Publications by authors named "Bing Wang"

2,409 Publications

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Metabolic Syndrome Mediates ROS-miR-193b-NFYA-Dependent Down Regulation of sGC and Contributes to Exercise-Induced Pulmonary Hypertension in HFpEF.

Circulation 2021 Jun 23. Epub 2021 Jun 23.

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA; Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Many patients with heart failure with preserved ejection fraction (HFpEF) have metabolic syndrome and develop exercise-induced pulmonary hypertension (EIPH). Increases in pulmonary vascular resistance in patients with HFpEF portend a poor prognosis; this phenotype is referred to as combined pre-and post-capillary PH (CpcPH). Therapeutic trials for EIPH and CpcPH have been disappointing, suggesting the need for strategies that target upstream mechanisms of disease. This work reports novel rat EIPH models and mechanisms of pulmonary vascular dysfunction centered around the transcriptional repression of the soluble guanylate cyclase (sGC) enzyme in pulmonary artery smooth muscle cells (PAVSMCs). We used obese ZSF-1 leptin-receptor knock-out rats (HFpEF model), obese ZSF-1 rats treated with SU5416 to stimulate resting PH (Obese+sugen, CpcPH model), and Lean ZSF-1 rats (controls). Right and left ventricular hemodynamics were evaluated via implanted-catheters during treadmill exercise. PA function was evaluated using MRI and myography. Overexpression of NFYA, a transcriptional-enhancer of sGCβ1, was performed by PA delivery of adeno-associated-virus 6 (AAV6). Treatment groups received SGLT2 inhibitor Empagliflozin in drinking water. PAVSMCs from rats and humans were cultured with Palmitic acid, Glucose, and Insulin (PGI) to induce metabolic-stress. Obese rats showed normal resting right ventricular systolic pressures (RVSP) which significantly increased during exercise, modeling EIPH. Obese+sugen rats showed anatomical PA remodeling and developed elevated RVSP at rest, which was exacerbated with exercise, modeling CpcPH. Myography and MRI during dobutamine-challenge revealed PA functional impairment of both obese groups. PAs of obese rats produced reactive oxygen species (ROS) and decreased sGCβ1 expression. Mechanistically, cultured PAVSMCs from obese rats, humans with diabetes or treated with PGI, showed increased mitochondrial-ROS, which enhanced miR-193b-dependent RNA-degradation of NFYA, resulting in decreased sGCβ1-cGMP signaling. Forced NYFA expression by AAV6 delivery increased sGCβ1 levels and improved exercise-PH in Obese+sugen rats. Treatment of Obese+sugen rats with Empagliflozin improved metabolic syndrome, reduced mitochondrial ROS and miR-193b levels, restored NFYA/sGC activity, and prevented EIPH. In HFpEF and CpcPH models, metabolic syndrome contributes to pulmonary vascular dysfunction and EIPH through enhanced ROS and miR-193b expression, which down-regulates NFYA-dependent sGCβ1 expression. AAV-mediated NFYA overexpression and SGLT2 inhibition restores NFYA-sGCβ1-cGMP signaling and ameliorates EIPH.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.053889DOI Listing
June 2021

Allosteric Activation of SARS-CoV-2 RNA-Dependent RNA Polymerase by Remdesivir Triphosphate and Other Phosphorylated Nucleotides.

mBio 2021 Jun 22:e0142321. Epub 2021 Jun 22.

Department of Microbiology, The Ohio State Universitygrid.261331.4, Columbus, Ohio, USA.

The catalytic subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) Nsp12 has a unique nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain that transfers nucleoside monophosphates to the Nsp9 protein and the nascent RNA. The NiRAN and RdRp modules form a dynamic interface distant from their catalytic sites, and both activities are essential for viral replication. We report that codon-optimized (for the pause-free translation in bacterial cells) Nsp12 exists in an inactive state in which NiRAN-RdRp interactions are broken, whereas translation by slow ribosomes and incubation with accessory Nsp7/8 subunits or nucleoside triphosphates (NTPs) partially rescue RdRp activity. Our data show that adenosine and remdesivir triphosphates promote the synthesis of A-less RNAs, as does ppGpp, while amino acid substitutions at the NiRAN-RdRp interface augment activation, suggesting that ligand binding to the NiRAN catalytic site modulates RdRp activity. The existence of allosterically linked nucleotidyl transferase sites that utilize the same substrates has important implications for understanding the mechanism of SARS-CoV-2 replication and the design of its inhibitors. interrogations of the central replicative complex of SARS-CoV-2, RNA-dependent RNA polymerase (RdRp), by structural, biochemical, and biophysical methods yielded an unprecedented windfall of information that, in turn, instructs drug development and administration, genomic surveillance, and other aspects of the evolving pandemic response. They also illuminated the vast disparity in the methods used to produce RdRp for experimental work and the hidden impact that this has on enzyme activity and research outcomes. In this report, we elucidate the positive and negative effects of codon optimization on the activity and folding of the recombinant RdRp and detail the design of a highly sensitive assay of RdRp-dependent RNA synthesis. Using this assay, we demonstrate that RdRp is allosterically activated by nontemplating phosphorylated nucleotides, including naturally occurring alarmone ppGpp and synthetic remdesivir triphosphate.
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http://dx.doi.org/10.1128/mBio.01423-21DOI Listing
June 2021

Characteristics and in-hospital outcomes of COVID-19 patients with acute or subacute liver failure.

Dig Liver Dis 2021 May 31. Epub 2021 May 31.

COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, PR China; Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, 110840, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.dld.2021.05.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165077PMC
May 2021

Long non-coding RNA CDKN2B-AS1 enhances LPS-induced apoptotic and inflammatory damages in human lung epithelial cells via regulating the miR-140-5p/TGFBR2/Smad3 signal network.

BMC Pulm Med 2021 Jun 14;21(1):200. Epub 2021 Jun 14.

Department of Intensive Care Unit, The Second Clinical Medical College, Jingzhou Central Hospital, Yangtze University, No. 1 Renmin Road, Jingzhou District, Jingzhou, 434000, Hubei, China.

Background: Sepsis is a complicated disease with systemic inflammation or organ dysfunction, and it is the leading cause of acute lung injury (ALI). Long non-coding RNAs (lncRNAs) have played important roles in the pathogenesis of sepsis. This study was designed to explore the biological function and regulatory mechanism of cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) in lipopolysaccharide (LPS)-induced lung injury.

Methods: ALI model was established after human lung epithelial cell line BEAS-2B was exposed to LPS. CDKN2B-AS1, microRNA-140-5p (miR-140-5p) and transforming Growth Factor Beta Receptor II (TGFBR2) levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was measured using Cell Counting Kit-8 (CCK-8). Cell apoptosis was assessed by caspase3 activity and flow cytometry. Inflammatory cytokines were examined via enzyme-linked immunosorbent assay (ELISA). Protein analysis was performed through western blot. Dual-luciferase reporter, RNA immunoprecipitation (RIP) and pull-down assays were applied to validate the interaction between targets.

Results: CDKN2B-AS1 and TGFBR2 were abnormally upregulated in sepsis patients. Functionally, CDKN2B-AS1 or TGFBR2 knockdown promoted cell growth but inhibited cell apoptosis and inflammatory response in LPS-treated BEAS-2B cells. Moreover, the regulation of CDKN2B-AS1 in LPS-induced cell injury was achieved by increasing the TGFBR2 expression. CDKN2B-AS1 was identified as a miR-140-5p sponge and TGFBR2 was a target of miR-140-5p. Furthermore, CDKN2B-AS1 could regulate the TGFBR2/Smad3 pathway by sponging miR-140-5p.

Conclusions: These results suggested that CDKN2B-AS1 contributed to the LPS-mediated apoptosis and inflammation in BEAS-2B cells via the miR-140-5p/TGFBR2/Smad3 axis.
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http://dx.doi.org/10.1186/s12890-021-01561-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201744PMC
June 2021

Alginate-based composites for environmental applications: A critical review.

Crit Rev Environ Sci Technol 2018 Dec;49(4):318-356

Department of Agricultural and Biological Engineering, University of Florida, Gainesville, FL 32611, USA.

Alginate-based composites have been extensively studied for applications in energy and environmental sectors due to their biocompatible, nontoxic, and cost-effective properties. This review is designed to provide an overview of the synthesis and application of alginate-based composites. In addition to an overview of current understanding of alginate biopolymer, gelation process, and cross-linking mechanisms, this work focuses on adsorption mechanisms and performance of different alginate-based composites for the removal of various pollutants including dyes, heavy metals, and antibiotics in water and wastewater. While encapsulation in alginate gel beads confers protective benefits to engineered nanoparticles, carbonaceous materials, cells and microbes, alginate-based composites typically exhibit enhanced adsorption performance. The physical and chemical properties of alginate-based composites determine the effectiveness under different application conditions. A series of alginate-based composites and their physicochemical and sorptive properties have been summarized. This critical review not only summarizes recent advances in alginate-based composites but also presents a perspective of future work for their environmental applications.
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http://dx.doi.org/10.1080/10643389.2018.1547621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193857PMC
December 2018

Evaluation of sodium orthovanadate as a radioprotective agent under total-body irradiation and partial-body irradiation conditions in mice.

Int J Radiat Biol 2021 Jun 14:1-32. Epub 2021 Jun 14.

Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.

Our previous study indicated that sodium orthovanadate (vanadate), a strong inhibitor of p53, effectively suppressed the lethality from the hematopoietic (HP) and gastrointestinal (GI) syndromes after 12 Gy total-body irradiation (TBI) in mice. This conclusion, however, was inconsistent with the fact that p53 plays a radioprotective role in the intestinal epithelium. The death after TBI of around 12 Gy was attributed to a combined effect of HP and GI syndromes. To verify the effect from prophylactic administration of p53 inhibitor on protection of HP and GI syndromes, in this study, the radioprotective effects from vanadate were investigated in TBI and lower half-body irradiation (partial-body irradiation: PBI) mouse models. Female ICR mice were given a single injection of vanadate or vehicle, followed by a lethal dose of TBI or PBI. Radioprotective effects of vanadate against the irradiations were evaluated by analyzing survival rate, body weight, hematopoietic parameters, and histological changes in the bone marrow and intestinal epithelium. TBI-induced HP syndrome was effectively suppressed by vanadate treatment. After TBI, the vanadate-treated mice retained better bone marrow cellularity and showed markedly higher survival rate compared to the vehicle-treated animals. In contrast, vanadate did not relieve loss of intestinal crypts and failed to rescue mice from GI death after PBI. Vanadate is a p53 inhibitor that has been shown to be beneficial as a radiation protective agent against HP but was not effective in protecting against acute GI radiation injury.
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http://dx.doi.org/10.1080/09553002.2021.1941377DOI Listing
June 2021

Property Regulation of Conjugated Oligoelectrolytes with Polyisocyanide to Achieve Efficient Photodynamic Antibacterial Biomimetic Hydrogels.

ACS Appl Mater Interfaces 2021 Jun 14;13(24):27955-27962. Epub 2021 Jun 14.

Institute of Biophysics, Hebei University of Technology, Tianjin 300401, P. R. China.

Fabricating antibacterial hydrogels with antimicrobial drugs and synthetic biocompatible biomimetic hydrogels is a promising strategy for practical medical applications. Here, we report a bicomponent hydrogel composed of a biomimetic polyisocyanopetide (PIC) hydrogel and a photodynamic antibacterial membrane-intercalating conjugated oligoelectrolyte (COE). The aggregation behavior and aggregate size of the COEs in water can be regulated using the PIC hydrogel, which could induce COEs with higher reactive oxygen species (ROS) production efficiency and increased association of COEs toward bacteria, therefore enhancing the antibacterial efficiency. This strategy provides a facile method for developing biomimetic hydrogels with high antibacterial capability.
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http://dx.doi.org/10.1021/acsami.1c06659DOI Listing
June 2021

Using Liposomes to Alleviate the Toxicity of Chelerythrine, a Natural PKC Inhibitor, in Treating Non-Small Cell Lung Cancer.

Front Oncol 2021 27;11:658543. Epub 2021 May 27.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Aim Of The Study: CHE can inhibit the proliferation of lung cancer cells and induce apoptosis. However, despite having toxicity, CHE has not been thoroughly investigated in term of its antitumor effect. The present study evaluated the antitumor effect of CHE on non-small cell lung cancer cell line HCC827.

Methods: The antitumor effect of CHE on HCC827 was evaluated, and its potential work mechanism was investigated. CHE long circulation liposomes (CHELPs) modified with polyethylene glycol have been optimized and characterized by pharmacokinetic studies. A HCC827 xenograft model was developed on BALB/c nude mice for the assessment of the effects of CHE and CHELP.

Results: CHE might inhibit HCC827 growth through the ROS/PKC-/caspase 3 pathway and glycolysis. The optimized CHELP remained stable after storage for 10 days at 4°C and exhibited sustained drug release, showing approximately one-fifteenth of the clearance rate and 86 times the absorption concentration of free drug. While increasing the bioavailability of CHE, CHELP showed a good therapeutic effect on HCC827 tumor-bearing nude mice and reduced the toxicity of the free drug, improving the safety of CHE.

Conclusions: CHE is a candidate drug for NSCLC, and liposomes are effective in alleviating the toxicity of CHE.
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http://dx.doi.org/10.3389/fonc.2021.658543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190388PMC
May 2021

Revealing the Immune Infiltration Landscape and Identifying Diagnostic Biomarkers for Lumbar Disc Herniation.

Front Immunol 2021 27;12:666355. Epub 2021 May 27.

Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Intervertebral disc (IVD) degeneration and its inflammatory microenvironment ultimately led to discogenic pain, which is thought to originate in the nucleus pulposus (NP). In this study, key genes involved in NP tissue immune infiltration in lumbar disc herniation (LDH) were identified by bioinformatic analysis. Gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. The CIBERSORT algorithm was used to analyze the immune infiltration into NP tissue between the LDH and control groups. Hub genes were identified by the WGCNA R package in Bioconductor and single-cell sequencing data was analyzed using R packages. Gene expression levels were evaluated by quantitative real-time polymerase chain reaction. The immune infiltration profiles varied significantly between the LDH and control groups. Compared with control tissue, LDH tissue contained a higher proportion of regulatory T cells and macrophages, which are associated with the macrophage polarization process. The most significant module contained three hub genes and four subclusters of NP cells. Functional analysis of these genes was performed, the hub gene expression pattern was confirmed by PCR, and clinical features of the patients were investigated. Finally, we identified TGF-β and MAPK signaling pathways as crucial in this process and these pathways may provide diagnostic markers for LDH. We hypothesize that the hub genes expressed in the specific NP subclusters, along with the infiltrating macrophages play important roles in the pathogenesis of IVD degeneration and ultimately, disc herniation.
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http://dx.doi.org/10.3389/fimmu.2021.666355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190407PMC
May 2021

3D-Stretched Film Ni S Nanosheet/Macromolecule Anthraquinone Derivative Polymers for Electrocatalytic Overall Water Splitting.

Small 2021 Jun 13:e2101003. Epub 2021 Jun 13.

School of Resources, Environment and Materials, Guangxi Key Laboratory of Processing for Non-Ferrous Metals and Featured Materials, Guangxi University, Nanning, 530004, P. R. China.

For the first time, a new polymer electrode AQS/S is prepared by compositing Ni S nanosheets and macromolecular anthraquinone derivative (AQD) supported on nickel foam with flying colors. The AQS/S exhibits high crystalline structure and abundant S defects. Density of state calculation shows that AQD has stable internal bonding and easy external bonding with metals, conducive to the dispersion of metal reaction sites, ensuring excellent activity and high stability. Under 1.0 m KOH solution, ultralow overpotentials of 62 and 133 mV at 10 mA cm on AQS/S for hydrogen evolution reaction and on activated AQS/S (A-AQS/S) for oxygen evolution reaction, respectively, are achieved. 100 h chronopotentiometry and the cyclic voltammetry tests show that catalysts have high durability. The AQS/S‖A-AQS/S two-electrode system is also found to have good electrocatalytic activity for 1.43 V to get 10 mA cm  in overall water splitting, better than the state-of-the-art 20% Pt/C‖RuO combination.
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http://dx.doi.org/10.1002/smll.202101003DOI Listing
June 2021

Placental chorionic plate-derived mesenchymal stem cells ameliorate severe acute pancreatitis by regulating macrophage polarization via secreting TSG-6.

Stem Cell Res Ther 2021 Jun 10;12(1):337. Epub 2021 Jun 10.

Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command, Chengdu, 610083, China.

Background: Mesenchymal stem cells (MSCs) hold promising potential to treat systemic inflammatory diseases including severe acute pancreatitis (SAP). In our previous study, placental chorionic plate-derived MSCs (CP-MSCs) were found to possess superior immunoregulatory capability. However, the therapeutic efficacy of CP-MSCs on SAP and their underlying mechanism remain unclear.

Methods: The survival and colonization of exogenous CP-MSCs were observed by bioluminescence imaging and CM-Dil labeling in rodent animal models of SAP. The therapeutic efficacy of CP-MSCs on SAP rats was evaluated by pathology scores, the levels of pancreatitis biomarkers as well as the levels of inflammatory factors in the pancreas and serum. The potential protective mechanism of CP-MSCs in SAP rats was explored by selectively depleting M1 or M2 phenotype macrophages and knocking down the expression of TSG-6.

Results: Exogenous CP-MSCs could survive and colonize in the injured tissue of SAP such as the lung, pancreas, intestine, and liver. Meanwhile, we found that CP-MSCs alleviated pancreatic injury and systemic inflammation by inducing macrophages to polarize from M1 to M2 in SAP rats. Furthermore, our data suggested that CP-MSCs induced M2 polarization of macrophages by secreting TSG-6, and TSG-6 played a vital role in alleviating pancreatic injury and systemic inflammation in SAP rats. Notably, we found that a high inflammation environment could stimulate CP-MSCs to secrete TSG-6.

Conclusion: Exogenous CP-MSCs tended to colonize in the injured tissue and reduced pancreatic injury and systemic inflammation in SAP rats through inducing M2 polarization of macrophages by secreting TSG-6. Our study provides a new treatment strategy for SAP and initially explains the potential protective mechanism of CP-MSCs on SAP rats.
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http://dx.doi.org/10.1186/s13287-021-02411-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193892PMC
June 2021

Robust Molecular Dipole-Enabled Defect Passivation and Control of Energy Level Alignment for High-Efficiency Perovskite Solar Cells.

Angew Chem Int Ed Engl 2021 Jun 9. Epub 2021 Jun 9.

Georgia Institute of Technology, School of Materials Science and Engineering, 771 Ferst Dr., NW, 3100K, Molecular Science & Engineering Bldg., 30332, Atlanta, UNITED STATES.

The ability to passivate defects and modulate the interface energy-level alignment (IEA) is key to boost the performance of perovskite solar cells (PSCs). Herein, we report a robust route that simultaneously allows defect passivation and reduced energy difference between perovskite and hole transport layer (HTL) via the judicious placement of polar chlorine-terminated silane molecules at the interface. Density functional theory (DFT) points to effective passivation of the halide vacancies on perovskite surface by the silane chlorine atoms. An integrated experimental and DFT study demonstrates that the dipole layer formed by the silane molecules decreases the perovskite work function, imparting an Ohmic character to the perovskite/HTL contact. The corresponding PSCs manifest a nearly 20% increase in power conversion efficiency over pristine devices and a markedly enhanced device stability. As such, the use of polar molecules to passivate defects and tailor the IEA in PSCs presents a promising platform to advance the performance of PSCs.
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http://dx.doi.org/10.1002/anie.202105512DOI Listing
June 2021

Comparison of liver biochemical abnormality between COVID-19 patients with liver cirrhosis versus COVID-19 alone and liver cirrhosis alone: A STROBE observational study.

Medicine (Baltimore) 2021 May;100(19):e25497

COVID-19 Study Group, General Hospital of Northern Theater Command.

Abstract: Coronavirus disease (COVID-19) patients frequently develop liver biochemical abnormality. However, liver biochemical abnormality in COVID-19 patients with liver cirrhosis is under-recognized.Patients hospitalized during COVID-19 pandemic in China (ie, from February to April 2020) were screened. All of 17 COVID-19 patients with liver cirrhosis consecutively admitted to the Wuhan Huoshenshan Hospital were identified. Meanwhile, 17 age-, sex-, and severity-matched COVID-19 patients without liver cirrhosis admitted to this hospital were selected as a control group; all of 14 cirrhotic patients without COVID-19 consecutively admitted to the Department of Gastroenterology of the General Hospital of Northern Theater Command were selected as another control group. Incidence of liver biochemical abnormality and decompensated events were primarily compared.Among the COVID-19 patients with liver cirrhosis, the incidence of liver biochemical abnormality at admission and during hospitalization were 76.50% and 84.60%, respectively; 7 (41.20%) had decompensated events at admission; 1 was transferred to intensive care unit due to gastrointestinal bleeding. Among the COVID-19 patients without liver cirrhosis, the incidence of liver biochemical abnormality at admission and during hospitalization were 58.80% (P = .271) and 60.00% (P = .150), respectively. Among the cirrhotic patients without COVID-19, the incidence of liver biochemical abnormality at admission and during hospitalization were 69.20% (P = .657) and 81.80% (P = .855), respectively; 11 (78.60%) had decompensated events at admission (P = .036). None died during hospitalization among the three groups.Liver biochemical abnormality is common in COVID-19 patients with liver cirrhosis. Management of decompensated events in cirrhotic patients without COVID-19 should not be neglected during COVID-19 pandemic.
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http://dx.doi.org/10.1097/MD.0000000000025497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133226PMC
May 2021

Cathepsin B-responsive multifunctional peptide conjugated gold nanorods for mitochondrial targeting and precise photothermal cancer therapy.

J Colloid Interface Sci 2021 May 26;601:714-726. Epub 2021 May 26.

Department of Polymer Materials, Zhejiang Sci-Tech University, Hangzhou 310018, China. Electronic address:

Nanomaterials have shown great potential in cancer therapy, but the phenomenon of poor tumor recognition without cellular organelle accumulation usually leads to reduced therapeutic effects and enhanced side effects. Herein, we resolved this issue by employing a multifunctional peptide coating mainly composed of, from the inside out, a mitochondrial targeting segment, a cathepsin B-responsive segment and a zwitterionic antifouling segment. Then gold nanorods were modified with a peptide via ligand exchange, displaying excellent photothermal property and superior stability both before and after enzyme treatment. The in vitro and in vivo results showed that this nanoplatform possessed good biocompatibility, satisfactory mitochondria targeting ability, prolonged blood circulation lifetime and enhanced cellular uptake in tumors. This nanoplatform promoted effective near-infrared light-triggered subcellular hyperthermia treatment in vitro and exhibited excellent tumor ablation ability in vivo. These findings suggested that this multifunctional nanoplatform could significantly enhance the therapeutic efficiency of photothermal therapy based on activated mitochondrial targeting.
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http://dx.doi.org/10.1016/j.jcis.2021.05.135DOI Listing
May 2021

Comparison of Stockpiling and Composting on Reducing Antibiotic Resistant Bacteria and Resistance Genes in Beef Cattle Manure.

Appl Environ Microbiol 2021 Jun 4:AEM0075021. Epub 2021 Jun 4.

Department of Civil and Environmental Engineering, University of Nebraska - Lincoln, Lincoln, NE 68588, USA.

Manure storage methods can affect the concentration and prevalence of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in cattle manure prior to land application. The objective of this study was to compare stockpiling and composting with respect to their effectiveness in reducing ARB and ARGs in beef cattle manure in a field scale study. Field experiments were conducted in different seasons with different bulking agents for composting. For both the winter-spring cycle and the summer-fall cycle, ARB concentrations declined below the limit of quantification rapidly in both composting piles and stockpiles, however, ARB prevalence was significantly greater in the composting piles than in the stockpiles. This was likely due to the introduction of ARB from bulking agents. There was no significant change in ARG concentrations between initial and final concentrations for either manure storage treatments during the winter-spring cycle, but a significant reduction of ARGs (B) and (O) and (Q) over time were observed for both the composting and stockpile during the summer-fall cycle. Results from this study suggest that (1) bulking agent may be an important source of ARB and ARGs for composting; (2) during cold months the heterogeneity of the temperature profile in composting piles could result in poor ARG reduction; (3) during warm months both stockpiling and composting can be effective in reducing ARG abundance. Proper treatment of manure is essential to reduce the spread of antibiotic resistance and protect human health. Stockpiling and composting are two manure storage methods which can reduce antibiotic resistance bacteria and resistance genes, although few field scale studies have examined the relative efficiency of each method. This study examined the ability of both methods in both a winter-spring and summer-fall cycle, while also accounting for heterogeneity within field scale manure piles. This study determined that bulking agents used in composting could contribute antibiotic resistant bacteria and resistance genes. Additionally, seasonal variation could hinder the efficacy of composting in colder months due to heterogeneity in temperature within the pile; however, in warmer months, either method of manure storage could be effective in reducing the spread of antibiotic resistance.
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http://dx.doi.org/10.1128/AEM.00750-21DOI Listing
June 2021

ANLN promotes carcinogenesis in oral cancer by regulating the PI3K/mTOR signaling pathway.

Head Face Med 2021 Jun 3;17(1):18. Epub 2021 Jun 3.

Oncological Department of Oral and Maxillofacial Surgery, Xinjiang Medical University Affiliated First Hospital, Stomatological School of Xinjiang Medical University, Stomatology Research Institute of Xinjiang Province, No.137 Liyushan South Road, 830054, Urumqi, PR China.

Background: Oral cancer is a malignant disease that threatenshuman life and greatly reducespatientquality of life. ANLN was reported to promote the progression of cancer. This study aims to investigate the role of ANLNin oral cancer and the underlying molecular mechanism.

Methods: ANLN expression was downregulated by RNAi technology. The effect of ANLN on cell behaviors, including proliferation, cell cycle progression, invasion, and apoptosis, was detected. Western blotting analysis was used to explore the mechanism by whichANLN functions in oral cancer.

Results: Data from TCGA database showed that ANLN was expressed at significantly higher levels in tumor tissues thanin normal control tissues. Patients with higher ANLN expression exhibitedshorter survivaltimes. ANLN was alsoabundantly expressedin the cancer cell lines CAL27 and HN30. When ANLN was knocked down in CAL27 and HN30 cells, cell proliferation and colony formation weredecreased. The cell invasion ability was also inhibited. However, the cell apoptosis rate was increased. In addition, the levels of critical members of the PI3K signaling pathway, includingPI3K, mTOR, Akt, and PDK-1, were significantlyreducedafter ANLN was knocked down in CAL27 cells.

Conclusions: ANLN contributes to oral cancerprogressionand affects activation ofthe PI3K/mTOR signaling pathway. This study providesa new potential targetfor drug development and treatment in oral cancer.
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http://dx.doi.org/10.1186/s13005-021-00269-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173900PMC
June 2021

IFI35 is involved in the regulation of the radiosensitivity of colorectal cancer cells.

Cancer Cell Int 2021 Jun 3;21(1):290. Epub 2021 Jun 3.

Central Laboratory, The First People's Hospital of Taicang, Taicang Affiliated Hospital of Soochow University, No. 58 Changsheng South Road, Taicang, 215400, Jiangsu, China.

Background: Interferon regulatory factor-1 (IRF1) affects the proliferation of colorectal cancer (CRC). Recombinant interferon inducible protein 35 (IFI35) participates in immune regulation and cell proliferation. The aim of the study was to examine whether IRF1 affects the radiation sensitivity of CRC by regulating IFI35.

Methods: CCL244 and SW480 cells were divided into five groups: blank control, IFI35 upregulation, IFI35 upregulation control, IFI35 downregulation, and IFI35 downregulation control. All groups were treated with X-rays (6 Gy). IFI35 activation by IRF1 was detected by luciferase reporter assay. The GEPIA database was used to examine IRF1 and IFI35 in CRC. The cells were characterized using CCK-8, EdU, cell cycle, clone formation, flow cytometry, reactive oxygen species (ROS), and mitochondrial membrane potential. Nude mouse animal models were used to detect the effect of IFI35 on CRC.

Results: IRF1 can bind to the IFI35 promoter and promote the expression of IFI35. The expression consistency of IRF1 and IFI35 in CRC, according to GEPIA (R = 0.68, p < 0.0001). After irradiation, the upregulation of IFI35 inhibited cell proliferation and colony formation and promoted apoptosis and ROS, while IFI35 downregulation promoted proliferation and colony formation and reduced apoptosis, ROS, and mitochondrial membrane potential were also reduced. The in vivo experiments supported the in vitro ones, with smaller tumors and fewer liver metastases with IFI35 upregulation.

Conclusions: IRF1 can promote IFI35 expression in CRC cells. IFI35 is involved in the regulation of radiosensitivity of CRC cells and might be a target for CRC radiosensitization.
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http://dx.doi.org/10.1186/s12935-021-01997-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176734PMC
June 2021

Improved Identification of Small Open Reading Frames Encoded Peptides by Top-Down Proteomic Approaches and De Novo Sequencing.

Int J Mol Sci 2021 May 22;22(11). Epub 2021 May 22.

Hubei Key Lab of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, No. 152 Luoyu Road, Wuhan 430079, China.

Small open reading frames (sORFs) have translational potential to produce peptides that play essential roles in various biological processes. Nevertheless, many sORF-encoded peptides (SEPs) are still on the prediction level. Here, we construct a strategy to analyze SEPs by combining top-down and de novo sequencing to improve SEP identification and sequence coverage. With de novo sequencing, we identified 1682 peptides mapping to 2544 human sORFs, which were all first characterized in this work. Two-thirds of these new sORFs have reading frame shifts and use a non-ATG start codon. The top-down approach identified 241 human SEPs, with high sequence coverage. The average length of the peptides from the bottom-up database search was 19 amino acids (AA); from de novo sequencing, it was 9 AA; and from the top-down approach, it was 25 AA. The longer peptide positively boosts the sequence coverage, more efficiently distinguishing SEPs from the known gene coding sequence. Top-down has the advantage of identifying peptides with sequential K/R or high K/R content, which is unfavorable in the bottom-up approach. Our method can explore new coding sORFs and obtain highly accurate sequences of their SEPs, which can also benefit future function research.
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http://dx.doi.org/10.3390/ijms22115476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197016PMC
May 2021

Qigong for women with breast cancer: An updated systematic review and meta-analysis.

Complement Ther Med 2021 May 28;60:102743. Epub 2021 May 28.

Department of Breast, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No. 725, Wanping South Road, Xuhui District, 200032, Shanghai, China. Electronic address:

Objective: The purpose of this review was to evaluate the effectiveness of Qigong in improving the quality of life and relieving fatigue, sleep disturbance, and cancer-related emotional disturbances (distress, depression, and anxiety) in women with breast cancer.

Methods: The PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Sinomed, Wanfang, VIP, and China National Knowledge Infrastructure databases were searched from their inceptions to March 2020 for controlled clinical trials. Two reviewers selected relevant trials that assessed the benefit of Qigong for breast cancer patients independently. A methodological quality assessment was conducted according to the criteria of the 12 Cochrane Back Review Group for risk of bias independently. A meta-analysis was performed by Review Manager 5.3.

Results: This review consisted of 17 trials, in which 1236 cases were enrolled. The quality of the included trials was generally low, as only five of them were rated high quality. The results showed significant effectiveness of Qigong on quality of life (n = 950, standardized mean difference (SMD), 0.65, 95 % confidence interval (CI) 0.23-1.08, P =  0.002). Depression (n = 540, SMD = -0.32, 95 % CI -0.59 to -0.04, P =  0.02) and anxiety (n = 439, SMD = -0.71, 95 % CI -1.32 to -0.10, P =  0.02) were also significantly relieved in the Qigong group. There was no significant benefit on fatigue (n = 401, SMD = -0.32, 95 % CI  0.71 to 0.07, P = 0.11) or sleep disturbance relief compared to that observed in the control group (n = 298, SMD = -0.11, 95 % CI  0.74 to 0.52, P = 0.73).

Conclusion: This review shows that Qigong is beneficial for improving quality of lifeand relieving depression and anxiety; thus, Qigong should be encouraged in women with breast cancer.
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http://dx.doi.org/10.1016/j.ctim.2021.102743DOI Listing
May 2021

Clinical characteristics and neuroimaging findings of seven patients with Dyke Davidoff Masson syndrome.

BMC Neurol 2021 May 31;21(1):213. Epub 2021 May 31.

Department of Radiology, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, 518020, Shenzhen, Guangdong, China.

Background: DDMS is a rare disease diagnosed by clinical and radiological characteristics. But the complexity of radiological and clinical manifestations of DDMS has become a challenge diagnostically. To date, the reported cases with DDMS had highly varied clinical manifestations including seizures, contralateral hemiplegia/hemiparesis, facial asymmetry, mental retardation, etc. In addition to typical clinical findings, some new characteristics have been recently added to the spectrum of DDMS. However, few cases have been reported to be associated with neuropsychiatric symptoms according to the literature. This study aimed to investigate the neuropsychiatric manifestations associated with Dyke-Davidoff-Masson syndrome (DDMS) and related imaging findings.

Methods: This study included 7 patients diagnosed with DDMS between 2014 and 2020. The clinical characteristics, neuropsychiatric manifestations, and radiological results were retrospectively evaluated.

Results: Seven patients (five males and two females) with a mean age of 28.0 ± 9.73 (range 15.0-41.0) years were included. Five patients were admitted to the psychiatric unit due to psychological and behavioral disorders. Two patients were referred to the neurology unit mainly due to epilepsy. Six patients had epileptic seizures, 4 had hemiplegia, 3 had mental retardation, 2 patients had external ear deformities, and 2 had facial asymmetry. Neuropsychiatric symptoms were presented in 6 (85.7 %) cases. Cases 2-6 developed affective disorders. Deficits in verbal communication, impairment of social interaction, lack of insight, adulia and hypobulia appeared in cases 1-4. Schizophrenia with apathy, and epileptic schizoid psychosis were observed in cases 4 and 5 respectively. Case 6 had behavioral disorders, hyperactivity, tic disorder, mental retardation, anxiety, catatonic symptoms and suicidal tendency. Case 7 had seizures and mental retardation, and no psychiatric symptoms were presented. Radiological examinations showed unilateral cerebral atrophy, enlarged lateral ventricles, and various compensatory hypertrophy of the skull in all cases. The midline structure has shifted to the affected side in 5(71.4 %) cases. Atrophy of the basal ganglia or brain stem was observed in 4(57.1 %) cases.

Conclusions: The hallmark imaging manifestations of DDMS facilitated the diagnosis in most cases. This study illustrated that a variety of psychoneurotic disorders and ear abnormalities were correlated with DDMS.
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http://dx.doi.org/10.1186/s12883-021-02242-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166082PMC
May 2021

Abdominal paracentesis drainage attenuates intestinal mucosal barrier damage through macrophage polarization in severe acute pancreatitis.

Exp Biol Med (Maywood) 2021 May 30:15353702211015144. Epub 2021 May 30.

College of Medicine, Southwest Jiaotong University, Chengdu 610031, China.

Abdominal paracentesis drainage (APD), as an effective treatment of severe acute pancreatitis (SAP) in clinical settings, can ameliorate intestinal barrier damage and the overall severity of SAP. However, the mechanism underlying therapeutic effects of APD on damaged intestinal mucosal barrier during SAP is still unclear. Here, SAP was induced by injecting 5% Na-taurocholate retrograde into the biliopancreatic duct of rats to confirm the benefits of APD on enteral injury of SAP and further explore the possible mechanism. Abdominal catheter was placed after SAP was induced in APD group. As control group, the sham group received no operation except abdominal opening and closure. By comparing changes among control group, sham group, and APD group, APD treatment obviously lowered the intestinal damage and reduced the permeation of intestinal mucosal barrier, which was evidenced by intestinal H&E staining, enteral expression of tight junction proteins, intestinal apoptosis measurement and detection of serum diamine oxidase, intestinal fatty acid binding protein and D-lactic acid. Furthermore, we found that APD polarized intestinal macrophages toward M2 phenotype by the determination of immunofluorescence and western blotting, and this accounts for the benefits of APD for intestinal injury in SAP. Importantly, the protective effect against intestinal injury by APD treatment was mediated through the inhibited ASK1/JNK pathway. In summary, APD improved the intestinal mucosal barrier damage in rats with SAP through an increasing portion of M2 phenotype macrophages in intestine via inhibiting ASK1/JNK pathway.
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http://dx.doi.org/10.1177/15353702211015144DOI Listing
May 2021

Complete Cytoreductive Surgery vs. Debulking Surgery for pseudomyxoma peritonei of appendiceal origin: A propensity score-matched study based on a single-center experience.

Eur J Surg Oncol 2021 May 19. Epub 2021 May 19.

Department of Myxoma, Aerospace Center Hospital, Beijing, China. Electronic address:

Objective: This study aimed to report the prognostic predictors and compare the long-term outcomes of complete cytoreductive surgery (CCRS) vs. debulking surgery (DS) in patients with pseudomyxoma peritonei (PMP) of appendiceal origin.

Methods: A retrospective analysis of 1008 consecutive patients with PMP undergoing primary surgery from January 2008 to December 2019 was performed. A propensity score-matched (PSM) analysis (1:1) was performed, and oncologic outcomes were compared between the CCRS and DS groups.

Results: Out of 1008 patients, 258 patients were excluded. Baseline characteristics differed significantly between the CCRS and DS groups (total n = 750). After PSM, 106 patients were selected from each group and the baseline characteristics were matched between groups. There were significant differences between groups in operative time, the incidence of major complications (P = 0.017), and the numbers of organs removed. The median follow-up was 28 (1-131) months. Median overall survival (OS) for the 212 patients was 52.0 months (95% CI 40.2-63.8), and 10-year OS was 39.0%. Median OS could not be calculated for the CCRS group; in the DS group, this value was 41 months (P = 0.010). The 10-year OS rate was 54.2% in the CCRS group and 31.2% in the DS group. Multivariate analyses identified CCRS (P = 0.012) and histopathologic subtype (P < 0.001) as independent prognostic factors for OS.

Conclusions: In this matched-pair analysis of patients with appendiceal PMP, CCRS was safe and associated with better prognosis than DS. The completeness of cytoreduction and histopathologic subtype were two independent prognostic factors for OS.
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http://dx.doi.org/10.1016/j.ejso.2021.05.015DOI Listing
May 2021

General Strategy to Fabricate Porous Co-Based Bimetallic Metal Oxide Nanosheets for High-Performance CO Sensing.

ACS Appl Mater Interfaces 2021 Jun 25;13(22):26318-26329. Epub 2021 May 25.

Science and Technology on Advanced Ceramic Fibers and Composites Laboratory, College of Aerospace Science and Engineering, National University of Defense Technology, Changsha 410073, PR China.

Two-dimensional (2D) porous bimetallic oxide nanosheets are attractive for high-performance gas sensing because of their porous structures, high surface areas, and cooperative effects. Nevertheless, it is still a huge challenge to synthesize these nanomaterials. Herein, we report a general strategy to fabricate porous cobalt-based bimetallic oxide nanosheets (Co-M-O NSs, M = Cu, Mn, Ni, and Zn) with an adjustable Co/M ratio and the homogeneous composition using metal-organic framework (MOF) nanosheets as precursors. The obtained Co-M-O NS possesses the porous nanosheet structure and ultrahigh specific surface areas (146.4-220.7 m g), which enhance the adsorption of CO molecules, support the transport of electrons, and expose abundant active sites for CO-sensing reaction. As a result, the Co-M-O NS exhibited excellent sensing performances including high response, low working temperature, fast response-recovery, good selectivity and stability, and ppb-level detection limitation toward CO. In particular, the Co-Mn-O NS showed the highest response of 264% to 100 ppm CO at low temperature (175 °C). We propose that the excellent sensing performance is ascribed to the specific porous nanosheet structure, the relatively highly active Co ratio resulting from cation substitution, and large amounts of chemisorbed oxygen species on the surface. Such a general strategy can also be introduced to design noble-metal-free bimetallic metal oxide nanosheets for gas sensing, catalysis, and other energy-related fields.
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http://dx.doi.org/10.1021/acsami.1c03508DOI Listing
June 2021

Epidemiology and detection of cement leakage in patients with spine metastases treated with percutaneous vertebroplasty: A 10-year observational study.

J Bone Oncol 2021 Jun 1;28:100365. Epub 2021 May 1.

Department of Orthopedic Surgery, Hainan Hospital of Chinese PLA General Hospital, Sanya, China.

Objectives: To investigate the epidemiology of cement leaks and further develop an algorithm to detect the high risk of cement leaks among advanced cancer patients with metastatic spinal disease treated with percutaneous vertebroplasty.

Methods: This study retrospectively analyzed 309 patients with metastatic spinal disease treated with percutaneous vertebroplasty. Patients were randomly divided into a training group and a validation group. In the training group, 13 potential characteristics were analyzed for their abilities to predict cement leaks. Discal cement leakage and paravertebral cement leakage were excluded from the analysis. Those characteristics identified as having significant predictive value were used to develop a predictive algorithm. Internal validation of the algorithm was performed based on discrimination and calibration qualities.

Results: Overall, cement leaks occurred in 61.17% (189/309) patients. Among the 13 characteristics analyzed, younger age (P = 0.03), extravertebral bone metastases (P = 0.02), increased number of treated vertebrae levels (P < 0.01), and cortical osteolytic destruction in the posterior wall (P = 0.01) were included in the algorithm. This algorithm generates a score between 0 and 16 points, with higher scores indicating a higher risk of cement leakage. The area under the receiver operating characteristic curve (AUROC) value for the algorithm was 0.75 in the training group and 0.69 in the validation group. The mean correct classification rates for the training and validation groups were 73.5% and 64.9%, respectively, and the corresponding P-values of the goodness-of-fit test were 0.70 and 0.50.

Conclusions: Cement leaks are common in patients with metastatic spinal disease treated with percutaneous vertebroplasty. The present study proposed and internally validated an algorithm that can be used to screen patients at high risk of cement leakage.
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http://dx.doi.org/10.1016/j.jbo.2021.100365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134071PMC
June 2021

Microarray profile of circular RNAs identifies hsa_circ_000455 as a new circular RNA biomarker for deep vein thrombosis.

Vascular 2021 May 22:17085381211016150. Epub 2021 May 22.

Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming, China.

Objects: Deep vein thrombosis is a type of severe venous thromboembolism that can result in high mortality and morbidity. The expression alternation of circular RNAs (circRNAs) has been found in various diseases. However, the function of circRNAs in deep vein thrombosis still remains unknown.

Method: The blood samples of deep vein thrombosis patients and health control were selected, circRNA microarray was performed, and qPCR was used to verify the expression of circRNAs. Also, GO/KEGG analysis was performed, and hsa_circ_RNA_000455-targeted miRNA-mRNA network was predicted.

Result: Here, we found that 303 circRNAs were differentially expressed in deep vein thrombosis using microarray, of which 83 circRNAs were upregulated and 220 circRNAs were downregulated. The expression of five circRNAs verified by quantitative real-time PCR was consistent with the result of microarray. GO analysis showed that the top 100 differentially expressed circRNAs in deep vein thrombosis patients were closely related to protein transport, cytoplasm, and Adenosine Triphosphate (ATP) binding. The most significantly enriched pathways by KEGG analysis included thyroid hormone-signaling pathway, endocytosis, proteoglycans in cancer, Fc gamma R-mediated phagocytosis, focal adhesion, insulin-signaling pathway, p53-signaling pathway, biosynthesis of antibiotics, bacterial invasion of epithelial cells, and AMP-activated protein kinase-signaling pathway. Then, hsa_circ_000455 was selected, and the function of hsa_circ_000455 in the pathogenesis of deep vein thrombosis was analyzed via circRNA-miRNA-mRNA network. We therefore hypothesized that hsa_circRNA_000455/hsa-miR-22-3p/NLRP3 may involve in the development of deep vein thrombosis.

Conclusion: This study provided valuable information on circRNA profile in deep vein thrombosis for the first time and gave clues on the possible role and mechanism of hsa_circRNA_000455 in deep vein thrombosis.
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http://dx.doi.org/10.1177/17085381211016150DOI Listing
May 2021

Silencing lncRNA AK136714 reduces endothelial cell damage and inhibits atherosclerosis.

Aging (Albany NY) 2021 05 18;13(10):14159-14169. Epub 2021 May 18.

Department of Geriatrics, Affiliated Hospital of Hebei University of Engineering, Handan 056000, Hebei Province, China.

Atherosclerosis correlates with ischemic cardio-cerebrovascular diseases such as coronary heart disease. Long non-coding RNAs (lncRNAs) can promote atherosclerosis. We investigated the role of the lncRNA AK136714 in atherosclerosis. Compared with the healthy group, lncRNA AK136714 expression was elevated in the plaque and plasma of the atherosclerosis patients in a GEO dataset. AK136714 silencing inhibited atherosclerosis formation in ApoE-/- mice. AK136714 silencing also protected the endothelial barrier and inhibited endothelial cell inflammation. assays showed that knockdown of AK136714 suppressed the inflammatory response and apoptosis in human umbilical vein endothelial cells (HUVECs). Moreover, AK136714 was found to bind directly to HuR to increase the mRNA stability of TNF-α, IL-1β and IL-6 mRNAs. In addition, AK136714 promoted the transcription of Bim. This study expands our understanding of the role of lncRNA AK136714 in atherosclerosis and provides potential drug targets for the treatment of atherosclerosis.
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http://dx.doi.org/10.18632/aging.203031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202876PMC
May 2021

Neutrophil extracellular traps promote gastric cancer metastasis by inducing epithelial‑mesenchymal transition.

Int J Mol Med 2021 Jul 20;48(1). Epub 2021 May 20.

The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.

The risks of tumor recurrence following the successful resection of the primary tumor have been known for decades; however, the precise mechanisms underlying treatment failures remain unknown. The formation of neutrophil extracellular traps (NETs) has increasingly been demonstrated to be associated with thrombi formation in cancer patients, as well as with the development and metastasis of cancer. The present study demonstrated that the level of peripheral blood NETs in patients with gastric cancer (GC) was associated with tumor progression, and patients with stage III/IV disease exhibited significant differences compared with the healthy controls and patients with stage I/II disease, which may be associated with an increased risk of metastasis. In addition, plasma from patients with stage III/IV GC was more prone to stimulate neutrophils to form NETs; thus, it was hypothesized that the formation of NETs may be affected by the tumor microenvironment. A higher deposition of NETs in GC tissues compared with normal resection margins was also identified. , following treatment with phorbol myristate acetate, which promotes the formation of NETs, or with DNAse‑1/GSK‑484, which inhibits the formation of NETs, it was found that the tumor migratory ability was altered; however, no significant changes were observed in cell proliferation and cell cycle progression. Epithelial‑mesenchymal transition (EMT) is a key event associated with dissemination and metastasis in GC pathogenesis. Finally, the present study demonstrated that NETs promote a more aggressive mesenchymal phenotype and promote the progression of GC and . On the whole, to the best of our knowledge, the present study reports a previously unknown role of NETs in the regulation of GC, which is associated with EMT and migration. Therefore, targeting NETs may prove to be therapeutically beneficial.
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http://dx.doi.org/10.3892/ijmm.2021.4960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128417PMC
July 2021

Exploration of the potential mechanism of Banxia Xiexin Decoction for the effects on TNBS-induced ulcerative colitis rats with the assistance of network pharmacology analysis.

J Ethnopharmacol 2021 Sep 15;277:114197. Epub 2021 May 15.

Experiment Center of Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address:

Ethnopharmacological Relevance: Banxia Xiexin Decoction (BXD), an ancient TCM prescription originating from Treatise on Febrile Diseases (Shang Han Lun) of the Han Dynasty, has been widely used in modern clinical practice, especially for gastrointestinal diseases, including ulcerative colitis (UC). However, the modern decoction method of BXD differs from that of the original method. Thus, an exploration of the influence of the different decoction methods on the pharmacological effects is interesting and significant.

Aim Of The Study: This study aimed to systematically compare the pharmacological effects of extracts of BXD on TNBS induce UC rats that were prepared by different methods, the ancient method and the modern method. The findings may provide important information for the further mechanical exploration of the classical prescription, contributing to the rational application and enhancing the understanding of BXD in modern applications or scientific research.

Methods: Fifty-four SD rats were randomly divided into the following nine groups at n = 6/group: control group; model group; salicylazosulfapyridine group; BXD ancient extraction method's low-dose group (BXD-AED-L, 3.6 g BXD-AED/kg), medium-dose group (BXD-AED-M, 7.2 g BXD-AED/kg), and high-dose group (BXD-AED-H, 14.4 g BXD-AED/kg); and BXD modern extraction method's low-dose group (BXD-MED-L, 1 g BXD-MED/kg), medium-dose group (BXD-MED-M, 2 g BXD-MED/kg), and high-dose group (BXD-MED-H, 4 g BXD-MED/kg). All the groups, except the control group, were rectally injected with 70 mg/kg ethanol solution containing TNBS (2,4,6-trinitrobenzenesulfonic acid) to establish the UC models. The pharmacological evaluations including disease activity index, colon weight index, macroscopic and histological evaluation of colon damage, and inflammatory cytokine levels (IL-4, IL-10, IL-1β, TNF-α, and IL-6)were measured. In the network pharmacology analysis, the "herbs-components-targets-disease" network was constructed and visually analyzed with which the targets with a strong correlation with UC were screened out.

Results: The results showed that both BXD-AED and BXD-MED might alleviate the severity of UC with different degrees according to the majority of indices that were evaluated. At similar doses, the BXD-AED groups performed better compared with the BXD-MED groups. With the assistance of the network pharmacology analysis, some key active components (quercetin, baicalein, wogonin, and baicalin) related to the anti-UC/inflammation were screened out. The contents of the components in BXD-AED were higher than those in BXD-MED. The joint results of the study indicated that BXD, an ancient TCM compound prescription, is an effective drug candidate for the modern treatment of UC.
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http://dx.doi.org/10.1016/j.jep.2021.114197DOI Listing
September 2021

Modified nanoscale zero-valent iron in persulfate activation for organic pollution remediation: a review.

Environ Sci Pollut Res Int 2021 May 18. Epub 2021 May 18.

Department of Chemistry and Chemical Engineering, Southwest Petroleum University, Chengdu, 610500, Sichuan, China.

Under the action of different activators, persulfate can produce sulfate radicals (SO·) with strong oxidizing ability, which can destruct many organic compounds. Meanwhile, persulfate is widely used in groundwater and soil remediation because of its fast reaction and wide application. With the high specific surface area and reactivity of nanoscale zero-valent iron (nZVI), it can enhance the degradation efficiency of the persulfate system on organic pollutants in soil and water as a persulfate activator. However, nZVI is easy to get oxidized and has a tendency to aggregation. To solve these problems, a variety of nZVI modification methods have been put forward and put into to applications in the activation of persulfate. This article will give a systematic introduction of the background and problems of nZVI-activated persulfate in the remediation of organic pollution. In addition, the modification methods and mechanisms of nZVI are summarized, and the applications and progress of modified nZVI-activated persulfate are reviewed. The factors that affect the removal of organic compounds by the activation system are discussed as well. Worldwide, the field studies and full-scale remediation using modified nZVI in persulfate activation are yet limited. However, the already known cases reveal the good prospect of applying modified nZVI in persulfate activation to organic pollution remediation.
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http://dx.doi.org/10.1007/s11356-021-13972-wDOI Listing
May 2021

Targeted PD-L1 PLGA/liposomes-mediated luteolin therapy for effective liver cancer cell treatment.

J Biomater Appl 2021 May 18:8853282211017701. Epub 2021 May 18.

Department Of Radiotherapy, Heng Shui City People's Hospital, Hengshui, China.

Stealth PLGA/Liposome nanoparticles (NPs) modified with tumor-targeting PD-L1 antibody for systemic delivery of luteolin for liver cancer were prepared. The morphologies and therapeutic effects of luteolin-loaded PD-L1 targeted stealth PLGA/Liposomes (L-PD-SP/Ls) were analyzed. Functional L-PD-P/L NPs composed of PLGA, DOPC and DSPE-PEG display low cell cytoxicity in HepG2 cells, and has more cell uptake ability than P/Ls NPs. L-PD-SP/Ls was more effective in inhibiting HepG2 cell proliferation than free luteolin in solution () and luteolin-loaded P/Ls (). Compared with the cell control group and the non-PD-L1 targeted group, the mediated effect of PD-L1 can significantly enhance the uptake of drugs by cells, and L-PD-SP/Ls can significantly reduce the expression of Bcl-2 and increase the level of LDH in cells. Our findings collectively support the utility of PD-L1-targeted P/L NPs as a potentially effective drug delivery system.
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http://dx.doi.org/10.1177/08853282211017701DOI Listing
May 2021