Publications by authors named "Xiaoping Zhang"

628 Publications

Cyclosporine modulates neutrophil functions via the SIRT6-HIF-1α-glycolysis axis to alleviate severe ulcerative colitis.

Clin Transl Med 2021 Feb;11(2):e334

Center for IBD Research, Department of Gastroenterology, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.

Background: Cyclosporine A (CsA) is routinely used to treat patients with steroid-refractory acute severe ulcerative colitis (ASUC). Here, we studied the underlying mechanisms of CsA-mediated alleviation in ASUC patients.

Methods: Neutrophil functions including expression of cytokines, apoptosis, and migration were measured by qRT-PCR, flow cytometry, and Transwell assay. Dynamic changes of glycolysis and tricarboxylic acid (TCA) cycle were measured by a Seahorse extracellular flux analyzer. Gene differences were determined and verified by RNA sequencing, qRT-PCR, and Western blotting. Small interfering RNA and inhibitors were used to knock down Sirtuin 6 (SIRT6) in HL-60 cells and block expression of SIRT6, hypoxia-inducible factor-1α (HIF-1α), and pyruvate dehydrogenase lipoamide kinase isozyme 4 (PDK4) in neutrophils.

Results: We found that HIF-1α expression and glycolysis significantly increased, while the release of IL-8, myeloperoxidase (MPO) and reactive oxygen species (ROS), the apoptosis, and ability of migration markedly decreased in neutrophils of ASUC patients who responded to CsA (Response group) compared with those who did not respond to CsA (Nonresponse group). We also observed that CsA-induced functional alternation of neutrophils was initiated through suppressing SIRT6 expression, which is responsible for expression of the downstream signaling molecules (e.g., HIF-1α, PFKFB3) and PDK4 ubiquitination, leading to fueling neutrophil glycolysis and TCA cycle. Furthermore, blockage of SIRT6 signaling demonstrated to be the same functional changes as CsA to decrease the migration of neutrophils.

Conclusions: The data reveal a novel mechanism of CsA in alleviating ASUC by promoting neutrophil HIF-1α expression and restricting excessive neutrophil activation in a SIRT6-HIF-1α-glycolysis axis, suggesting SIRT6 as a candidate target for maintaining mucosal homeostasis and treating intestinal inflammation.
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http://dx.doi.org/10.1002/ctm2.334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882115PMC
February 2021

Exploring the impact of transition in energy mix on the CO emissions from China's power generation sector based on IDA and SDA.

Environ Sci Pollut Res Int 2021 Feb 16. Epub 2021 Feb 16.

College of Management and Economics, Tianjin University, Tianjin, 300072, China.

The energy transition from coal and oil to renewable energy, nuclear energy, and natural gas is a fundamental way for emission reduction of China's power generation sector. Until now, research on the drivers of CO emissions from China's power generation sector has generally evaluated the energy mix as a whole, with a lack of exploration of the decomposition of different types of energy. This paper uses both index decomposition analysis (IDA) and structural decomposition analysis (SDA) to explore the impacts of energy transition on CO emissions in the power generation sector during periods of 2002-2007, 2007-2012, and 2012-2017. We find that the results of IDA and SDA are almost consistent, indicating that our results are robust. During the whole study period, CO emissions of power generation sector increased by 2447 Mt, of which the fossil fuel structure significantly contributed 642 Mt of incremental emissions (IDA). The thermal power generation efficiency was a dominator for reducing emissions, with a total reduction of 586 Mt (IDA). Simultaneously, the impacts of renewable energy and nuclear energy on emission reduction tend to be strengthening over time, with values changing from 38 Mt and -5 Mt in 2002-2007 to -219 Mt and -83 Mt (IDA) in 2012-2017, respectively. Based on the results, we put forward some suggestions such as promoting coal-to-gas, renewable energy, and nuclear energy in power generation to cut down CO emissions of China's power generation sector.
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http://dx.doi.org/10.1007/s11356-021-12599-1DOI Listing
February 2021

Treatment with a Urinary Bladder Matrix Alters the Innate Host Response to Pneumonia Induced by .

ACS Biomater Sci Eng 2021 Feb 2. Epub 2021 Feb 2.

Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.

has become the prominent cause of nosocomial pneumonia in recent years. In the meantime, some strains of have developed resistance to commonly used antibacterial drugs. The urinary bladder matrix (UBM) is a biologically derived scaffold material that has been used to promote site-appropriate tissue remodeling in a variety of body systems, partially through the modulation of the innate immune response. In this study, we seek to determine UBM efficacy in preventing bacterial pneumonia in mouse lungs using the Gram-negative bacterial strain . Our results show that the UBM prevented bacterial biofilm formation in both abiotic and biotic conditions through experimentation on polystyrene plates and culture on the apical surface of differentiated airway epithelial cells. Intratracheal treatment with UBM led to host protection from -induced respiratory infection in a murine pneumonia model. Transcriptomic analysis revealed the involvement of the enhanced host immune response in UBM-treated mice. Additionally, UBM-treated macrophages had an increased iNOS expression and enhanced phagocytosis activity. Therefore, the protection against -induced infection and the antibacterial function observed by UBM is potentially through both the anti-biofilm activity and enhanced host immunity following UBM treatment. Taken together, our results support further investigation of UBM as an alternative treatment to attenuate bacterial-induced respiratory infection.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01090DOI Listing
February 2021

A Comparative Study on NaFeMnPOF/C Cathode Materials Synthesized With Various Carbon Sources for Na-ion Batteries.

Front Chem 2020 13;8:633949. Epub 2021 Jan 13.

School of Iron and Steel, Soochow University, Suzhou, China.

NaFe6MnPOF/C composite materials are synthesized with various carbon sources via a simple spray-drying method in this study, and the effect of carbon sources on structure, morphology, and electrochemical properties of NaFeMnPOF/C materials are investigated in detail. XRD and SEM results indicate that the reduction ability of carbon sources has a key impact on the structure and morphology of NaFeMnPOF/C composite materials. Among these NaFeMnPOF/C materials, the sample prepared with ascorbic acid presents a uniform hollow spherical architecture. Electrochemical analysis demonstrates that the NaFeMnPOF/C sample prepared with ascorbic acid has optimal electrochemical performance. The sample shows high discharge capacities of 95.1 and 48.1 mAh g at 0.05C and 1C rates, respectively, and it exhibits an improved cycle stability (91.7% retention after 100 cycles at 0.5C), which are superior to NaFeMnPOF/C materials prepared with other carbon sources. This study demonstrates that the reduction ability of carbon sources significantly influences the electrochemical properties of fluorophosphate/C composite materials. This work also provides a promising strategy to obtain high performance cathode materials for sodium-ion batteries.
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http://dx.doi.org/10.3389/fchem.2020.633949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838565PMC
January 2021

Extracellular vesicles-released parathyroid hormone-related protein from Lewis lung carcinoma induces lipolysis and adipose tissue browning in cancer cachexia.

Cell Death Dis 2021 Jan 28;12(1):134. Epub 2021 Jan 28.

Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.

Cancer cachexia is a metabolic disorder characterized by skeletal muscle wasting and white adipose tissue browning. Specific functions of several hormones, growth factors, and cytokines derived from tumors can trigger cachexia. Moreover, adipose tissue lipolysis might explain weight loss that occurs owing to cachexia. Extracellular vesicles (EVs) are involved in intercellular communication. However, whether EVs participate in lipolysis induced by cancer cachexia has not been thoroughly investigated. Using Lewis lung carcinoma (LLC) cell culture, we tested whether LLC cell-derived EVs can induce lipolysis in 3T3-L1 adipocytes. EVs derived from LLC cells were isolated and characterized biochemically and biophysically. Western blotting and glycerol assay were used to study lipolysis. LLC cell-derived EVs induced lipolysis in vivo and vitro. EVs fused directly with target 3T3-L1 adipocytes and transferred parathyroid hormone-related protein (PTHrP), activating the PKA signaling pathway in 3T3-L1 adipocytes. Blocking PTHrP activity in LLC-EVs using a neutralizing antibody and by knocking down PTHR expression prevented lipolysis in adipocytes. Inhibiting the PKA signaling pathway also prevents the lipolytic effects of EVs. In vivo, suppression of LLC-EVs release by knocking down Rab27A alleviated white adipose tissue browning and lipolysis. Our data showed that LLC cell-derived EVs induced adipocyte lipolysis via the extracellular PTHrP-mediated PKA pathway. Our data demonstrate that LLC-EVs induce lipolysis in vitro and vivo by delivering PTHrP, which interacts with PTHR. The lipolytic effect of LLC-EVs was abrogated by PTHR knockdown and treatment with a neutralizing anti-PTHrP antibody. Together, these data show that LLC-EV-induced lipolysis is mediated by extracellular PTHrP. These findings suggest a novel mechanism of lipid droplet loss and identify a potential therapeutic strategy for cancer cachexia.
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http://dx.doi.org/10.1038/s41419-020-03382-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843996PMC
January 2021

Epigenetic Alteration Shaped by the Environmental Chemical Bisphenol A.

Front Genet 2020 11;11:618966. Epub 2021 Jan 11.

Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Bisphenol A (BPA) is extensively used in plastic products and epoxy resins. The epigenetic response to the environmental chemical BPA was involved in multiple dysfunctional categories, such as cancer, the reproductive system, metabolism, pubertal development, peripheral arterial disease, infant and childhood growth, and neurodevelopment outcomes. In this mini-review, we described the recent progress of the epigenetic effects of the environmental chemical BPA, including DNA methylation, histone methylation, and toxic epigenomics. Notably, the histone modification changes under BPA exposure are summarized in this review. DNA methylation accompanied by transcriptional changes in key genes affected by BPA exposure is related to various processes, including neural development, cancer pathways, and generational transmission. In addition, BPA could also affect histone modifications in many species, such as humans, rats, and zebrafish. Finally, we reviewed recent studies of the toxico-epigenomics approach to reveal the epigenetic effect of BPA exposure genome-wide.
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http://dx.doi.org/10.3389/fgene.2020.618966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830874PMC
January 2021

Identification of HIPK3 as a potential biomarker and an inhibitor of clear cell renal cell carcinoma.

Aging (Albany NY) 2021 Jan 20;13(3):3536-3553. Epub 2021 Jan 20.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Invasion and metastasis are the main causes of poor prognosis in patients with clear cell renal cell carcinoma (ccRCC). The homeodomain interacting protein kinases (HIPKs) can regulate cell proliferation and apoptosis. Little is known about the prognostic role of HIPKs in ccRCC. Here we use Kaplan-Meier survival analysis and multivariate analysis to analyze the correlation of overall survival (OS) and disease-free survival (DFS). ROC curves analyzed the relationship between clinicopathological parameters and HIPK3 expression in ccRCC. Univariate analysis and multivariate analysis confirmed that the expression of HIPK3 was associated with OS (HR, 0.701; P=0.041) and DFS (HR, 0.630; P=0.012). Low HIPK3 expression was a poor prognostic factor and HIPK3 expression was significantly down-regulated in ccRCC cancer tissues when compared with normal renal tissues. cell results also confirmed that HIPK3 over-expression could inhibit tumor growth and malignant characteristics. The results indicate that low expression of HIPK3 in ccRCC tissues is significantly associated with poor survival rates in tumor patients, and HIPK3 may be used as a valuable biomarker and inhibitor of ccRCC.
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http://dx.doi.org/10.18632/aging.202294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906163PMC
January 2021

Construction land suitability assessment in rapid urbanizing cities for promoting the implementation of United Nations sustainable development goals: a case study of Nanchang, China.

Environ Sci Pollut Res Int 2021 Jan 19. Epub 2021 Jan 19.

School of Earth Sciences and Engineering, Hohai University, Nanjing, 211100, China.

Cities, the main place of human settlements, are required to offer high-quality environments to citizens. To achieve this, it is essential to overcome several mega challenges of urbanization, population growth, economic development, environmental deterioration, and climate change. Urban infrastructure construction is capable of enhancing economic growth and promoting urban sustainability, while it will lead to many environmental problems if the infrastructure construction is not properly planned and designed. To address this challenge, this study aims to understand how to ensure the construction land expansion sustainably in rapidly urbanizing cities. In particular, this study analyzed the suitability of construction land expansion in Nanchang, a rapid urbanizing city in China, from 1995 to 2015. The results indicate that the urban expansion speed from 1995 to 2005 was faster than that from 2005 to 2015. The construction land in Nanchang was expanding towards "all directions" and sprawled towards surrounding districts and counties from the original core areas. Nevertheless, about 70% of the Nanchang area was allowable construction area (highly suitable expansion, relatively suitable expansion, and basically suitable expansion areas), indicating that the abundant reserved land resources for urban construction. This study also identified multiple suitability expansion paths of construction land, providing a scientific guidance for the land use planning of Nanchang city. Overall, this study provides a reference to the understanding of the construction land expansion for the achievement of United Nations sustainable development goals. It can also promote the understanding of spatial territory planning and practically enhance the capabilities of land use planning and design.
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http://dx.doi.org/10.1007/s11356-020-12336-0DOI Listing
January 2021

NNT-induced tumor cell "slimming" reverses the pro-carcinogenesis effect of HIF2a in tumors.

Clin Transl Med 2021 Jan;11(1):e264

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: HIF2a and lipid accumulation play key roles in the progression of clear cell renal cell carcinoma (ccRCC). Tumor cell "slimming" is a new concept in which tumor cells with abnormal lipids efficiently consume lipids to inhibit tumor progression without producing additional ATP. However, their respective regulatory mechanisms are still unclear. The purpose of this study is uncovering the links between these three key elements of ccRCC to elucidate new mechanisms of ccRCC metabolic abnormalities and providing a basis for new drug development for ccRCC.

Methods: Bioinformatics screening and analyses were performed in ccRCC according to TCGA-KIRC database. qRT-PCR, luciferase reporter assay, western blot, chromatin immunoprecipitation (ChIP) assays, and other biological methods were used to explore and verify related pathways. Various cell line models and animal models were used to perform related functional experiments.

Results: Screening based on sequencing data after HIF2a knockdown and three independent mitochondrial metabolism-related gene sets showed that nicotinamide nucleotide transhydrogenase (NNT) was a mediator between HIF2a and tumor cells "slimming." Further research showed that NNT had significant prognostic predictive value and was downregulated in ccRCC. It is regulated by HIF2a and can significantly activate lipid browning-mediated tumor cell "slimming." Mechanistic investigations indicated that HIF2a enhanced the expression of miR-455-5p via binding to HIF2a-related response elements in the miR-455-5p promoter, which suppresses NNT expression by binding to its 3' untranslated region.

Conclusions: Our study revealed a novel mechanism by which HIF2a decreased NNT level through a microRNA that suppressed tumor cell "slimming," resulting in the progression of ccRCC. This mechanism provides a fresh perspective of lipid accumulation in ccRCC and may help target novel strategies for the treatment of tumors with abnormal lipid metabolism.
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http://dx.doi.org/10.1002/ctm2.264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803359PMC
January 2021

MnO anchored polypyrrole nanotubes as an efficient sulfur host for high performance lithium-sulfur batteries.

J Colloid Interface Sci 2021 May 7;589:208-216. Epub 2021 Jan 7.

School of Iron and Steel, Soochow University, Suzhou 215000, China. Electronic address:

Lithium-sulfur batteries have attracted numerous attentions owing to their high theory discharge specific capacity and energy density. However, sulfur cathode usually suffers from poor cycle stability and slow reaction kinetics, caused by its poor conductivity, excessive volume changes during charge/discharge processes, complex sulfur species conversion reaction and the dissolution of polysulfide intermediates. Here, we present a free-standing framework of MnO nanoparticles combine with polypyrrole (PPy) nanotubes as host materials for lithium-sulfur batteries to overcome these issues. In this construction, PPy nanotubes serve as the excellent container of sulfur and physical barrier for the excessive volume expansion of sulfur during electrochemical reaction processes, and the nanotubes also provide an efficient conductive network for the rapid transmission of electrons and ions, while MnO nanoparticles facilitate trapping lithium polysulfides. The coordination of PPy nanotubes and MnO effectively alleviate the shuttle effect as well as enhance the utilization of sulfur. The obtained PPy@MnO-S sample shows high capacities of 1419.9 and 925.5 mAh g at 0.1 C and 1 C rate, respectively, and exhibits a low capacity fading rate of 0.062% per cycle for 800 cycles at 1 C rate. This work provides a new and effective way for the design of lithium-sulfur batteries with both high rate performance and long cycle stability.
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http://dx.doi.org/10.1016/j.jcis.2021.01.006DOI Listing
May 2021

NLRX1/FUNDC1/NIPSNAP1-2 axis regulates mitophagy and alleviates intestinal ischaemia/reperfusion injury.

Cell Prolif 2021 Jan 11:e12986. Epub 2021 Jan 11.

Department of Interventional and Vascular Surgery, Changzhou No. 2 People's Hospital, Changzhou, China.

Objectives: Mitophagy is considered to be a key mechanism in the pathogenesis of intestinal ischaemic reperfusion (IR) injury. NOD-like receptor X1 (NLRX1) is located in the mitochondria and is highly expressed in the intestine, and is known to modulate ROS production, mitochondrial damage, autophagy and apoptosis. However, the function of NLRX1 in intestinal IR injury is unclear.

Materials And Methods: NLRX1 in rats with IR injury or in IEC-6 cells with hypoxia reoxygenation (HR) injury were measured by Western blotting, real-time PCR and immunohistochemistry. The function of NLRX1-FUNDC1-NIPSNAP1/NIPSNAP2 axis in mitochondrial homeostasis and cell apoptosis were assessed in vitro.

Results: NLRX1 is significantly downregulated following intestinal IR injury. In vivo studies showed that rats overexpressing NLRX1 exhibited resistance against intestinal IR injury and mitochondrial dysfunction. These beneficial effects of NLRX1 overexpression were dependent on mitophagy activation. Functional studies showed that HR injury reduced NLRX1 expression, which promoted phosphorylation of FUN14 domain-containing 1 (FUNDC1). Based on immunoprecipitation studies, it was evident that phosphorylated FUNDC1 could not interact with the mitophagy signalling proteins NIPSNAP1 and NIPSNAP2 on the outer membrane of damaged mitochondria, which failed to launch the mitophagy process, resulting in the accumulation of damaged mitochondria and epithelial apoptosis.

Conclusions: NLRX1 regulates mitophagy via FUNDC1-NIPSNAP1/NIPSNAP2 signalling pathway. Thus, this study provides a potential target for the development of a therapeutic strategy for intestinal IR injury.
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http://dx.doi.org/10.1111/cpr.12986DOI Listing
January 2021

Molecular structure, expression, and function analysis of BAFF gene in Chinese sucker, Myxocyprinus asiaticus.

Fish Physiol Biochem 2021 Jan 6. Epub 2021 Jan 6.

Key laboratory of Eco-environment in the Three Gorges Reservoir Region of Ministry of Education, School of Life Sciences, Southwest University, No. 1 Tiansheng Road, Beibei District, Chongqing, 400715, China.

B cell activating factor (BAFF), belonging to the tumor necrosis factor superfamily (TNFSF), is a critical cytokine for B cell survival and immunoglobulin secretion. Here, the BAFF gene of Chinese sucker (Myxocyprinus asiaticus) (MaBAFF) was cloned using RT-PCR and RACE (rapid amplification of cDNA end) techniques. The open reading frame (ORF) of MaBAFF encodes a 272-amino acid protein containing a transmembrane domain, a TNF family signature, and a putative furin protease cleavage site as seen in BAFFs from other species. Tissue expression profiles of MaBAFF determined by absolute and relative quantification of real-time quantitative PCR (qPCR) showed that MaBAFF is widely distributed in various tissues, with the highest expression in spleen. MaBAFF can be detected during fertilized egg period by RT-PCR. Upon induction by A. hydrophila, the expression of MaBAFF was up-regulated in spleen from 48 to 72 h, and the expression of BAFF and IgM all reached a peak at 48 h in head kidney. The soluble BAFF gene (MasBAFF) had been cloned into pET30a. SDS-PAGE and Western blotting analysis confirmed that the His-MasBAFF was efficiently expressed in Escherichia coli Rosset (DE3). CCK-8 assay indicated that the MasBAFF recombinant protein (200 ng/ml) could prolong the survival of peripheral blood leukocytes. Based on ELISA screening and Western blotting, monoclonal antibody 1-F2A3 against recombinant MasBAFF was selected and used for immunohistochemistry, which showed that BAFF-positive cells were detected in spleen and head kidney. Our results raise the possibility that MaBAFF may be useful to enhance immune efficacy in Chinese sucker disease defense.
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http://dx.doi.org/10.1007/s10695-020-00906-5DOI Listing
January 2021

ACSS3 represses prostate cancer progression through downregulating lipid droplet-associated protein PLIN3.

Theranostics 2021 1;11(2):841-860. Epub 2021 Jan 1.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Current endocrine therapy for prostate cancer (PCa) mainly inhibits androgen/androgen receptor (AR) signaling. However, due to increased intratumoural androgen synthesis and AR variation, PCa progresses to castration-resistant prostate cancer (CRPC), which ultimately becomes resistant to endocrine therapy. A search for new therapeutic perspectives is urgently needed. By screening lipid metabolism-related gene sets and bioinformatics analysis in prostate cancer database, we identified the key lipid metabolism-related genes in PCa. Bisulfite genomic Sequence Polymerase Chain Reaction (PCR) (BSP) and Methylation-Specific Polymerase Chain Reaction (PCR) (MSP) were preformed to detect the promoter methylation of ACSS3. Gene expression was analyzed by qRT-PCR, Western blotting, IHC and co-IP. The function of ACSS3 in PCa was measured by CCK-8, Transwell assays. LC/MS, Oil Red O assays and TG and cholesterol measurement assays were to detect the levels of TG and cholesterol in cells. Resistance to Enzalutamide in C4-2 ENZR cells was examined in a xenograft tumorigenesis model in vivo. We found that acyl-CoA synthetase short chain family member 3 (ACSS3) was downregulated and predicted a poor prognosis in PCa. Loss of ACSS3 expression was due to gene promoter methylation. Restoration of ACSS3 expression in PCa cells significantly reduced LD deposits, thus promoting apoptosis by increasing endoplasmic reticulum (ER) stress, and decreasing de novo intratumoral androgen synthesis, inhibiting CRPC progression and reversing Enzalutamide resistance. Mechanistic investigations demonstrated that ACSS3 reduced LD deposits by regulating the stability of the LD coat protein perilipin 3 (PLIN3). Our study demonstrated that ACSS3 represses prostate cancer progression through downregulating lipid droplet-associated protein PLIN3.
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http://dx.doi.org/10.7150/thno.49384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738848PMC
January 2021

The Identification of Critical mA RNA Methylation Regulators as Malignant Prognosis Factors in Prostate Adenocarcinoma.

Front Genet 2020 4;11:602485. Epub 2020 Dec 4.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

RNA methylation accounts for over 60% of all RNA modifications, and N-methyladenosine (mA) is the most common modification on mRNA and lncRNA of human beings. It has been found that mA modification occurs in microRNA, circRNA, rRNA, and tRNA, etc. The mA modification plays an important role in regulating gene expression, and the abnormality of its regulatory mechanism refers to many human diseases, including cancers. Pitifully, as it stands there is a serious lack of knowledge of the extent to which the expression and function of mA RNA methylation can influence prostate cancer (PC). Herein, we systematically analyzed the expression levels of 35 mA RNA methylation regulators mentioned in literatures among prostate adenocarcinoma patients in the Cancer Genome Atlas (TCGA), finding that most of them expressed differently between cancer tissues and normal tissues with the significance of < 0.05. Utilizing consensus clustering, we divided PC patients into two subgroups based on the differentially expressed mA RNA methylation regulators with significantly different clinical outcomes. To appraise the discrepancy in total transcriptome between subgroups, the functional enrichment analysis was conducted for differential signaling pathways and cellular processes. Next, we selected five critical genes by the criteria that the regulators had a significant impact on prognosis of PC patients from TCGA through the last absolute shrinkage and selection operator (LASSO) Cox regression and obtained a risk score by weighted summation for prognosis prediction. The survival analysis curve and receiver operating characteristic (ROC) curve showed that this signature could excellently predict the prognosis of PC patients. The univariate and multivariate Cox regression analyses proved the independent prognostic value of the signature. In summary, our effort revealed the significance of mA RNA methylation regulators in prostate cancer and determined a mA gene expression classifier that well predicted the prognosis of prostate cancer.
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http://dx.doi.org/10.3389/fgene.2020.602485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746824PMC
December 2020

Regulating Crystal Structure and Atomic Arrangement in Single-Component Metal Oxides through Electrochemical Conversion for Efficient Overall Water Splitting.

ACS Appl Mater Interfaces 2020 Dec 10;12(51):57038-57046. Epub 2020 Dec 10.

International Research Center for Renewable Energy, State Key Laboratory of Multiphase Flow in Power Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China.

Single-component transition-metal oxide (TMO: FeO, NiO, or CoO) nanosheets grown on nickel foam (NF) were electrochemically optimized with Li ion (Na ion)-induced conversion reaction for bifunctional electrocatalysis. The optimum FeO/NF-Li electrocatalyst exhibits low overpotentials of 239 mV for hydrogen evolution reaction and 276 mV for oxygen evolution reaction at a current density of 100 mA cm. A two-electrode water splitting cell using FeO/NF-Li as both anode and cathode requires only 1.60 V to achieve a current density of 10 mA cm. The impressive water splitting performance of the FeO/NF-Li electrode is revealed to be attributed to Li-induced electrochemical conversion, which alters the crystal structure, creating more active sites for electrocatalytic reactions, as well as introduces O vacancies increasing the electron density and the intrinsic conductivity. More importantly, the atomic arrangement is regulated from tetrahedral Fe(Td) to octahedral Fe(Oh) coordination, which acts as catalytically active sites with reduced Gibbs free energy for the rate-determining steps. This electrochemical conversion reaction can be extended to other TMOs (i.e., NiO/NF and CoO/NF) for promoted electrocatalytic water splitting performances. This study provides an in-depth understanding on the nature of atomic and electronic structure evolution to promote the electrocatalytic activity.
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http://dx.doi.org/10.1021/acsami.0c16659DOI Listing
December 2020

Applications of direct analysis in real time mass spectrometry in food analysis: A review.

Rapid Commun Mass Spectrom 2021 Mar;35(6):e9013

Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation, East China University of Technology, Nanchang, China.

Rationale: Direct analysis in real time (DART) combined with mass spectrometry (MS) detection has become one of the most broadly used analytical approaches for the direct molecular characterization of food samples with regard to their chemical quality, safety, origin, and authentication. The major advantages of DART-MS for food analysis include high chemical sensitivity and specificity, high speed and throughput of analysis, simplicity, and the obviation of tedious sample preparation and solvents.

Methods: The recent applications of DART coupled with different mass analyzers, including quadrupole, ion trap, Orbitrap, and time of flight, are discussed. In addition, sample pretreatment methods that have been coupled with DART-MS are discussed.

Results: We summarize the applications of DART-MS in food science and industry published in the period from 2005 to this date. The applications and analytical characteristics are systematically categorized across the three major types of foods: solid foods, liquid foods, and viscous foods.

Conclusions: DART-MS has proved its high suitability for the direct, rapid, and high-throughput molecular analysis of very different food samples with minimal or no sample preparation, thus offering a high-speed alternative to liquid chromatography/mass spectrometry (LC/MS) and gas chromatography/mass spectrometry (GC/MS) approaches that are traditionally employed in food analysis.
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http://dx.doi.org/10.1002/rcm.9013DOI Listing
March 2021

Soil carbon and associated bacterial community shifts driven by fine root traits along a chronosequence of Moso bamboo (Phyllostachys edulis) plantations in subtropical China.

Sci Total Environ 2021 Jan 9;752:142333. Epub 2020 Sep 9.

China National Bamboo Research Center, Key Laboratory of Resources and Utilization of Bamboo of State Forestry Administration, Hangzhou 310012, PR China. Electronic address:

Moso bamboo (Phyllostachys edulis) is widely considered to be effective in capturing and sequestering atmospheric C, but the long-term effects of extensive management strategies on soil organic carbon (SOC), bacterial communities, fine root (FR, ø ≤ 2 mm) traits, and their inherent connection remain unclear. In this study, we simultaneously measured the SOC content of the bulk and rhizosphere soil fractions, the aggregate stability, the chemical composition of SOC (solid-state C nuclear magnetic resonance [NMR]), the bacterial community structure in the rhizosphere, and the FR morphological traits including biomass, specific root length (SRL), and root length density (RLD) along a chronosequence (stand age of 19, 37, and 64 years) of extensively managed Moso bamboo plantations and in an adjacent secondary forest as a control. The organic C content in both the rhizosphere and bulk soil increased rapidly with plantation age in the 0-20- and 20-40-cm soil layers, accompanied by an increase in the aggregate stability. FR traits including biomass, SRL, and RLD also increased continuously in response to soil C:N:P stoichiometry. All of these traits were significantly correlated with SOC, occluded particulate organic C (oPOC), and mineral-associated organic C (MOC), suggesting that FR traits could drive the soil C sequestration with the plantation age. Further analysis indicated that the microbial biomass C (MBC) content, MBC/total organic carbon (TOC) ratio, and bacterial abundance decreased with the plantation age, and the shift from soil oligotrophy to copiotrophy bacteria were mainly driven by changes in FR traits and SOC properties. Such a reassembly of bacterial communities combined with an increase in root biomass is favorable for the accumulation of stable C functional groups (alkyl C or aromatic C). Our findings indicate that extensive management regimes of Moso bamboo plantations could promote long-term soil C sequestration especially in the rhizosphere by promoting the formation of soil aggregates and organic-mineral complexes and by shifting bacterial community composition, and that these changes can be inferred through changes in the FR traits.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142333DOI Listing
January 2021

Rox8 promotes microRNA-dependent messenger RNA decay.

Proc Natl Acad Sci U S A 2020 12 17;117(48):30520-30530. Epub 2020 Nov 17.

Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China;

The Hippo pathway is an evolutionarily conserved regulator of organ growth and tumorigenesis. In , oncogenic Ras cooperates with loss-of-cell polarity to promote Hippo pathway-dependent tumor growth. To identify additional factors that modulate this signaling, we performed a genetic screen utilizing the in vivo tumor model and identified Rox8, a RNA-binding protein (RBP), as a positive regulator of the Hippo pathway. We found that overexpression suppresses whereas depletion potentiates Hippo-dependent tissue overgrowth, accompanied by altered Yki protein level and target gene expression. Mechanistically, Rox8 directly binds to a target site located in the 3' UTR, recruits and stabilizes the targeting of miR-8-loaded RISC, which accelerates the decay of messenger RNA (mRNA). Moreover, TIAR, the human ortholog of Rox8, is able to promote the degradation of mRNA when introduced into and destabilizes mRNA in human cells. Thus, our study provides in vivo evidence that the Hippo pathway is posttranscriptionally regulated by the collaborative action of RBP and microRNA (miRNA), which may provide an approach for modulating Hippo pathway-mediated tumorigenesis.
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http://dx.doi.org/10.1073/pnas.2013449117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720199PMC
December 2020

Development and Validation of a Seven-Gene Signature for Predicting the Prognosis of Lung Adenocarcinoma.

Biomed Res Int 2020 17;2020:1836542. Epub 2020 Aug 17.

Department of Respiration, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing 314000, China.

Background: Prognosis is a main factor affecting the survival of patients with lung adenocarcinoma (LUAD), yet no robust prognostic model of high effectiveness has been developed. This study is aimed at constructing a stable and practicable gene signature-based model via bioinformatics methods for predicting the prognosis of LUAD sufferers.

Methods: The mRNA expression data were accessed from the TCGA-LUAD dataset, and paired clinical information was collected from the GDC website. R package "edgeR" was employed to select the differentially expressed genes (DEGs), which were then used for the construction of a gene signature-based model via univariate COX, Lasso, and multivariate COX regression analyses. Kaplan-Meier and ROC survival analyses were conducted to comprehensively evaluate the performance of the model in predicting LUAD prognosis, and an independent dataset GSE26939 was accessed for further validation.

Results: Totally, 1,655 DEGs were obtained, and a 7-gene signature-based risk score was developed and formulated as risk_score = 0.000245∗NTSR1 + (7.13 - 05)∗RHOV + 0.000505∗KLK8 + (7.01 - 05)∗TNS4 + 0.000288∗C1QTNF6 + 0.00044∗IVL + 0.000161∗B4GALNT2. Kaplan-Meier survival curves revealed that the survival rate of patients in the high-risk group was lower in both the TCGA-LUAD dataset and GSE26939 relative to that of patients in the low-risk group. The relationship between the risk score and clinical characteristics was further investigated, finding that the model was effective in prognosis prediction in the patients with different age (age > 65, age < 65) and TNM stage (N0&N1, T1&T2, and tumor stage I/II). In sum, our study provides a robust predictive model for LUAD prognosis, which boosts the clinical research on LUAD and helps to explore the mechanism underlying the occurrence and progression of LUAD.
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http://dx.doi.org/10.1155/2020/1836542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641279PMC
August 2020

Molecular Level Insight Into the Benefit of Myricetin and Dihydromyricetin Uptake in Patients With Alzheimer's Diseases.

Front Aging Neurosci 2020 23;12:601603. Epub 2020 Oct 23.

College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.

Alzheimer's disease (AD) is a neurodegenerative disease with a high incidence rate and complicated pathogenesis. Currently, all anti-AD drugs treat the symptoms of the disease, and with currently no cure for AD. Flavonoid containing natural products, Myricetin (MYR) and Dihydromyricetin (DMY), are abundant in fruits and vegetables, and have been approved as food supplements in some countries. Interestingly, MYR and DMY have been reported to have anti-AD effects. However, the underlying anti-AD mechanism of action of MYR and DMY is complex with many facets being identified. In this review, we explore the benefit of MYR and DMY in AD patients from a molecular level. Their mechanism of action are discussed from various aspects including amyloid β-protein (Aβ) imbalance, neuroinflammation, dyshomeostasis of metal ions, autophagy disorder, and oxidative stress.
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http://dx.doi.org/10.3389/fnagi.2020.601603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645199PMC
October 2020

Mass spectrometry distinguishing C=C location and cis/trans isomers: A strategy initiated by water radical cations.

Anal Chim Acta 2020 Dec 16;1139:146-154. Epub 2020 Sep 16.

Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation, East China University of Technology, Nanchang, PR China. Electronic address:

We present an approach for the elucidation of C=C bond position and cis/trans isomers, which is achieved by the reaction of ambient water radical cations and double bonds, followed by the fragmentation of epoxide radical cations to generate diagnostic ions in tandem mass spectrometry. Hexenol double bond positional isomers and cis/trans isomers which exhibit different properties and biological functions are characterized as a proof of concept. The merits of the approach include the simplicity of experimental setup, rapid derivatization (within seconds), the obviation of organic solvents, as well as easy spectral interpretation.
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http://dx.doi.org/10.1016/j.aca.2020.09.027DOI Listing
December 2020

Neurexin-2 is a potential regulator of inflammatory pain in the spinal dorsal horn of rats.

J Cell Mol Med 2020 Dec 8;24(23):13623-13633. Epub 2020 Nov 8.

Department of Anesthesiology and Pain Medicine, The Affiliated Hospital of Jiaxing University (First hospital of Jiaxing), Jiaxing, China.

Chronic pain is one of the serious conditions that affect human health and remains cure still remains a serious challenge as the molecular mechanism remains largely unclear. Here, we used label-free proteomics to identify potential target proteins that regulate peripheral inflammatory pain and reveal its mechanism of action. Inflammation in peripheral tissue was induced by injecting complete Freund's adjuvant (CFA) into rat hind paw. A proteomic method was adopted to compare the spinal dorsal horn (SDH) in peripheral inflammatory pain (PIP) model rats with controls. Differential proteins were identified in SDH proteome by label-free quantification. The role of screened target proteins in the PIP was verified by small interfering RNA (siRNA). A total of 3072 and 3049 proteins were identified in CFA and normal saline (NS) groups, respectively, and 13 proteins were identified as differentially expressed in the CFA group. One of them, neurexin-2, was validated for its role in the inflammatory pain. Neurexin-2 was up-regulated in the CFA group, which was confirmed by quantitative PCR. Besides, intrathecal siRNA-mediated knock-down of neurexin-2 attenuated CFA-induced mechanical and thermal hyperalgesia and reduced the expression of SDH membrane glutamate receptors (eg mGlu receptor 1, AMPA receptor) and postsynaptic density (eg PSD-95, DLG2). These findings increased the understanding of the role of neurexin-2 in the inflammatory pain, implicating that neurexin-2 acts as a potential regulatory protein of inflammatory pain through affecting synaptic plasticity in the SDH of rats.
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http://dx.doi.org/10.1111/jcmm.15707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754071PMC
December 2020

Folic acid-modified Exosome-PH20 enhances the efficiency of therapy via modulation of the tumor microenvironment and directly inhibits tumor cell metastasis.

Bioact Mater 2021 Apr 9;6(4):963-974. Epub 2020 Oct 9.

Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

High accumulation of hyaluronan (HA) in the tumor microenvironment leads to an increase in the interstitial pressure and reduction perfusion of drugs. Furthermore, high molecular-weight (HMW)-HA suppresses M1 macrophage polarization, enhances M2 polarization, and induces immunosuppression. Hyaluronidase treatment have attempted to decrease the quantity of HA in tumors. However, hyaluronidase-driven HA degradation driven accelerates tumor cell metastasis, which is a major cause of mortality in cancer patients. Thus, we designed a novel exosome-based drug delivery system (DDS), named Exos-PH20-FA, using genetic engineering to express human hyaluronidase (PH20) and self-assembly techniques to modify the exosomes with folic acid (FA). Our results show that Exos-PH20-FA degraded HMW-HA to low-molecular-weight (LMW)-HA. Moreover, LMW-HA polarized macrophages to the M1 phenotype and reduced the number of relevant immunosuppressive immunocytes which changed the immune microenvironment from an immunosuppressive to immunosupportive phenotype. Furthermore, we demonstrated Exos-PH20-FA directly reduced hyaluronidase-induced metastasis of tumor cells. This tumor treatment also allowed an enhanced delivery of chemotherapy by tumor-targeting effect with FA modification. Our findings indicate that Exos-PH20-FA improves tumor treatment efficiency and reduces the side effects of hyaluronidase treatment, namely tumor cell metastasis. This all-in-one exosome-based HA targeting DDS maybe a promising treatment that yields more efficient and safer results.
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http://dx.doi.org/10.1016/j.bioactmat.2020.09.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560580PMC
April 2021

Combined Microbial Consortium Inoculation and Black Locust Planting Is Effective in the Bioremediation of Waste Drill Cuttings.

Front Microbiol 2020 30;11:536787. Epub 2020 Sep 30.

College of Resource Sciences and Technology, Sichuan Agricultural University, Chengdu, China.

Waste drill cuttings (WDCs), produced during gas and oil drilling consisting of 80% rock cuttings and 20% drilling muds, are an increasingly potent source of environmental pollution. We studied the efficiency of bioaugmentation and phytoremediation to remediate WDCs in an experiment where WDCs were incubated in a greenhouse for 120 days with and without black locust () plant and with or without bacterial and fungal consortium inoculant. The pollutant removal rates were highest in inoculated and planted treatment, followed by inoculated treatment and planted treatment. The small decrease in contaminant level in the control treatment suggested that indigenous microorganisms in WDCs had little pollutant degradation capability. In the inoculated and planted treatments, after 120 days, the germination rate of red clover seeds was on the same level as in the natural soil, showing a marked decrease in the ecotoxicity of WDC. Both the bacterial and fungal richness and bacterial diversity increased in all the treatments over time, whereas fungal diversity increased only in the not-inoculated treatments. The activity of laccase enzyme played a key role in the bioremediation process. The enzyme activities were mostly governed by inoculated consortium and soil bacterial community, and black locust affected the bioremediation mainly through its effect on N content that further affected bacterial and fungal communities.
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http://dx.doi.org/10.3389/fmicb.2020.536787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555700PMC
September 2020

Different maturities drive proteomic and metabolomic changes in Chinese black truffle.

Food Chem 2021 Apr 25;342:128233. Epub 2020 Sep 25.

Soil and Fertilizer Institute, Sichuan Academy of Agricultural Sciences, Chengdu 610066, China. Electronic address:

Chinese black truffle (Tuber indicum) is rich in nutrition. However, commercial interests lead to the aroma components and nutrients of T. indicum being greatly affected by overexploitation without consideration of their maturity. This study investigated the proteomic and metabolomic profiles of truffle fruiting bodies at different maturities using a meta-proteomic approach. Among the 3007 identified proteins, the most up-expressed protein in the mature ascocarps was involved in the peptidyl-diphthamide biosynthetic process, while thiamine metabolism was the most differentially expressed pathway. Furthermore, a total of 54 metabolites identified upon LC-MS differed significantly, with 30 being up-expressed in the mature ascocarps, including organic acids, carnitine substances and polysaccharides. Additionally, the ash, protein, fat, crude fiber and total sugar contents were all higher in the mature ascocarps. Overall, our findings reveal that mature truffles have a higher nutritional value, providing a basis for further exploring protein functionality of T. indicum at different maturities.
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http://dx.doi.org/10.1016/j.foodchem.2020.128233DOI Listing
April 2021

TUG1 enhances high glucose-impaired endothelial progenitor cell function via miR-29c-3p/PDGF-BB/Wnt signaling.

Stem Cell Res Ther 2020 10 15;11(1):441. Epub 2020 Oct 15.

Department of Interventional & Vascular Surgery, Tenth People's Hospital of Tongji University, Shanghai, 200072, China.

Background: Diabetes is associated with the dysfunction of endothelial progenitor cells (EPCs), characterized as impaired angiogenesis, a phenomenon thought to be involved in the development of diabetic foot. lncRNA plays an essential role in microvascular dysfunction and signaling pathways in patients with diabetes. lncRNA taurine upregulated gene 1 (TUG1) participates in angiogenesis in various cells. However, the mechanisms of TUG1 activity in EPCs have not been elucidated.

Methods: We isolated and then characterized EPCs from the peripheral blood of mice using immunofluorescence and flow cytometry. Western blot detected the wnt/β-catenin pathway in high glucose-treated EPCs. Bioinformatics analysis predicted a putative binding site for TUG1 on miR-29c-3p. The interactions among TUG1, platelet-derived growth factor-BB (PDGF-BB), and miR-29c-3p were analyzed by luciferase assays. In vivo, diabetic mouse ischemic limb was treated with normal saline or TUG1 overexpression lentiviruses.

Results: We found that EPC migration, invasion, and tube formation declined after treatment with high glucose, but improved with TUG1 overexpression. Mechanically, wnt/β-catenin pathway and autophagy were involved in the function of TUG1 overexpression in high glucose-treated EPCs. Moreover, TUG1 regulates the PDGF-BB/wnt pathway and function of high glucose-treated EPCs via miR-29c-3p. In vivo, injection of TUG1 lentivirus in a diabetic mouse ischemic limb model stimulated angiogenesis.

Conclusions: Our findings suggest that TUG1 restores high glucose-treated EPC function by regulating miR-29c-3p/PDGF-BB/Wnt signaling.
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http://dx.doi.org/10.1186/s13287-020-01958-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558752PMC
October 2020

Restoring the epigenetically silenced PCK2 suppresses renal cell carcinoma progression and increases sensitivity to sunitinib by promoting endoplasmic reticulum stress.

Theranostics 2020 15;10(25):11444-11461. Epub 2020 Sep 15.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Tumors have significant abnormalities in various biological properties. In renal cell carcinoma (RCC), metabolic abnormalities are characteristic biological dysfunction that cannot be ignored. Despite this, many aspects of this dysfunction have not been fully explained. The purpose of this study was to reveal a new mechanism of metabolic and energy-related biological abnormalities in RCC. Molecular screening and bioinformatics analysis were performed in RCC based on data from The Cancer Genome Atlas (TCGA) database. Regulated pathways were investigated by qRT-PCR, immunoblot analysis and immunohistochemistry. A series of functional analyses was performed in cell lines and xenograft models. By screening the biological abnormality core dataset-mitochondria-related dataset and the metabolic abnormality core dataset-energy metabolism-related dataset in public RCC databases, PCK2 was found to be differentially expressed in RCC compared with normal tissue. Further analysis by the TCGA database showed that PCK2 was significantly downregulated in RCC and predicted a poor prognosis. Through additional studies, it was found that a low expression of PCK2 in RCC was caused by methylation of its promoter region. Restoration of PCK2 expression in RCC cells repressed tumor progression and increased their sensitivity to sunitinib. Finally, mechanistic investigations indicated that PCK2 mediated the above processes by promoting endoplasmic reticulum stress. Collectively, our results identify a specific mechanism by which PCK2 suppresses the progression of renal cell carcinoma (RCC) and increases sensitivity to sunitinib by promoting endoplasmic reticulum stress. This finding provides a new biomarker for RCC as well as novel targets and strategies for the treatment of RCC.
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http://dx.doi.org/10.7150/thno.48469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546001PMC
September 2020

Impact of inflammation and immunotherapy in renal cell carcinoma.

Oncol Lett 2020 Nov 21;20(5):272. Epub 2020 Sep 21.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

Substantial research attention has been directed at exploring the mechanisms and treatment of renal cell carcinoma (RCC). Indeed, the association between inflammation and tumor phenotypes has been at the center of cancer research. Concomitant with research on the inflammation response and inflammatory molecules involved in RCC, new breakthroughs have emerged. A large body of knowledge now shows that treatments targeting inflammation and immunity in RCC provide substantial clinical benefits. Adequate analysis and a better understanding of the mechanisms of inflammatory factors in the occurrence and progression of RCC are highly desirable. Currently, numerous RCC treatments targeted at inflammation and immunotherapy are available. The current review describes in detail the link between inflammation and RCC.
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http://dx.doi.org/10.3892/ol.2020.12135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520756PMC
November 2020

Authors' Response to the Letter to the Editor: Increased Circulating Angiopoietin-Like Protein 8 Levels Are Associated with Thoracic Aortic Dissection and Higher Inflammatory Conditions.

Cardiovasc Drugs Ther 2020 12 3;34(6):881. Epub 2020 Oct 3.

Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing, 100029, China.

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http://dx.doi.org/10.1007/s10557-020-07025-6DOI Listing
December 2020

CYP17 inhibitors improve the prognosis of metastatic castration-resistant prostate cancer patients: A meta-analysis of published trials.

J Cancer Res Ther 2020 Sep;16(5):990-1001

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background And Aims: CYP17 inhibitors can block androgen production both intratumorally and systemically, thus attenuating the progression of prostate cancer (PCa). Many randomized controlled trials (RCTs) showed promising results that men with metastatic castration-resistant PCa (mCRPC) might benefit from treatment with CYP17 inhibitors such as abiraterone acetate and orteronel. The goal of this study was to evaluate the efficacy of CYP17 inhibitors for the prognosis in patients with mCRPC.

Materials And Methods: Studies were identified in PubMed/MEDLINE, the Cochrane Library, and the Web of Science. The RCTs with mCRPC patients focusing on the efficacy of CYP17 inhibitors were involved. Then, we analyzed the patients' prognosis such as overall survival (OS) and radiographic progression-free survival (RPFS).

Results: A meta-analysis of the pooled data from seven randomized Phase III clinical trials was performed to compare 5516 mCRPC patients with CYP17 inhibitors versus that with placebo. Compared to placebo, the CYP17 inhibitors significantly increased the OS (pooled hazard ratios [HR]: 0.816, 95% confidence interval [CI]: 0.750-0.887), RPFS (pooled HR: 0.647, 95% CI: 0.557-0.752), and time to prostate-specific antigen (PSA) progression (pooled HR: 0.599, 95% CI: 0.517-0.693). Additional endpoints such as PSA response rate, objective response assessed by Response Evaluation Criteria in Solid Tumors, and time to initiation of chemotherapy were included in this study and were found having significant improvement with CYP17 inhibitors compared to placebo.

Conclusion: This research showed that CYP17 inhibitors had a significant improvement on prognosis of patients with mCRPC within a relative safety profile both in pre- and post-chemotherapy trials. These expected results provide evidence for the use of CYP17 inhibitors to treat mCRPCs.
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http://dx.doi.org/10.4103/jcrt.JCRT_295_18DOI Listing
September 2020