Publications by authors named "Jing Chen"

5,258 Publications

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Potential Synergy Mechanism of Processing Methods for the Basic Remedies of Qixue Shuangbu Prescription Based on Integrated Metabolomics Strategy and Network Pharmacology Study.

J Chromatogr Sci 2021 May 10. Epub 2021 May 10.

Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, PR China.

Qixue Shuangbu Prescription (QSP) is a famous traditional Chinese medicine (TCM) formula widely used for the treatment of chronic heart failure (CHF). Previous clinical studies have found that the efficacy of processed QSP has been significantly enhanced in the treatment of CHF. However, the synergistic mechanisms of processed QSP to enhance the treatment of CHF are still unclear. Generally, the changes in clinical effects mainly result from the variations of inside chemical basis caused by the TCM processing procedure. In this study, we developed a network pharmacology-integrated metabolomics strategy to clarify the difference of the effective compounds between crude and processed QSP, and further explain the mechanism of processed QSP to produce a synergistic effects. As a result, 69 different compounds were successfully screened, identified, quantified and verified as the most potential marker compounds. These different chemical components may play an anti-CHF and enhance the therapeutic effect through 52 action pathways such as estrogen signaling pathway, ubiquitin mediated proteolysis, protein processing in endoplasmic reticulum, etc. This study revealed that the proposed network pharmacology-integrated metabolomics strategy was a powerful tool for explaining the mechanism of synergistic action in the processing of QSP, further controlling the quality and understanding the processing mechanism of TCM formulae.
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http://dx.doi.org/10.1093/chromsci/bmab053DOI Listing
May 2021

Low CFB expression is independently associated with poor overall and disease-free survival in patients with lung adenocarcinoma.

Oncol Lett 2021 Jun 19;21(6):478. Epub 2021 Apr 19.

Yunnan Key Laboratory of Laboratory Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.

Complement factor B (CFB) serves a pivotal role in the alternative signaling pathway of the complement system and exerts a key role in the labelling of target particles, resulting from effective clearance of the target. The present study aimed to investigate the association between low expression levels of CFB and the clinical features and survival status of patients with lung adenocarcinoma (LUAD). Patient data were based on RNA-sequencing and clinical data from The Cancer Genome Atlas database. All patients were divided into two groups based on the median expression of CFB. Kaplan-Meier curve and univariate Cox regression analyses were used to investigate the association between CFB and survival status. Gene set enrichment analysis was used to examine the effects of CFB expression on signaling pathway impairment. Furthermore, reverse transcription-quantitative PCR (RT-qPCR) and western blotting were used to verify the relative expression levels of CFB in LUAD tissues. The data revealed that residual tumor classification, Karnofsky performance score and cancer stage were associated with overall survival, and that Karnofsky performance score and stage were associated with disease-free survival. The results demonstrated that high expression levels of CFB were associated with increased patient overall and disease-free survival according to both continuous and categorical models. The results of multivariate analysis identified that high expression levels of CFB were associated with increased overall and disease-free survival according to both the continuous model [hazard ratio (HR), 0.48; 95% confidence interval (95% CI), 0.25-0.93; P=0.029 for overall survival; HR, 0.29; 95% CI, 0.15-0.59; P=0.001 for disease-free survival] and the categorical model (HR, 0.46; 95% CI, 0.22-0.93; P=0.031 for overall survival; HR, 0.25; 95% CI, 0.12-0.55; P=0.001 for disease-free survival) after adjusting for corresponding covariates (residual tumour classification, Karnofsky performance score and stage). Furthermore, the results of both RT-qPCR and western blotting indicated that the relative mRNA and protein expression levels of CFB in lung tumor tissues were downregulated compared with those in adjacent non-tumor tissues. Collectively, the present results suggested that CFB expression was an independent predictor of overall and disease-free survival in patients with LUAD.
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http://dx.doi.org/10.3892/ol.2021.12739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100962PMC
June 2021

Analysis of natural variation of the rice blast resistance gene Pike and identification of a novel allele Pikg.

Mol Genet Genomics 2021 May 9. Epub 2021 May 9.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

Plant major resistance (R) genes are effective in detecting pathogen signal molecules and triggering robust defense responses. Investigating the natural variation in R genes will allow identification of the critical amino acid residues determining recognition specificity in R protein and the discovery of novel R alleles. The rice blast resistance gene Pike, comprising of two adjacent CC-NBS-LRR genes, namely, Pike-1 and Pike-2, confers broad-spectrum resistance to Magnaporthe oryzae. Here, we demonstrated that Pike-1 determined Pike-specific resistance through direct interaction with the pathogen signal molecule AvrPik. Analysis of natural variation in 79 Pike-1 variants in the Asian cultivated rice Oryza sativa and its wild relatives revealed that the CC and NBS regions, particularly the CC region of the Pike-1 protein were the most diversified. We also found that balancing selection had occurred in O. sativa and O. rufipogon to maintain the genetic diversity of the Pike-1 alleles. By analysis of amino acid sequences, we identified 40 Pike-1 variants in these rice germplasms. These variants were divided into three major groups that corresponded to their respective clades. A new Pike allele, designated Pikg, that differed from Pike by a single amino acid substitution (D229E) in the Pike-1 CC region of the Pike protein was identified from wild rice relatives. Pathogen assays of Pikg transgenic plants revealed a unique reaction pattern that was different from that of the previously identified Pike alleles, namely, Pik, Pikh, Pikm, Pikp, Piks and Pi1. These findings suggest that minor amino acid residues in Pike-1/Pikg-1 determine pathogen recognition specificity and plant resistance. As a new blast R gene derived from rice wild relatives, Pikg has potential applications in rice breeding.
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http://dx.doi.org/10.1007/s00438-021-01795-wDOI Listing
May 2021

Various effects of bariatric surgery on mortality and incidences of obesity-related co-morbidities at different follow-up times at a population level.

Surg Obes Relat Dis 2021 Apr 9. Epub 2021 Apr 9.

Healthcare-Associated Infection Control Center, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, China.

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http://dx.doi.org/10.1016/j.soard.2021.04.006DOI Listing
April 2021

Three-Dimensional-Printable Thermo/Photo-Cross-Linked Methacrylated Chitosan-Gelatin Hydrogel Composites for Tissue Engineering.

ACS Appl Mater Interfaces 2021 May 7. Epub 2021 May 7.

Physik-Department, Lehrstuhl für Funktionelle Materialien, Technische Universität München, James-Franck-Str. 1, 85748 Garching, Germany.

Biomimetic constructs imitating the functions, structures, and compositions of normal tissues are of great importance for tissue repair and regeneration. Three-dimensional (3D) printing is an innovative method to construct intricate biomimetic 3D tissue engineering scaffolds with spatiotemporal deposition of materials to control the intrinsic architectural organization and functional performance of the scaffold. However, due to the lack of bioinks with suitable printability, high structural integrity, and biological compatibility, producing constructs that mimic the anisotropic 3D extracellular environments remains a challenge. Here, we present a printable hydrogel ink based on methylacrylate-modified chitosan (ChMA) and gelatin (GelMA) embedding nanohydroxyapatite (nano-Hap). This polymer composite is first physically cross-linked by thermal gelation for postprinting structural stability, followed by covalent photo-cross-linking of ChMA and GelMA to form a long-term stable structure. The rheological behavior of the hydrogels and the mechanical strengths of the printed constructs are tuned by adjusting the content of GelMA, which in turn enhances the shape retention after printing and enables the precise deposition of multilayered 3D scaffolds. Moreover, the formulated biomaterial inks exhibit biological characteristics that effectively support the spreading and proliferation of stem cells seeded on the scaffolds after 7 days of in vitro culture. Adding Hap has minor influences on the mechanical rigidity and cytocompatibility of the hydrogels compared with the group free of Hap. Together, the printable biomaterial inks with shear thinning and good structural integrity, along with biological cues, are promising for tissue engineering application.
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http://dx.doi.org/10.1021/acsami.1c01321DOI Listing
May 2021

Application of Proteomics and Metabonomics to Reveal the Molecular Basis of Atractylodis Macrocephalae Rhizome for Ameliorating Hypothyroidism Instead of Hyperthyroidism.

Front Pharmacol 2021 20;12:664319. Epub 2021 Apr 20.

College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.

As the treatments of diseases with Chinese herbs are holistic and characterized by multiple components, pathways, and targets, elucidating the efficacy of Chinese herbs in treating diseases, and their molecular basis, requires a comprehensive, network-based approach. In this study, we used a network pharmacology strategy, as well as proteomics and metabonomics, to reveal the molecular basis by which rhizome (AMR) ameliorates hypothyroidism. Eighteen main compounds from AMR and its fractions (volatile oil fraction, crude polysaccharides fraction, lactones fraction, oligosaccharide fraction, and atractyloside fraction) were identified by HPLC, and their targets were screened using the TCMSP database and Swiss Target Prediction. Disease targets were gathered from the TTD, CTD and TCMSP databases. Hub targets were screened by different plug-ins, such as Bisogene, Merge, and CytoNCA, in Cytoscape 3.7.1 software and analyzed for pathways by the DAVID database. Hypothyroidism and hyperthyroidism pharmacological models were established through systems pharmacology based on proteomic and metabolomic techniques. Finally, AMR and its fractions were able to ameliorate the hypothyroidism model to different degrees, whereas no significant improvements were noted in the hyperthyroidism model. The lactones fraction and the crude polysaccharides fraction were considered the most important components of AMR for ameliorating hypothyroidism. These amelioration effects were achieved through promoting substance and energy metabolism. In sum, the integrative approach used in this study demonstrates how network pharmacology, proteomics, and metabolomics can be used effectively to elucidate the efficacy, molecular basis, and mechanism of action of medicines used in TCM.
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http://dx.doi.org/10.3389/fphar.2021.664319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095350PMC
April 2021

Clinical characteristics of tumor lysis syndrome in childhood acute lymphoblastic leukemia.

Sci Rep 2021 May 6;11(1):9656. Epub 2021 May 6.

Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China.

Tumor lysis syndrome (TLS) is a common and fatal complication of childhood hematologic malignancies, especially acute lymphoblastic leukemia (ALL). The clinical features, therapeutic regimens, and outcomes of TLS have not been comprehensively analyzed in Chinese children with ALL. A total of 5537 children with ALL were recruited from the Chinese Children's Cancer Group, including 79 diagnosed with TLS. The clinical characteristics, treatment regimens, and survival of TLS patients were analyzed. Age distribution of children with TLS was remarkably different from those without TLS. White blood cells (WBC) count ≥ 50 × 10/L was associated with a higher risk of TLS [odds ratio (OR) = 2.6, 95% CI = 1.6-4.5]. The incidence of T-ALL in TLS children was significantly higher than that in non-TLS controls (OR = 4.7, 95% CI = 2.6-8.8). Hyperphosphatemia and hypocalcemia were more common in TLS children with hyperleukocytosis (OR = 2.6, 95% CI = 1.0-6.9 and OR = 5.4, 95% CI = 2.0-14.2, respectively). Significant differences in levels of potassium (P = 0.004), calcium (P < 0.001), phosphorus (P < 0.001) and uric acid (P < 0.001) were observed between groups of TLS patients with and without increased creatinine. Laboratory analysis showed that older age was associated with a higher level of creatinine. Calcium level was notably lower in males. WBC count, lactate dehydrogenase, and creatinine levels were significantly higher in T-ALL subgroup, whereas procalcitonin level was higher in B-ALL children. Older age, infant, a higher level of WBC and T-ALL were risk factors TLS occurrence. Hyperleukocytosis has an impact on the severity of TLS, while renal injury may be an important feature in the process of TLS.
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http://dx.doi.org/10.1038/s41598-021-88912-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102476PMC
May 2021

Two new -acetyl-ᴅ-glucosamine derivatives from the medical algae-derived endophytic fungus .

Nat Prod Res 2021 May 7:1-4. Epub 2021 May 7.

Department of Pharmacy, Qingdao Hospital of Traditional Chinese Medicine, Qingdao, China.

Two new -acetyl-ᴅ-glucosamine derivatives, penichryfurans A () and B (), were obtained from the fermentation of an endophytic fungus which inhabited the marine medical red alga . Their structures were established by detailed spectroscopic analysis of 1D and 2D NMR in combination with HRESIMS data. The absolute configurations were determined by the (Mo(OAc))-induced CD and comparison of the calculated and experimental electronic curcular dichroism (ECD) spectra. Both compounds were evaluated for their cytotoxic activities against A549, HeLa, and HepG2 cell lines, among which compound exhibited strong cytotoxicity towards the HepG2 cell line with an IC value of 9.0 μM.
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http://dx.doi.org/10.1080/14786419.2021.1889543DOI Listing
May 2021

The Cell-impermeable Ru(II) Polypyridyl Complex as a Potent Intracellular Photosensitizer under Visible Light Irradiation via Ion-Pairing with Suitable Lipophilic Counter-Anions.

Free Radic Biol Med 2021 May 3. Epub 2021 May 3.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, And University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, 100085, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China; Joint Institute for Environmental Science, Research Center for Eco-Environmental Sciences and Hong Kong Baptist University, Hong Kong PR China. Electronic address:

Developing the cell-impermeable Ru(II) polypyridyl cationic complexes as effective photosensitizers (PS) which have high cellular uptake and photo-toxicity, but low dark toxicity, is quite challenging. Here we found that the highly reactive singlet oxygen (O) can be generated by the irradiation of a typical Ru(II) polypyridyl complex Ru(II)tris(tetramethylphenanthroline) ([Ru(TMP)]) under visible light irradiation by ESR with TEMPO (2,2,6,6-tetramethyl-4-piperidone-N-oxyl) as O probe. Effective cellular and nuclear delivery of cationic [Ru(TMP)] was achieved through our recently developed ion-pairing method, and 2,3,4,5-tetrachlorophenol (2,3,4,5-TeCP) was found to be the most effective among all chlorophenols tested. The accelerated cellular, especially nuclear uptake of [Ru(TMP)] results in the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and DNA strand breaks, caspase 3/7 activation and cell apoptosis in HeLa cells upon light irradiation. More importantly, compared with other traditional photosensitizers, [Ru(TMP)] showed significant photo-toxicity but low dark toxicity. Similar effects were observed when 2,3,4,5-TeCP was substituted by the currently clinically used anti-inflammatory drug flufenamic acid. This represents the first report that the cell-impermeable Ru(II) polypyridyl complex ion-paired with suitable lipophilic counter-anions functions as potent intracellular photosensitizer under visible light irradiation mainly via a O-mediated mechanism. These findings should provide new perspectives for future investigations on other metal complexes with similar characteristics as promising photosensitizers for potential photodynamic therapy.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.04.035DOI Listing
May 2021

Atrial cardiopathy in embolic stroke of undetermined source.

Brain Behav 2021 May 4:e02160. Epub 2021 May 4.

Department of Neurology, Beijing Shijiitan Hospital, Capital Medical University, Beijing, China.

Introduction: Atrial cardiopathy is one of the most common potential sources of thromboembolism for embolic stroke of undetermined source (ESUS). The study aims to investigate the incidence of atrial cardiopathy (defined by severe left atrial enlargement (sLAE) or elevated serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) > 250 pg/ml) in patients with ESUS and compare with other stroke subtypes.

Methods: We retrospectively collected data of 936 consecutive patients with diffusion-weighted imaging-confirmed acute ischemic stroke. The incidence of atrial cardiopathy was examined in ESUS, large artery atherosclerosis (LAA), and small vessel disease (SVD) strokes. Clinical characteristics were compared between ESUS patients with atrial cardiopathy (AC-ESUS) and patients with atrial fibrillation-induced cardioembolism (AF-CE) stroke.

Results: 245 patients were diagnosed with ESUS, while others were diagnosed with LAA (n = 312), SVD (n = 258), and AF-CE (n = 121) strokes. The incidence of sLAE in ESUS patients was higher than in LAA or SVD group (5.3% vs. 1.6% and 1.2%, respectively, p = .005) and higher than in combined LAA/SVD group (5.3% vs. 1.4%, p = .001). The incidence of elevated serum NT-proBNP in ESUS patients was not statistically different from that in LAA or SVD group. Compared with patients with AF-CE stroke, AC-ESUS patients had milder manifestations, had less hemorrhagic transformation, had better short-term outcome, and had fewer in-hospital complications.

Conclusions: The incidence of sLAE was higher in ESUS patients than in patients with noncardioembolic strokes. AC-ESUS was milder when compared to AF-CE stroke.
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http://dx.doi.org/10.1002/brb3.2160DOI Listing
May 2021

Letter to the Editor Regarding "Microvascular Decompression versus Stereotactic Radiosurgery for Trigeminal Neuralgia: A Single-Institution Experience".

World Neurosurg 2021 May;149:279

Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, China. Electronic address:

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http://dx.doi.org/10.1016/j.wneu.2021.01.074DOI Listing
May 2021

Reduced circulating exosomal miR-382 predicts unfavorable outcome in non-small cell lung cancer.

Int J Clin Exp Pathol 2021 15;14(4):469-474. Epub 2021 Apr 15.

Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China Chengdu, China.

Circulating microRNAs (miRNAs) have been demonstrated as robust and promising biomarkers for non-small cell lung cancer (NSCLC). Our aim was to determine the significance of serum exosomal miR-382 in NSCLC. Circulating exosomes were collected from 126 patients with NSCLC and 60 normal controls before treatment and one month after surgery. The circulating exosomal miR-382 expression was measured with quantitative RT-PCR (qRT-PCR) in all the participants. Our findings demonstrated that circulating exosomal miR-382 was very reduced in NSCLC. In addition, it showed high accuracy for discriminating NSCLC patients from healthy subjects. Interestingly, serum exosomal miR-382 improved the diagnostic accuracy of carcinoembryonic antigen (CEA). Moreover, its level increased significantly one month following surgical resection. Reduced circulating exosomal miR-382 was positively associated with poor clinical variables. NSCLC cases with lower serum exosomal miR-382 suffered worse overall survival (OS) and serum exosomal miR-382 was independently associated with OS. Taken together, circulating exosomal miR-382 is a robust biomarker for evaluating the progression of NSCLC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085833PMC
April 2021

A green deep eutectic solvent modified magnetic titanium dioxide nanoparticles for the solid-phase extraction of chymotrypsin.

Talanta 2021 Aug 30;230:122341. Epub 2021 Mar 30.

Department of Microbiology, College of Basic Medicine, Central South University, Changsha, 410083, PR China.

Magnetic titanium dioxide nanoparticles modified with green deep eutectic solvent (DES) composed of choline chloride (ChCl) and xylitol (Xyl) (FeO@TiO@[ChCl][Xyl]) were synthesized and applied to the solid-phase extraction(MSPE) of chymotrypsin (Chy). The physicochemical properties and morphology of FeO@TiO@[ChCl][Xyl] was characterized by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), Zeta potential, X-ray diffraction (XRD), vibrating sample magnetometer (VSM) and transmission electron microscope (TEM). The experiment parameters such as initial concentration of Chy, extraction time, pH value, ionic strength, extraction temperature and sample matrix were effectively optimized. Under the optimal experimental conditions, the extraction capacity of FeO@TiO@[ChCl][Xyl] obtained a significantly improvement after the modification of FeO@TiO nanoparticles by [ChCl][Xyl], and reached up to 347.8 mg g. In the elution experiment, 10% sodium dodecyl sulfate-acetic acid (SDS-HAc) was used as eluent, achieving an elution rate of 85.9% for the Chy on FeO@TiO@[ChCl][Xyl]. And the FeO@TiO@[ChCl][Xyl] still maintained a good extraction capacity for Chy after six times of reuse. The application result in the extraction of Chy from porcine pancreas crude extract showed a good practical application ability for Chy extraction. All the results indicated that the synthesized FeO@TiO@[ChCl][Xyl] has good application potential in the extraction of biomolecular molecules such as protein.
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http://dx.doi.org/10.1016/j.talanta.2021.122341DOI Listing
August 2021

MicroRNA-760 resists ambient PM-induced apoptosis in human bronchial epithelial cells through elevating heme-oxygenase 1 expression.

Environ Pollut 2021 Apr 23;284:117213. Epub 2021 Apr 23.

School of Public Health, Qingdao University, Qingdao, China. Electronic address:

PM (particles matter smaller aerodynamic diameter of 2.5 μm) exposure, a major environmental risk factor for the global burden of diseases, is associated with high risks of respiratory diseases. Heme-oxygenase 1 (HMOX1) is one of the major molecular antioxidant defenses to mediate cytoprotective effects against diverse stressors, including PM-induced toxicity; however, the regulatory mechanism of HMOX1 expression still needs to be elucidated. In this study, using PM as a typical stressor, we explored whether microRNAs (miRNAs) might modulate HMOX1 expression in lung cells. Systematic bioinformatics analysis showed that seven miRNAs have the potentials to target HMOX1 gene. Among these, hsa-miR-760 was identified as the most responsive miRNA to PM exposure. More importantly, we revealed a "non-conventional" miRNA function in hsa-miR-760 upregulating HMOX1 expression, by targeting the coding region and interacting with YBX1 protein. In addition, we observed that exogenous hsa-miR-760 effectively elevated HMOX1 expression, reduced the reactive oxygen agents (ROS) levels, and rescued the lung cells from PM-induced apoptosis. Our results revealed that hsa-miR-760 might play an important role in protecting lung cells against PM-induced toxicity, by elevating HMOX1 expression, and offered new clues to elucidate the diverse functions of miRNAs.
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http://dx.doi.org/10.1016/j.envpol.2021.117213DOI Listing
April 2021

Basic leucine zipper (bZIP) transcription factor genes and their responses to drought stress in ginseng, Panax ginseng C.A. Meyer.

BMC Genomics 2021 May 1;22(1):316. Epub 2021 May 1.

College of Life Science, Jilin Agricultural University, 2888 Xincheng Street, 130118, Changchun, Jilin, China.

Background: Ginseng is an important medicinal herb in Asia and Northern America. The basic leucine zipper (bZIP) transcription factor genes play important roles in many biological processes and plant responses to abiotic and biotic stresses, such as drought stress. Nevertheless, the genes remain unknown in ginseng.

Results: Here, we report 91 bZIP genes identified from ginseng, designated PgbZIP genes. These PgbZIP genes were alternatively spliced into 273 transcripts. Phylogenetic analysis grouped the PgbZIP genes into ten groups, including A, B, C, D, E, F, G, H, I and S. Gene Ontology (GO) categorized the PgbZIP genes into five functional subcategories, suggesting that they have diversified in functionality, even though their putative proteins share a number of conserved motifs. These 273 PgbZIP transcripts expressed differentially across 14 tissues, the roots of different ages and the roots of different genotypes. However, the transcripts of the genes expressed coordinately and were more likely to form a co-expression network. Furthermore, we studied the responses of the PgbZIP genes to drought stress in ginseng using a random selection of five PgbZIP genes, including PgbZIP25, PgbZIP38, PgbZIP39, PgbZIP53 and PgbZIP54. The results showed that all five PgbZIP genes responded to drought stress in ginseng, indicating that the PgbZIP genes play important roles in ginseng responses to drought stress.

Conclusions: These results provide knowledge and gene resources for deeper functional analysis of the PgbZIP genes and molecular tools for enhanced drought tolerance breeding in ginseng.
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http://dx.doi.org/10.1186/s12864-021-07624-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088647PMC
May 2021

Angiotensin (1-7) alleviates post-resuscitation myocardial dysfunction by suppressing oxidative stress through the PI3K-Akt-eNOS signaling pathway.

J Cardiovasc Pharmacol 2021 Apr 20. Epub 2021 Apr 20.

Department of Anesthesiology, The Second People's Hospital of Chengdu Xindu District, Chengdu 610501, China. Department of traditional Chinses medicine, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China. Department of Anesthesiology, The Chengdu Fifth People's Hospital, Chengdu 610501, China. Department of General Practice, Guizhou Provincial People's Hospital, Guiyang 550002, China. Department of Emergency, West China Hospital of Sichuan University, Chengdu 610041, China. Department of Anesthesiology, Chengdu Integrated TCM & Western Medicine Hospital, Chengdu 610501, China. Department of Emergency, Guizhou Provincial People's Hospital, Guiyang 550002, China.

Abstract: There is increasing evidence that angiotensin (1-7) [Ang (1-7)] is an endogenous biologically active component of the renin-angiotensin system. However, the role of the Ang (1-7)-MasR axis in post-resuscitation myocardial dysfunction (PRMD) and its associated mechanism are still unclear. In the present study, we investigated the effect of the Ang (1-7)-MasR axis on myocardial injury after cardiac arrest-cardiopulmonary resuscitation-restoration of spontaneous circulation (CA-CPR-ROSC). We established a model of oxygen/glucose deprivation-reperfusion in myocardial cells in vitro and a rat model of CA-CPR-ROSC in vivo. The cell apoptosis rate and the expression of the superoxide anion 3-nitrotyrosine were decreased in the Ang (1-7) group in vitro and in vivo. The mean arterial pressure was decreased, while +LVdp/dtmax and -LVdp/dtmax were increased in rats in the Ang (1-7) group. The mRNA and protein levels of Ang II type 1 receptor, MasR, phosphoinositide 3-kinase (PI3K), protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) were increased in the Ang (1-7) group in vivo. These results indicate that the Ang (1-7)-MasR axis can alleviate PRMD by reducing myocardial tissue damage and oxidative stress through activation of the PI3K-Akt-eNOS signaling pathway and provide a new direction for the clinical treatment of PRMD.
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http://dx.doi.org/10.1097/FJC.0000000000001037DOI Listing
April 2021

Vibrational Spectral Analysis of Natisite (NaTiSiO) and its Structure Evolution in Water and Sulfuric Acid Solutions.

Materials (Basel) 2021 Apr 27;14(9). Epub 2021 Apr 27.

National Engineering Laboratory for Hydrometallurgical Cleaner Production Technology, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.

Natisite (NaTiSiO) is a layered sodium titanosilicate containing TiO square pyramids. The structure evolution of natisite in water and acid solutions is the basis for its potential applications. With NaSiO as the silicon source, natisite with the shape of the square sheet was selectively prepared from the hydrothermal method with 14.3 mol/L NaOH solution at 240 °C. Natisite has 20 Raman active modes and 22 infrared active modes from the first-principles calculations within density functional theory, and the calculated Raman and infrared spectra agree well with the experimental ones. The characteristic Raman peak at 844 cm is caused by the symmetric stretching of the apical Ti-O bond in the TiO unit, assigning to and modes. Natisite remains relatively stable in water with a sodium leaching percentage of lower than 6%. When washing with sulfuric acid solutions, the interlayer spacing of natisite is reduced due to the extensive removal of sodium ions, and an intermediate composed of SiO and newly formed TiO units may be formed. Moreover, after washing with water and acid solutions, 95.5%, 63.4%, and 35.2% of Na, Si, and Ti in natisite can be leached in total, respectively, resulting in the structural disintegration of natisite.
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http://dx.doi.org/10.3390/ma14092259DOI Listing
April 2021

Does COVID-19 Affect the Behavior of Buying Fresh Food? Evidence from Wuhan, China.

Int J Environ Res Public Health 2021 04 22;18(9). Epub 2021 Apr 22.

School of Transportation, Southeast University, No. 2, Southeast University Road, Jiangning District, Nanjing 211189, China.

COVID-19 first appeared in Wuhan city of Hubei Province in China in December 2019. It has a substantial impact on human life all around the world, especially for citizens. The threat of COVID-19 has resulted in people shopping online to get fresh food and reduce outdoor trips. Collecting data from adult internet users in Wuhan, China in 2020, this study aims to explore the influence of COVID-19 on fresh food shopping behavior. In addition, a comparison and ordered logit model are constructed to demonstrate the changes and effects of COVID-19. The results suggest that more citizens in Wuhan city will buy fresh food online and the cost and frequency are also increased. The experience of online shopping for fresh food during the lock-down days has promoted more online shopping. The factors, such as frequency of online shopping before the COVID-19 outbreak, frequency of online shopping during the COVID-19 pandemic, and age, have a negative effect on the proportion of online shopping after the lock-down days, while the proportion of online shopping before the COVID-19 outbreak, the proportion of online shopping during the COVID-19 pandemic, and travel time of in-store shopping before the COVID-19 outbreak have a positive effect. The results provide insights for managers, city planners, and policymakers.
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http://dx.doi.org/10.3390/ijerph18094469DOI Listing
April 2021

Local NF-κB activation promotes parathyroid hormone synthesis and secretion in uremic patients.

Endocrinology 2021 Apr 29. Epub 2021 Apr 29.

Division of Nephrology, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Secondary hyperparathyroidism (SHPT) in uremic patients characterizes by parathyroid gland (PTG) hyperplasia and parathyroid hormone (PTH) elevation. Previously, we demonstrated that NF-κB activation contributed to parathyroid cell proliferation in chronic kidney disease (CKD) rats. Although vitamin D inhibits inflammation and ameliorates SHPT, the contribution of vitamin D deficiency to SHPT via local NF-κB activation remains to be clarified. PTGs collected from 10 uremic patients with advanced SHPT were used to test the expressions of vitamin D receptor (VDR), NF-κB, and proliferating cell nuclear antigen (PCNA). Freshly excised PTG tissues were incubated for 24 h in vitro with VDR activator (VDRA) calcitriol or NF-κB inhibitor Pyrrolidine Thiocarbamate (PDTC). Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to investigate the regulation of PTH transcription by NF-κB. We found higher levels of activated NF-κB and lower expression of VDR in nodular hyperplastic PTGs than in diffuse hyperplasia. In cultured PTG tissues, treatment with VDRA or PDTC inhibited NF-κB activation and PCNA expression, and downregulated preproPTH mRNA and intact PTH levels. ChIP assays demonstrated the presence of NF-κB binding sites in PTH promoter. Furthermore, in luciferase reporter assays, addition of exogenous p65 significantly increased PTH-luciferase activity by 2.4-fold (p<0.01), while mutation of NF-κB binding site at position -908 of the PTH promoter suppressed p65-induced PTH reporter activity (p<0.01). In summary, local NF-κB activation contributes to SHPT and mediates the transcriptional activation of PTH directly in uremic patients. Vitamin D deficiency may be involved in SHPT via the activation of NF-κB pathway.
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http://dx.doi.org/10.1210/endocr/bqab084DOI Listing
April 2021

Effects of Wireless Remote Microphone on Speech Recognition in Noise for Hearing Aid Users in China.

Front Neurosci 2021 12;15:643205. Epub 2021 Apr 12.

Beijing Institute of Otolaryngology, Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

This study was aimed at evaluating improvements in speech-in-noise recognition ability as measured by signal-to-noise ratio (SNR) with the use of wireless remote microphone technology. These microphones transmit digital signals via radio frequency directly to hearing aids and may be a valuable assistive listening device for the hearing-impaired population of Mandarin speakers in China. Twenty-three adults (aged 19-80 years old) and fourteen children (aged 8-17 years old) with bilateral sensorineural hearing loss were recruited. The Mandarin Hearing in Noise Test was used to test speech recognition ability in adult subjects, and the Mandarin Hearing in Noise Test for Children was used for children. The subjects' perceived SNR was measured using sentence recognition ability at three different listening distances of 1.5, 3, and 6 m. At each distance, SNR was obtained under three device settings: hearing aid microphone alone, wireless remote microphone alone, and hearing aid microphone and wireless remote microphone simultaneously. At each test distance, for both adult and pediatric groups, speech-in-noise recognition thresholds were significantly lower with the use of the wireless remote microphone in comparison with the hearing aid microphones alone ( < 0.05), indicating better SNR performance with the wireless remote microphone. Moreover, when the wireless remote microphone was used, test distance had no effect on speech-in-noise recognition for either adults or children. Wireless remote microphone technology can significantly improve speech recognition performance in challenging listening environments for Mandarin speaking hearing aid users in China.
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http://dx.doi.org/10.3389/fnins.2021.643205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072043PMC
April 2021

Population Pharmacokinetics and Safety of Oral Tetra-Arsenic Tetra-Sulfide Formula in Pediatric Acute Promyelocytic Leukemia.

Drug Des Devel Ther 2021 21;15:1633-1640. Epub 2021 Apr 21.

Department of Pediatric, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People's Republic of China.

Background: An oral tetra-arsenic tetra-sulfide (ASS) formula has been recommended as an outpatient post-remission treatment for Chinese adults with acute promyelocytic leukemia (APL) but limited data are available for children. In this exploratory study, we aimed to evaluate the pharmacokinetics and safety of the ASS formula in children.

Methods: Eleven newly diagnosed and one relapsed pediatric patient (4-14 years of age) treated with the ASS formula were included. Blood samples were collected from 12 children, and drug concentrations were quantified by ICP-MS. Population pharmacokinetic analysis and Monte-Carlo simulation were performed using NONMEM software. Toxic effects were graded according to the NCI-CTCAE, Version 3.

Results: A total of 107 arsenic concentrations (0.1-75.0 µg L) were used for population pharmacokinetic analysis. The median (range) of estimated weight-normalized CL and volume distribution at steady-state were 45.26 (35.63-82.18) L h kg and 230.37 (85.96-495.68) L kg, respectively. No patients discontinued ASS treatment owing to adverse events, and there were no drug-related adverse events over grades 3-4. All newly diagnosed APL patients were in MCR with a median follow-up of 28 months (range, 23 to 37 months). Both the estimated 3-year EFS and OS rates were 100%.

Conclusion: The pharmacokinetics and safety oral ASS formula was evaluated for the first time in pediatric APL. The pharmacokinetic assessment demonstrated that the dosing regimen of 60 mg/kg/d TID resulted in a higher steady-state through concentration in children than that which was achieved in adults. The results of this study indicate that the ASS formula is safe in newly diagnosed pediatric APL patients.
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http://dx.doi.org/10.2147/DDDT.S305244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071704PMC
April 2021

Cationic Glycopolymers with Aggregation-Induced Emission for the Killing, Imaging, and Detection of Bacteria.

Biomacromolecules 2021 May 28;22(5):2224-2232. Epub 2021 Apr 28.

Key Laboratory of New Membrane Materials, Ministry of Industry and Information Technology, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, P. R. China.

Cationic glycopolymers with structures similar to those of typical poly(ionic liquid)s (PILs) were synthesized the quaternization reaction of poly(4-vinyl pyridine) with halogen-functionalized d-mannose and tetraphenylethylene units. Such postpolymerization modification provided PILs with aggregation-induced emission effect as well as specific carbohydrate-protein recognition with lectins such as concanavalin A. The interactions between cationic glycopolymers and different microorganisms, including Gram-positive and Gram-negative , were used for the killing, imaging, and detection of bacteria. Besides, these sugar-containing PILs showed a relatively low hemolysis rate due to the presence of saccharide units, which may have potential application in the field of biomaterials.
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http://dx.doi.org/10.1021/acs.biomac.1c00298DOI Listing
May 2021

Cyanidin-3-O-glucoside and cisplatin inhibit proliferation and downregulate the PI3K/AKT/mTOR pathway in cervical cancer cells.

J Food Sci 2021 Apr 28. Epub 2021 Apr 28.

College of Food Science, Shenyang Agricultural University, Shenyang, China.

Natural compounds have been increasingly investigated as substances enhancing the effect of drugs and reducing drug-related adverse reactions. The objective of this study was to determine how a combination of cisplatin (DDP) with cyanidin-3-O-glucoside (C3G) affected malignancy features of cervical cancer cells. The results demonstrated that the proliferation of HeLa cells treated with 5 µg/ml DDP, 400 µg/ml C3G, or a combination of both (5 µg/ml DDP and 400 µg/ml C3G) was inhibited by 17.43%, 34.98%, and 63.38%, respectively. The IC values for DDP and the DDP/C3G combination treatments in HeLa cells were 18.53 and 6.435 µg/ml, respectively. Flow cytometry analysis indicated that treatment with DDP, C3G, or the combination induced G1 cell cycle arrest and apoptosis in HeLa cells. Furthermore, after treatment, cyclin D1 and Bcl-2 levels decreased; Bax, cleaved caspase-3, p53, and TIMP-1 were activated; and the PI3K/AKT/mTOR signaling pathway was modulated. These anticancer effects were enhanced in cells treated with the combination of DDP and C3G compared to those treated with DDP or C3G alone. Our study indicates that C3G increases the antitumor activity of DDP, suggesting a potential strategy to reduce adverse effects associated with chemotherapy in cervical cancer. PRACTICAL APPLICATION: Natural biologically active food ingredients are suggested to have a potential to enhance the effect of chemotherapy in cancer. We believe that our study makes a significant contribution to the literature because it revealed, for the first time, that C3G could increase the antitumor activity of DDP, suggesting a potential strategy to reduce adverse effects associated with chemotherapy in cervical cancer.
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http://dx.doi.org/10.1111/1750-3841.15740DOI Listing
April 2021

The typically developing pediatric foot - The data of the 1744 children in China.

Foot Ankle Surg 2021 Apr 20. Epub 2021 Apr 20.

Department of Orthopedic Surgery, Chongqing Medical University First Affiliated Hospital, China. Electronic address:

Background: The medial longitudinal arch (MLA) improves with age in childhood. However, it still causes parents to worry that children have flat feet. Due to the lack of a standard to quantitatively assess the arch development in kids at certain age, the pediatricians judge the flat feet by experience, causing many cases to be overtreated. The aim of this study was to plot the distribution of MLA parameters in children.

Methods: Children without lower limb deformity and lower limb pain were recruited from 12 primary schools and kindergartens in Chongqing province-level city. Foot length (FL) and navicular height (NH) was measured manually, arch index (AI) and arch volume (AV) were measured with the Foot Plantar Scanner. Each parameter was measured in both weight-bearing and non-weight-bearing positions. Significant differences were also compared between the measurements of consecutive years.

Results: This study was the first to use a three-dimensional laser surface scanner to measure the MLA parameters of children aged 3-12 years in China. 1744 children (871 girls, 873 boys) participated in this study. FL, NH, AI and AV varied significantly with age in both the weight-bearing and non-weight-bearing positions. These parameters have significant differences between the weighted and non-weighted positions (p < 0.05).

Conclusions: The age distribution characteristics of these parameters indicated that the MLA improves with age. The establishment of a developmental scale for the children's MLA is necessary.
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http://dx.doi.org/10.1016/j.fas.2021.04.005DOI Listing
April 2021

ER stress modulates apoptosis in A431 cell subjected to EtNBSe-PDT via the PERK pathway.

Photodiagnosis Photodyn Ther 2021 Apr 24;34:102305. Epub 2021 Apr 24.

Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China. Electronic address:

Photodynamic therapy (PDT) is a promising modality against various cancers including squamous cell carcinoma (SCC) with which the induction of apoptosis is an effective mechanism. Here, we initially describe the preclinical activity of 5-ethylamino-9-diethylaminobenzo [a] phenoselenazinium(EtNBSe)-mediated PDT treatment in SCC. Results of our studies suggest that EtNBSe-PDT provokes a cellular state of endoplasmic reticulum (ER) stress triggering the PERK/ eIF2α signaling pathway and induces the appearance of apoptosis in A431 cells at the meantime. With ER stress inhibitor 4-PBA or eIF2α inhibitor ISRIB, suppressing the EtNBSe-PDT induced ER stress substantially promotes apoptosis of A431 cells. Furthermore, we demonstrate that ATF4, whose expression is ER-stress-inducible and elevated in response to the PERK/eIF2α signaling pathway activation, contributes to cytoprotection against EtNBSe-PDT induced apoptosis. In a mouse model bearing A431 cells, EtNBSe shows intense phototoxicity and when associated with decreased ER stress, EtNBSe-PDT ameliorates tumor growth. Taken together, our study reveals an antagonistic activity of ER stress against EtNBSe-PDT treatment via inhibiting apoptosis in A431 cells. With further development, these results provide a proof-of-concept that downregulation of ER stress response has a therapeutic potential to improve EtNBSe-PDT sensitivity in SCC patients via the promotion of induced apoptosis.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102305DOI Listing
April 2021

Farnesyl pyrophosphate is a new danger signal inducing acute cell death.

PLoS Biol 2021 Apr 26;19(4):e3001134. Epub 2021 Apr 26.

School of Life Sciences, Institute for Immunology, Ministry of Education Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Key Lab for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, China.

Cell death is a vital event in life. Infections and injuries cause lytic cell death, which gives rise to danger signals that can further induce cell death, inflammation, and tissue damage. The mevalonate (MVA) pathway is an essential, highly conserved and dynamic metabolic pathway. Here, we discover that farnesyl pyrophosphate (FPP), a metabolic intermediate of the MVA pathway, functions as a newly identified danger signal to trigger acute cell death leading to neuron loss in stroke. Harboring both a hydrophobic 15-carbon isoprenyl chain and a heavily charged pyrophosphate head, FPP leads to acute cell death independent of its downstream metabolic pathways. Mechanistically, extracellular calcium influx and the cation channel transient receptor potential melastatin 2 (TRPM2) exhibit essential roles in FPP-induced cell death. FPP activates TRPM2 opening for ion influx. Furthermore, in terms of a mouse model constructing by middle cerebral artery occlusion (MCAO), FPP accumulates in the brain, which indicates the function of the FPP and TRPM2 danger signal axis in ischemic injury. Overall, our data have revealed a novel function of the MVA pathway intermediate metabolite FPP as a danger signal via transient receptor potential cation channels.
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http://dx.doi.org/10.1371/journal.pbio.3001134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075202PMC
April 2021

Off-Label Use of Antineoplastic Drugs to Treat Malignancies: Evidence From China Based on a Nationwide Medical Insurance Data Analysis.

Front Pharmacol 2021 8;12:616453. Epub 2021 Apr 8.

Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.

Cancer is a leading cause of morbidity and mortality worldwide. Off-label (OL) use of antineoplastic drugs to treat malignancies is prevalent. In this study, we quantified and characterized OL use of antineoplastic drugs to treat malignancies in China. This was a retrospective study using nationwide data collected from 2008 to 2010. Use of antineoplastic drugs was considered OL if they were used for indications not reflected in the package insert published by the National Medical Products Administration at the time of prescription. Descriptive analysis and Spearman rank correlation were used to evaluate the frequency and pattern of OL drug use. In total, 51,382 patients with malignancies, 24 categories of antineoplastic drugs, and 77 types of malignancies treated with OL drugs were included in this study. Twenty commonly used antineoplastic drugs (ICD encoded as L01) were used OL in 10-61% of cases, and four commonly used endocrine therapy antineoplastic drugs (ICD encoded as L02) were used OL in 10-19% of cases. There was a significant negative correlation between the disease constituent ratio and the average OL use rate of antineoplastic drugs for various malignancies. In contrast, there was a significant positive correlation between the average OL use rate of antineoplastic drugs and the number of malignancies treated with OL drugs. This study provided information regarding OL use of antineoplastic drugs for treatment of malignancies, and showed that OL use was prevalent. In addition, uncommon malignancies were more likely to be treated with OL antineoplastic drugs. Furthermore, more commonly used antineoplastic drugs were more likely to be used OL.
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http://dx.doi.org/10.3389/fphar.2021.616453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060556PMC
April 2021

Sodium Sensitivity, Sodium Resistance, and Incidence of Hypertension: A Longitudinal Follow-Up Study of Dietary Sodium Intervention.

Hypertension 2021 Apr 26:HYPERTENSIONAHA12016758. Epub 2021 Apr 26.

Department of Epidemiology and Key Laboratory of Cardiovascular Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing, China (J.-F.H., X.L., J.-C.C., J.-X.L., J. Cao, D.-F.G.).

Cross-sectional studies have reported that high sodium sensitivity is more common among individuals with hypertension. Experimental studies have also reported various animal models with sodium-resistant hypertension. It is unknown, however, whether sodium sensitivity and resistance precede the development of hypertension. We conducted a feeding study, including a 7-day low-sodium diet (1180 mg/day) followed by a 7-day high-sodium diet (7081 mg/day), among 1718 Chinese adults with blood pressure (BP) <140/90 mm Hg. We longitudinally followed them over an average of 7.4 years. Three BP measurements and 24-hour urinary sodium excretion were obtained on each of 3 days during baseline observation, low-sodium and high-sodium interventions, and 2 follow-up studies. Three trajectories of BP responses to dietary sodium intake were identified using latent trajectory analysis. Mean (SD) changes in systolic BP were -13.7 (5.5), -4.9 (3.0), and 2.4 (3.0) mm Hg during the low-sodium intervention and 11.2 (5.3), 4.4 (4.1), and -0.2 (4.1) mm Hg during the high-sodium intervention (<0.001 for group differences) in high sodium-sensitive, moderate sodium-sensitive, and sodium-resistant groups, respectively. Compared with individuals with moderate sodium sensitivity, multiple-adjusted odds ratios (95% CIs) for incident hypertension were 1.43 (1.03-1.98) for those with high sodium sensitivity and 1.43 (1.03-1.99) for those with sodium resistance (=0.006 for nonlinear trend). Furthermore, a J-shaped association between systolic BP responses to sodium intake and incident hypertension was identified (<0.001). Similar results were observed for diastolic BP. Our study indicates that individuals with either high sodium sensitivity or sodium resistance are at an increased risk for developing hypertension.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16758DOI Listing
April 2021

A novel epigenetic mechanism unravels hsa-miR-148a-3p-mediated CYP2B6 downregulation in alcoholic hepatitis disease.

Biochem Pharmacol 2021 Apr 23;188:114582. Epub 2021 Apr 23.

Department of Toxicology, School of Public Health, Qingdao University, Qingdao, China. Electronic address:

Cytochrome P450 (CYP) enzymes play critical roles in drug transformation, and the total CYPs are markedly decreased in alcoholic hepatitis (AH), a fatal alcoholic liver disease. miRNAs are endogenous small noncoding RNAs that regulate many essential biological processes. Knowledge concerning miRNA regulation of CYPs in AH disease is limited. Here we presented the changes of key CYPs in liver samples of AH patients retrieved from GEO database, performed in silico prediction of miRNAs potentially targeting the dysregulated CYP transcripts, and deciphered a novel mechanism underlying miRNA mediated CYPs expression in liver cells. Nine miRNAs were predicted to regulate CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2J2, and CYP3A4, among which hsa-miR-148a-3p was selected as a case study. Biochemical and molecular evidences demonstrated that miR-148a promoted CYP2B6 expression by increasing mRNA stability via directly binding to the 3'UTR sequence, and that this positive posttranscriptional regulation was AGO1/2-dependent. Further, luciferase reporter gene assay and RNA secondary structure analysis illustrated that the seedless target site, not the seed target site, controlled miR-148a-mediated CYP2B6 upregulation. Moreover, we identified HNF4A as a liver-specific transcription factor of MIR-148A through EMSA and chromatin immunoprecipitation experiments. In conclusion, ethanol downregulated miR-148a in hepatocytes through HNF4A regulation, which eventually decreased CYP2B6 expression. Our finding will benefit the understanding of dysregulated drug metabolism in AH patients and highlight an unconventional mechanism for epigenetic regulation of CYP gene expression.
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http://dx.doi.org/10.1016/j.bcp.2021.114582DOI Listing
April 2021

Dural arteriovenous fistula, a rare cause of rapidly progressive dementia in a patient with bilateral thalamic lesions: a case report.

Ann Palliat Med 2021 Apr 15. Epub 2021 Apr 15.

Department of Neurology, Peking University First Hospital, Beijing, China.

There are many causes of bilateral thalamic lesions, but few cases of dural arteriovenous fistula (DAVF) associated with such lesions have been reported previously. Here, we describe an adult man with reversible rapid progressive dementia (RPD) in whom bilateral thalamic lesions were caused by a DAVF that had six supply arteries and drained into both the venous sinus and cortical veins. A 53-year-old man presented with memory decline and abnormal behavior. Head computed tomography (CT) revealed insignificant low density in the bilateral thalami and high density in the right occipital lobe. Brain magnetic resonance imaging showed hyperintensities in the thalami on T2-weighted images. Magnetic resonance venogram revealed no sign of the straight sinus, but multiple tortuous vessels in the cistern of the vein of Galen. Digital subtraction angiography revealed DAVFs near the tentorium cerebelli draining into the vein of Galen, which caused the vasogenic oedema of the thalami. The patient was then treated by transarterial embolization of the feeders. He gradually recovered after the surgery. RPD with bithalamic lesions caused by DAVF is rare but reversible. Therefore, the early recognition and intervention of DAVFs is crucial for the good prognosis of patients so that fistulas can be embolized in time.
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http://dx.doi.org/10.21037/apm-20-1481DOI Listing
April 2021