Publications by authors named "Qi Pang"

118 Publications

Different photocurrent response of CsPbBr particles.

J Chem Phys 2022 Jun;156(23):234702

Materials Genome Institute, Shanghai University, Shanghai 200444, People's Republic of China.

Zero-dimensional (0D) all-inorganic cesium lead halide perovskites, particularly CsPbBr, have been attracting wide attention due to their excellent optical properties and stability. The research also focuses on the origin of green emission from CsPbBr, which has a bandgap located in the ultraviolet B (UVB) region. So far, both CsPbBr without visible emission and with green emission have been successfully prepared; however, the origin of green emission remains controversial. Photocurrent response is one of the effective approaches to explore how the photo-excited carriers influence the photo-physical properties of materials. In our study, CsPbBr particles without visible emission and with green emission were synthesized and their photocurrent response was investigated. The former showed a positive photocurrent response, while the latter showed a negative photocurrent response. The negative response was believed to be due to a built-in electric field constructed by the charged excitons in green-emissive CsPbBr. From our calculations, numerous vacancies of Br are easier to appear in green-emissive CsPbBr lattices, which could combine the neutral excitons to form charged excitons. This work may contribute to the explanation of the origin of green emission of CsPbBr to some extent.
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http://dx.doi.org/10.1063/5.0095106DOI Listing
June 2022

Career adaptability of newly graduated nurses at an obstetrics and gynaecology hospital in China: A qualitative study.

J Nurs Manag 2022 May 4. Epub 2022 May 4.

Nursing Department, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.

Aim: The aim of this study was to gain insight into factors affecting career adaptability of newly graduated nurses and ways to improve them.

Background: Newly graduated nurses face an important transition from student to professional. Unfortunately, the nurse turnover rate is high due to maladaptation. Factors influencing career adaptability and improvement methods have not been clearly addressed.

Methods: Using a descriptive qualitative study with thematic analysis, 15 newly graduated nurses from a tertiary obstetrics and gynaecology teaching hospital in China were interviewed.

Results: Six themes affecting career adaptability were found: personality, self-confidence, occupational care focus, work-related stress, basic professional competency and gap between reality and expectations. Four themes improving career adaptability were identified: strong social support, self-adjustment, self-development and career preparation. Eight subthemes were also identified.

Conclusions: Individual, family and work factors were among those affecting career adaptability among newly graduated nurses. Newly graduated nurses would improve their career adaptability through self-adjustment and social support. Helping them to promote these factors and measures is conducive to improving their career adaptability and reducing staff turnover.

Implications For Nursing Management: Nurse managers should be aware of the key factors affecting career adaptability among newly graduated nurses and design targeted improvement programmes.
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http://dx.doi.org/10.1111/jonm.13661DOI Listing
May 2022

Irisin protects against vascular calcification by activating autophagy and inhibiting NLRP3-mediated vascular smooth muscle cell pyroptosis in chronic kidney disease.

Cell Death Dis 2022 Mar 30;13(3):283. Epub 2022 Mar 30.

Department of Nephrology, Xuanwu Hospital, Capital Medical University, Changchun Street 45#, 100053, Beijing, China.

Irisin protects the cardiovascular system against vascular diseases. However, its role in chronic kidney disease (CKD) -associated vascular calcification (VC) and the underlying mechanisms remain unclear. In the present study, we investigated the potential link among Irisin, pyroptosis, and VC under CKD conditions. During mouse vascular smooth muscle cell (VSMC) calcification induced by β-glycerophosphate (β-GP), the pyroptosis level was increased, as evidenced by the upregulated expression of pyroptosis-related proteins (cleaved CASP1, GSDMD-N, and IL1B) and pyroptotic cell death (increased numbers of PI-positive cells and LDH release). Reducing the pyroptosis levels by a CASP1 inhibitor remarkably decreased calcium deposition in β-GP-treated VSMCs. Further experiments revealed that the pyroptosis pathway was activated by excessive reactive oxygen species (ROS) production and subsequent NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in calcified VSMCs. Importantly, Irisin effectively inhibited β-GP-induced calcium deposition in VSMCs in vitro and in mice aortic rings ex vivo. Overexpression of Nlrp3 attenuated the suppressive effect of Irisin on VSMC calcification. In addition, Irisin could induce autophagy and restore autophagic flux in calcified VSMCs. Adding the autophagy inhibitor 3-methyladenine or chloroquine attenuated the inhibitory effect of Irisin on β-GP-induced ROS production, NLRP3 inflammasome activation, pyroptosis, and calcification in VSMCs. Finally, our in vivo study showed that Irisin treatment promoted autophagy, downregulated ROS level and thereby suppressed pyroptosis and medial calcification in aortic tissues of adenine-induced CKD mice. Together, our findings for the first time demonstrated that Irisin protected against VC via inducing autophagy and inhibiting VSMC pyroptosis in CKD, and Irisin might serve as an effective therapeutic agent for CKD-associated VC.
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http://dx.doi.org/10.1038/s41419-022-04735-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967887PMC
March 2022

Irisin alleviates vascular calcification by inhibiting VSMC osteoblastic transformation and mitochondria dysfunction via AMPK/Drp1 signaling pathway in chronic kidney disease.

Atherosclerosis 2022 04 16;346:36-45. Epub 2022 Feb 16.

Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China. Electronic address:

Background And Aims: Vascular calcification (VC) is an intricate active process, significantly controlled by vascular smooth muscle cells (VSMCs). Mitochondrial dysfunction plays a pivotal role in VC and VSMCs osteoblastic transformation. We previously reported that decreased levels of Irisin were independently associated with VC in hemodialysis patients. The present study aimed to investigate the role of Irisin in VC, especially in VSMCs osteoblastic transformation and mitochondrial function.

Methods: In vitro, VSMCs calcification was induced by β-glycerophosphate, while in vivo VC was triggered by adenine and high phosphorus diet. Alizarin red, Von Kossa staining, and calcium and Alp activity were performed to test VC. Western blot and immunohistochemical staining were employed to analyze the expression of proteins associated with VSMCs osteoblastic transformation and AMPK signaling. Mitochondrial membrane potential (MMP) and structures were observed by immunofluorescence staining.

Results: Irisin alleviated VSMCs calcification induced by β-glycerophosphate. Mechanistically, Irisin activated AMPK and downregulated the expression of Drp1, further alleviating mitochondria fission and VSMCs osteoblastic transformation. In vivo, Irisin decreased serum creatinine, urea and phosphorous levels in chronic kidney disease (CKD) mice. Importantly, Irisin treatment postponed CKD-associated VC with the upregulation of α-Sma and p-AMPK expression, and the downregulation of Runx2 and Drp1 expression.

Conclusions: Our results firstly reveal that Irisin inhibits CKD-associated VC. Irisin suppresses VSMCs osteoblastic transformation and mitochondria dysfunction via AMPK/Drp1 signaling.
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http://dx.doi.org/10.1016/j.atherosclerosis.2022.02.007DOI Listing
April 2022

Long non-coding RNA AC122108.1 promotes lung adenocarcinoma brain metastasis and progression through the Wnt/β-catenin pathway by directly binding to aldolase A.

Ann Transl Med 2021 Dec;9(23):1729

Department of Neurosurgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Brain metastasis (BM) is a major pathological subtype of lung adenocarcinoma (LAD), but the pathogenic mechanisms of BM remain unclear. The potential prognostic biomarkers and therapeutic targets for BM of LAD urgently need to be identified. AC122108.1 is a recently discovered new long non-coding ribonucleic acid (RNA).

Methods: AC122108 was found to be overexpressed in a LAD BM cell model, and upregulated in 64.52% of LAD BM tissues. AC122108 is an independent factor of BM during LAD development; however, the molecular mechanisms and clinical significance of AC122108.1 in LAD have not yet been established. Additionally, and experiments showed that the direct binding of AC122108.1 with aldolase A (ALDOA) enhanced the proliferation, apoptosis, invasiveness, migration, and metastasis of LAD cells.

Results: This RNA-protein complex decreased the stability of the β-catenin destruction complex, leading to the accumulation of β-catenin in the cytoplasm and ultimately its translocation into the nucleus to activate Wnt(wingless/integrated)/β-catenin signaling.

Conclusions: Overall, AC122108.1 promotes LAD BM and its progression through the Wnt/β-catenin pathway by directly binding to ALDOA. This study provides insights into the regulatory mechanism of the LAD BM. AC122108.1 may serve as a potential therapeutic target and prognostic biomarker of LAD.
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http://dx.doi.org/10.21037/atm-21-5707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743723PMC
December 2021

RNA binding protein NKAP protects glioblastoma cells from ferroptosis by promoting SLC7A11 mRNA splicing in an mA-dependent manner.

Cell Death Dis 2022 01 21;13(1):73. Epub 2022 Jan 21.

Department of Neurosurgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.

Ferroptosis is a form of cell death characterized by lipid peroxidation. Previous studies have reported that knockout of NF-κB activating protein (NKAP), an RNA-binding protein, increased lipid peroxidation level in naive T cells and induced cell death in colon cancer cells. However, there was no literature reported the relationship between NKAP and ferroptosis in glioblastoma cells. Notably, the mechanism of NKAP modulating ferroptosis is still unknown. Here, we found NKAP knockdown induced cell death in glioblastoma cells. Silencing NKAP increased the cell sensitivity to ferroptosis inducers both in vitro and in vivo. Exogenous overexpression of NKAP promoted cell resistance to ferroptosis inducers by positively regulating a ferroptosis defense protein, namely cystine/glutamate antiporter (SLC7A11). The regulation of SLC7A11 by NKAP can be weakened by the mA methylation inhibitor cycloleucine and knockdown of the mA writer METTL3. NKAP combined the "RGAC" motif which was exactly in line with the mA motif "RGACH" (R = A/G, H = A/U/C) uncovered by the mA-sequence. RNA Immunoprecipitation (RIP) and Co-Immunoprecipitation (Co-IP) proved the interaction between NKAP and mA on SLC7A11 transcript. Following its binding to mA, NKAP recruited the splicing factor proline and glutamine-rich (SFPQ) to recognize the splice site and then conducted transcription termination site (TTS) splicing event on SLC7A11 transcript and the retention of the last exon, screened by RNA-sequence and Mass Spectrometry (MS). In conclusion, NKAP acted as a new ferroptosis suppressor by binding to mA and then promoting SLC7A11 mRNA splicing and maturation.
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http://dx.doi.org/10.1038/s41419-022-04524-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783023PMC
January 2022

var. Improves Cognitive Impairment under Amyloid Beta-Induced Alzheimer's Disease Model.

Biomed Res Int 2022 7;2022:4513998. Epub 2022 Jan 7.

Department of Food Science and Nutrition, Institute of Kimchi Research, Pusan National University, Busan 46241, Republic of Korea.

Abnormal production and degradation of amyloid beta (A) in the brain lead to oxidative stress and cognitive impairment in Alzheimer's disease (AD). var. (CJM) is widely used as an herbal medicine and has antibacterial and anti-inflammatory properties. This study focused on the protective effect of the ethyl acetate fraction from CJM (ECJM) on A -induced control mice. In the T-maze and novel object recognition test, ECJM provided higher spatial memory and object recognition compared to A treatment alone. In the Morris water maze test, ECJM-administered mice showed greater learning and memory abilities than A -induced control mice. Additionally, ECJM-administered mice experienced inhibited lipid peroxidation and nitric oxide production in a dose-dependent manner. The present study indicates that ECJM improves cognitive impairment by inhibiting oxidative stress in A -induced mice. Therefore, CJM may be useful for the treatment of AD and may be a potential material for functional foods.
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http://dx.doi.org/10.1155/2022/4513998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759886PMC
January 2022

Modulating optical properties and interfacial electron transfer of CsPbBr perovskite nanocrystals via indium ion and chlorine ion co-doping.

J Chem Phys 2021 Dec;155(23):234701

Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.

In this work, we demonstrated an in situ approach for doping CsPbBr nanocrystals (NCs) with In and Cl with a ligand-assisted precipitation method at room temperature. The In and Cl co-doped NCs are characterized by the powder x-ray diffraction patterns, ultraviolet-visible, photoluminescence (PL) spectroscopy, time-resolved PL (TRPL), ultraviolet photoelectron spectroscopy, x-ray photoelectron spectroscopy, and transmission electron microscopy. Based on PL and TRPL results, the non-radiative nature of In-doping induced localized impurity states is revealed. Furthermore, the impact of In and Cl doping on charge transfer (CT) from the NCs to molecular acceptors was investigated and the results indicate that the CT at the interface of NCs can be tuned and promoted by In and Cl co-doping. This enhanced CT is attributed to the enlarged energy difference between relevant states of the molecular acceptor and the NCs by In and Cl upon co-doping. This work provides insight into how to control interfacial CT in perovskite NCs, which is important for optoelectronic applications.
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http://dx.doi.org/10.1063/5.0076037DOI Listing
December 2021

NOX4-derived ROS-induced overexpression of FOXM1 regulates aerobic glycolysis in glioblastoma.

BMC Cancer 2021 Nov 5;21(1):1181. Epub 2021 Nov 5.

Department of Neurosurgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.

Background: Increased expression of the transcription factor Forkhead box M1 (FOXM1) has been reported to play an important role in the progression and development of multiple tumors, but the molecular mechanisms that regulate FOXM1 expression remain unknown, and the role of FOXM1 in aerobic glycolysis is still not clear.

Methods: The expression of FOXM1 and NADPH oxidase 4 (NOX4) in normal brain tissues and glioma was detected in data from the TCGA database and in our specimens. The effect of NOX4 on the expression of FOXM1 was determined by Western blot, qPCR, reactive oxygen species (ROS) production assays, and luciferase assays. The functions of NOX4 and FOXM1 in aerobic glycolysis in glioblastoma cells were determined by a series of experiments, such as Western blot, extracellular acidification rate (ECAR), lactate production, and intracellular ATP level assays. A xenograft mouse model was established to test our findings in vivo.

Results: The expression of FOXM1 and NOX4 was increased in glioma specimens compared with normal brain tissues and correlated with poor clinical outcomes. Aberrant mitochondrial reactive oxygen species (ROS) generation of NOX4 induced FOXM1 expression. Mechanistic studies demonstrated that NOX4-derived MitoROS exert their regulatory role on FOXM1 by mediating hypoxia-inducible factor 1α (HIF-1α) stabilization. Further research showed that NOX4-derived MitoROS-induced HIF-1α directly activates the transcription of FOXM1 and results in increased FOXM1 expression. Overexpression of NOX4 or FOXM1 promoted aerobic glycolysis, whereas knockdown of NOX4 or FOXM1 significantly suppressed aerobic glycolysis, in glioblastoma cells. NOX4-induced aerobic glycolysis was dependent on elevated FOXM1 expression, as FOXM1 knockdown abolished NOX4-induced aerobic glycolysis in glioblastoma cells both in vitro and in vivo.

Conclusion: Increased expression of FOXM1 induced by NOX4-derived MitoROS plays a pivotal role in aerobic glycolysis, and our findings suggest that inhibition of NOX4-FOXM1 signaling may present a potential therapeutic target for glioblastoma treatment.
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http://dx.doi.org/10.1186/s12885-021-08933-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571893PMC
November 2021

Identification and validation of an autophagy-related signature for predicting survival in lower-grade glioma.

Bioengineered 2021 12;12(2):9692-9708

Department of Neurosurgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Abnormal levels of autophagy have been implicated in the pathogenesis of multiple diseases, including cancer. However, little is known about the role of autophagy-related genes (ARGs) in low-grade gliomas (LGG). Accordingly, the aims of this study were to assess the prognostic values of ARGs and to establish a genetic signature for LGG prognosis. Expression profile data from patients with and without primary LGG were obtained from The Cancer Genome Atlas (TCGA) and Genome Tissue Expression databases, respectively, and consensus clustering was used to identify clusters of patients with distinct prognoses. Nineteen differentially expressed ARGs were selected with threshold values of FDR < 0.05 and |log2 fold change (FC)| ≥ 2, and functional analysis revealed that these genes were associated with autophagy processes as expected. An autophagy-related signature was established using a Cox regression model of six ARGs that separated patients from TCGA training cohort into high- and low-risk groups. Univariate and multivariate Cox regression analysis indicated that the signature-based risk score was an independent prognostic factor. The signature was successfully validated using the TCGA testing, TCGA entire, and Chinese Glioma Genome Atlas cohorts. Stratified analyses demonstrated that the signature was associated with clinical features and prognosis, and gene set enrichment analysis revealed that autophagy- and cancer-related pathways were more enriched in high-risk patients than in low-risk patients. The prognostic value and expression of the six signature-related genes were also investigated. Thus, the present study constructed and validated an autophagy-related prognostic signature that could optimize individualized survival prediction in LGG patients.
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http://dx.doi.org/10.1080/21655979.2021.1985818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810042PMC
December 2021

Enhanced Photoluminescence of All-Inorganic Manganese Halide Perovskite-Analogue Nanocrystals by Lead Ion Incorporation.

J Phys Chem Lett 2021 Oct 13;12(41):10204-10211. Epub 2021 Oct 13.

Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.

Herein, we develop an effective approach for incorporating lead (Pb) ions into manganese (Mn) halide perovskite-analogue nanocrystals (PA NCs) of CsMn(Cl/Br)·2HO via room-temperature supersaturation recrystallization. Pb-incorporated Mn-PA NCs exhibit strong orange emission upon UV light illumination, a peak centered at 600 nm assigned to Mn transition (T → A) with a photoluminescence quantum yield (PLQY) of 41.8% compared to the pristine Mn-PA NCs with very weak PL (PLQY = 0.10%). The significant enhancement of PLQY is attributed to the formation of [Mn(Cl/Br)(OH)]-[Pb(Cl/Br)(OH)]-[Mn(Cl/Br)(OH)] chain network structure, in which Pb effectively dilutes the Mn concentration to reduce magnetic coupling between Mn pairs to relax the spin and parity selection rules. In addition, excited energy can effectively transfer from the [Pb(Cl/Br)(OH)] unit to Mn luminescence centers owing to the low activation energy. Pb-incorporated PA NCs also exhibit excellent stability. The combined strong PL and high stability make Pb-incorporated Mn-based PA NCs an excellent candidate for potential optronic applications.
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http://dx.doi.org/10.1021/acs.jpclett.1c02997DOI Listing
October 2021

Hypoxic preconditioning reduces NLRP3 inflammasome expression and protects against cerebral ischemia/reperfusion injury.

Neural Regen Res 2022 Feb;17(2):395-400

Department of Neurosurgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China.

Hypoxic preconditioning can protect against cerebral ischemia/reperfusion injury. However, the underlying mechanisms that mediate this effect are not completely clear. In this study, mice were pretreated with continuous, intermittent hypoxic preconditioning; 1 hour later, cerebral ischemia/reperfusion models were generated by middle cerebral artery occlusion and reperfusion. Compared with control mice, mice with cerebral ischemia/reperfusion injury showed increased Bederson neurological function scores, significantly increased cerebral infarction volume, obvious pathological damage to the hippocampus, significantly increased apoptosis; upregulated interleukin-1β, interleukin-6, and interleukin-8 levels in brain tissue; and increased expression levels of NOD-like receptor family pyrin domain containing 3 (NLRP3), NLRP inflammasome-related protein caspase-1, and gasdermin D. However, hypoxic preconditioning significantly inhibited the above phenomena. Taken together, these data suggest that hypoxic preconditioning mitigates cerebral ischemia/reperfusion injury in mice by reducing NLRP3 inflammasome expression. This study was approved by the Medical Ethics Committee of the Fourth Hospital of Baotou, China (approval No. DWLL2019001) in November 2019.
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http://dx.doi.org/10.4103/1673-5374.314317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464000PMC
February 2022

NOX4-Derived ROS Mediates TGF-1-Induced Metabolic Reprogramming during Epithelial-Mesenchymal Transition through the PI3K/AKT/HIF-1 Pathway in Glioblastoma.

Oxid Med Cell Longev 2021 27;2021:5549047. Epub 2021 Jun 27.

Department of Neurosurgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.

Current studies on tumor progression focus on the roles of cytokines in the tumor microenvironment (TME), and recent research shows that transforming growth factor-1 (TGF-1) released from TME plays a pivotal role in tumor development and malignant transformation. The alteration in cellular metabolism is a hallmark of cancer, which not only provides cancer cells with ATP for fuel cellular reactions, but also generates metabolic intermediates for the synthesis of essential cellular ingredients, to support cell proliferation, migration, and invasion. Interestingly, we found a distinct metabolic change during TGF-1-induced epithelial-mesenchymal transition (EMT) in glioblastoma cells. Indeed, TGF-1 participates in metabolic reprogramming, and the molecular basis is still not well understood. NADPH oxidases 4 (NOX4), a member of the Nox family, also plays a key role in the biological effects of glioblastoma. However, the relationship between NOX4, TGF-1, and cellular metabolic changes during EMT in glioblastoma remains obscure. Here, our findings demonstrated that TGF-1 upregulated NOX4 expression accompanied by reactive oxygen species (ROS) through Smad-dependent signaling and then induced hypoxia-inducible factor 1 (HIF-1) overexpression and nuclear accumulation resulting in metabolic reprogramming and promoting EMT. Besides, inhibition of glycolysis reversed EMT suggesting a causal relationship between TGF-1-induced metabolic changes and tumorigenesis. Moreover, TGF-1-induced metabolic reprogramming and EMT which modulated by NOX4/ROS were blocked when the phosphoinositide3-kinase (PI3K)/AKT/HIF-1 signaling pathways were inhibited. In conclusion, these suggest that NOX4/ROS induction by TGF-1 can be one of the main mechanisms mediating the metabolic reprogramming during EMT of glioblastoma cells and provide promising strategies for cancer therapy.
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http://dx.doi.org/10.1155/2021/5549047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257383PMC
January 2022

Protective effects of krill oil on high fat diet-induced cognitive impairment by regulation of oxidative stress.

Free Radic Res 2021 Jul 28;55(7):799-809. Epub 2021 Jun 28.

Department of Food Science and Nutrition, Pusan National University, Busan, Republic of Korea.

Consumption of high fat diet (HFD) increases risk of cognitive impairment and memory deficit by elevation of oxidative stress in the brain. In this study, we investigated the protective effects of krill oil (KO) against HFD-induced cognitive impairment in mice. The mice were fed with HFD for 10 weeks, and then KO was orally administered at doses of 100, 200, or 500 mg/kg/d for 4 weeks. To evaluate the cognitive abilities, we carried out the behavior tests, such as T-maze, novel object recognition test, and Morris water maze test. The HFD-induced cognitive impairment mice showed impairments in both spatial memory and novel object cognitive abilities. However, administration of KO at doses of 100, 200, or 500 mg/kg/d improved spatial memory ability and novel object cognition by increase of the exploration of new route and novel object. In addition, KO-administered group improved learning and memory abilities, showing shorter latency to reach hidden platform compared with control group. Furthermore, levels of reactive oxygen species (ROS), lipid peroxidation, and nitric oxide (NO) were significantly elevated by consumption of HFD, indicating that consumption of HFD induces oxidative stress in the brain. However, administration of KO attenuated oxidative stress by decrease of the ROS levels, lipid peroxidation, and NO. This study suggests that KO improves HFD-induced cognitive impairment by attenuation of oxidative stress in the brain. Therefore, KO may play as a promising agent in treatment and prevention of HFD-induced cognitive impairment.
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http://dx.doi.org/10.1080/10715762.2021.1944623DOI Listing
July 2021

Design and preparation of three-dimensional hetero-electrocatalysts of NiCo-layered double hydroxide nanosheets incorporated with silver nanoclusters for enhanced oxygen evolution reactions.

Nanoscale 2021 Jul 16;13(25):11150-11160. Epub 2021 Jun 16.

School of Chemistry and Chemical Engineering, Guangxi University/Guangxi Key Laboratory of Electrochemical Energy Materials, 100 University Road, Nanning 530004, China.

Layered double hydroxides (LDHs) are one of the most effective electrocatalysts. However, it is still necessary to improve the lower conductivity and limited active sites of LDHs to enhance their catalytic performance. Targeted generation of vacancies on the catalyst's surface by the incorporation of metal nanoparticles has been explored as a promising strategy to synthesize highly efficient electrocatalysts. Herein, we designed and prepared novel three-dimensional (3D) hetero-electrocatalysts of NiCo-layered double hydroxide nanosheets incorporated with silver nanoclusters on a Ni foam (labeled as [email protected]/NF) by a one-pot hydrothermal method. We also conducted experimental and theoretical investigations to demonstrate the high electrocatalytic performance of the [email protected]/NF hetero-electrocatalysts for OERs and the underlying mechanism. The resulting hetero-electrocatalysts show a low overpotential of 262 mV at a current density of 10 mA cm, and even exhibit low overpotentials of 300 mV at a high current density of 50 mA cm and 324 mV at 100 mA cm, and a small Tafel slope of 41 mV dec as well as excellent durability for 80 h for OERs in 1.0 M KOH. The excellent performance is attributed to the synergistic effects between Ag nanoclusters and LDHs. The population engineering effect of silver not only helps to modulate the intrinsic properties of active sites but also induces the generation of abundant oxygen vacancies on the surface; finally, it facilitates the rate-determining step of OERs (ΔG (O* → OOH*) = 1.31 eV) to gain high performance. The one-pot silver incorporating strategy and the resulting high performance pave new ways for the further development of highly efficient electrocatalysts for OERs.
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http://dx.doi.org/10.1039/d1nr01147bDOI Listing
July 2021

A novel lncRNA ARST represses glioma progression by inhibiting ALDOA-mediated actin cytoskeleton integrity.

J Exp Clin Cancer Res 2021 Jun 7;40(1):187. Epub 2021 Jun 7.

Department of Histology and Embryology, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, People's Republic of China.

Background: Glioma is one of the most aggressive malignant brain tumors that is characterized with inevitably infiltrative growth and poor prognosis. ARST is a novel lncRNA whose expression level is significantly decreased in the patients with glioblastoma multiforme. However, the exact mechanisms of ARST in gliomagenesis are largely unknown.

Methods: The expressions of ARST in the glioma samples and cell lines were analyzed by qRT-PCR. FISH was utilized to detect the distribution of ARST in the glioma cells. CCK-8, EdU and flow cytometry were used to examine cellular viability, proliferation and apoptosis. Transwell and wound-healing assays were performed to determine the migratory and invasive abilities of the cells. Intracranial tumorigenesis models were established to explore the roles of ARST in vivo. RNA pulldown assay was used to examine proteins that bound to ARST. The activities of key enzymes in the glycolysis and production of lactate acid were measured by colorimetry. In addition, RIP, Co-IP, western blot and immunofluorescence were used to investigate the interaction and regulation between ARST, F-actin, ALDOA and cofilin.

Results: In this study, we reported that ARST was downregulated in the gliomas. Overexpression of ARST in the glioma cells significantly suppressed various cellular vital abilities such as cell growth, proliferation, migration and invasion. The tumorigenic capacity of these cells in vivo was reduced as well. We further demonstrated that the tumor suppressive effects of ARST could be mediated by a direct binding to a glycolytic enzyme aldolase A (ALDOA), which together with cofilin, keeping the polymerization and depolymerization of actin filaments in an orderly dynamic equilibrium. Upregulation of ARST interrupted the interaction between ALDOA and actin cytoskeleton, which led to a rapid cofilin-dependent loss of F-actin stress fibers.

Conclusions: Taken together, it is concluded that ARST performs its function via a non-metabolic pathway associated with ALDOA, which otherwise modifies the morphology and invasive properties of the glioma cells. This has added new perspective to its role in tumorigenesis, thus providing potential target for glioma diagnosis, therapy, and prognosis.
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http://dx.doi.org/10.1186/s13046-021-01977-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183030PMC
June 2021

Oxiracetam Mediates Neuroprotection Through the Regulation of Microglia Under Hypoxia-Ischemia Neonatal Brain Injury in Mice.

Mol Neurobiol 2021 Aug 22;58(8):3918-3937. Epub 2021 Apr 22.

Department of Histology and Embryology, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, 44# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.

In neonatal hypoxic-ischemic brain damage (HIBD), in addition to damage caused by hypoxia and ischemia, over-activation of inflammation leads to further deterioration of the condition, thus greatly shortening the optimal treatment time window. Ischemic penumbra, the edematous area encompassing the infarct core, is characterized by typical activation of microglia and overt inflammation, and prone to incorporate into the infarct core gradually after ischemia onset. If treated in time, the cells located in the penumbra can survive, thereby impeding the expansion of the infarction. We demonstrated for the first time that in the acute phase of HIBD in neonatal mice, treatment of Oxiracetam (ORC) significantly curtailed the size of ischemic penumbra together with drastic reduction of infarction. By staining various cellular markers, we found that the penumbra was defined and concentrated with activated microglia. We also analyzed transmission electron microscopy and Luminex assay results to elucidate the mechanisms involved. We further confirmed that ORC switched polarization of microglia from the inflammatory towards the alternatively activated phenotype, thus promoting microglia from being neurotoxic into neuroprotective. Meanwhile, ORC decreased proliferation of microglia; however, their functions of phagocytosis and autophagy were otherwise enhanced. Last, we clarified that ORC promoted autophagy through the AMPK/mTOR pathway, which further induced the transition of the inflammatory to the alternatively activated phenotype in microglia. The pro-inflammatory factors secretion was inhibited as well, thereby reducing the progression of the infarction. Taken together, it is concluded that Oxiracetam reduced the expansion of ischemic infarction in part via regulating the interplay between microglia activation and autophagy, which would delay the progression of HIBD and effectively prolong the time window for the clinical treatment of HIBD.
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http://dx.doi.org/10.1007/s12035-021-02376-zDOI Listing
August 2021

Sulforaphane protects human umbilical vein endothelial cells from oxidative stress via the miR-34a/SIRT1 axis by upregulating nuclear factor erythroid-2-related factor 2.

Exp Ther Med 2021 Mar 7;21(3):186. Epub 2021 Jan 7.

Department of Cardiology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.

Oxidative stress-induced vascular endothelial cell dysfunction serves an essential role in the initiation and development of atherosclerosis. Sulforaphane (SFN), a naturally occurring antioxidant, has previously demonstrated to exert protective effects on the endothelium against oxidative stress. However, further studies are required to determine its underlying molecular mechanism prior to clinical application. Accumulating evidence suggests that alterations in the microRNA (miRNA/miR)-34a/sirtuin-1 (SIRT1) axis occur with oxidative stress. Therefore, the present study aimed to investigate if SFN exerts a protective role against oxidative stress in vascular endothelial cells through regulation of the miR-34a/SIRT1 axis. Human umbilical vein endothelial cells (HUVECs) were treated with HO in the presence or absence of SFN pretreatment. Cell viability and apoptosis were analyzed using CellTiter-Blue and flow cytometry, respectively. Reverse transcription-quantitative PCR and western blot analyses were performed to determine changes in the expression levels of miR-34a and SIRT1. The expression levels of miR-34a and SIRT1 were artificially regulated following transfection with miR-34a mimic and inhibitor or SIRT1expression plasmid and small interfering RNA, respectively. Subsequently, the effect of the expression changes of miR-34 and SIRT1 on oxidative stress-induced cell injury was investigated. Dual-luciferase reporter assay was used to confirm the targeted binding of miR-34a to SIRT1. SFN was found to ameliorate cellular damage caused by HO and inhibited intracellular reactive oxygen species production. In addition, miR-34a upregulation was accompanied with reduced SIRT1 expression in HUVECs, following HO treatment. miR-34a was revealed to directly target SIRT1 by binding to its 3'-untranslated region. Down-regulation of miR-34a and up-regulation of SIRT1 increased the survival of HUVECs under oxidative stress. Taken together, the results of the present study suggest that SFN may protect HUVECs from oxidative stress by inducing changes in the miR-34a/SIRT1 axis via upregulation of nuclear factor erythroid-2-related factor 2 expression.
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http://dx.doi.org/10.3892/etm.2021.9617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812584PMC
March 2021

Pb(II) detection and versatile bio-imaging of green-emitting carbon dots with excellent stability and bright fluorescence.

Nanoscale 2021 Feb;13(4):2472-2480

School of Chemistry and Chemical Engineering, Guangxi University, Nanning, 530004, China.

Green-emitting carbon dots (G-CDs) were synthesized via a simple and green hydrothermal method using betaine hydrochloride and sulfadiazine as carbon and nitrogen sources, respectively. Excellent luminescence stability with varying pH, salt concentrations, temperature is found with excitation-independent emission. G-CDs can be successfully used for the detection of Pb(ii) in the range of 0-200 μM. There was good linear relationship between the Pb(ii) concentration and G-CD fluorescence intensity with a correlation coefficient of 0.993, and the limit of detection (LOD) was 3.0174 μmol L-1. Due to its good biocompatibility, G-CDs can be successfully applied to zebrafish imaging as well as cell imaging, and the results show that G-CDs is more suitable for the zebrafish embryo imaging. Our results suggested that the obtained G-CDs can be used as multifunctional probes, highlighting their potential in different biological studies.
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http://dx.doi.org/10.1039/d0nr07245aDOI Listing
February 2021

Surgical methodology and protocols for preventing implanted cerebral catheters from becoming obstructed during and after neurosurgery.

J Neurosci Methods 2021 02 4;349:109020. Epub 2020 Dec 4.

Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, KY, 40536, United States. Electronic address:

Background: Convection Enhanced Delivery (CED) into targeted brain areas has been tested in animal models and clinical trials for the treatment of various neurological diseases.

New Method: We used a series of techniques, to in effect, maintain positive pressure inside the catheter relative to the outside, that included a hollow stylet, a high volume bolus of solution to clear the line, a low and slow continuous flow rate during implantation, and heat sealing the catheter at the time of implantation.

Results: 120 catheters implanted into brain parenchyma of 89 adult female rhesus monkeys across four sets of experiments. After experiencing a high delivery failure rate - non patent catheters - (19 %) because of tissue entrapment and debris and/or blood clots in the catheter tip, we developed modifications, including increasing the bolus infusion volume from 10 to 20 μl such that by the third experiment, the failure rate was 8 % (1 of 12 implants). Increasing the bolus volume to 100 μl and maintaining positive pressure in the catheter during preparation and implantation yielded a failure rate of 0 % (0/12 implants) by the fourth experiment.

Comparison With Existing Methods: We provide a retrospective analysis to reveal how several different manipulations affect catheter patency and how post-op MRI examination is essential for assessing catheter patency in situ.

Conclusions: The results of the present study identified that the main cause of the catheter blockages were clots that rendered the catheter non-patent. We resolved this by modifying the surgical procedures that prevented these clots from forming.
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http://dx.doi.org/10.1016/j.jneumeth.2020.109020DOI Listing
February 2021

Antioxidant Activity and Acteoside Analysis of .

Antioxidants (Basel) 2020 Nov 19;9(11). Epub 2020 Nov 19.

Department of Plant Science and Technology, Chung-Ang University, Anseong 17546, Korea.

This study determined acteoside and its content in via HPLC/UV and LC/ESI-MS to obtain insights into the potential use of this plant as an antioxidant agent. Moreover, 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (OH), and O radical scavenging activity assays were performed to assess in vitro antioxidative activity. The DPPH, OH, and O radical scavenging activities of leaf EtOH extracts at a 250 μg/mL concentration were 88.32%, 94.48%, and 14.36%, respectively, whereas those of stem extracts at the same concentration were 88.15%, 88.99%, and 15.36%, respectively. The contents of acteoside in leaves and stems were 162.11 and 29.68 mg/g, respectively. Acteoside was identified as the main antioxidant compound in leaves, which resulted in DPPH, OH, and O radical scavenging activities of 82.84%, 89.46%, and 30.31%, respectively, at a 25 μg/mL concentration. These results indicate that leaves and stems containing the antioxidant acteoside can be used as natural ingredients for functional and nutritional supplements.
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http://dx.doi.org/10.3390/antiox9111148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699419PMC
November 2020

RabGEF1 functions as an oncogene in U251 glioblastoma cells and is involved in regulating AKT and Erk pathways.

Exp Mol Pathol 2021 02 7;118:104571. Epub 2020 Nov 7.

Department of Neurosurgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, China. Electronic address:

Background: RabGEF1 is a guanine-nucleotide exchange factor for RAB-5, which plays an oncogenic role in certain human cancers. However, the function of RabGEF1 in glioma has not been studied. Here, we report that the down-regulation of RabGEF1 inhibits the proliferation and metastasis, and induces autophagy of U251 glioblastoma cells.

Methods: The expression of RabGEF1 in glioma and normal tissues were measured by immunohistochemistry. Four siRNAs targeting different sites of RabGEF1 were conducted and the interference efficiencies were verified by qRT-PCR assay. Western blot was used to detect the expression of interest proteins. Cell proliferation was detected using CCK-8 and clone formation assay. Cell migration and invasion were analyzed by scratch assay and transwell assay, respectively. Flow cytometry was used to detect cell cycle distribution and apoptosis.

Results: RabGEF1 was significantly up-regulated in human glioma tissues. RabGEF1 knockdown reduced cell viability, induced cell cycle arrest and apoptosis in U251 cells. Cell migration and invasion were also inhibited when RabGEF1 silencing. Mechanism studies showed that Cyclin D1 and CDK4/6 were significantly down-regulated when RabGEF1 silencing. p53 and caspase mediated apoptotic pathway was activated by down-regulation of RabGEF1. Moreover, RabGEF1 knockdown also induced autophagy in glioma cells. The investigation of AKT and Erk pathways suggested that phosphorylated AKT, p70S6K and phosphorylated Erk were all decreased when RabGEF1 silencing.

Conclusion: In conclusion, our data suggest that RabGEF1 is up-regulated in human glioma and down-regulation of RabGEF1 inhibited cell proliferation and metastasis, and induced autophagy of U251 glioblastoma cells, which might be mediated by inactivation of AKT and Erk signaling pathways.
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http://dx.doi.org/10.1016/j.yexmp.2020.104571DOI Listing
February 2021

Bandgap Engineering of Lead-Free Double Perovskite CsAgInCl Nanocrystals via Cu-Doping.

J Phys Chem Lett 2020 Oct 22;11(19):8392-8398. Epub 2020 Sep 22.

Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.

Lead-free double perovskites (DPs) with excellent moisture, light, and heat stability have been explored as alternatives to toxic lead halide perovskite (APbX) (A for monovalent cation and X for Cl, Br, or I). However, the bandgaps of the current DPs are generally larger and either indirect or direct forbidden, which leads to weak visible light absorption and limitation for photovoltaic and other optoelectronic applications. Herein, we demonstrate the first synthesis of Cu-doped CsAgInCl double perovskite nanocrystals via a facile hot-injection solution approach. The electronic bandgap can be dramatically tuned from ∼3.60 eV (CsAgInCl, parent) to ∼2.19 eV (Cu-doped CsAgInCl) by varying the Cu doping amount. We conclude that the decrease of bandgap is attributed to the overlap of the Ag-d/In-p/Cl-p orbitals and the Cu-3d orbitals in the valence band. The wide tunability of the optical and electronic properties makes Cu-Doped CsAgInCl DP NCs promising candidates for future optoelectronic device applications.
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http://dx.doi.org/10.1021/acs.jpclett.0c02553DOI Listing
October 2020

TRIM31 enhances chemoresistance in glioblastoma through activation of the PI3K/Akt signaling pathway.

Exp Ther Med 2020 Aug 21;20(2):802-809. Epub 2020 May 21.

Department of Neurosurgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, P.R. China.

Temozolomide (TMZ) resistance is a complication of treatment of glioma, and new strategies are urgently required to overcome chemoresistance in glioma cells. In the present study, it was demonstrated that tripartite motif-containing 31 (TRIM31) was abnormally upregulated in glioma tissues and cell lines compared with normal samples. Furthermore, the role of TRIM31 was assessed by overexpressing and knocking down its expression. Overexpression of TRIM31 increased cell viability, increased TMZ IC values and inhibited apoptosis in A172 and U251 cells; whereas overexpression of TRIM31 decreased the expression of the apoptosis-associated protein p53. Knockdown of TRIM31 increased apoptosis in cells treated with TMZ. Additionally, the mechanisms by which TRIM31 affected glioma cells treated with TMZ were determined. Overexpression of TRIM31 increased phosphorylation of AKT and inhibiting the PI3K/AKT signaling pathway abolished the increase in cell viability and decreased phospho-Akt protein expression in TRIM31 overexpressing A172 cells treated with TMZ. Together, the findings suggest that TRIM31 may be a potentially novel target for glioma chemotherapy.
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http://dx.doi.org/10.3892/etm.2020.8782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388422PMC
August 2020

Determinants affecting the prognosis of decompressive craniectomy for traumatic brain injury.

Pak J Med Sci 2020 May-Jun;36(4):770-775

Qi Pang, Department of Neurosurgery, Shandong Provincial Hospital affiliated to Shandong University, 324 Jingwuweiqi Road, Jinan, 250012, China.

Objective: This research was designed to investigate the prognostic determinants of patients with traumatic brain injury (TBI) undergoing decompressive craniectomy (DC).

Methods: The present study was a retrospective single center research including a total of 112 patients undergoing DC for TBI in Liaocheng People's Hospital between January 2017 and December 2018. The results were measured by Extended Glasgow Outcome Sale (GOSE). The prognostic determinants were identified by univariate and binary logistic regression analysis between the deaths and survivors or favorable and unfavorable outcomes.

Results: At the six-month follow-up, the mortality was 45.5% including 37 (33.0%) patients died within 30 days. The independent prognostic factors of 30-day mortality were age (p=0.033), D-dimer level at admission (p=0.032) and postoperative hypernatremia (p=0.014). Seventy five patients survived more than 30 days after DC, among which 27 (36.0%) patients had unfavorable prognosis (GOSE 1-4) and 48 (64.0%) patients presented favorable prognosis (GOSE 5-8). After 30 days from DC, the occurrence of post-traumatic hydrocephalus(PTH) (p= 0.008) was associated with unfavorable prognosis.

Conclusions: Although DC is an effective treatment for TBI patients, the mortality and morbidity risk remain high. A combination of age, D-dimer level at admission and postoperative hypernatremia may be a good prognostic factor for 30-day mortality. Developing an accurate therapy strategy to prevent and control PTH may be beneficial to the 6-month prognosis for TBI patients undergoing DC.
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http://dx.doi.org/10.12669/pjms.36.4.2045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260895PMC
June 2020

Utilization of electromyography during selective obturator neurotomy to treat spastic cerebral palsy accompanied by scissors gait.

J Integr Neurosci 2019 Sep;18(3):305-308

Department of Neurosurgery, the Affiliated Provincial Hospital, Shandong University, Jinan, Shandong Province, 250021, P. R. China.

Selective obturator neurotomy is a commonly used neurosurgical intervention for spastic cerebral palsy with scissors gait. Here we report the use of surface electromyography to assess the accuracy and effect of selective obturator neurotomy procedures. Selective obturator neurotomy was carried out on 18 patients while using intraoperative electromyography. Contractions of adductor muscles were recorded by electromyography before and after neurotomy and assessed using root mean square and integrated electromyography tests. Passive and voluntary movements were recorded for all patients. Our results show that adductor spasms and adductive deformity of hip were improved in all patients with spastic cerebral palsy. Adductor muscle spatiality was improved significantly, confirmed by a significant decrease in the values of root mean square and integrated electromyography in both passive and voluntary movements after surgery. We show that electromyography is an effective tool for accurately and safely targeting nerve tracts during selective obturator neurotomy. Thus, we demonstrate a valuable noninvasive method to objectively evaluate the effect of treatment in spastic cerebral palsy patients.
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http://dx.doi.org/10.31083/j.jin.2019.03.146DOI Listing
September 2019

Ubenimex induces apoptotic and autophagic cell death in rat GH3 and MMQ cells through the ROS/ERK pathway.

Drug Des Devel Ther 2019 12;13:3217-3228. Epub 2019 Sep 12.

Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, People's Republic of China.

Purpose: Ubenimex, an aminopeptidase N (APN) inhibitor, is widely known for its use as an adjunct therapy for cancer therapy. However, in recent studies, it has also conferred antitumour effects in many cancers, but its anticancer mechanism is largely unknown. This study aims to investigate the specific anticancer activities and mechanisms of ubenimex in GH3 and MMQ cells.

Materials And Methods: In this study, we investigated the anticancer effects of ubenimex in GH3 and MMQ cells. Cell viability and cell death were assessed by the Cell Counting Kit-8 kit (CCK-8) and a LIVE/DEAD cell imaging kit. Apoptosis and intracellular reactive oxygen species (ROS) generation were assessed by flow cytometry and fluorescence microscopy. Autophagosome formation was detected by transmission electron microscopy, and autophagic flux was measured with mRFP-GFP-LC3 adenoviral transfection. The protein expression level was detected by Western blotting.

Results: The results revealed that treatment with ubenimex induced apoptotic and autophagic cell death in GH3 and MMQ cells, which resulted in decreased viability, an increased proportion of apoptotic cells, and autophagosome formation. Further experiments showed that ubenimex induced ROS generation and activated the ROS/ERK pathway. The ROS scavenger NAC could attenuate ubenimex-induced apoptosis and autophagy.

Conclusion: Our studies revealed that ubenimex exerted anticancer effects by inducing apoptotic and autophagic cell death in GH3 and MMQ cells, rendering it a possible effective adjunctive therapy for pituitary treatment.
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http://dx.doi.org/10.2147/DDDT.S218371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750015PMC
February 2020

NKAP alters tumor immune microenvironment and promotes glioma growth via Notch1 signaling.

J Exp Clin Cancer Res 2019 Jul 6;38(1):291. Epub 2019 Jul 6.

Department of Histology and Embryology, School of Basic Medical Science, Shandong University Cheeloo College of Medicine, 44# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.

Background: Glioma is one of the most aggressive malignant brain tumors which is characterized with highly infiltrative growth and poor prognosis. NKAP (NF-κB activating protein) is a widely expressed 415-amino acid nuclear protein that is overexpressed by gliomas, but its function in glioma was still unknown.

Methods: CCK8 and EDU assay was used to examine the cell viability in vitro, and the xenograft models in nude mice were established to explore the roles of NAKP in vivo. The expressions of NKAP, Notch1 and SDF-1 were analyzed by immunofluorescence analysis. The expression of NKAP and Notch1 in glioma and normal human brain samples were analyzed by immunohistochemical analysis. In addition, CHIP, Gene chip, western blot, flow cytometry, immunofluorescence, ELISA and luciferase assay were used to investigate the internal connection between NKAP and Notch1.

Results: Here we showed that overexpression of NKAP in gliomas could promote tumor growth by contributing to a Notch1-dependent immune-suppressive tumor microenvironment. Downregulation of NKAP in gliomas had abrogated tumor growth and invasion in vitro and in vivo. Interestingly, compared to the control group, inhibiting NKAP set up obstacles to tumor-associated macrophage (TAM) polarization and recruitment by decreasing the secretion of SDF-1 and M-CSF. To identify the potential mechanisms involved, we performed RNA sequencing analysis and found that Notch1 appeared to positively correlate with the expression of NKAP. Furthermore, we proved that NKAP performed its function via directly binding to Notch1 promoter and trans-activating it. Notch1 inhibition could alleviate NKAP's gliomagenesis effects.

Conclusion: these observations suggest that NKAP promotes glioma growth by TAM chemoattraction through upregulation of Notch1 and this finding introduces the potential utility of NKAP inhibitors for glioma therapy.
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http://dx.doi.org/10.1186/s13046-019-1281-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612223PMC
July 2019

Perinatal Outcomes After Emergency Cervical Cerclage for Cervical Insufficiency with Prolapsed Membranes.

Med Sci Monit 2019 Jun 6;25:4202-4206. Epub 2019 Jun 6.

Department of Obstetrics and Gynecology, Sixth Medical Center of the People's Liberation Army (PLA) General Hospital, Beijing, China (mainland).

BACKGROUND To study the clinical effective of emergency cervical cerclage (ECC) in pregnant women who have cervical insufficiency with prolapsed membranes. MATERIAL AND METHODS This study was devised as a retrospective cohort in a single medical center, in which we collected clinical data from patient records. Inclusion criteria were: physical examination indicated ECC was performed at 15 to 25 gestational weeks at the Sixth Medical Center of the PLA General Hospital, and singleton pregnancy. The collected clinical data included: duration of pregnancy at delivery, interval between ECC and delivery, neonatal weight, neonatal mortality, neonatal morbidity, and Neonatal Intensive Care Unit (NICU) admission. RESULTS We included 50 women with singleton pregnancies. No surgical complications occurred in any patients. The gestational age at cerclage was 21.3±2.2 weeks. No patients had membrane damage due to surgery. No surgical complications were reported. Five (10%) patients underwent chorioamnionitis. The time interval between ECC and delivery was 11.2±7.1 weeks. The mean gestational age at delivery was 34.1 weeks. The rate of vaginal delivery was 96%. Ten patients had pregnancy lasting longer than 36 weeks. The mean neonate delivery weight was 2510.7 g. Twenty neonates were admitted to the Neonatal Intensive Care Unit (NICU), and the mean NICU stay was 21 days. CONCLUSIONS ECC has good perinatal results. Our results provide clinical evidence for the efficacy and risks of ECC.
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http://dx.doi.org/10.12659/MSM.916480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6568028PMC
June 2019

1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) Induces the Apoptosis of Dopaminergic Neurons via Oxidative Stress and Neuroinflammation.

Oxid Med Cell Longev 2019 7;2019:1292891. Epub 2019 Mar 7.

Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.

Several studies have revealed the neurotoxicity of 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo). However, the underlying mechanism has not been completely elucidated, particularly . This study was designed to study the neurotoxicity of TaClo by stereotactically injecting TaClo into the striatum of Wistar rats. After the TaClo injections, rats were subjected to an open field test, and their distance travelled and tracks showed decreasing trends over time. The results of liquid chromatography-mass spectrometry analysis showed that the motor dysfunction of the TaClo-treated rats was accompanied by reduced dopamine levels in the striatum. Based on the diffusion tensor imaging data, the apparent diffusion coefficient of the nigrostriatal pathway was significantly increased, and subsequent histological staining revealed the demyelination of nigrostriatal fibres after the TaClo treatment. TaClo induced a loss of tyrosine hydroxylase-positive cells in the substantia nigra compacta. Regarding the underlying mechanism, TaClo caused oxidative stress in the nigrostriatal system by increasing the production of reactive oxygen species and reducing the mitochondria membrane potential. Meanwhile, the elevated expression of Iba-1, TNF-, IL-6, Cox-2, and iNOS indicated microglial activation and a strong innate immune response in the nigrostriatal system. In addition, activated caspase-3 levels were increased. Thus, both mitochondrial impairments and the innate immune response are involved in TaClo-induced neurotoxicity.
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http://dx.doi.org/10.1155/2019/1292891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431519PMC
July 2019
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