Publications by authors named "Xu Luo"

192 Publications

The complete plastome sequence of Pei (Araceae).

Mitochondrial DNA B Resour 2021 28;6(8):2112-2113. Epub 2021 Jun 28.

College of Life Science, Guizhou University, Guiyang, China.

The complete plastome of is reported in this study. The whole plstome contains 164,293 bp, including a large single copy region (90,089 bp) and a small single copy region (24,871 bp), which were separated by a pair of inverted repeat regions (24,881 bp of IRB and 24,982 bp of IRA). Totally, 130 genes were identified, containing 86 coding-protein, 8 rRNA (4 rRNA species), and 36 tRNA genes. Phylogenetic analysis based on common protein coding genes of 10 Araceae species showed that is original than other species in the genus . The whole plastome of and other species should facilitate further works for the genus about genetic diversity, phylogenetic analysis, and so on.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/23802359.2021.1923411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245090PMC
June 2021

Incidental diagnosis of nonfunctional bladder paraganglioma: a case report and literature review.

BMC Urol 2021 Jul 8;21(1):98. Epub 2021 Jul 8.

Department of Urology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China.

Background: Nonfunctional bladder paragangliomas is a rare urological disease. It may present clinical, radiology and pathological features similar to bladder cancer, Only scarce reports have been reported. Urologist must identify this generally benign neuroendocrine neoplasm to avoid misdiagnosis.

Case Presentation: A 62-year-old female presented the outpatient department of our hospital with the symptoms of stomachache, frequent micturition, and urination pain for 20 days. Diagnosed with high blood pressure 1 year ago, administered Amlodipine besylate tablets 5 mg po qd occasionally, did not check blood pressure; denied any tumor observation in the family history. Color ultrasound of the urinary system showed a 38 mm × 34 mm hypoechoic mass on the right side of the bladder, CDFI: in the masses, blood supply was sufficient. Cystoscope showed bladder occupying lesion. Biopsy diagnosis: papillary polypoid cystitis was suspected as a malignant change (Fig. 3a). Then, the patient was admitted to our urological department. Further, computer tomography urography considered bladder cancer. Cystoscopy and biopsy failed to define the nature of the lesions in our outpatient department, which prompted a transurethral resection of the bladder tumor. histopathological and immunohistochemical results were diagnosed as bladder paragangliomas. For the reason, the tumor was removed by partial resection of the bladder. The postoperative recovery and follow-up were uneventful.

Conclusions: Nonfunctional bladder paragangliomas are occasionally found on imaging studies with the symptoms of urinary tract infection or/and intermittent painless hematuria. It may present clinical, radiology and pathological features similar to bladder cancer, so knowledge of this generally benign neuroendocrine neoplasm is of great importance to avoid misdiagnosis. It should be accompanied by the clinical and pathological characteristics of the patient and image changes. Partial resection of the bladder can effectively treat this disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12894-021-00863-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265019PMC
July 2021

MiR-494-mediated Effects on the NF-κB Signaling Pathway Regulate Lipopolysaccharide-Induced Acute Kidney Injury in Mice.

Immunol Invest 2021 Jul 8:1-13. Epub 2021 Jul 8.

Department of Clinical Laboratory, Cangzhou Central Hospital, Cangzhou, China.

Objective: To explore the effects of miR-494 inhibition through the NF-κB signaling pathway on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) mouse model.

Methods: The AKI mice induced by LPS were treated with miR-494 antagomir, and the kidney parameters and indicators of oxidative stress were detected. HE and TUNEL staining were performed to observe the kidney histopathology and the apoptosis in renal tubular epithelial cells (RTECs), respectively. The ROS level was measured using dihydroethidium (DHE) staining. In addition, qRT-PCR, western blotting, immunohistochemistry (IHC), and ELISA were also used to detect gene or protein expression.

Results: LPS-induced AKI mice injected with the miR-494 antagomir showed reduced blood urea nitrogen (BUN) and serum creatinine (Cr) with improved kidney histopathology. The expression levels of -IKKα/β, -IκBα and p65 NF-κB in the nucleus were increased in kidney tissues from the LPS-induced AKI mice, and they were decreased by the miR-494 antagomir. Moreover, the results of IHC showed that the miR-494 antagomir downregulated p65 NF-κB in kidney tissues from the LPS-induced AKI mice, accompanied by decreased levels of TNF-α, IL-1β, IL-6, MDA, NO, and ROS but increased levels of SOD and GSH. In addition, the LPS-induced AKI mice had increased apoptosis in RTECs, as well as increased Caspase-3 and Bax and decreased Bcl-2, which were reversed by the miR-494 antagomir.

Conclusions: The inhibition of miR-494 could reduce inflammatory responses and improve oxidative stress in kidney tissues from LPS-induced AKI mice by blocking the NF-κB pathway accompanying by reduced apoptosis in RTECs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08820139.2021.1944184DOI Listing
July 2021

Working Memory Load Effects on the Tilt Aftereffect.

Front Psychol 2021 15;12:618712. Epub 2021 Jun 15.

Department of Psychology, School of Psychology, Guizhou Normal University, Guiyang, China.

Prolonged exposure to an oriented stimulus causes a subsequent test stimulus to be perceived as tilted in the opposite direction, a phenomenon referred to as the tilt aftereffect (TAE). Previous studies have demonstrated that high-level cognitive functions such as attention can modulate the TAE, which is generally well-known as a low-level perceptual process. However, it is unclear whether working memory load, another high-level cognitive function, could modulate the TAE. To address this issue, here we developed a new paradigm by combining a working memory load task with a TAE task. Participants firstly remembered a stream of digits (Experiment 1) or four color-shape conjunctions (Experiment 2) under high/low load conditions, and then recognized the probe stimuli (digits or a color-shape conjunction), which were presented at the center of an adapting grating. After the recognition task (i.e., the adaptation stage), participants performed an orientation judgment task to measure their TAEs. The result of Experiment 1, where the load stimuli were digits, showed that the magnitude of the TAEs were reduced under the condition of the high working memory load compared to that of the low working memory load. However, we failed to replicate the finding in Experiment 2, where the load stimuli were color-shape conjunctions. Together, our two experiments provided mixed evidence regarding the working memory load effects on the TAE and further replications are needed in future work.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyg.2021.618712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239138PMC
June 2021

Investigation of the Mechanism of Complement System in Diabetic Nephropathy via Bioinformatics Analysis.

J Diabetes Res 2021 24;2021:5546199. Epub 2021 May 24.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072 Sichuan, China.

Objectives: Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) throughout the world, and the identification of novel biomarkers via bioinformatics analysis could provide research foundation for future experimental verification and large-group cohort in DN models and patients.

Methods: GSE30528, GSE47183, and GSE104948 were downloaded from Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs). The difference of gene expression between normal renal tissues and DN renal tissues was firstly screened by GEO2R. Then, the protein-protein interactions (PPIs) of DEGs were performed by STRING database, the result was integrated and visualized via applying Cytoscape software, and the hub genes in this PPI network were selected by MCODE and topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to determine the molecular mechanisms of DEGs involved in the progression of DN. Finally, the Nephroseq v5 online platform was used to explore the correlation between hub genes and clinical features of DN.

Results: There were 64 DEGs, and 32 hub genes were identified, enriched pathways of hub genes involved in several functions and expression pathways, such as complement binding, extracellular matrix structural constituent, complement cascade related pathways, and ECM proteoglycans. The correlation analysis and subgroup analysis of 7 complement cascade-related hub genes and the clinical characteristics of DN showed that C1QA, C1QB, C3, CFB, ITGB2, VSIG4, and CLU may participate in the development of DN.

Conclusions: We confirmed that the complement cascade-related hub genes may be the novel biomarkers for DN early diagnosis and targeted treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5546199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169258PMC
May 2021

Downregulation of SOX9 suppresses breast cancer cell proliferation and migration by regulating apoptosis and cell cycle arrest.

Oncol Lett 2021 Jul 6;22(1):517. Epub 2021 May 6.

Department of Oncology, Tumor Hospital of Gansu Province, Lanzhou, Gansu 730050, P.R. China.

SRY-related high-mobility group box 9 (SOX9) is an important transcriptional factor that regulates diverse genes involved in development and stemness. Dysregulation of SOX9 encourages carcinogenesis in various types of cancer, including breast cancer. The present study aimed to explore the role of SOX9 in triple-negative breast cancer (TNBC). SOX9 expression was significantly upregulated in the TNBC MDA-MB-231, MDA-MB-436 and MDA-MB-468 cell lines compared with that in BT-549 cells. Based on a lentivirus assay, SOX9 inhibition in MDA-MB-231 and MDA-MB-436 cells suppressed cell proliferation and colony formation. Apoptosis was increased and the cell cycle was arrested at the G/G phase in SOX9-knockdown cells. Transwell and wound-healing assays demonstrated that SOX9 inhibition decreased the migration and invasion of MDA-MB-231 and MDA-MB-436 cells. RNA sequencing identified that numerous genes were regulated by SOX9, including nucleophosmin, thioredoxin reductase 1, succinate dehydrogenase complex subunit D, nuclear receptor binding SET domain protein 2, eukaryotic translation initiation factor 4γ1 and glycogen phosphorylase L. Overall, the current study suggested that SOX9 acted as an oncogene in TNBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2021.12778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114479PMC
July 2021

Emotional exhaustion in front-line healthcare workers during the COVID-19 pandemic in Wuhan, China: the effects of time pressure, social sharing and cognitive appraisal.

BMC Public Health 2021 04 30;21(1):829. Epub 2021 Apr 30.

Chongqing Health Center for Women and Children, No.120 Longshan Road, Yubei District, Chongqing, China.

Background: With the increasing spread of COVID-19, healthcare workers, especially front-line medical staff, have become more vulnerable to emotional exhaustion.

Objectives: This study aimed to determine the influence of time pressure on the emotional exhaustion of front-line healthcare workers, and explore the effects of social sharing and cognitive reappraisal on this.

Methods: This cross-sectional study was conducted in March 2020. A total of 232 questionnaires were completed by front-line healthcare workers in Wuhan city, Hubei province, China. Hierarchical linear regression and conditional process analysis were performed to explore the relationships among time pressure, social sharing, cognitive reappraisal, and emotional exhaustion.

Results: Time pressure was positively associated with social sharing and emotional exhaustion. Social sharing presented the dark side, a negative effect that was always kept concealed, in terms of the impact on emotional exhaustion. Cognitive reappraisal negatively moderated the relationship between time pressure and social sharing, and it further indirectly influenced the relationship between time pressure and emotional exhaustion through social sharing.

Conclusions: Our findings shed light on how time pressure influences the emotional exhaustion of healthcare workers during the COVID-19 period. Although social sharing is commonly regarded as a positive behavior, we identified a dark side in terms of its impact. We also identified that improving cognitive reappraisal may present a positive strategy toward alleviating emotional exhaustion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12889-021-10891-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085471PMC
April 2021

Vascular endothelial growth factor B inhibits insulin secretion in MIN6 cells and reduces Ca and cyclic adenosine monophosphate levels through PI3K/AKT pathway.

World J Diabetes 2021 Apr;12(4):480-498

Department of Pathophysiology, School of Basic Medicine, Binzhou Medical University, Yantai 264003, Shandong Province, China.

Background: Type 2 diabetes (T2D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance, resulting in an increase in blood glucose. However, the mechanism involved in this lack of insulin secretion is unclear. The level of vascular endothelial growth factor B (VEGF-B) is significantly increased in T2D patients. The inactivation of VEGF-B could restore insulin sensitivity in db/db mice by reducing fatty acid accumulation. It is speculated that VEGF-B is related to pancreatic β-cell dysfunction and is an important factor affecting β-cell secretion of insulin. As an model of normal pancreatic β-cells, the MIN6 cell line can be used to analyze the mechanism of insulin secretion and related biological effects.

Aim: To study the role of VEGF-B in the insulin secretion signaling pathway in MIN6 cells and explore the effect of VEGF-B on blood glucose regulation.

Methods: The MIN6 mouse pancreatic islet β-cell line was used as the model system. By administering exogenous VEGF-B protein or knocking down VEGF-B expression in MIN6 cells, we examined the effects of VEGF-B on insulin secretion, Ca and cyclic adenosine monophosphate (cAMP) levels, and the insulin secretion signaling pathway.

Results: Exogenous VEGF-B inhibited the secretion of insulin and simultaneously reduced the levels of Ca and cAMP in MIN6 cells. Exogenous VEGF-B also reduced the expression of phospholipase C gamma 1 (PLCγ1), phosphatidylinositol 3-kinase (PI3K), serine/threonine kinase (AKT), and other proteins in the insulin secretion pathway. Upon knockdown of VEGF-B, MIN6 cells exhibited increased insulin secretion and Ca and cAMP levels and upregulated expression of PLCγ1, PI3K, AKT, and other proteins.

Conclusion: VEGF-B can regulate insulin secretion by modulating the levels of Ca and cAMP. VEGF-B involvement in insulin secretion is related to the expression of PLCγ1, PI3K, AKT, and other signaling proteins. These results provide theoretical support and an experimental basis for the study of VEGF-B in the pathogenesis of T2D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4239/wjd.v12.i4.480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040075PMC
April 2021

Single Transition Metal Atom Bound to the Unconventional Phase of the MoS Monolayer for Catalytic Oxygen Reduction Reaction: A First-Principles Study.

ACS Appl Mater Interfaces 2021 Apr 12;13(15):17412-17419. Epub 2021 Apr 12.

College of Optoelectronic Engineering, Chongqing University, Chongqing 400044, P. R. China.

Supported single-atom catalysts (SACs) have received a lot of attention due to their super-high atom utilization and outstanding catalytic performance. However, the instability of the supported transition-metal (TM) atoms hampers their widespread applications. Exploration of an appropriate substrate to stabilize the supported single atom is crucial for the future implementation of SACs. In recent years, two-dimensional materials have been proposed as possible substrates due to their large specific surface areas, but their chemically inert surfaces are difficult to stabilize TM atoms without defecting or doping. Herein, by means of systematic first-principles calculations, we demonstrate that the defect-free MoS monolayer in the unconventional phase (1T') can effectively immobilize single TM atoms owing to its unique electrophilic property as compared to the conventional 2H phase. As a prototype probe, we investigated oxygen reduction reaction (ORR) catalyzed by a total of 21 single TM atoms stabilized on 1T'-MoS and successfully screened out two candidates, Cu and [email protected]'-MoS, which have a low overpotential of 0.41 and 0.32 V respectively, outperforming most of the previously reported ORR catalysts. Furthermore, we reveal that the adsorption energy of the ORR intermediate, *OH, provides an excellent descriptor to assess the ORR activity, which is further determined by the -band center of the supported TM adatoms, thus being a great advantage for future design of stable and high-performance SACs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c21597DOI Listing
April 2021

Toxic effect of fluorene-9-bisphenol to green algae Chlorella vulgaris and its metabolic fate.

Ecotoxicol Environ Saf 2021 Mar 30;216:112158. Epub 2021 Mar 30.

Shenzhen Key Laboratory of Environmental Chemistry and Ecological Remediation, College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China. Electronic address:

Fluorene-9-bisphenol (BHPF), a bisphenol A (BPA) alternative, has recently attracted attention due to its wide use and potential toxicity. However, the toxic effects and fate of BHPF in freshwater algae remains to be elucidated. In this study, the impact of BHPF on Chlorella vulgaris was explored and the removal and bioaccumulation of BHPF by Chlorella vulgaris were investigated. Results showed that C. vulgaris was sensitive to BHPF at the concentration of >1 mg L, and lipid peroxidation was significantly increased under the exposure of >0.1 mg BHPF L. An oxidative stress was caused by BHPF, as the activities of superoxide dismutase (SOD) were significantly decreased in algal cells by >0.5 mg BHPF L. The removal rate of BHPF was significantly enhanced by the addition of algae. In addition, the increasing accumulation of BHPF in algae at concentrations ranging from 0.5 to 5 mg L was observed and may contribute for the increased toxicity of BHPF to C. vulgaris. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) results demonstrated that three metabolites of BHPF were identified in algal cells, which may pose an unexpected effect in aquatic environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2021.112158DOI Listing
March 2021

Glucose deprivation-induced endoplasmic reticulum stress response plays a pivotal role in enhancement of TRAIL cytotoxicity.

J Cell Physiol 2021 Sep 15;236(9):6666-6677. Epub 2021 Feb 15.

Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Abnormalities of the tumor vasculature result in insufficient blood supply and development of a tumor microenvironment that is characterized by low glucose concentrations, low extracellular pH, and low oxygen tensions. We previously reported that glucose-deprived conditions induce metabolic stress and promote tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cytotoxicity. In this study, we examined whether the metabolic stress-associated endoplasmic reticulum (ER) stress response pathway plays a pivotal role in the enhancement of TRAIL cytotoxicity. We observed no significant cytotoxicity when human colorectal cancer SW48 cells were treated with various doses of TRAIL (2-100 ng/ml) for 4 h or glucose (0-25 mM) for 24 h. However, a combination of TRAIL and low glucose-induced dose-dependent apoptosis through activation of caspases (-8, -9, and -3). Studies with activating transcription factor 4 (ATF4), C/EBP-homologous protein (CHOP), p53 upregulated modulator of apoptosis (PUMA), or death receptor 5 (DR5)-deficient mouse embryonic fibroblasts or HCT116 cells suggest that the ATF4-CHOP-PUMA axis and the ATF4-CHOP-DR5 axis are involved in the combined treatment-induced apoptosis. Moreover, the combined treatment-induced apoptosis was completely suppressed in BH3 interacting-domain death agonist (Bid)- or Bcl-2-associated X protein (Bax)-deficient HCT116 cells, but not Bak-deficient HCT116 cells. Interestingly, the combined treatment-induced Bax oligomerization was suppressed in PUMA-deficient HCT116 cells. These results suggest that glucose deprivation enhances TRAIL-induced apoptosis by integrating the ATF4-CHOP-PUMA axis and the ATF4-CHOP-DR5 axis, consequently amplifying the Bid-Bax-associated mitochondria-dependent pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.30329DOI Listing
September 2021

7,8-Dihydroxyflavone Enhanced Colonic Cholinergic Contraction and Relieved Loperamide-Induced Constipation in Rats.

Dig Dis Sci 2021 Feb 2. Epub 2021 Feb 2.

Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Background: Whether 7,8-dihydroxyflavone (7,8-DHF), a tyrosine kinase receptor B (TrkB) agonist, modulates colonic smooth muscle motility and/or alleviates constipation has not yet been studied.

Aims: Here, we aimed to determine how 7,8-DHF influences carbachol (CCh)-stimulated contraction of colonic strips and the in vivo effect of 7,8-DHF on constipation.

Methods: Muscle strips were isolated from rat colons for recording contractile tension and performing western blotting. Constipation was induced in rats with loperamide.

Results: Although it specifically activated TrkB, 7,8-DHF applied alone neither activated PLCγ1 in the colonic strips nor induced colonic strip contraction. However, 7,8-DHF enhanced CCh-stimulated PLCγ1 activation and strip contraction. The PLCγ1 antagonist U73122 suppressed both CCh-stimulated and 7,8-DHF-enhanced/CCh-stimulated contraction. While clarifying the underlying mechanism, we revealed that 7,8-DHF augmented muscarinic M3 receptor expression in the colonic strips. The M3-selective antagonist tarafenacin specifically inhibited the 7,8-DHF-enhanced/CCh-stimulated contraction of the colonic strips. Since 7,8-DHF increased Akt phosphorylation, and LY294002 (an antagonist of PI3K upstream of Akt) dramatically inhibited both 7,8-DHF-augmented M3 expression and 7,8-DHF-enhanced/CCh-stimulated contractions, we assumed that 7,8-DHF/TrkB/Akt was associated with the modulation of M3 expression in the colonic strips. ANA-12, a specific TrkB antagonist, not only inhibited TrkB activation by 7,8-DHF but also suppressed 7,8-DHF-enhanced cholinergic contraction, 7,8-DHF/CCh-mediated activation of PLCγ1/Akt, and M3 overexpression in colonic strips. In vivo 7,8-DHF, also by promoting intestinal motility and M3 expression, significantly alleviated loperamide-induced functional constipation in rats.

Conclusions: Our results suggest that 7,8-DHF regulates colonic motility possibly via a TrkB/Akt/M3 pathway and may be applicable for alleviating constipation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10620-020-06817-yDOI Listing
February 2021

Complete mitochondrial genome of fire-tailed myzornis () and white-browed fulvetta ().

Mitochondrial DNA B Resour 2020 Sep 8;5(3):3307-3309. Epub 2020 Sep 8.

Key Laboratory for Conserving Wildlife with Small Populations in Yunnan/Faculty of Biodiversity and Conservation, Southwest Forestry University, Kunming, China.

In this study, the complete mitochondrial genomes of and were sequenced and described for the first time. The whole mitochondrial genomes of and are 17,397 bp and 16,961 bp in length, with the G + C percentage 46.34% and 47.36%, respectively. Both genomes contain 13 protein-coding genes, 22 transfer RNA genes, 2 ribosome RNA genes, and 1 non-coding control region. The arrangement of genes is identical to mitochondrial genomes of Sylviidae species reported previously. A phylogenetic reconstruction supported that and are members of family Sylviidae. The mitochondrial genomes of these two species reported here would be helpful in better understanding the phylogeny and evolution of Sylviidae.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/23802359.2020.1814884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782492PMC
September 2020

Renal Urothelial Carcinoma Complicated by Inferior Vena Cava Tumor Thrombus and Acute Pyelonephritis.

Urology 2021 Feb 26;148:e1-e2. Epub 2020 Dec 26.

Department of Urology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China. Electronic address:

Renal urothelial carcinoma (UC) with inferior vena cava tumor thrombus is rare, especially when it is concomitant with acute pyelonephritis. In this report, a 70-year-old diabetic man with right flank pain, intermittent painless gross hematuria, and recurrent high fever was described. On the basis of the symptoms, physical examination, cytology and imaging results, renal UC with extension into inferior vena cava, and acute pyelonephritis was established. The patient was unresponsive to antimicrobial chemotherapy. Nephroureterectomy, lymphadenectomy, thrombectomy, and bladder cuff excision were performed. Postoperative histopathological examination revealed high grade UC and lymph node metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urology.2020.12.016DOI Listing
February 2021

Activation of the Melanocortin-1 Receptor by NDP-MSH Attenuates Oxidative Stress and Neuronal Apoptosis through PI3K/Akt/Nrf2 Pathway after Intracerebral Hemorrhage in Mice.

Oxid Med Cell Longev 2020 12;2020:8864100. Epub 2020 Nov 12.

Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.

Oxidative stress and neuronal apoptosis play crucial roles in secondary brain injury (SBI) after intracerebral hemorrhage (ICH). Recently, Nle4-D-Phe7--melanocyte-stimulating hormone (NDP-MSH), a synthetic agonist of the melanocortin-1 receptor (Mc1r), has been proved to inhibit neuroinflammatory in several diseases. This study is aimed at exploring if NDP-MSH could reduce oxidative stress and neuronal apoptosis following ICH, as well as the potential mechanism. A mouse ICH model was induced by autologous blood injection. NDP-MSH was intraperitoneally injected at 1 h after ICH. Mc1r siRNA and PI3K inhibitor LY294002 were administrated to inhibit the expression of Mc1r and phosphorylation of PI3K, respectively. Neurological test, brain water content, enzyme-linked immunosorbent assay (ELISA), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), immunofluorescence, and Western blot analysis were utilized in this study. The results exhibited that Mc1r was mainly expressed in neurons, and its level in the ipsilateral hemisphere was significantly elevated after ICH. NDP-MSH treatment significantly attenuated the neurological deficits and brain water content 24 hours after ICH, which was accompanied by the inhibition of oxidative stress and neuronal apoptosis. The administration of NDP-MSH after ICH significantly promoted the expression of Mc1r, p-PI3K, p-Akt, and p-Nrf2, followed by an increase of Bcl-2 and reduction of cleaved caspase-3. Conversely, downregulating the expression of Mc1r and phosphorylation of PI3K aggravated the neurological deficits and brain edema at 24 hours after ICH, meanwhile, the effect of NDP-MSH on the expression of Mc1r, p-PI3K, p-Akt, p-Nrf2, Bcl-2, and cleaved caspase 3 was also abolished. In conclusion, our data suggest that the activation of Mc1r by NDP-MSH ameliorates oxidative stress and neuronal apoptosis through the PI3K/Akt/Nrf2 signaling pathway after ICH in mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8864100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676969PMC
May 2021

A two-dimensional organic-inorganic lead iodide perovskite: poly[bis(3-fluorocyclobutylammonium) [di-μ-iodido-diiodidoplumbate(VI)]].

Acta Crystallogr C Struct Chem 2020 Dec 25;76(Pt 12):1096-1099. Epub 2020 Nov 25.

Key Laboratory of Organo-Phamaceutical Chemistry of Jiangxi Province, College of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou 341000, People's Republic of China.

In recent years, great technological advances have been achieved in the growth of hybrid organic-inorganic perovskites (HOIPs) and these have attracted extensive attention due to their optoelectronic properties, structural tunability and stability. We present here a new two-dimensional hybrid organic-inorganic perovskite, namely, poly[bis(3-fluorocyclobutylammonium) [di-μ-iodido-diiodidoplumbate(VI)]], {(CHFN)[PbI]}, showing a two-dimensional reticular layer with the organic cations in the middle of the meshes. The calculated experimental band gap is 2.44 eV and the band gap is calculated as 2.20 eV theoretically, which further suggests the potential of this compound as a semiconductor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1107/S2053229620015272DOI Listing
December 2020

The multifaceted roles of nucleophagy in cancer development and therapy.

Cell Biol Int 2021 Feb 1;45(2):246-257. Epub 2020 Dec 1.

Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Autophagy is an evolutionarily conserved process in which the cell degrades its own components and recycles the biomolecules for survival and homeostasis. It is an important cellular process to eliminate pathogens or damaged organelles. Nucleophagy, also termed as nuclear autophagy, is a more recently described subtype of autophagy, in which nuclear components, such as nuclear lamina and DNA, are to be degraded. Nucleophagy plays a double-facet role in the development of cancer. On one hand, the clearance of damaged DNA or nuclear structures via autophagic pathway is crucial to maintain nuclear integrity and prevent tumorigenesis. On the other hand, in later stages of tumor growth, nucleophagy may facilitate cancer cell survival and metastasis in the nutrient-depleted microenvironment. In this review, we discuss the relationship between nucleophagy and cancer along with potential intervention methods to target cancer through manipulating nucleophagy. Given the known observations about nucleophagy, it could be promising to target different nuclear components during the processes of nucleophagy, especially nuclear lamina. Further research on investigating the role of nucleophagy in oncological context could focus on dissecting its remaining molecular pathways and their connection to known tumor suppressors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cbin.11504DOI Listing
February 2021

[Intraspecific Variation in Growth and Alkaline Phosphatase Activity of Strains in Response to Different Phosphorus Concentrations and Sources].

Huan Jing Ke Xue 2020 Sep;41(9):4088-4094

Department of Ecology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.

The cyanobacterial species are ubiquitous in tropical regions, and its successful invasion into temperate zones has been partially attributed to its ability of survival in low P availability and the existence of multiple ecotypes. To explore the physiological response of different strains to phosphorus fluctuations, four strains of isolated from the Zhenhai Reservoir were used to investigate their growth and alkaline phosphatase (ALP) activity at different inorganic phosphorus (Pi) concentrations (HP=7.13 mg ·L, MP=0.64 mg ·L, LP=0.03 mg ·L) and different phosphorus forms [dipotassium hydrogen phosphate (KHPO), sodium pyrophosphate (KP O), sodium polyphosphate (KPO), D-glucose-6-phosphate (D-G-6-P), adenosine triphosphate (ATP), cyclic adenosine monophosphate (cAMP)]. Four strains showed a similar growth response to phosphate changes: their biomass increased with an increase in Pi concentrations, while the ALP activity showed the opposite trend. The ALP activity of N8 was significantly lower than that of other three strains, regardless of inorganic phosphorus concentrations, suggesting that this strain had a higher adaptability to phosphorus fluctuations. When cultured with different phosphorus forms, the biomass of N8 and N9 in three dissolved inorganic phosphorus (DIP) compounds were significantly higher than those in three dissolved organic phosphorus (DOP) compounds, with the maximum and minimum specific growth rate in KHPOand ATP treatments, respectively. preferred DIP although they can also utilize DOP to sustain its growth. Under the DOP conditions, the ALP activity of N8 in the ATP treatment was significantly higher than that in the other two organic phosphorus compounds, while we did not observe similar results in N9, indicating that strain N8 was more sensitive to DIP deficiency. Our results showed an intraspecific variation within strains from the same reservoir. Compared with the other strains, strain N8 represented better adaptability to phosphorus fluctuations and DIP deficiency. Variations within strains may make this species more adaptable to environmental changes and enhance its competitive advantage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13227/j.hjkx.201912180DOI Listing
September 2020

Association between obesity and the risk of uterine fibroids: a systematic review and meta-analysis.

J Epidemiol Community Health 2021 Feb 16;75(2):197-204. Epub 2020 Oct 16.

School of Basic Medicine, Qingdao University, Qingdao, China.

Background: Uterine fibroids (UFs) are the most common form of sex steroid hormone-dependent benign tumours that grow in the walls of the uterus. Several observational studies have examined the association between obesity and the risk of UFs, but findings are inconsistent. The objective of this systematic review and meta-analysis is to further examine the association of obesity with the risk/prevalence of UFs.

Methods: A literature search was performed in three databases (PubMed, EMBASE and Web of Science) from 1 January 1992 to 30 May 2020. We used random-effect models to calculate the pooled ORs with corresponding 95% CIs. Additionally, we performed a dose-response meta-analysis to analyse the effect of body mass index (BMI), weight change since age 18, waist-to-hip ratio and waist circumference on the risk/prevalence of UFs.

Results: A total of 22 articles, covering 24 studies including 325 899 participants and 19 593 cases, were selected based on our inclusion criteria. We found a positive association between obesity and the risk/prevalence of UFs (OR, 1.19; 95% CI, 1.09 to 1.29). Among participants with the highest BMI, the pooled OR was 1.19 (1.09 to 1.31) when compared to participants with normal BMI. For weight change since age 18, the pooled OR (95% CI) of UFs was 1.26 (1.12 to 1.42) among the highest change group when compared with no change. Additionally, our meta-analysis indicated the relationship of BMI with risk of UFs to be an inverse J-shaped pattern.

Conclusions: The results of this meta-analysis suggest that obesity may increase the risk/prevalence of UFs, and the association is non-linear.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jech-2019-213364DOI Listing
February 2021

Chinese Clinical Named Entity Recognition in Electronic Medical Records: Development of a Lattice Long Short-Term Memory Model With Contextualized Character Representations.

JMIR Med Inform 2020 Sep 4;8(9):e19848. Epub 2020 Sep 4.

Radiology Department, Beilun District People's Hospital, Ningbo, China.

Background: Clinical named entity recognition (CNER), whose goal is to automatically identify clinical entities in electronic medical records (EMRs), is an important research direction of clinical text data mining and information extraction. The promotion of CNER can provide support for clinical decision making and medical knowledge base construction, which could then improve overall medical quality. Compared with English CNER, and due to the complexity of Chinese word segmentation and grammar, Chinese CNER was implemented later and is more challenging.

Objective: With the development of distributed representation and deep learning, a series of models have been applied in Chinese CNER. Different from the English version, Chinese CNER is mainly divided into character-based and word-based methods that cannot make comprehensive use of EMR information and cannot solve the problem of ambiguity in word representation.

Methods: In this paper, we propose a lattice long short-term memory (LSTM) model combined with a variant contextualized character representation and a conditional random field (CRF) layer for Chinese CNER: the Embeddings from Language Models (ELMo)-lattice-LSTM-CRF model. The lattice LSTM model can effectively utilize the information from characters and words in Chinese EMRs; in addition, the variant ELMo model uses Chinese characters as input instead of the character-encoding layer of the ELMo model, so as to learn domain-specific contextualized character embeddings.

Results: We evaluated our method using two Chinese CNER datasets from the China Conference on Knowledge Graph and Semantic Computing (CCKS): the CCKS-2017 CNER dataset and the CCKS-2019 CNER dataset. We obtained F1 scores of 90.13% and 85.02% on the test sets of these two datasets, respectively.

Conclusions: Our results show that our proposed method is effective in Chinese CNER. In addition, the results of our experiments show that variant contextualized character representations can significantly improve the performance of the model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/19848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501578PMC
September 2020

The defluorination of perfluorooctanoic acid by different vacuum ultraviolet systems in the solution.

Water Environ Res 2021 Mar 15;93(3):455-463. Epub 2020 Sep 15.

College of Civil Engineering and Architecture, Zhejiang University, Hangzhou, China.

Perfluorooctanoic acid (PFOA) is one kind of persistent organic pollutants that is often detected in water. In recent years, the effective degradation technologies of PFOA have attracted widespread attentions. Thus, in this study, the defluorination efficiency of PFOA in different systems (i.e., ultraviolet (UV), vacuum ultraviolet (VUV), vacuum ultraviolet/persulfate (VUV/PS) and vacuum ultraviolet/residual chlorine (VUV/RC)) was evaluated. Moreover, the different impact factors (i.e., the initial concentrations of persulfate and PFOA, temperature, anions, and initial pH values) on PFOA degradation by VUV/PS system were investigated. The results showed that VUV system was more effective than UV system for PFOA defluorination. VUV system combined with persulfate would further enhance the defluorination efficiency while residual chlorine would decrease it. In VUV/PS system, the defluorination efficiency of PFOA was the best as the molar ratio of PFOA and persulfate at 1:60. Moreover, higher temperature, lower initial PFOA concentration, and acid condition were favorable for the defluorination of PFOA. Under the different influence factors, the defluorination efficiency of PFOA fitted well to the first-order reaction kinetic model. When the temperature was range from 20°C to 40°C, the value of activation energy was 8.73 kJ/mol. Besides, the inhibition effect of three kinds of anions on PFOA defluorination followed the order:  > Cl  >  . PRACTITIONER POINTS: The defluorination efficiency of perfluorooctanoic acid (PFOA) in water by different VUV systems was compared. VUV system is more effective than UV system for PFOA defluorination. Persulfate will enhance the defluorination efficiency by VUV system. Hypochlorite will decrease the defluorination efficiency by VUV system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/wer.1448DOI Listing
March 2021

Outdoor-to-indoor transport of ultrafine particles: Measurement and model development of infiltration factor.

Environ Pollut 2020 Dec 13;267:115402. Epub 2020 Aug 13.

Department of Building Science, School of Architecture, Tsinghua University, Beijing, 100084, China; Beijing Key Laboratory of Indoor Air Quality Evaluation and Control, Tsinghua University, Beijing, 100084, China. Electronic address:

Ambient ultrafine particles (UFPs: particles of diameter less than 100 nm) cause significant adverse health effects. As people spend most time indoors, the outdoor-to-indoor transport of UFPs plays a critical role in the accuracy of personal exposure assessments. Herein, a strategy was proposed to measure and analyze the infiltration factor (F) of UFPs, an important parameter quantifying the fraction of ambient air pollutants that travel inside and remain suspended indoors. Ninety-three measurements were conducted in 11 residential rooms in all seasons in Beijing, China, to investigate F of UFPs and its associated influencing factors. A multilevel regression model incorporating eight possible factors that influence infiltration was developed to predict F and F (defined as the ratio of indoor to outdoor UFP concentrations without indoor sources, but with indoor secondary organic aerosol (SOA) formation). It was found that the air change rate was the most important factor and coagulation was considerable, while the influence of SOA formation was much smaller than that of other factors. Our regression model accurately predicted daily-average F. The annually-averaged F of UFPs was 0.66 ± 0.10, which is higher than that of PM and PM, demonstrating the importance of controlling indoor UFPs of outdoor origin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2020.115402DOI Listing
December 2020

The third model of Bax/Bak activation: a Bcl-2 family feud finally resolved?

F1000Res 2020 6;9. Epub 2020 Aug 6.

Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Alaska Medical Center, Omaha, ME, 68198-7696, USA.

Bax and Bak, two functionally similar, pro-apoptotic proteins of the Bcl-2 family, are known as the gateway to apoptosis because of their requisite roles as effectors of mitochondrial outer membrane permeabilization (MOMP), a major step during mitochondria-dependent apoptosis. The mechanism of how cells turn Bax/Bak from inert molecules into fully active and lethal effectors had long been the focal point of a major debate centered around two competing, but not mutually exclusive, models: direct activation and indirect activation. After intensive research efforts for over two decades, it is now widely accepted that to initiate apoptosis, some of the BH3-only proteins, a subclass of the Bcl-2 family, directly engage Bax/Bak to trigger their conformational transformation and activation. However, a series of recent discoveries, using previously unavailable CRISPR-engineered cell systems, challenge the basic premise that undergirds the consensus and provide evidence for a novel and surprisingly simple model of Bax/Bak activation: the membrane (lipids)-mediated spontaneous model. This review will discuss the evidence, rationale, significance, and implications of this new model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12688/f1000research.25607.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411521PMC
October 2020

Venetoclax causes metabolic reprogramming independent of BCL-2 inhibition.

Cell Death Dis 2020 08 13;11(8):616. Epub 2020 Aug 13.

Cancer Research UK Beatson Institute, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1QH, UK.

BH3-mimetics are a new class of anti-cancer drugs that inhibit anti-apoptotic Bcl-2 proteins. In doing so, BH3-mimetics sensitise to cell death. Venetoclax is a potent, BCL-2 selective BH3-mimetic that is clinically approved for use in chronic lymphocytic leukaemia. Venetoclax has also been shown to inhibit mitochondrial metabolism, this is consistent with a proposed role for BCL-2 in metabolic regulation. We used venetoclax to understand BCL-2 metabolic function. Similar to others, we found that venetoclax inhibited mitochondrial respiration. In addition, we also found that venetoclax impairs TCA cycle activity leading to activation of reductive carboxylation. Importantly, the metabolic effects of venetoclax were independent of cell death because they were also observed in apoptosis-resistant BAX/BAK-deficient cells. However, unlike venetoclax treatment, inhibiting BCL-2 expression had no effect on mitochondrial respiration. Unexpectedly, we found that venetoclax also inhibited mitochondrial respiration and the TCA cycle in BCL-2 deficient cells and in cells lacking all anti-apoptotic BCL-2 family members. Investigating the basis of this off-target effect, we found that venetoclax-induced metabolic reprogramming was dependent upon the integrated stress response and ATF4 transcription factor. These data demonstrate that venetoclax affects cellular metabolism independent of BCL-2 inhibition. This off-target metabolic effect has potential to modulate venetoclax cytotoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-020-02867-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426836PMC
August 2020

Controlling nutritional status score and prognostic nutrition index predict the outcome after severe traumatic brain injury.

Nutr Neurosci 2020 Aug 11:1-8. Epub 2020 Aug 11.

Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.

Objectives: Immune-nutritional status is correlated with a clinical outcome in critical illness. Recently, controlling nutritional status (CONUT) score and prognostic nutrition index (PNI) has been reported to predict prognosis following cancer and other diseases. The aim of this study was to explore the relationship between the CONUT score and PNI and 6-month outcome in patients with severe traumatic brain injury (STBI).

Methods: We retrospectively analyzed the clinical data of 78 patients with STBI, including the CONUT score and PNI. Patients were divided into high CONUT group and low CONUT group. Patients were also divided into high PNI and low PNI group respectively. The 6-month outcome was evaluated by the modified Rankin scale (mRS). The unfavorable outcome was defined as mRS score ≥3.

Results: The unfavorable outcome group had lower Glasgow coma scale (GCS) scores, serum albumin, total cholesterol, PNI, and higher CONUT scores ( < 0.05). Both CONUT scores and PNI were strongly correlated with mRS ( = 0.429,  < 0.05;  = -0.590, < 0.05, respectively). After adjustment for confounding factors, the odds ratios of CONUT scores and PNI for predicting unfavorable outcome were 10.478 (95% CI: 2.793-39.301) and -0.039 (95% CI: 0.008-0.204), respectively. The area under the curve (AUC) of CONUT scores for predicting unfavorable outcome was 0.777 (95% CI: 0.674-0.880, < 0.01), which was similar to PNI (0.764, 95% CI: 0.657-0.87, < 0.01).

Conclusion: Both CONUT scores and PNI might be novel independent predictors of the poor outcome in STBI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/1028415X.2020.1804097DOI Listing
August 2020

BAX-dependent mitochondrial pathway mediates the crosstalk between ferroptosis and apoptosis.

Apoptosis 2020 10;25(9-10):625-631

Department of Surgery, School of Medicine, University of Pittsburgh, 5117 Centre Ave, Pittsburgh, PA, 15213, USA.

Ferroptosis is considered a distinctive form of cell death compared to other types of death such as apoptosis. It is known to result from iron-dependent accumulation of lipid peroxides rather than caspase activation. However, we reported recently that ferroptosis interplays with apoptosis. In this study, we investigated a possible mechanism of this interplay between ferroptosis and apoptosis. Results from our studies reveal that combined treatment of the ferroptotic agent erastin and the apoptotic agent TRAIL effectively disrupted mitochondrial membrane potential (ΔΨm) and subsequently promoted caspase activation. The alterations of mitochondrial membrane potential are probably due to an increase in oligomerization of BAX and its accumulation at the mitochondria during treatment with erastin and TRAIL. Interestingly, the combined treatment-promoted apoptosis was effectively inhibited in BAX-deficient HCT116 cells, but not BAK-deficient cells. These results indicate that the BAX-associated mitochondria-dependent pathway plays a pivotal role in erastin-enhanced TRAIL-induced apoptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10495-020-01627-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529973PMC
October 2020

Drp-1 as Potential Therapeutic Target for Lipopolysaccharide-Induced Vascular Hyperpermeability.

Oxid Med Cell Longev 2020 26;2020:5820245. Epub 2020 Jun 26.

Department of Critical Care Medicine, The First People's Hospital of Chenzhou, Affiliated Chenzhou Hospital, Southern Medical University, Chenzhou 423000, China.

Mitochondria-dependent apoptotic signaling has a critical role in the pathogenesis of vascular hyperpermeability (VH). Dynamin-related protein-1- (Drp-1-) mediated mitochondrial fission plays an important role in mitochondrial homeostasis. In the present study, we studied the involvement of Drp-1 in resistance to VH induced by lipopolysaccharide (LPS). To establish the model of LPS-induced VH, LPS at 15 mg/kg was injected into rats and rat pulmonary microvascular endothelial cells were exposed to 500 ng/ml LPS . We found that depletion of Drp-1 remarkedly exacerbated the mitochondria-dependent apoptosis induced by LPS, as evidenced by reduced apoptosis, mitochondrial membrane potential (MMP) depolarization, and activation of caspase-3 and caspase-9. Increased FITC-dextran flux indicated endothelial barrier disruption. In addition, overexpression of Drp-1 prevented LPS-induced endothelial hyperpermeability and upregulated mitophagy, as evidenced by the loss of mitochondrial mass and increased PINK1 expression and mitochondrial Parkin. However, the mitophagy inhibitor, 3-Methyladenine, blocked these protective effects of Drp-1. Furthermore, inhibition of Drp-1 using mitochondrial division inhibitor 1 markedly inhibited LPS-induced mitophagy and aggravated LPS-induced VH, as shown by increased FITC-dextran extravasation. These findings implied that Drp-1 strengthens resistance to mitochondria-dependent apoptosis by regulating mitophagy, suggesting Drp-1 as a possible therapeutic target in LPS-induced VH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/5820245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336239PMC
May 2021

TRIB3 destabilizes tumor suppressor PPARα expression through ubiquitin-mediated proteasome degradation in acute myeloid leukemia.

Life Sci 2020 Sep 1;257:118021. Epub 2020 Jul 1.

Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China; Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. Electronic address:

Aims: Tribbles homolog 3 (TRIB3) is emerging as a multifunctional oncoprotein associated with various cellular events in different tumors. However, the regulatory mechanism of TRIB3 in acute myeloid leukemia (AML) remains unknown. This study aims to investigate the molecular mechanisms and uncover the functions of TRIB3 in AML.

Methods: Western blotting and quantitative real-time PCR were used to analyze the expression levels of TRIB3, peroxisome proliferator-activated receptor α (PPARα), apoptosis markers and autophagy markers in AML cells. Flow cytometry was used to assess cell apoptosis. The interaction of TRIB3 and PPARα was evaluated by immunofluorescence, coimmunoprecipitation, and in vivo ubiquitination assays.

Key Findings: We demonstrated that downregulating TRIB3 in leukemic cells effectively induced apoptosis and autophagy by regulating the degradation of PPARα. Mechanistically, TRIB3 interacted with PPARα and contributed to its destabilization by promoting its ubiquitination. When PPARα was activated by its specific agonist clofibrate, the apoptosis and autophagy of AML cells were significantly enhanced. These results were confirmed by rescue experiments. Blocking PPARα expression using the PPARα inhibitor GW6471 reversed the functional influence of TRIB3 on AML cells.

Significance: The aim of this study is to provide evidence of the degradation of PPARα by TRIB3 via ubiquitin-dependent proteasomal degradation. This process meditates the progression of AML and prolongs the survival of leukemic cells. As a result, these data indicate that TRIB3 is a novel and promising therapeutic target for AML treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2020.118021DOI Listing
September 2020

HLY78 protects blood-brain barrier integrity through Wnt/β-catenin signaling pathway following subarachnoid hemorrhage in rats.

Brain Res Bull 2020 09 18;162:107-114. Epub 2020 Jun 18.

Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China. Electronic address:

Wnt/β-catenin signaling plays an essential role in blood-brain barrier (BBB) formation and maintenance under pathophysiological conditions. HLY78, a lycorine derivative, has been identified as a novel activator of Wnt/β-catenin signaling in vitro. However, the effects of HLY78 on the BBB function in subarachnoid hemorrhage (SAH) are not yet validated. The present study was designed to investigate the impacts of HLY78 on the BBB in an endovascular perforation induced SAH model of Sprague-Dawley rats. Western blot, immunofluorescence staining, neurological function, brain water content, and Evans blue assay were performed after SAH induction. The results revealed that the expression of phosphorylated low-density lipoprotein receptor-related protein 6 (p-LRP6) was significantly increased after SAH and further augmented by HLY78. Administration of HLY78 significantly improved neurobehavioral functions and attenuated BBB leakage following SAH. Moreover, HLY78 markedly increased the β-catenin expression followed with the up-regulation of Occludin, ZO-1, and Claudin-5 after SAH, which was reversed by LRP6 siRNA. In conclusion, HLY78 could preserve BBB integrity, possibly through the Wnt/β-catenin signaling pathway. HLY78 might be a potential treatment option to protect BBB integrity following SAH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainresbull.2020.06.003DOI Listing
September 2020
-->