEDLINE | ID: mdl-37607510

An unstable influenza genome leads to the virus resistance to antiviral drugs that target viral proteins. Thus, identification of host factors essential for virus replication may pave the way to develop novel antiviral therapies. In this study, we investigated the roles of the poly(ADP-ribose) polymerase enzyme, tankyrase 1 (TNKS1), and the endogenous small noncoding RNA, miR-9-1, in influenza A virus (IAV) infection. Increased expression of TNKS1 was observed in IAV-infected human lung epithelial cells and mouse lungs. TNKS1 knockdown by RNA interference repressed influenza viral replication. A screen using TNKS1 3'-untranslation region (3'-UTR) reporter assays and predicted microRNAs identified that miR-9-1 targeted TNKS1. Overexpression of miR-9-1 reduced influenza viral replication in lung epithelial cells as measured by viral mRNA and protein levels as well as virus production. miR-9-1 induced type I interferon production and enhanced the phosphorylation of STAT1 in cell culture. The ectopic expression of miR-9-1 in the lungs of mice by using an adenoviral viral vector enhanced type I interferon response, inhibited viral replication, and reduced susceptibility to IAV infection. Our results indicate that miR-9-1 is an anti-influenza microRNA that targets TNKS1 and enhances cellular antiviral state.


Influenza A virus , Influenza, Human , Interferon Type I , MicroRNAs , Tankyrases , Animals , Humans , Mice , Antiviral Agents/pharmacology , Host-Pathogen Interactions , Influenza A virus/physiology , Influenza, Human/genetics , MicroRNAs/genetics , Tankyrases/genetics , Virus Replication
9.
Viruses ; 15(7)2023 06 22.
Article En | MEDLINE | ID: mdl-37515100

Influenza A virus (IAV) is an eight-segment negative-sense RNA virus and is subjected to gene recombination between strains to form novel strains, which may lead to influenza pandemics. Seasonal influenza occurs annually and causes great losses in public healthcare. In this study, we examined the role of interferon-induced protein with tetratricopeptide repeats 1 and 2 (IFIT1 and IFIT2) in influenza virus infection. Knockdown of IFIT1 or IFIT2 using a lentiviral shRNA increased viral nucleoprotein (NP) and nonstructural protein 1 (NS1) protein levels, as well as progeny virus production in A/Puerto Rico/8/34 H1N1 (PR/8)-infected lung epithelial A549 cells. Overexpression of IFIT1 or IFIT2 reduced viral NP and NS1 RNA and protein levels in PR/8-infected HEK293 cells. Overexpression of IFIT1 or IFIT2 also inhibited influenza virus infection of various H1N1 strains, including PR/8, A/WSN/1933, A/California/07/2009 and A/Oklahoma/3052/2009, as determined by a viral reporter luciferase assay. Furthermore, knockdown of IFIT1 or IFIT2 increased while overexpression of IFIT1 or IFIT2 decreased viral RNA, complementary RNA, and mRNA levels of NP and NS1, as well as viral polymerase activities. Taken together, our results support that both IFIT1 and -2 have anti-influenza virus activities by inhibiting viral RNA synthesis.


Influenza A Virus, H1N1 Subtype , Influenza, Human , Orthomyxoviridae Infections , Humans , Interferons , Influenza A Virus, H1N1 Subtype/genetics , RNA, Viral/genetics , HEK293 Cells , Tetratricopeptide Repeat , RNA-Binding Proteins/genetics , Influenza, Human/genetics , Viral Nonstructural Proteins/genetics , Virus Replication/genetics
10.
Urol J ; 20(5): 337-343, 2023 Oct 23.
Article En | MEDLINE | ID: mdl-37330690

PURPOSE: This study aimed to assess the importance of computed tomography (CT) imaging in the diagnostic and prognostic evaluation of renal epithelioid angiomyolipoma (EAML). MATERIALS AND METHODS: This study comprised 63 patients diagnosed with renal EAML in the First Affiliated Hospital of Soochow University during 2010-2021, who met the inclusion criteria. The clinical, pathological, and therapeutic features were analyzed to determine the optimum diagnostic and therapeutic approaches. RESULTS: Of the 63 participants, 20 were men and 43 women aged 24-74 years (average, 45.5 years). In 35 and 28 participants, the tumor was located on the left and right sides, respectively. All the patients underwent CT scanning. Most of the patients (54/63) with EAMLs demonstrated hyperattenuation, one showed isoattenuation, and eight showed hypoattenuation compared with renal parenchyma on unenhanced CT images. The diameter of each tumor was 2-25 cm (average, 5.6 cm). All the participants underwent surgical treatment. Of these, 53 were followed up for 4-128 months (median, 64 months). Among the followed-up patients, one died of the tumor, one died due to acute severe pancreatitis, and two had an ipsilateral recurrence. CONCLUSION: EAML is a relatively rare renal angiomyolipoma depleted in fat. A characteristic of hyperattenuation on unenhanced CT images in EAML can help distinguish this tumor from clear cell renal cell carcinoma. Surgical resection is the main treatment. Most EAMLs are benign, and only a few have malignant potential. However, post-surgery recurrence and metastasis may occur, especially in elderly patients, and thus close follow-up is recommended.

11.
Food Chem ; 426: 136574, 2023 Nov 15.
Article En | MEDLINE | ID: mdl-37302305

This study investigated the flavor characteristics of semi-dried yellow croaker made by KCl instead of partial NaCl combined with ultrasound treatment before and after low temperature vacuum heating. The electronic tongue, electronic nose, free amino acids, 5'-nucleotides, and gas chromatography-ion mobility spectrometry were employed. Electronic nose and electronic tongue results showed that different treatment groups had different sensitive signals to smell and taste. The odor and taste of each group were mainly affected by Na+ and K+. The difference between the groups becomes larger after thermal treatment. Ultrasound and thermal treatment both changed the content of taste components. In addition, each group contained 54 volatile flavor compounds. Among them, the combined treatment method gave semi-dried large yellow croaker pleasant flavor characteristics. Besides, it also improved the content of flavor substances. In conclusion, the semi-dried yellow croaker under sodium-reduced conditions showed better performance in flavor characteristics.


Heating , Perciformes , Animals , Temperature , Vacuum , Gas Chromatography-Mass Spectrometry
12.
Trends Parasitol ; 39(2): 101-112, 2023 02.
Article En | MEDLINE | ID: mdl-36496327

In recent years, with the development of microbial research technologies, microbiota research has received widespread attention. The parasitoid wasp genus Nasonia is a good model organism for studying insect behavior, development, evolutionary genetics, speciation, and symbiosis. This review describes key advances and progress in the field of the Nasonia-microbiome interactions. We provide an overview of the advantages of Nasonia as a model organism for microbiome studies, list research methods to study the Nasonia microbiome, and discuss recent discoveries in Nasonia microbiome research. This summary of the complexities of Nasonia-microbiome relationships will help to contribute to a better understanding of the interactions between animals and their microbiomes and establish a clear research direction for Nasonia-microbiome interactions in the future.


Microbiota , Wasps , Animals , Biological Evolution , Wasps/genetics , Insecta/genetics , Microbiota/genetics , Symbiosis
13.
Front Aging Neurosci ; 14: 1013943, 2022.
Article En | MEDLINE | ID: mdl-36408108

Mitochondrial dysfunction plays a key role in the pathogenesis of Alzheimer's disease (AD). The translocase of the outer membrane (TOM) complex controls the input of mitochondrial precursor proteins to maintain mitochondrial function under pathophysiological conditions. However, its role in AD development remains unclear. TOM70 is an important translocase present in the TOM complex. In the current study, we found that TOM70 levels were reduced in the peripheral blood and hippocampus of the APP/PS1 mice. In addition, we examined the whole-blood mRNA levels of TOM70 in patients with AD, dementia with Lewy bodies (DLB), and post-stroke dementia (PSD). Our study revealed that the mRNA level of TOM70 was decreased in the blood samples of patients with AD, which was also correlated with the progression of clinical stages. Therefore, we proposed that the expression of TOM70 could be a promising biomarker for AD diagnosis and monitoring of disease progression.

14.
Mol Microbiol ; 118(6): 731-743, 2022 12.
Article En | MEDLINE | ID: mdl-36308071

Acute respiratory infection by influenza virus is a persistent and pervasive public health problem. Antiviral innate immunity initiated by type I interferon (IFN) is the first responder to pathogen invasion and provides the first line of defense. We discovered that Axin1, a scaffold protein, was reduced during influenza virus infection. We also found that overexpression of Axin1 and the chemical stabilizer of Axin1, XAV939, reduced influenza virus replication in lung epithelial cells. This effect was also observed with respiratory syncytial virus and vesicular stomatitis virus. Axin1 boosted type I IFN response to influenza virus infection and activated JNK/c-Jun and Smad3 signaling. XAV939 protected mice from influenza virus infection. Thus, our studies provide new mechanistic insights into the regulation of the type I IFN response and present a new potential therapeutic of targeting Axin1 against influenza virus infection.


Axin Protein , Influenza, Human , Interferons , Animals , Humans , Mice , Axin Protein/metabolism , Epithelial Cells , Immunity, Innate , Influenza, Human/immunology , Influenza, Human/metabolism , Interferons/metabolism , Virus Replication
15.
Article En | MEDLINE | ID: mdl-36124013

Purpose: The aim of the study is to investigate the prognostic value of plasma interleukin-35 in the surgical treatment of patients with clear cell renal cell carcinoma (ccRCC). Material and Methods. Plasma IL-35 levels were measured in patients with ccRCC. The cut-off value of IL-35 was determined by the receiver operating characteristic (ROC) analysis and the area under the curve (AUC). The effects of the IL-35 and other clinicopathological characteristics on overall survival (OS) and progression-free survival (PFS) were evaluated using the univariate and multivariate logistic regression analysis. Result: Sixty-four ccRCC patients admitted to the urology department at the First Affiliated Hospital of Soochow University were selected, of whom 50 were diagnosed with localized ccRCC. Plasma interleukin-35 levels were significantly higher in patients with ccRCC than that in healthy controls. The cut-off value of IL-35 was 99.7 pg/mL. Multivariate analysis selected by univariate analyses demonstrated that the preoperative IL-35 was an independent prognostic factor for 5-year OS (OR: 1.02, 95% CI: 1.01 to 1.04, p < 0.0001) and 5-year PFS (OR: 1.02, 95% CI: 1.00 to 1.03, p=0.011) in all patients with localized ccRCC. Conclusion: Current results indicate that preoperative IL-35 is an independent prognostic marker for OS and RFS in patients with localized ccRCC after surgery.

16.
Comput Intell Neurosci ; 2022: 9945687, 2022.
Article En | MEDLINE | ID: mdl-35875779

The interbasin water transfer project has realized the optimal allocation of water resources, improved economic benefits, improved people's life and welfare, and had an impact on the ecology. Taking Anhui Jianghuai water transfer project as an example, this study uses morphological spatial pattern analysis (MSPA) to identify the core area, selects the patches in the core area, identifies the source according to the patch importance index, constructs the basic resistance surface according to the resistance factor, modifies the basic resistance surface by using the landscape connectivity index, and constructs the ecological corridor by combining the minimum cumulative resistance (MCR) model and the loop model (curve) to build the ecological network of the completed Huaihe River Water Transfer Project (Anhui). The results show that there are 83 sources, 197 potential ecological corridors, and 80 ecological nodes in the ecological network of Anhui Jianghuai project. Ecological network optimization strategies and protection suggestions are put forward for ecological sources, ecological corridors, and ecological nodes, respectively, so as to provide scientific reference and basis for the ecological environment protection and high-quality development of Anhui Jianghuai water transfer project.


Conservation of Natural Resources , Ecology , China , Conservation of Natural Resources/methods , Humans , Rivers , Water , Water Resources
17.
BMC Med Genomics ; 15(1): 108, 2022 05 09.
Article En | MEDLINE | ID: mdl-35534881

BACKGROUND: The clinical consequences of atherosclerosis are significant source of morbidity and mortality throughout the world, while the molecular mechanisms of the pathogenesis of atherosclerosis are largely unknown. METHODS: In this study, we integrated the DNA methylation and gene expression data in atherosclerotic plaque samples to decipher the underlying association between epigenetic and transcriptional regulation. Immune cell classification was performed on the basis of the expression pattern of detected genes. Finally, we selected ten genes with dysregulated methylation and expression levels for RT-qPCR validation. RESULTS: Global DNA methylation profile showed obvious changes between normal aortic and atherosclerotic lesion tissues. We found that differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were highly associated with atherosclerosis by being enriched in atherosclerotic plaque formation-related pathways, including cell adhesion and extracellular matrix organization. Immune cell fraction analysis revealed that a large number of immune cells, especially macrophages, activated mast cells, NK cells, and Tfh cells, were specifically enriched in the plaque. DEGs associated with immune cell fraction change showed that they were mainly related to the level of macrophages, monocytes, resting NK cells, activated CD4 memory T cells, and gamma delta T cells. These genes were highly enriched in multiple pathways of atherosclerotic plaque formation, including blood vessel remodeling, collagen fiber organization, cell adhesion, collagen catalogic process, extractable matrix assembly, and platelet activation. We also validated the expression alteration of ten genes associated with infiltrating immune cells in atherosclerosis. CONCLUSIONS: In conclusion, these findings provide new evidence for understanding the mechanisms of atherosclerotic plaque formation, and provide a new and valuable research direction based on immune cell infiltration.


Atherosclerosis , Plaque, Atherosclerotic , Atherosclerosis/genetics , Atherosclerosis/metabolism , Atherosclerosis/pathology , DNA Methylation , Gene Expression , Humans , Macrophages , Plaque, Atherosclerotic/genetics , Plaque, Atherosclerotic/metabolism
18.
J Cell Mol Med ; 26(8): 2285-2298, 2022 04.
Article En | MEDLINE | ID: mdl-35201667

Influenza virus causes approximately 291,000 to 646,000 human deaths worldwide annually. It is also a disease of zoonotic importance, affecting animals such as pigs, horses, and birds. Even though vaccination is being used to prevent influenza virus infection, there are limited options available to treat the disease. Long noncoding RNAs (lncRNAs) are RNA molecules with more than 200 nucleotides that do not translate into proteins. They play important roles in the physiological and pathological processes. In this study, we identified a novel transcript, Lnc-PINK1-2:5 that was upregulated by influenza virus. This lncRNA was predominantly located in the nucleus and was not affected by type I interferons. Overexpression of Lnc-PINK1-2:5 reduced the influenza viral mRNA and protein levels in cells as well as titres in culture media. Knockdown of Lnc-PINK1-2:5 using CRISPR interference enhanced the virus replication. Antiviral activity of Lnc-PINK1-2:5 was independent of influenza virus strains. RNA sequencing analysis revealed that Lnc-PINK1-2:5 upregulated thioredoxin interacting protein (TXNIP) during influenza virus infection. Overexpression of TXNIP reduced influenza virus infection, suggesting that TXNIP is an antiviral gene. Knockdown of TXNIP abolished the Lnc-PINK1-2:5-mediated increase in influenza virus infection. In conclusion, the newly identified Lnc-PINK1-2:5 isoform is an anti-influenza lncRNA acting through the upregulation of TXNIP gene expression.


Influenza A virus , Influenza, Human , Orthomyxoviridae Infections , RNA, Long Noncoding , Animals , Antiviral Agents , Horses/genetics , Humans , Influenza A virus/metabolism , Influenza, Human/genetics , Orthomyxoviridae Infections/genetics , Protein Kinases , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Swine
19.
Neuropsychiatr Dis Treat ; 17: 2587-2598, 2021.
Article En | MEDLINE | ID: mdl-34408420

BACKGROUND: Early cognitive impairment after transient ischemic stroke (TIA)/mild ischemic stroke (MIS) is common but easily overlooked. It has been demonstrated that DNA methylation plays a significant role in cognitive impairment and ischemic stroke. Furthermore, it has been reported that the RIN3 gene influences transportation of the amyloid ß-protein. However, to our knowledge, there has been no research related to correlations between RIN3 methylation and early-onset cognitive impairment after TIA/MIS. Therefore, this study aimed to investigate this relationship in TIA/MIS patients. METHODS: This study include 28 control subjects and 84 patients with TIA/MIS who were evaluated within 7 days of TIA/MIS onset using four single-domain cognitive scales. In addition, DNA methylation of whole blood was tested. RIN3 methylation was compared between TIA/MIS and control groups and between TIA/MIS patients with early cognitive impairment and those without early cognitive impairment. Clinical variables and RIN3 methylation sites with statistical differences were then used to construct a predictive model. RESULTS: Hypomethylation of the RIN3 gene was observed in the whole blood of TIA/MIS patients relative to healthy controls. Furthermore, patients with early cognitive impairment after TIA/MIS had hypomethylation of RIN3 relative to those without early cognitive impairment. CONCLUSION: RIN3 methylation is strongly associated with TIA/MIS and TIA/MIS with early cognitive impairment. It is possible to influence the disease process by methylation via appropriate lifestyle and clinical interventions, and methylation of RIN3 gene sites may predict the occurrence of TIA/MIS with early cognitive impairment.

20.
Cancer Cell Int ; 21(1): 404, 2021 Aug 17.
Article En | MEDLINE | ID: mdl-34399755

BACKGROUND: Encouraged by the goal of developing an effective treatment strategy for prostate cancer, this study explored the mechanism involved in metformin-mediated inhibition of AR-negative prostate cancer. METHODS: Cell behaviors of DU145 and PC3 cells were determined by CCK8 test, colony formation experiment and scratch test. Flow cytometry was used to detect cell cycle distribution. Cell autophagy was induced with metformin, and an autophagy inhibitor, 3-MA, was used to assess the level of autophagy. Detection of LC3B by immunofluorescence was conducted to determine autophagy level. Cell proliferation, autophagy and cell cycle were examined by performing Western blot. DU145 and PC3 cell lines were transfected with AMPK siRNA targeting AMPK-α1 and AMPK-α2. Tumor formation experiment was carried out to evaluate the anti-prostate cancer effect of metformin in vivo. RESULTS: The inhibitory effect of metformin on the proliferation of prostate cancer cell lines was confirmed in this study, and the mechanism of such an effect was related to autophagy and the block of cell cycle at G0/G1 phase. Metformin also induced the activation of AMPK, markedly promoted expression of LC3II, and down-regulated the expression of p62/SQSTM1. Animal experiments showed that the tumor volume of metformin group was smaller, meanwhile, the levels of p-AMPK (Thr172) and LC3B were up-regulated and the Ki-67 level was down-regulated, without abnormalities in biochemical indicators. CONCLUSION: This study found that autophagy induction might be the mechanism through which metformin suppressed the growth of AR-negative prostate cancer. Moreover, the activation of AMPK/autophagy pathway might be a therapeutically effective for treating AR-negative prostate cancer in the future.

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