Publications by authors named "Haibo Zhao"

109 Publications

Selective Inhibition of Aurora Kinase A by AK-01/LY3295668 Attenuates MCC Tumor Growth by Inducing MCC Cell Cycle Arrest and Apoptosis.

Cancers (Basel) 2021 Jul 23;13(15). Epub 2021 Jul 23.

Southern California Institute for Research and Education, Long Beach, CA 90822, USA.

Merkel cell carcinoma (MCC) is an often-lethal skin cancer with increasing incidence and limited treatment options. Although immune checkpoint inhibitors (ICI) have become the standard of care in advanced MCC, 50% of all MCC patients are ineligible for ICIs, and amongst those treated, many patients develop resistance. There is no therapeutic alternative for these patients, highlighting the urgent clinical need for alternative therapeutic strategies. Using patient-derived genetic insights and data generated in our lab, we identified aurora kinase as a promising therapeutic target for MCC. In this study, we examined the efficacy of the recently developed and highly selective AURKA inhibitor, AK-01 (LY3295668), in six patient-derived MCC cell lines and two MCC cell-line-derived xenograft mouse models. We found that AK-01 potently suppresses MCC survival through apoptosis and cell cycle arrest, particularly in MCPyV-negative MCC cells without RB expression. Despite the challenge posed by its short in vivo durability upon discontinuation, the swift and substantial tumor suppression with low toxicity makes AK-01 a strong potential candidate for MCC management, particularly in combination with existing regimens.
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http://dx.doi.org/10.3390/cancers13153708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345130PMC
July 2021

Effect of chain length on the structure and physicochemical properties of active compound/linear dextrin composites.

Carbohydr Polym 2021 Oct 6;269:118304. Epub 2021 Jun 6.

State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences, Jinan 250353, China; School of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan 250353, China.

Three linear dextrins (LDs) with different chain length were obtained through fractionating short-chain LD by gradient precipitation with 65%, 70% and 75% alcohol, signed as 65LD, 70LD, and 75LD, respectively. The LDs were employed to encapsulate arachidonic acid (ARA) and geranic acid (GA). Fourier infrared spectrometry, differential scanning calorimetry and thermogravimetric analysis confirmed the formation of ARA/LD and GA/LD composites. The ARA/65LD and GA/75LD composites showed higher crystallinity, indicating the formation of more ordered and compact structures in ARA/65LD and GA/75LD composites. The micromorphology of ARA/65LD composite was a clear ellipsoidal like structure, whereas GA/75LD composite presented a spherical shape. The release behavior, thermal, photochemical and antioxidant abilities of ARA and GA were improved after forming composites. Overall, the longer chain LD displayed better encapsulation efficiency with the longer chain ARA, while the shorter chain LD had higher encapsulation capability with GA.
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http://dx.doi.org/10.1016/j.carbpol.2021.118304DOI Listing
October 2021

Chain-Elongated Ionic Liquid Electrolytes for Low Self-Discharge All-Solid-State Supercapacitors at High Temperature.

ChemSusChem 2021 Sep 11;14(18):3895-3903. Epub 2021 Aug 11.

Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, P. R. China.

High power and good stability enable supercapacitors to work efficiently at high temperatures. However, the high-temperature-induced excessive ion transfer of the electrolyte would lead to severe self-discharge behavior, which has often been overlooked but can be highly detrimental. In this study, solid electrolytes consisting of poly(ethylene oxide) (PEO), bentonite clay, and ionic liquids (IL)[email protected][EMIM][BF ] (PCE), [email protected][BMIM][BF ] (PCB), and [email protected][HMIM][BF ] (PCH) lead to dramatic decreases in self-discharge when used in all-solid-state supercapacitors at high temperature of 70 °C, which correlate with chain elongation (i. e., [EMIM ]<[BMIM ]<[HMIM ]). Benefiting from both cation adsorption and high-temperature stabilization by bentonite clay, PCH-based supercapacitors (IL=[HMIM][BF ]) deliver an extremely low self-discharge rate, with only a 30.7 % voltage drop over 10 h at 70 °C (44.5 % for 38 h), which is much lower than that of traditional liquid supercapacitors (63.7 % drop over 10 h at 70 °C). This improvement in high-temperature self-discharge behavior is found to be from the decrease in diffusion-controlled faradaic process. Based on the longer-chain [HMIM ], soft-packaged supercapacitors exhibit a low self-discharge rate and work consistently at 70 °C. This chain-elongation strategy provides a new possibility for the suppression of self-discharge behavior in supercapacitors and further aids long-term energy storage by supercapacitors at high temperatures.
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http://dx.doi.org/10.1002/cssc.202101294DOI Listing
September 2021

Myeloperoxidase in the pericardial fluid improves the performance of prediction rules for postoperative atrial fibrillation.

J Thorac Cardiovasc Surg 2021 Jun 22. Epub 2021 Jun 22.

Beijing Chao-yang Hospital affiliated to Capital Medical University, Beijing, P.R. China.

Objectives: After surgery, inflammation is a prominent factor influencing postoperative atrial fibrillation. Myeloperoxidase is a major contributor to inflammatory responses after surgical tissue damage. We evaluated whether myeloperoxidase is associated with postoperative atrial fibrillation clinically and in an animal model.

Methods: This prospective cohort study included patients undergoing isolated coronary artery bypass grafting. Myeloperoxidase concentrations in blood and pericardial fluid were determined at baseline and 6, 12, and 18 hours after coronary artery bypass grafting. Myeloperoxidase activity in blood, pericardial fluid, and atrium were also evaluated in a canine coronary artery bypass grafting model. Electrophysiologic, histologic, and immunohistochemistry analyses were performed to explore underlying mechanisms.

Results: Postoperative atrial fibrillation occurred in 45 of 137 patients (32.8%). Patients with postoperative atrial fibrillation had significantly higher serum and pericardial myeloperoxidase levels. Individual clinical and surgical factors had moderate predictive value (area under the curve, 0.760) for postoperative atrial fibrillation. Discrimination improved remarkably when myeloperoxidase was combined with other parameters (area under the curve, 0.901). Pericardial myeloperoxidase at 6 hours postoperatively was the strongest independent predictor of postoperative atrial fibrillation (odds ratio, 19.215). The rate of postoperative atrial fibrillation increased exponentially across pericardial myeloperoxidase grades. Compared with controls, coronary artery bypass grafting-treated dogs showed higher atrial fibrillation vulnerability and maintenance, shorter atrial effective refractory period, attenuated connexin 43 expression, and increased myocardial and pericardial myeloperoxidase activity. Connexin 43 expression and atrial effective refractory period were strongly negatively correlated with myocardial and pericardial myeloperoxidase activity.

Conclusions: Myeloperoxidase is linked to postoperative atrial fibrillation, and the ability to predict postoperative atrial fibrillation was remarkably improved by adding pericardial myeloperoxidase. Myeloperoxidase-related atrial structural and electrical remodeling is a physiologic substrate for this arrhythmia.
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http://dx.doi.org/10.1016/j.jtcvs.2021.06.027DOI Listing
June 2021

Slippery damper of an overlay for arresting and manipulating droplets on nonwetting surfaces.

Nat Commun 2021 May 26;12(1):3154. Epub 2021 May 26.

Department of Mechanical Engineering, The University of Hong Kong, Hong Kong, Hong Kong.

In diverse processes, such as fertilization, insecticides, and cooling, liquid delivery is compromised by the super-repellency of receiving surfaces, including super-hydro-/omni-phobic and superheated types, a consequence of intercalated air pockets or vapor cushions that promote droplet rebounds as floating mass-spring systems. By simply overlaying impacting droplets with a tiny amount of lubricant (less than 0.1 vol% of the droplet), their interfacial properties are modified in such a way that damper-roller support is attached to the mass-spring system. The overlayers suppress the out-of-plane rebounds by slowing the departing droplets through viscous dissipation and sustain the droplets' in-plane mobility through self-lubrication, a preferential state for scenarios such as shedding of liquid in spray cooling and repositioning of droplets in printing. The footprint of our method can be made to be minimal, circumventing surface contamination and toxification. Our method enables multifunctional and dynamic control of droplets that impact different types of nonwetting surfaces.
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http://dx.doi.org/10.1038/s41467-021-23511-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154893PMC
May 2021

Swerchirin exerts anticancer activity on SKOV3 human ovartian cancer cells via induction of mitochondrial apoptosis, G2/M cell cycle arrest and inhibition of Raf/MEK/ERK cascade.

J BUON 2021 Jan-Feb;26(1):288

Department of Gynecology, Juning No.1 People's Hospital, Jining, Shandong 272100, China.

Retraction of: 'Swerchirin exerts anticancer activity on SKOV3 human ovarian cancer cells via induction of mitochondrial apoptosis, G2/M cell cycle arrest and inhibition of Raf/MEK/ERK cascade', by Lan Luo, Haibo Zhao, Qian Luo, JBUON 2018;23(1):111-116; PMID:29552769. Following the publication of the above article, readers drew to our attention that part of the data was unreliable. The authors were requested to provide the raw data to prove the originality, but were unable to do so. After an investigation, the Editors of JBUON decided to retract this article. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.
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March 2021

Systematic inhibitor selectivity between PARP1 and PARP2 enzymes: Molecular implications for ovarian cancer personalized therapy.

J Mol Recognit 2021 Jul 8;34(7):e2891. Epub 2021 Mar 8.

Department of Gynaecology, Cangzhou People's Hospital Affiliated to Cangzhou Medical College, Cangzhou, China.

Human poly(ADP-ribose) polymerases (PARPs) are a class of nuclear enzymes involved in the pathogenesis of diverse gynecologic tumors. The PARP1 and PARP2 are the two most documented members in PARP family, which have been approved as the druggable targets of ovarian and cervical cancers. Selective targeting of the two enzymes with small-molecule inhibitors is a great challenge due to the high conservation in catalytic domain and active site. Here, we investigate the systematic selectivity profile of sophisticated PARP inhibitors between the two enzymes. Computational methods are used to model/optimize the complex structures of inhibitor ligands with PARP1/2 catalytic domains and then to estimate the theoretical Fenzymatic assays exhibit a good consistence with theoretical selectivity over six tested inhibitor samples (r  = 0.857). It is revealed that the inhibitor selectivity is conferred from the exquisite difference in the residue composition and structural architecture of both the local activity sites and the whole catalytic domains of the two enzymes. In particular, the TMZ50 and ME0328 show strong selectivity between PARP1 and PARP2, but only the former has a potent activity on the two enzymes, whereas the latter can only inhibit the enzymes moderately. These compounds can be considered as potential lead molecular entities to develop new specific PARP-selective inhibitor drugs for personalized therapy combating gynecologic cancers.
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http://dx.doi.org/10.1002/jmr.2891DOI Listing
July 2021

Physicochemical properties and in vitro digestibility of hydrothermal treated Chinese yam (Dioscorea opposita Thunb.) starch and flour.

Int J Biol Macromol 2021 Apr 10;176:177-185. Epub 2021 Feb 10.

State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences, Jinan, Shandong 250353, China; College of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan, Shandong 250353, China. Electronic address:

The objective of this study was to investigate the effects of hydrothermal treatments (heat-moisture treatment (HMT) and annealing (ANN)) on the physicochemical properties and in vitro digestibility of yam starch and yam flour. Hydrothermal treatments decreased the pasting properties of yam starch and yam flour. Compared with yam starch, HMT significantly (p < 0.05) reduced the pasting viscosities of yam flour. Both HMT and ANN caused an increase of the gelatinization temperatures (T, T, and T) and a decrease of enthalpy (△H). The increasement in ratio of 1047/1022 cm and 995/1022 cm suggested that HMT and ANN resulted in an increase in short-range order. The crystalline pattern of all samples was still A-type, and HMT yam starch exhibited higher crystallinity (26.20%). The most significant inhibition of in vitro digestibility was found in HMT yam flour, with slowly digestible starch and resistant starch contents increasing by 3.73% and 4.40%, respectively. Hydrothermal treatments made the no-starch ingredients in yam flour agglomerate and adhere to starch granules. Confocal laser scanning microscopy showed that the starch being coated or embedded by protein was a possible reason for the differences in physicochemical properties and in vitro digestibility between yam starch and yam flour.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.064DOI Listing
April 2021

Genome-Scale CRISPR-Cas9 Transcriptional Activation Screening in Metformin Resistance Related Gene of Prostate Cancer.

Front Cell Dev Biol 2020 26;8:616332. Epub 2021 Jan 26.

Department of Urology, Huizhou Municipal Central Hospital, Huizhou, China.

Metformin is a classic type II diabetes drug which possesses anti-tumor properties for various cancers. However, different cancers do not respond to metformin with the same effectiveness or acquire resistance. Thus, searching for vulnerabilities of metformin-resistant prostate cancer is a promising strategy to improve the therapeutic efficiency of the drug. A genome-scale CRISPR-Cas9 activation library search targeting 23,430 genes was conducted to identify the genes that confer resistance to metformin in prostate cancer cells. Candidate genes were selected by total reads of sgRNA and sgRNA diversity, and then a CCK8 assay was used to verify their resistance to metformin. Interestingly, we discovered that the activation of ECE1, ABCA12, BPY2, EEF1A1, RAD9A, and NIPSNAP1 contributed to resistance to metformin in DU145 and PC3 cell lines. Notably, a high level of RAD9A, with poor prognosis in PCa, was the most significant gene in the CCK8 assay. Furthermore, we discerned the tumor immune microenvironment with RAD9A expression by CIBERSORT. These results suggested that a high level of RAD9A may upregulate regulatory T cells to counterbalance metformin in the tumor immune microenvironment.
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http://dx.doi.org/10.3389/fcell.2020.616332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870801PMC
January 2021

Solving Gravimetric-Volumetric Capacitive Paradox of 2D Materials through Dual-Functional Chemical Bonding-Induced Self-Constructing Graphene-MXene Monoliths.

ACS Appl Mater Interfaces 2021 Feb 27;13(5):6339-6348. Epub 2021 Jan 27.

Key Laboratory of Advanced Technologies of Materials (Ministry of Education), School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P.R. China.

High electrical conductivity and all-open microstructure characteristics intrinsically endow both graphene and MXenes with superior electrochemical energy storage capability. However, the above two-dimensional (2D) thicker electrodes (>20 μm) severely dilute their unique rapid electronic-ionic transferring characteristic, posing a paradox of high gravimetric and high volumetric capacitive properties due to massively excessive macropores or an unduly restacked issue. Herein, we elaborately construct novel monolithic NH-graphene and TiCT MXene ([email protected]) composites through dual-functional induced self-assembly with the help of both covalent and hydrogen bonding interactions. Notably, much thicker monolithic [email protected] electrodes (>90 μm) fabricated by a conventional roll-coating method without any further compaction treatment can simultaneously deliver two times gravimetric (gra.) and volumetric (vol.) performance than those of pure graphene (in vol.) or MXene (in gra.) materials. Moreover, monolithic [email protected] supercapacitors can remarkably present two times energy density as that of graphene and four times as MXene, respectively. Such greatly enhanced electrochemical properties are closely related to the appropriate equilibrium of the volumetric density and the open structure, which can effectively guarantee the rapid transfer of both electrons and ions in the thick monolithic [email protected] electrodes. Undoubtedly, dual-functional chemical bonding-induced self-constructing [email protected] monoliths efficiently solve the long-existing gra. and vol. capacitive paradox of the thicker 2D materials used in supercapacitors, which will guide the design of high-performance capacitive materials and promote their practical application in electrochemical energy storage.
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http://dx.doi.org/10.1021/acsami.0c21257DOI Listing
February 2021

Mechanism of IL-6-related spontaneous atrial fibrillation after coronary artery grafting surgery: IL-6 knockout mouse study and human observation.

Transl Res 2021 07 16;233:16-31. Epub 2021 Jan 16.

Beijing Chao-yang Hospital affiliated to Capital Medical University, Beijing, PR China.

Clinical observation and ex vivo studies have established a strong association between inflammation and postoperative atrial fibrillation (POAF). However, it is unclear whether the inflammatory phenotype is causally linked to this event or is an epiphenomenon, and it is not known which inflammatory meditators may increase susceptibility to POAF. The limitations of available animal models of spontaneous POAF (sPOAF) makes it difficult to select an experimental system. Here, we provide experimental and clinical evidence for mechanistic involvement of interleukin-6 (IL-6) in sPOAF.

Phase I: We established a mouse model of cardiac surgery with nonpaced sPOAF. IL-6 knockout mice were protected from sPOAF compared with wild-type mice.

Phase Ii: At 48 hours after surgery, the heart was separated into 6 regions and cultured. IL-6 was expressed in all regions, with highest abundance in the left atrium (LA). In PHASE III, we demonstrated that IL-6 in the LA elicited early profibrotic properties in atria via the pSTAT3/STAT3 signaling pathway and contributed to sPOAF.

Phase Iv: In a translational prospective clinical study, we demonstrated that humans with POAF had a higher IL-6 concentration in pericardial drainage (PD). This study provides preliminary evidence of a causal relationship between IL-6 and POAF in a novel nonpaced sPOAF mouse model. IL-6 is a crucial prerequisite for eliciting profibrotic properties in cardiac myocytes via the pSTAT3 pathway during the early postoperative period, leading to an increased susceptibility to POAF. Measuring IL-6 in PD could be a new noninvasive biomarker for the clinical prediction of POAF.
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http://dx.doi.org/10.1016/j.trsl.2021.01.007DOI Listing
July 2021

Formation of high amylose corn starch/konjac glucomannan composite film with improved mechanical and barrier properties.

Carbohydr Polym 2021 Jan 6;251:117039. Epub 2020 Sep 6.

State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences, Jinan, 250353, China; School of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan, 250353, China.

Recently, starch-based packaging materials have become one of research hot points. In the present study, glycerol-plasticized composite films based on high amylose corn starch (HCS) and konjac glucomannan (KGM) were developed. The influence of KGM on the film-forming properties of HCS and the physicochemical properties of the resulting films were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetric (TG) analysis and water vapor permeability (WVP). The crystallinity and the proportion of short-range order structure of the films increased first and then declined with the addition of KGM. The micromorphology of the films exhibited the more even texture after KGM was incorporated in. The tensile strength, elongation at break and water resistance of HCS film were also improved significantly. The synergistic effect between HCS and KGM improved the film-forming ability of HCS. The optimal addition amount of KGM was 0.3 %.
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http://dx.doi.org/10.1016/j.carbpol.2020.117039DOI Listing
January 2021

Estrogens decrease osteoclast number by attenuating mitochondria oxidative phosphorylation and ATP production in early osteoclast precursors.

Sci Rep 2020 07 20;10(1):11933. Epub 2020 Jul 20.

Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, 4301 W. Markham St. #587, Little Rock, 72205-7199, USA.

Loss of estrogens at menopause is a major cause of osteoporosis and increased fracture risk. Estrogens protect against bone loss by decreasing osteoclast number through direct actions on cells of the myeloid lineage. Here, we investigated the molecular mechanism of this effect. We report that 17β-estradiol (E) decreased osteoclast number by promoting the apoptosis of early osteoclast progenitors, but not mature osteoclasts. This effect was abrogated in cells lacking Bak/Bax-two pro-apoptotic members of the Bcl-2 family of proteins required for mitochondrial apoptotic death. FasL has been previously implicated in the pro-apoptotic actions of E. However, we show herein that FasL-deficient mice lose bone mass following ovariectomy indistinguishably from FasL-intact controls, indicating that FasL is not a major contributor to the anti-osteoclastogenic actions of estrogens. Instead, using microarray analysis we have elucidated that ERα-mediated estrogen signaling in osteoclast progenitors decreases "oxidative phosphorylation" and the expression of mitochondria complex I genes. Additionally, E decreased the activity of complex I and oxygen consumption rate. Similar to E, the complex I inhibitor Rotenone decreased osteoclastogenesis by promoting osteoclast progenitor apoptosis via Bak/Bax. These findings demonstrate that estrogens decrease osteoclast number by attenuating respiration, and thereby, promoting mitochondrial apoptotic death of early osteoclast progenitors.
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http://dx.doi.org/10.1038/s41598-020-68890-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371870PMC
July 2020

Interleukin-6 Receptor Asp358 A>C Polymorphism Is Associated With Postoperative Atrial Fibrillation.

Ann Thorac Surg 2021 01 17;111(1):102-108. Epub 2020 Jun 17.

Cardiac Center, Cardiac Center, Beijing Chao-yang Hospital Affiliated With Capital Medical University, Beijing, China.

Background: This study examined the associations of single-nucleotide polymorphisms in the interleukin-6 receptor gene (Asp358 A>C) and the interleukin-6 promoter (-174G>C and -597G>A) with interleukin-6 levels and postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG).

Methods: The study enrolled 371 Chinese Han patients who were undergoing CABG. Serum interleukin-6 levels were measured preoperatively and at 6, 12, and 18 hours postoperatively. Genotypes for the 3 polymorphisms were determined.

Results: Overall, POAF developed in 30.2% of patients. The CC genotype and C allele frequencies for the interleukin-6 receptor Asp358 A>C polymorphism were significantly higher in patients with POAF than in patients without POAF (P = .003), and the interleukin-6 levels were significantly higher in patients with the CC genotype compared with A allele carriers at 6, 12, and 18 hours in the overall cohort and at 12 and 18 hours in the POAF subgroup, but there were no significant differences in the non-POAF subgroup. However, the allele and genotype frequencies of the interleukin-6 -174G>C and -597G>A polymorphisms were similar among groups, and there were no differences in interleukin-6 levels at any time point between the C/A allele carriers and the patients with GG genotypes. Univariate analysis showed that the CC genotype for interleukin-6 receptor Asp358 A>C, age, and history of cerebrovascular disease were associated with POAF. Multivariable regression showed that the CC genotype was independently related to the development of POAF (odds ratio, 2.01; 95% confidence interval: 1.15 to 3.52; P = .014).

Conclusions: The interleukin-6 receptor Asp358 A>C polymorphism may contribute to genetic susceptibility to POAF after CABG.
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http://dx.doi.org/10.1016/j.athoracsur.2020.04.123DOI Listing
January 2021

Inhibition of PI3K by copanlisib exerts potent antitumor effects on Merkel cell carcinoma cell lines and mouse xenografts.

Sci Rep 2020 06 1;10(1):8867. Epub 2020 Jun 1.

Department of Dermatology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer with steadily increasing incidence and poor prognosis. Despite recent success with immunotherapy, 50% of patients still succumb to their diseases. To date, there is no Food and Drug Administration-approved targeted therapy for advanced MCC. Aberrant activation of phosphatidylinositide-3-kinase (PI3K)/AKT/mTOR pathway is frequently detected in MCC, making it an attractive therapeutic target. We previously found PI3K pathway activation in human MCC cell lines and tumors and demonstrated complete clinical response in a Stage IV MCC patient treated with PI3K inhibitor idelalisib. Here, we found that both PI3K-α and -δ isoforms are abundantly expressed in our MCC cell lines and clinical samples; we therefore examined antitumor efficacy across a panel of five PI3K inhibitors with distinctive isoform-specificities, including idelalisib (PI3K-δ), copanlisib (PI3K-α/δ), duvelisib (PI3K-γ/δ), alpelisib (PI3K-α), and AZD8186 (PI3K-β/δ). Of these, copanlisib exerts the most potent antitumor effects, markedly inhibiting cell proliferation, survival, and tumor growth by suppressing PI3K/mTOR/Akt activities in mouse models generated from MCC cell xenografts and patient-derived tumor xenografts. These results provide compelling preclinical evidence for application of copanlisib in advanced MCC with aberrant PI3K activation for which immunotherapy is insufficient, or patients who are unsuitable for immunotherapy.
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http://dx.doi.org/10.1038/s41598-020-65637-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264292PMC
June 2020

The effects of acetylated distarch phosphate from tapioca starch on rheological properties and microstructure of acid-induced casein gel.

Int J Biol Macromol 2020 Sep 11;159:1132-1139. Epub 2020 May 11.

State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences, Jinan, Shandong 250353, China; College of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan, Shandong 250353, China.

This study aimed to investigate the effects of acetylated distarch phosphate (ADSP) from tapioca starch on the rheological properties and microstructure of acid-induced casein gel using dynamic rheological tests, creep recovery, confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM). The rheological results showed that the casein and casein/ADSP gels displayed shear-thinning behavior. The apparent viscosity and viscoelasticity (G' and G″) of casein/ADSP gels increased with ADSP content, except for 2.0% ADSP. The power law model indicated that ADSP increased the structural strength of the casein/ADSP gels. The creep recovery data were fitted using Burger's model, which showed that the highest instantaneous elasticity and stiffness was observed when the ADSP concentration was 1.5%. The fractal dimension obtained from CLSM indicated that the disorder of the casein network decreased with ADSP concentration. SEM micrographs suggested that the porosity of casein/ADSP gels was decreased by ADSP and that a higher concentration of ADSP (2.0%) broke the continuity of the network structure. The results of this study could potentially facilitate the improvement of the stability of yogurt and provide valuable information for the manufacturers.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.05.049DOI Listing
September 2020

Solubilisation of micellar casein powders by high-power ultrasound.

Ultrason Sonochem 2020 Oct 15;67:105131. Epub 2020 Apr 15.

School of Food Science and Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China. Electronic address:

High protein milk ingredients, such as micellar casein powder (MCP), exhibit poor solubility upon reconstitution in water, particularly after long-time storage. In this study, ultrasonication (20 kHz, power density of 0.75 W/ml) was used to improve the solubility of aged MCP powders. For all the MCP powders (concentration varying from 0.5 to 5%, and storage of MCP at 50 °C for up to 10 days) it was found that short time ultrasonication (2.5 min) reduced the size of the protein particles from >30 μm to ∼0.1 μm, as measured by light scattering. This resulted in an improvement of solubility (>95%) for all the MCP powders. Cryo-electron microscopy and small x-ray angle scattering showed that the MCP powders dissolved into particles with morphologies and internal structure similar to native casein micelles in bovine milk. SDS-PAGE and RP-HLPC showed that ultrasonication did not affect the molecular weight of the individual casein molecules. Compared to overhead stirring using a 4-blade stirrer, ultrasonication required less than 10 times the drawn electrical energy density to achieve a particle size 10 times smaller.
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http://dx.doi.org/10.1016/j.ultsonch.2020.105131DOI Listing
October 2020

Unraveling and Regulating Self-Discharge Behavior of TiCT MXene-Based Supercapacitors.

ACS Nano 2020 Apr 23;14(4):4916-4924. Epub 2020 Mar 23.

Key Laboratory of Advanced Technologies of Materials (Ministry of Education), School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P.R. China.

Rich chemistry and surface functionalization provide MXenes enhanced electrochemical activity yet severely exacerbate their self-discharge behavior in supercapacitors. However, this self-discharge behavior and its related mechanism are still remaining issues. Herein, we propose a chemically interface-tailored regulation strategy to successfully unravel and efficiently alleviate the self-discharge behavior of TiCT MXene-based supercapacitors. As a result, TiCT MXenes with fewer F elements (∼0.65 atom %) show a positive self-discharge rate decline of ∼20% in comparison with MXenes with higher F elements (∼8.09 atom %). Such decline of the F elements can highly increase tight-bonding ions corresponding to an individual self-discharge process, naturally resulting in a dramatic 50% increase of the transition potential (). Therefore, the mixed self-discharge rate from both tight-bonding (contain fewer F elements) and loose-bonding ions (contain more F elements) is accordingly lowered. Through chemically interface-tailored engineering, the significantly changed average oxidation state and local coordination information on MXene affected the interaction of ion counterparts, which was evidently revealed by X-ray absorption fine structures. Theoretically, this greatly improved self-discharge performance was proven to be from higher adsorption energy between the interface of the electrode and the electrolyte by density functional theory. Therefore, this chemically interface-tailored regulation strategy can guide the design of high-performance MXene-based supercapacitors with low self-discharge behavior and will promote its wider commercial applications.
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http://dx.doi.org/10.1021/acsnano.0c01056DOI Listing
April 2020

Comparison of two different minimally invasive percutaneous nephrostomy sheaths for the treatment of staghorn stones.

BJU Int 2020 06 21;125(6):898-904. Epub 2020 Mar 21.

Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.

Objective: To compare the safety and effectiveness of using a conventional nephrostomy sheath (NS) vs using a new NS with suction and evacuation functions in minimally invasive percutaneous nephrolithotomy (MPCNL) for the treatment of staghorn stones.

Patients And Methods: A prospective and randomised study of 60 patients with staghorn stones randomly assigned into two groups of 30 patients. One group underwent MPCNL using conventional NS, whereas the other group underwent MPCNL with suction-evacuation NS (SENS). Patient demographics, stone characteristics, intraoperative data, perioperative data, and surgical results were collected and analysed.

Results: The patient demographics and stone characteristics were similar amongst the two groups. The SENS group had a significantly lower peak and a significantly lower average renal pelvic pressure (RPP) throughout the procedure. The SENS group was more efficient for stone removal and had a much shorter stone treatment time, a lesser use of the stone extractor, and ultimately a higher stone-free rate (SFR). The effects of a lower RPP and shorter stone treatment time translated into less severe postoperative complications as measured per modified Clavien grade.

Conclusion: Using SENS in MPCNL for the treatment of staghorn stones has the advantages of lower RPP, increased effectiveness in stone retrieval, decreased surgery related complications, and an improved SFR.
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http://dx.doi.org/10.1111/bju.15031DOI Listing
June 2020

A Direction Self-Tuning Two-Dimensional Piezoelectric Vibration Energy Harvester.

Sensors (Basel) 2019 Dec 21;20(1). Epub 2019 Dec 21.

School of Physics and Materials Science, Energy Materials and Devices Key Lab of Anhui Province for Photoelectric Conversion, Anhui University, Hefei 230601, China.

Most work from the last decade on the piezoelectric vibration energy harvester (PVEHs) focuses on how to increase its frequency bandwidth but ignores the effect of vibration direction on the output performance of the harvester. However, both the frequency and the direction of the vibration in a real environment are time-variant. Therefore, improving the capability of PVEH to harvest multi-directional vibration energy is also important. This work presents a direction self-tuning two-dimensional (2D) PVEH, which consists of a spring-mass system and a direction self-tuning structure. The spring-mass system is sensitive to external vibration, and the direction self-tuning structure can automatically adjust its plane perpendicular to the direction of the external excitation driven by an external torque. The direction self-tuning mechanism is first theoretically analyzed. The experimental results show that this direction self-tuning PVEH can efficiently scavenge vibration energy in the 2D plane, and its output performance is unaffected by vibration direction and is very stable. Meanwhile, the effect of the initial deflection angle and the vibration acceleration on the direction self-tuning time of the PVEH is investigated. The direction self-tuning mechanism can also be used in other PVEHs with different energy conversion methods for harvesting multi-direction vibration energy.
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http://dx.doi.org/10.3390/s20010077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982908PMC
December 2019

Improvement of the rheological and textural properties of calcium sulfate-induced soy protein isolate gels by the incorporation of different polysaccharides.

Food Chem 2020 Apr 4;310:125983. Epub 2019 Dec 4.

State Key Laboratory of Biobased Material and Green Papermaking, and College of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan 250353, China. Electronic address:

In this study, the effects of the addition of various polysaccharides (konjac gum, gellan gum, and curdlan gum) on the rheological and textural properties of calcium sulfate-induced soy protein isolate gels were investigated. The incorporation of konjac gum and curdlan gum at 0.3 and 0.5% (w/v) concentrations and gellan gum at 0.5% concentration significantly enhanced (P < 0.05) the hardness and water-holding capacity of the resultant gels. The increased elastic moduli during and after gelation, reinforced fracture stress, and lowered onset gelling temperature indicated that the addition of the abovementioned polysaccharides strengthened gel structures and accelerated gelation. Confocal laser scanning microscopy analysis revealed that the polysaccharides also improved gel microstructures, with the gels containing konjac gum displaying the highest homogeneity. The findings of this study may provide important information for the development of innovative soy protein isolate-based gel products with improved texture.
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http://dx.doi.org/10.1016/j.foodchem.2019.125983DOI Listing
April 2020

MicroRNA-429 inhibits cancer cell proliferation and migration by targeting AKT1 in renal cell carcinoma.

Mol Clin Oncol 2020 Jan 25;12(1):75-80. Epub 2019 Oct 25.

Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510700, P.R. China.

MicroRNAs (miRNAs or miR) serve as oncogenes and tumor suppressors. In a previous study, it was revealed that has-miRNA-429 (miR-429) is a tumor suppressor in 786-O renal cell carcinoma (RCC) cells. However, its mechanism in RCC remains to be determined. The present study aimed to explain the functional role and mechanism of miR-429 in RCC pathogenesis. Luciferase reporter assays demonstrated that miR-429 overexpression reduced the transcriptional activity of AKT serine/threonine kinase 1 (AKT1). Reverse transcripton-quantitative (RT-q) PCR and western blot analysis indicated that the mRNA and protein expression of AKT1 was downregulated in 786-O RCC cell lines when miR-429 was overexpressed, indicating that miR-429 may directly target AKT1 in RCC. Therefore, miR-429 overexpression enhanced the inhibition of tumor size and weight in nude mice . The current study indicated that the novel miR-429-regulated pathway may provide insights into RCC oncogenesis and metastasis.
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http://dx.doi.org/10.3892/mco.2019.1940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888107PMC
January 2020

Decreased expression levels of ELOVL6 indicate poor prognosis in hepatocellular carcinoma.

Oncol Lett 2019 Dec 9;18(6):6214-6220. Epub 2019 Oct 9.

Department of Physical Examination, Jining First People's Hospital, Jining, Shandong 272000, P.R. China.

The present study aimed to investigate the expression of elongation of very long-chain fatty acids family member 6 (ELOVL6) in hepatocellular carcinoma (HCC) tissues, and to determine its role in the development of HCC. A total of 377 HCC specimens were collected for tissue microarray and immunohistochemistry analyses. The ELOVL6 IHC score for HCC tissues was 0.97±0.71, which was significantly lower than that of the matched adjacent normal tissues (1.32±0.68; P<0.001). Patients with low levels of ELOVL6 expression were older (P=0.014) and possessed larger sized tumors (P=0.039) than patients with high expression levels. Additionally, Kaplan-Meier analysis revealed that patients with low ELOVL6 expression levels also had significantly poorer overall (P<0.001) and disease-free (P=0.029) survival times, and a greater probability of recurrence. The tumor size, tumor-node-metastasis (TNM) stage, vascular invasion and ELOVL6 expression were all shown to be prognostic variables for overall survival in patients with HCC. Multivariate analysis revealed that vascular invasion (P<0.001), TNM stage (P<0.001) and ELOVL6 expression (P=0.001) were independent prognostic variables for overall survival. In addition, vascular invasion (P=0.032) and ELOVL6 expression (P=0.041) were independent risk factors for disease-free survival, and vascular invasion (P=0.019) and ELOVL6 expression (P=0.045) were independent risk factors associated with HCC recurrence. The present study revealed that in patients with HCC, ELOVL6 expression level was reduced in HCC tissues, and that higher ELOVL6 expression levels correlated with longer survival times. This indicates that ELOVL6 may serves as an independent marker of poor patient outcome.
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http://dx.doi.org/10.3892/ol.2019.10974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865704PMC
December 2019

Change in Serum Level of Interleukin 6 and Delirium After Coronary Artery Bypass Graft.

Am J Crit Care 2019 11;28(6):462-470

Yuling Chen and Fangqin Wu are doctoral candidates, Ying Wu is dean and professor, Shu Ding is a postgraduate student, Xinwei Feng is a teacher, Li Sun, Xiangjun Tao, and Jinglian Li are postgraduate students, Ruiying Ma and Weiwei Liu are teachers, and Yadi Feng is a postgraduate student, School of Nursing, Capital Medical University, Beijing, China. Sai Lu is a senior lecturer and research fellow, College of Health and Biomedicine, Institute for Health and Sport, Victoria University, Mel-bourne, Australia. Yuzhi Shen and Haibo Zhao are charge nurses, Heart Center, Beijing Chao-Yang Hospital, Beijing, China.

Background: Serum level of interleukin 6 (IL-6) is known to be associated with postoperative delirium. However, no consensus has emerged on the postoperative time point at which IL-6 level may predict postoperative delirium after coronary artery bypass graft surgery.

Objectives: To compare trends in IL-6 levels in patients with and without postoperative delirium and to examine the relationship between IL-6 levels at different times and postoperative delirium after coronary artery bypass graft.

Methods: A prospective cohort study of patients who underwent their first elective isolated coronary artery bypass graft between November 2013 and August 2015 at a cardiac intensive care unit in Beijing, China. Concentrations of IL-6 were measured before the operation and at the 6th, 12th, and 18th postoperative hours. Participants were assessed for postoperative delirium twice daily for 5 days. Univariate and multivariate logistic regression analyses were done to determine associations between IL-6 levels at different time points, postoperative changes in IL-6 levels, and the occurrence of postoperative delirium.

Results: Postoperative delirium was diagnosed in 85 of 266 patients (32%). Levels of IL-6 were significantly higher in patients with postoperative delirium than in patients without it at the 6th, 12th, and 18th postoperative hours ( = .03, .004, and .001, respectively). Change in IL-6 level (odds ratio, 2.97; 95% CI, 1.20-7.31; = .02) and IL-6 level of 583 pg/mL or higher at the 18th postoperative hour (odds ratio, 5.20; 95% CI, 1.84-14.70; = .002) were associated with higher incidence of postoperative delirium.

Conclusion: Interleukin 6 level (≥ 583 pg/mL) at the 18th postoperative hour may serve as a potent predictor of postoperative delirium in coronary artery bypass graft patients.
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http://dx.doi.org/10.4037/ajcc2019976DOI Listing
November 2019

Effects of native starch and modified starches on the textural, rheological and microstructural characteristics of soybean protein gel.

Int J Biol Macromol 2020 Jan 5;142:237-243. Epub 2019 Oct 5.

State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong 250353, China; College of Food Science and Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong 250353, China.

The effects of native starch (NS), acetylated starch (AS), and acetylated distarch phosphate (ADSP) on the gel properties of soybean protein thermal gel were investigated using texture analysis, low-field nuclear magnetic resonance (LF-NMR) spectroscopy, dynamic rheometry and scanning electron microscopy. The results of the textural profile analysis showed that 10% ADSP increased the hardness and chewiness of the mixed gel, while NS and AS led to decreases in the textural properties. The results of the LF-NMR analysis indicated that the AS improved the water-holding capacity of the mixed gel due to the transformation of weakly bound water to strongly bound water. During heating and cooling, the rheological profiles of the elastic (G') and viscous modulus (G″) of all the samples exhibited a two-stage pattern of decrease and then increase, and the final values of G' and G″ reached maxima when the ADSP content was 10%. The scanning electron microscopy images showed that the ADSP granules dispersed in the gel network. The integrity of the starch granules was crucial for regulating the properties of the soybean protein gel. These results provided information about the further design and preparation of soybean protein foods containing modified starch.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.09.095DOI Listing
January 2020

Mitochondrial E3 ubiquitin ligase 1 promotes autophagy flux to suppress the development of clear cell renal cell carcinomas.

Cancer Sci 2019 Nov 28;110(11):3533-3542. Epub 2019 Sep 28.

Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors in the urinary system. Surgical intervention is the preferred treatment for ccRCC, but targeted biological therapy is required for postoperative recurrent or metastatic ccRCC. Autophagy is an intracellular degradation system for misfolded/aggregated proteins and dysfunctional organelles. Defective autophagy is associated with many diseases. Mul1 is a mitochondrion-associated E3 ubiquitin ligase and involved in the regulation of divergent pathophysiological processes such as mitochondrial dynamics, and thus affects the development of various diseases including cancers. Whether Mul1 regulates ccRCC development and what is the mechanism remain unclear. Histochemical staining and immunoblotting were used to analyze the levels of Mul1 protein in human renal tissues. Statistical analysis of information associated with tissue microarray and The Cancer Genome Atlas (TCGA) database was conducted to show the relationship between Mul1 expression and clinical features and survival of ccRCC patients. Impact of Mul1 on rates of cell growth and migration and autophagy flux were tested in cultured cancer cells. Herein we show that Mul1 promoted autophagy flux to facilitate the degradation of P62-associated protein aggresomes and adipose differentiation-related protein (ADFP)-associated lipid droplets and suppressed the growth and migration of ccRCC cells. Levels of Mul1 protein and mRNA were significantly reduced so that autophagy flux was likely blocked in ccRCC tissues, which is potentially correlated with enhancement of malignancy of ccRCC and impairment of patient survival. Therefore, Mul1 may promote autophagy to suppress the development of ccRCC.
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http://dx.doi.org/10.1111/cas.14192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825007PMC
November 2019

Fate of Mercury in Volatiles and Char during in Situ Gasification Chemical-Looping Combustion of Coal.

Environ Sci Technol 2019 Jul 20;53(13):7887-7892. Epub 2019 Jun 20.

State Key Laboratory of Coal Combustion, School of Energy and Power Engineering , Huazhong University of Science and Technology , 1037 Luoyu Road , Wuhan , 430074 , PR China.

Mercury emission is an important issue during in-situ gasification chemical-looping combustion ( iG-CLC) of coal. This work focused on experimentally "isolating" two elementary subprocesses (coal pyrolysis and char gasification) during iG-CLC of coal, identifying mercury distribution within the two subprocesses, and examining the effects of a hematite oxygen carrier (OC) on the mercury fate. The mercury measurement accuracy was carefully ensured by comparing online measurements (by a VM 3000 instrument) and benchmark measurements (by the standard Ontario Hydro Method, ASTM D6784) as well as repeated tests (10 times for each case). The mercury mass balance was 115% for the entire iG-CLC. A total of 44.7% of the mercury was released as the gas phase form within the coal pyrolysis process at a typical CLC operation temperature (950 °C), whereas 13.4% was released during the char gasification process. The release rate and amount of mercury were minimally affected by the presence of OC; however, the OC promoted the conversion of Hg(g) to Hg(g). Only a small amount of mercury was absorbed by the OC and transported into the air reactor along with carbon residue, released as Hg(g) and Hg(g) or remained in the OC and coal ash as particulate mercury.
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http://dx.doi.org/10.1021/acs.est.8b06931DOI Listing
July 2019

Influence of carboplatin on the proliferation and apoptosis of ovarian cancer cells through mTOR/p70s6k signaling pathway.

J BUON 2018 Nov-Dec;23(6):1732-1738

Department of Obstetrics and Gynecology, Chinese PLA General Hospital, No.28, Fuxing Rd, Beijing 100853,China.

Purpose: To investigate the influence of carboplatin on the proliferation and apoptosis of ovarian cancer cells through mTOR/P70S6K signaling pathway.

Methods: The mRNA and protein expressions were detected via Western blotting and RT-PCR to study whether the mTOR/p70S6K signaling pathway was activated in OVCAR-3 and Caov-3 ovarian cancer cell lines. After cells were treated with different concentrations of carboplatin, the mRNA and protein expressions of mTOR, p70S6K and 4E-BP1 were detected via RT-PCR and Western blotting. OVCAR-3 cells were treated with 20 and 50 μM carboplatin for 4 hrs, and then apoptosis was analyzed and assessed. OVCAR-3 cells were treated with different concentrations of carboplatin (20, 50, 100, 150 and 200 μM) for 24 and 48 hrs, respectively.

Results: The mTOR signaling pathway was activated in OVCAR-3 and Caov-3 ovarian cancer cell lines. The mRNA level of mTOR in Caov-3 cells was higher, but that of p70S6K was lower. Carboplatin significantly reduced the mRNA expression of mTOR (p<0.01), whereas the mRNA expressions of p70S6K and 4E-BP1 in carboplatin-treated cells were increased in a dose-dependent manner (p<0.01). Carboplatin inhibited the mTOR protein expression in a dose-dependent manner (p<0.01). The proliferation of OVCAR-3 cells exposed to carboplatin was reduced compared with that of untreated cells (p<0.01), and the inhibitory effect of carboplatin on the proliferation of OVCAR-3 cells was time- and dose-dependent.

Conclusion: The mTOR/p70S6K pathway was activated in ovarian cancer. Carboplatin could rapidly inhibit the expression of mTOR, and the phosphorylation of its major downstream effectors p70S6K and 4E-binding protein 1 (4E-BP1) arrested cells in G0/G1 phase and induced ovarian cancer cell apoptosis.
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August 2019

Silencing of LncRNA steroid receptor RNA activator attenuates polycystic ovary syndrome in mice.

Biochimie 2019 Feb 1;157:48-56. Epub 2018 Nov 1.

Department of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China. Electronic address:

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and has a prevalence of 1 in 15 women worldwide. This study aims to investigate the role of lncRNA SRA in the pathological processes of polycystic ovary syndrome (PCOS).

Methods: Twenty five-day old female C57BL/6 mice received subcutaneous injection of 60 mg/kg dehydroepiandrosterone for 20 days to induce PCOS. Lentivirus containing lncRNA SRA-specific shRNA was subcapsularly injected into the ovaries of PCOS mice. Granulosa cell was primary cultured to explore the mechanism of DHEA-induced inflammatory responses. H&E staining was used to examine the histological changes of ovaries. ELISA was used to assess serum insulin level and proinflammatory cytokines and angiogenetic factors contents in ovary tissue. The expression levels of LncRNA SRA and proteins involved in the NF-κB signaling pathway were detected through Quantitative real-time PCR and Western blot. The nuclear translocation of NF-κB was observed by immunofluorescence and the activity of NF-κB-DNA binding was detected using EMSA.

Results: Silencing of lncRNA SRA changed insulin release, attenuated ovary injury and reduced the production of angiogenetic factors in the PCOS mice. In addition, shRNA targeting lncRNA SRA inhibited DHEA-induced pro-inflammatory cytokines production and NF-κB nuclear translocation in the ovary of PCOS mice and primary granulosa cells.

Conclusion: Silencing of lncRNA Steroid Receptor RNA Activator (SRA) attenuates polycystic ovary syndrome (PCOS) in mice. LncRNA SRA plays important roles in the development of PCOS.
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http://dx.doi.org/10.1016/j.biochi.2018.10.021DOI Listing
February 2019
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