Publications by authors named "Jing Yang"

4,981 Publications

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The neutrophil to lymphocyte ratio is an independent predictor for severe COVID-19 : Evidence from a multicenter case-control study and meta-analyses.

Wien Klin Wochenschr 2021 Aug 3. Epub 2021 Aug 3.

Department of Critical Care Medicine, West China Hospital of Sichuan University, No. 37, Guoxue Alley, 610041, Chengdu, Sichuan Province, China.

Purpose: The aim of this study was to determine whether the neutrophil to lymphocyte ratio (NLR) can predict severe Coronavirus disease 2019 (COVID-19).

Patients And Methods: A multicenter case-control study was conducted to investigate whether the NLR can help predict the severity of COVID-19. Patients confirmed to have COVID-19 between 16 January 2020 and 15 March 2020 were enrolled. Furthermore, meta-analyses were conducted based on both previous studies and our case-control study.

Results: In the case-control study, 213 patients (severe: 81) were included. The results suggested that the NLR was an independent risk factor (odds ratio [OR], 1.155, 95% confidence interval [95% CI]: 1.043-1.279, P = 0.006) and a great predictor (the area under the ROC curve was 0.728, 95% CI: 0.656-0.800) for severe COVID-19. In total, 18 datasets from 16 studies combined with our case-control study (severe: 1211; non-severe: 5838) were included in the meta-analyses and the results showed that the NLR of the severe COVID-19 group was significantly higher than that of the non-severe group (SMD = 1.10, 95% CI: 0.90-1.31, P < 0.001). Based on the 2 × 2 data from 6 studies, the SROC of NLR for predicting severe COVID-19 was 0.802, with a sensitivity of 0.67 (95% CI: 0.61-0.72) and a specificity of 0.75 (95% CI: 0.73-0.78).

Conclusion: Based on a multicenter case-control study and a meta-analysis, we found that the initial NLR was a great predictor of severe COVID-19.
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http://dx.doi.org/10.1007/s00508-021-01917-9DOI Listing
August 2021

Protein stoichiometry, structural plasticity and regulation of bacterial microcompartments.

Curr Opin Microbiol 2021 Jul 30;63:133-141. Epub 2021 Jul 30.

Institute of Systems Molecular and Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, United Kingdom; Materials Innovation Factory and Department of Chemistry, University of Liverpool, Liverpool L7 3NY, United Kingdom.

Bacterial microcompartments (BMCs) are self-assembling prokaryotic organelles consisting of a polyhedral proteinaceous shell and encapsulated enzymes that are involved in CO fixation or carbon catabolism. Addressing how the hundreds of building components self-assemble to form the metabolically functional organelles and how their structures and functions are modulated in the extremely dynamic bacterial cytoplasm is of importance for basic understanding of protein organelle formation and synthetic engineering of metabolic modules for biotechnological applications. Here, we highlight recent advances in understanding the protein composition and stoichiometry of BMCs, with a particular focus on carboxysomes and propanediol utilization microcompartments. We also discuss relevant research on the structural plasticity of native and engineered BMCs, and the physiological regulation of BMC assembly, function and positioning in native hosts.
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http://dx.doi.org/10.1016/j.mib.2021.07.006DOI Listing
July 2021

Pinocembrin Inhibits the Proliferation and Metastasis of Breast Cancer Suppression of the PI3K/AKT Signaling Pathway.

Front Oncol 2021 16;11:661184. Epub 2021 Jul 16.

Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang City, China.

The survival rate of breast cancer (BC) patients remains poor, thus the identification of safe and effective new drugs is crucial to improve therapeutic outcomes and overall survival. Pinocembrin (PCB), a pharmacologically active ingredient of Pinus heartwood, Eucalyptus, Euphorbia, Populus, and Sparattosperma leucanthum, has been widely applied for the treatment of various diseases and possesses anticancer activities. In vitro assays were performed to investigate the antiproliferation and antimetastasis activities of PCB in BC cells. A tumorigenesis assay with the use of murine BC models was performed to assess the antiproliferation activities of PCB . Moreover, the molecular mechanisms underlying the anticancer activities of PCB in BC cells were explored. The results showed that the anti-inhibitory and antiproliferation activities of PCB in BC might involve cell cycle (G2/M phase) arrest and apoptosis. PCB downregulated the expression levels of proteins involved in cell cycle progression and apoptosis, including cyclinB1, Cdc2, PARP1, Bcl-2, and survivin, and upregulated protein levels of cleaved PARP1, cleaved caspase3, cleaved caspase9, and BAX. In a murine subcutaneous tumor model, PCB suppressed the growth of MCF-7 cells . Low concentrations of PCB also significantly inhibited the migration and invasion abilities of BC cells. Mechanistically, PCB administration was correlated to suppression of the PI3K/AKT signaling pathway. Inhibition of the proliferation of BC cells by PCB involved cell cycle (G2/M phase) arrest and apoptosis and . Low concentrations of PCB also significantly inhibited the migration and invasion abilities of BC cells. These findings suggest that PCB might be an effective agent for treatment of BC patients.
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http://dx.doi.org/10.3389/fonc.2021.661184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322951PMC
July 2021

Migratory fishbones in the pharynx: A report of two cases.

Clin Case Rep 2021 Jul 26;9(7):e04548. Epub 2021 Jul 26.

Department of Otolaryngology Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University) Zhuhai China.

The possibility of fishbone migration into the surrounding tissues, especially in cases where it cannot be identified on routine inspection. Early diagnosis of migratory fishbone and therapeutic management are essential for optimal patient survival.
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http://dx.doi.org/10.1002/ccr3.4548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312238PMC
July 2021

lncRNA TSPEAR-AS2, a Novel Prognostic Biomarker, Promotes Oral Squamous Cell Carcinoma Progression by Upregulating PPM1A via Sponging miR-487a-3p.

Dis Markers 2021 17;2021:2217663. Epub 2021 Jul 17.

Department of Oral and Maxillofacial Surgery, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.

Background: Long noncoding RNA (lncRNA) critically impacts the modulation of tumor developments and progressions. Our study is aimed at investigating the expressing patterns, clinical significance, and biological roles of lncRNA TSPEAR-AS2 (TSPEAR-AS2) in oral squamous cell carcinoma (OSCC). . The expressing states achieved by TSPEAR-AS2 were examined in OSCC specimens and cell lines by RT-PCR. The clinical significance of TSPEAR-AS2 was statistically analyzed. OSCC proliferating, invading, and migrating processes were examined with the use of wound healing assays, transwell, colony formation, and cell counting kit-8. Additionally, the downstream molecular mechanism of TSPEAR-AS2 in OSCC was explored.

Results: TSPEAR-AS2 was overexpressed in OSCC tumors and cells. High TSPEAR-AS2 was associated with advanced TNM stage. Patients with high TSPEAR-AS2 expression displayed a shorter disease-free survival and total survival of OSCC patients than those with low TSPEAR-AS2 expressing level. It was found that knockdown of TSPEAR-AS2 could inhibit the proliferating, invading, and migrating processes pertaining to OSCC cells. Luciferase reporter tests and RNA pull-down results revealed that TSPEAR-AS2 enhanced the expressions of PPM1A by regulating miR-487a-3p, and TSPEAR-AS2 could be adopted as a miR-487a-3p sponge to inhibit PPM1A expression.

Conclusion: Our study highlighted the significance of the TSPEAR-AS2/miR-487a-3p/PPM1A axis within OSCC progression and offered a novel biomarker and novel strategies for OSCC treatments.
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http://dx.doi.org/10.1155/2021/2217663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313349PMC
July 2021

Genomic Profiling of Circulating Tumor DNA from Patients with Extensive-Stage Small Cell Lung Cancer Identifies Potentially Actionable Alterations.

J Cancer 2021 22;12(17):5099-5105. Epub 2021 Jun 22.

Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Comprehensive genomic profiling may help uncover potentially actionable alterations in small cell lung cancer (SCLC) patients who have progressed on standard chemotherapy. However, tissue procurement may be extremely challenging for extensive-stage patients. We aimed to investigate the possibility of genomic profiling and detecting actionable alterations from blood in Chinese SCLC patients. Blood samples collected from extensive-stage SCLC pateints were subjected to circulating tumor DNA (ctDNA) extraction and targeted-next generation sequencing (NGS) using a 150-gene panel. A total of 1,300 aberrations were detected in 128 genes and 89.2% (116/130) patients harbored at least one oncogenic alteration. The most frequently mutated genes included (82.3%), (56.2%), (40.8%) etc. and 54.6% of the patients had concurrent mutations. The RTK/RAS/RAF axis was the most frequently mutated oncogenic pathway. Samples harboring alterations in the DNA damaging repair (DDR), Notch, PI3K/mTOR, RTK/RAS/RAF, and Wnt pathways exhibited significantly higher blood tumor mutational burden (bTMB) than their wildtype counterparts. Classification based on OncoKB criteria detected potentially actionable alterations in about 50% of the population, half of which were bTMB-H and bMSI-H, indicating response to immune checkpoint inhibitors. Alterations in the RTK/RAS/RAF, DDR, and PI3K/mTOR also suggested potential sensitivity to matched targeted therapies or emerging investigational agents. Blood-based panel NGS is promising for delineating genomic landscape of SCLC and may also shed some light on treatment selection for Chinese SCLC patients.
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http://dx.doi.org/10.7150/jca.55134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317512PMC
June 2021

Predictive Value of Neutrophil/Lymphocyte Ratio (NLR) on Cardiovascular Events in Patients with COVID-19.

Int J Gen Med 2021 24;14:3899-3907. Epub 2021 Jul 24.

Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.

Background: The research on the association between coronavirus disease 2019 (COVID-19) and cardiovascular disease (CVD) is still insufficient.

Aim: This study aimed to investigate the association between neutrophil/lymphocyte ratio (NLR) and risk of cardiovascular events in patients with COVID-19.

Methods: Our study included 159 patients with COVID-19 who were measured for NLR value within the first 24 hours of admission. They were followed up for 6 months after discharge and then the relationship between levels of NLR and risk of cardiovascular events was assessed.

Results: In all included patients with COVID-19, NLR values in patients with cardiovascular events [16.28 (4.95-45.18)] were significantly higher than patients without cardiovascular events [4.75 (2.60-7.47)]. A multivariate logistic regression model revealed that elevated NLR value [increased per SD, 2.41 (1.43-4.29), <0.001; increased 1 of NLR, 2.05 (1.33-4.01), =0.010] was significantly and independently associated with increased risk of CVD history on admission after adjustment of related confounding factors. Then, Cox regression analysis revealed that elevated NLR value had a significant association with increased risk of cardiovascular events [increased per SD, 2.36 (1.42-4.36), <0.001; Increased 1 of NLR, 2.00 (1.30-3.97), =0.014] after adjustments of these same confounding factors. Furthermore, the ROC curve suggested that NLR value (AUC=0.803, 95% CI=0.731-0.875, <0.001, sensitivity 81.2%, and specificity 82.6%) has a good predictive value for cardiovascular events during follow-up.

Conclusion: High NLR value was clinically associated with elevated risk of cardiovascular events in patients with COVID-19, which might be a potential biomarker for predicting cardiovascular events in the current COVID-19 pandemic.
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http://dx.doi.org/10.2147/IJGM.S317380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318887PMC
July 2021

A Commentary on "Transmuscular Quadratus Lumborum and Lateral Femoral Cutaneous Nerve Block in Total Hip Arthroplasty".

Clin J Pain 2021 Aug 2. Epub 2021 Aug 2.

Department of Anesthesiology, West China Hospital, Sichuan University, 37# Wainan Guoxue Road, Chengdu 610041, People's Republic of China.

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http://dx.doi.org/10.1097/AJP.0000000000000964DOI Listing
August 2021

Tungsten Oxide/Reduced Graphene Oxide Aerogel with Low-Content Platinum as High-Performance Electrocatalyst for Hydrogen Evolution Reaction.

Small 2021 Jul 30:e2102159. Epub 2021 Jul 30.

The Key Laboratory of Low-Carbon Chemistry & Energy Conservation of Guangdong Province, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, State Key Laboratory of Optoelectronic Materials and Technologies, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, 510006, P. R. China.

Designing cost-effective, highly active, and durable platinum (Pt)-based electrocatalysts is a crucial endeavor in electrochemical hydrogen evolution reaction (HER). Herein, the low-content Pt (0.8 wt%)/tungsten oxide/reduced graphene oxide aerogel (LPWGA) electrocatalyst with excellent HER activity and durability is developed by employing a tungsten oxide/reduced graphene oxide aerogel (WGA) obtained from a facile solvothermal process as a support, followed by electrochemical deposition of Pt nanoparticles. The WGA support with abundant oxygen vacancies and hierarchical pores plays the roles of anchoring the Pt nanoparticles, supplying continuous mass transport and electron transfer channels, and modulating the surface electronic state of Pt, which endow the LPWGA with both high HER activity and durability. Even under a low loading of 0.81 μg cm , the LPWGA exhibits a high HER activity with an overpotential of 42 mV at 10 mA cm , an excellent stability under 10000-cycle cyclic voltammetry and 40 h chronopotentiometry at 10 mA cm , a low Tafel slope (30 mV dec ), and a high turnover frequency of 29.05 s at η = 50 mV, which is much superior to the commercial Pt/C and the low-content Pt/reduced graphene oxide aerogel. This work provides a new strategy to design high-performance Pt-based electrocatalysts with greatly reduced use of Pt.
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http://dx.doi.org/10.1002/smll.202102159DOI Listing
July 2021

Daily Dose of Bovine Lactoferrin Prevents Ethanol-induced Liver Injury and Death in Male Mice by Regulating Hepatic Alcohol Metabolism and Modulating Gut Microbiota.

Mol Nutr Food Res 2021 Jul 30:e2100253. Epub 2021 Jul 30.

School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou, Jiangsu, 215123, China.

Scope: Lactoferrin (Lf) has a protective potential to liver, but whether it can prevent alcoholic liver injury (ALI) remains unclear.

Methods And Results: Four groups of male C57BL/6J mice were fed with different diets, namely, AIN-93G diet for control (CON) and ethanol (EtOH) groups, and AIN-93G diet with 0.4% and 4% casein replaced by Lf for low-dose Lf (LLf) and high-dose Lf (HLf) groups, respectively. ALI was induced by giving 20% ethanol ad libitum combined with four "binges". Lf could remarkably decrease EtOH-induced mortality. Lf promoted aldehyde dehydrogenase-2 (ALDH2) expression and suppressing cytochrome P450 2E1 (CYP2E1) overexpression, resulting in the reduced hepatic superoxide and inflammation levels, which ultimately led to the hepatic injury alleviation. However, HLf increased acetyl-CoA carboxylase and fatty acid synthase protein levels, which suggested that excessive intake might weaken the beneficial effects of Lf. Moreover, LLf increased the relative abundances of Akkermansia and Lactobacillus. Additionally, we found that Lf likely exerted action in its digestive product forms rather than intact Lf molecular in normal condition.

Conclusion: LLf could ameliorate ALI, which was associated with the regulation of hepatic alcohol metabolism and the modulation of gut microbiota. However, excessive Lf intake might result in a diminished benefit. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/mnfr.202100253DOI Listing
July 2021

Emergence of Novel Recombinant Type 2 Porcine Reproductive and Respiratory Syndrome Viruses with high pathogenicity for piglets in China.

J Infect 2021 Jul 27. Epub 2021 Jul 27.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal, Infectious Diseases and Zoonoses, Yangzhou 225009, China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2021.07.033DOI Listing
July 2021

Polycyclic polyprenylated acylphloroglucinols with immunosuppressive activity from Hypericum perforatum and absolute configurations assignment of previously reported analogues.

Bioorg Chem 2021 Jul 6;114:105144. Epub 2021 Jul 6.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

Hyperformitins A-I (1-9), nine undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) with double-bond migration, along with four new isomers hyperformitins J-M (10-13), were isolated from Hypericum perforatum. Their structures and absolute configurations were determined by spectroscopic analyses including HRESIMS, IR, UV, NMR, and ECD, as well as optical rotation (OR) calculations. The absolute configurations of previously reported analogues, garsubellins D and C as well as garcinielliptones L and M, were assigned for the first time by NMR spectra and specific rotations analyses assisting with OR calculations. Selected compounds were tested for their immunosuppressive activities against lipopolysaccharide (LPS)-induced B lymphocyte proliferation. Compounds 1, 3, 4, 5, 7, and 11 showed inhibition activities against the proliferation of B lymphocyte with IC values ranging from 4.1 to 9.7 μM. Furthermore, the neuroprotective activities of the isolates against corticosterone (CORT)-induced injury in PC12 cells were also tested, and compounds 1, 12, and 13 exhibited neuroprotective effects with cell viabilities of 68.0%, 71.3%, and 68.4%, respectively under the concentration of 10 μM.
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http://dx.doi.org/10.1016/j.bioorg.2021.105144DOI Listing
July 2021

Decarboxylated osteocalcin, a possible drug for type 2 diabetes, triggers glucose uptake in MG63 cells.

World J Diabetes 2021 Jul;12(7):1102-1115

Department of Endocrinology, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China.

Background: Uncarboxylated osteocalcin (GluOC) has been reported to improve glucose metabolism, prevent type 2 diabetes, and decrease the severity of obesity in mice with type 2 diabetes. GluOC can increase glucose uptake in a variety of cells. Glucose metabolism is the main source of energy for osteoblast proliferation and differentiation. We hypothesized that decarboxylated osteocalcin (dcOC), a kind of GluOC, can increase glucose uptake in MG63 cells (osteoblast-like osteosarcoma cells) and influence their proliferation and differentiation.

Aim: To investigate the effects of dcOC on glucose uptake in human osteoblast-like osteosarcoma cells and the possible signaling pathways involved.

Methods: MG63 cells (human osteoblast-like osteosarcoma cells) were treated with dcOC (0, 0.3, 3, 10, or 30 ng/mL) for 1 and 72 h, and glucose uptake was measured by flow cytometry. The effect of dcOC on cell proliferation was measured with a CCK-8 assay, and alkaline phosphatase (ALP) enzyme activity was measured. PI3K was inhibited with LY294002, and hypoxia-inducible factor 1 alpha (HIF-1α) was silenced with siRNA. Then, GPRC6A (G protein-coupled receptor family C group 6 subtype A), total Akt, phosphorylated Akt, HIF-1α, and glucose transporter 1 (GLUT1) levels were measured by Western blot to elucidate the possible pathways by which dcOC modulates glucose uptake.

Results: The glucose uptake of MG63 cells was significantly increased compared with that of the paired control cells after short-term (1 h) treatment with dcOC at different concentrations (0.3, 3, and 10 ng/mL groups, < 0.01; 30 ng/mL group, < 0.05). Glucose uptake of MG63 cells was significantly increased compared with that of the paired control cells after long-term (72 h) treatment with dcOC at different concentrations (0.3, 3, and 10 ng/mL groups, < 0.01; 30 ng/mL group, < 0.05). DcOC triggered Akt phosphorylation in a dose-dependent manner, and the most effective stimulatory concentration of dcOC for short-term (1 h) was 3 ng/mL ( < 0.01). LY294002 abolished the dcOC-mediated (1 h) promotion of Akt phosphorylation and glucose uptake without affecting GLUT1 protein expression. Long-term dcOC stimulation triggered Akt phosphorylation and increased the protein levels of HIF-1α, GLUT1, and Runx2 in a dose-dependent manner. Inhibition of HIF-1α with siRNA abolished the dcOC-mediated glucose uptake and substantially decreased GLUT1 protein expression. DcOC intervention promoted cell proliferation in a time- and dose-dependent manner as determined by the CCK-8 assay. Treatment with both 3 ng/mL and 10 ng/mL dcOC affected the ALP activity in MG63 cells after 72 h ( < 0.01).

Conclusion: Short- and long-term dcOC treatment can increase glucose uptake and affect proliferation and ALP activity in MG63 cells. This effect may occur through the PI3K/Akt, HIF-1α, and GLUT1 signaling factors.
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http://dx.doi.org/10.4239/wjd.v12.i7.1102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311485PMC
July 2021

Small molecule inhibition of deubiquitinating enzyme JOSD1 as a novel targeted therapy for leukemias with mutant JAK2.

Leukemia 2021 Jul 29. Epub 2021 Jul 29.

Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Mutations in the Janus Kinase 2 (JAK2) gene resulting in constitutive kinase activation represent the most common genetic event in myeloproliferative neoplasms (MPN), a group of diseases involving overproduction of one or more kinds of blood cells, including red cells, white cells, and platelets. JAK2 kinase inhibitors, such as ruxolitinib, provide clinical benefit, but inhibition of wild-type (wt) JAK2 limits their clinical utility due to toxicity to normal cells, and small molecule inhibition of mutated JAK2 kinase activity can lead to drug resistance. Here, we present a strategy to target mutated JAK2 for degradation, using the cell's intracellular degradation machinery, while sparing non-mutated JAK2. We employed a chemical genetics screen, followed by extensive selectivity profiling and genetic studies, to identify the deubiquitinase (DUB), JOSD1, as a novel regulator of mutant JAK2. JOSD1 interacts with and stabilizes JAK2-V617F, and inactivation of the DUB leads to JAK2-V617F protein degradation by increasing its ubiquitination levels, thereby shortening its protein half-life. Moreover, targeting of JOSD1 leads to the death of JAK2-V617F-positive primary acute myeloid leukemia (AML) cells. These studies provide a novel therapeutic approach to achieving selective targeting of mutated JAK2 signaling in MPN.
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http://dx.doi.org/10.1038/s41375-021-01336-9DOI Listing
July 2021

Ultra-Fast Label-Free Serum Metabolic Diagnosis of Coronary Heart Disease via a Deep Stabilizer.

Adv Sci (Weinh) 2021 Jul 29:e2101333. Epub 2021 Jul 29.

State Key Laboratory for Oncogenes and Related Genes, School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, P. R. China.

Although mass spectrometry (MS) of metabolites has the potential to provide real-time monitoring of patient status for diagnostic purposes, the diagnostic application of MS is limited due to sample treatment and data quality/reproducibility. Here, the generation of a deep stabilizer for ultra-fast, label-free MS detection and the application of this method for serum metabolic diagnosis of coronary heart disease (CHD) are reported. Nanoparticle-assisted laser desorption/ionization-MS is used to achieve direct metabolic analysis of trace unprocessed serum in seconds. Furthermore, a deep stabilizer is constructed to map native MS results to high-quality results obtained by established methods. Finally, using the newly developed protocol and diagnosis variation characteristic surface to characterize sensitivity/specificity and variation, CHD is diagnosed with advanced accuracy in a high-throughput/speed manner. This work advances design of metabolic analysis tools for disease detection as it provides a direct label-free, ultra-fast, and stabilized platform for future protocol development in clinics.
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http://dx.doi.org/10.1002/advs.202101333DOI Listing
July 2021

Topologically convergent and divergent morphological gray matter networks in early-stage Parkinson's disease with and without mild cognitive impairment.

Hum Brain Mapp 2021 Jul 28. Epub 2021 Jul 28.

Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.

Patients with Parkinson's disease with mild cognitive impairment (PD-M) progress to dementia more frequently than those with normal cognition (PD-N), but the underlying neurobiology remains unclear. This study aimed to define the specific morphological brain network alterations in PD-M, and explore their potential diagnostic value. Twenty-four PD-M patients, 17 PD-N patients, and 29 healthy controls (HC) underwent a structural MRI scan. Similarity between interregional gray matter volume distributions was used to construct individual morphological brain networks. These were analyzed using graph theory and network-based statistics (NBS), and their relationship to neuropsychological tests was assessed. Support vector machine (SVM) was used to perform individual classification. Globally, compared with HC, PD-M showed increased local efficiency (p = .001) in their morphological networks, while PD-N showed decreased normalized path length (p = .008). Locally, similar nodal deficits were found in the rectus and lingual gyrus, and cerebellum of both PD groups relative to HC; additionally in PD-M nodal deficits involved several frontal and parietal regions, correlated with cognitive scores. NBS found that similar connections were involved in the default mode and cerebellar networks of both PD groups (to a greater extent in PD-M), while PD-M, but not PD-N, showed altered connections involving the frontoparietal network. Using connections identified by NBS, SVM allowed discrimination with high accuracy between PD-N and HC (90%), PD-M and HC (85%), and between the two PD groups (65%). These results suggest that default mode and cerebellar disruption characterizes PD, more so in PD-M, whereas frontoparietal disruption has diagnostic potential.
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http://dx.doi.org/10.1002/hbm.25606DOI Listing
July 2021

Infection Inhibits Histone Crotonylation to Regulate Immune Response of Porcine Alveolar Macrophages.

Front Immunol 2021 8;12:696061. Epub 2021 Jul 8.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

() is an obligate intracellular parasite that can infect almost all warm-blooded animals, causing serious public health problems. Lysine crotonylation (Kcr) is a newly discovered posttranslational modification (PTM), which is first identified on histones and has been proved relevant to procreation regulation, transcription activation, and cell signaling pathway. However, the biological functions of histone crotonylation have not yet been reported in macrophages infected with . As a result, a total of 1,286 Kcr sites distributed in 414 proteins were identified and quantified, demonstrating the existence of crotonylation in porcine alveolar macrophages. According to our results, identified histones were overall downregulated. HDAC2, a histone decrotonylase, was found to be significantly increased, which might be the executor of histone Kcr after parasite infection. In addition, infection inhibited the crotonylation of H2B on K12, contributing on the suppression of epigenetic regulation and NF-B activation. Nevertheless, the reduction of histone crotonylation induced by parasite infection could promote macrophage proliferation activating PI3K/Akt signaling pathway. The present findings point to a comprehensive understanding of the biological functions of histone crotonylation in porcine alveolar macrophages, thereby providing a certain research basis for the mechanism research on the immune response of host cells against infection.
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http://dx.doi.org/10.3389/fimmu.2021.696061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312545PMC
July 2021

Zuoguiwan Ameliorates Cognitive Deficits and Neuro-Inflammation in Streptozotocin-Induced Alzheimer's Disease Rats.

Neuroimmunomodulation 2021 Jul 28:1-7. Epub 2021 Jul 28.

Department of Biochemistry, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, China.

Introduction: Alzheimer's disease is the most popular neurodegenerative disorder with no effective drugs to stop the progression. Zuoguiwan (ZGW), a traditional Chinese herbal medicine, has been applied in many diseases. Our study aimed to detect the function and mechanisms of ZGW in Alzheimer's disease (AD).

Methods: The rat models of AD were established by streptozotocin (STZ), and the function of ZGW on cognitive dysfunction was measured with the Morris water maze test. The concentration of pro-inflammatory mediators was accessed by enzyme-linked immunosorbent assay. The relative mRNA expression of ERβ was detected by real-time quantitative PCR.

Results: The treatment with ZGW could suppress the cognitive impairment by the findings of escape latency and time spent in the target quadrant and the increased concentration of IL-1β, IL-6, and TNF-α induced by STZ. STZ might repress the mRNA levels of ERβ, and ZGW management weakened the declined mRNA expression of ERβ. ZGW might play a protective role in AD rats against the injury of STZ on cognition and neuro-inflammation by improving the mRNA expression of ERβ.

Conclusion: The results indicated that ZGW might be a novel therapeutic strategy to slow the process of AD by modulating ERβ.
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http://dx.doi.org/10.1159/000516396DOI Listing
July 2021

10-Day and 14-day high-dose dual therapy for the treatment of Helicobacter pylori: A propensity score matching analysis.

Helicobacter 2021 Jul 28:e12833. Epub 2021 Jul 28.

Department of Gastroenterology, Daping Hospital, Army Medical University, Chongqing, China.

Background: Inconsistent eradication rates for Helicobacter pylori have been reported worldwide with dual therapy, perhaps owing to the difference in dose administration and treatment duration. This retrospective study aimed to determine whether high-dose dual therapy (HDDT) with different regimens leads to different eradication rates. The study compares the efficacy and safety of HDDT 10-day vs 14-day and investigates the factors that might affect the eradication rates.

Materials And Methods: Two comparable treatment groups were based on propensity score matching (PSM). Patients were divided into two groups based on the therapy they underwent: 10-day HDDT and 14-day HDDT (20 mg esomeprazole and 750 mg amoxicillin, administered four times daily). The eradication rates, adverse events (AEs), patient compliance, CYP2C19 gene polymorphisms, and antibiotic resistance rates of the two groups were compared.

Results: The intention to treat (ITT) analysis showed that the eradication rates for 10-day and 14-day groups were 78.4% (95% CI 69.6%-87.2%) and 89.7% (95% CI 83.3%-96.2%; p = .039), respectively, while the per-protocol (PP) eradication rates were 80.0% (95% CI 71.3%-88.7%) and 92.9% (95% CI 87.4%-98.5%; p = .014), respectively. The corresponding drug-related AEs were 6.8% (6/88) and 5.7% (5/88; p = .755). No significant differences were observed between the compliance rates of the two groups. The CYP2C19 gene polymorphism had no effect on the eradication rates of the two groups.

Conclusion: The results showed that the 14-day HDDT affords a higher H. pylori eradication rate than the 10-day HDDT.
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http://dx.doi.org/10.1111/hel.12833DOI Listing
July 2021

Identification of CD105+ Extracellular Vesicles as a Candidate Biomarker for Metastatic Breast Cancer.

J Surg Res 2021 Jul 24;268:168-173. Epub 2021 Jul 24.

Department of Surgery, University of California San Diego, La Jolla, California. Electronic address:

Background: Extracellular vehicles (EVs) released by malignant tumor cells can mediate the immune response and promote metastasis through intercellular communication. EV analysis is an emerging cancer surveillance tool with advantages over traditional liquid biopsy methods. The aim of this pilot study is to identify actionable EV signatures in metastatic breast cancer.

Materials And Methods: Under an IRB-approved protocol for the analysis of patient plasma, samples were collected from women with newly diagnosed or progressive metastatic breast cancer and from women without cancer. Enriched EVs were analyzed via a bead-based multiplex assay designed to detect 37 distinct tumor-relevant epitopes. The mean fluorescent intensity of EV epitopes meeting a minimum threshold of detectability was compared between groups via independent samples t-test. Subgroup analysis was conducted for metastatic breast cancer patients who were positive for estrogen and/or progesterone receptors and negative for HER2. Other variables potentially affecting CD105 levels were also analyzed.

Results: CD105 was found to have a significantly higher mean fluorescent intensity in participants with metastatic breast cancer compared to control participants (P = 0.04). ER/PR+ subgroup analysis revealed a similar pattern compared to control participants (P = 0.01). Other analyzed variables were not found to have a significant correlation with CD105 levels.

Conclusions: CD105 EV levels were significantly higher in samples from participants with breast cancer compared to controls. Given that CD105 is known to mediate angiogenesis and promote metastasis, EV-associated CD105 in plasma represents a potential biomarker for diagnosis, surveillance and therapeutic targeting in patients with metastatic breast cancer.
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http://dx.doi.org/10.1016/j.jss.2021.06.050DOI Listing
July 2021

Adaptation of African swine fever virus to HEK293T cells.

Transbound Emerg Dis 2021 Jul 27. Epub 2021 Jul 27.

State Key Laboratory of Veterinary Biotechnology, National High Containment Facilities for Animal Diseases Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.

African swine fever (ASF), caused by African swine fever virus (ASFV), is a highly contagious disease with high morbidity and mortality in domestic pigs. Although adaptation of ASFV to Vero cells has been investigated, the phenotypic changes and the corresponding genomic variations during adaptation of ASFV to other cell lines remain unclear. To obtain a cell-adapted ASFV strain, different cell lines were tested to determine whether they support ASFV infection. Interestingly, the ASFV wild-type strain ASFV-HLJ/18 can infect HEK293T cells and replicate at a low level. After continuous passaging, the adapted ASFV strain can replicate efficiently in both HEK293T and Vero cells. However, the adapted ASFV strain displayed reduced infectivity in primary porcine alveolar macrophages compared to the corresponding wild-type strain. Furthermore, stepwise losses at the left variable end of the MGF genes and accumulative mutations were identified during passaging, indicating that the ASFV strain gradually adapted to HEK293T cells. Comparison of MGF deletions in other cell culture-adapted ASFV strains revealed that the deletions of MGF300 (1L, 2R and 4L) and MGF360 genes (8L, 9L, 10L and 11L) play an important role for the adaptation of ASFV to HEK293T cells at the early stage. The biological functions of the deletions and mutants associated with ASFV infection in HEK293T cells and pigs warrant further study. Overall, our findings provide new targets to elucidate the molecular mechanism of adaptation of ASFV to cell lines.
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http://dx.doi.org/10.1111/tbed.14242DOI Listing
July 2021

sp. nov. and sp. nov., isolated from faeces of Tibetan antelope () and leaves of dandelion (), respectively, on the Qinghai-Tibet Plateau.

Int J Syst Evol Microbiol 2021 Jul;71(7)

Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.

In the present study, four bacterial strains, two (S-713 and 406) isolated from faecal samples of Tibetan antelopes and the other two (S-531 and 1598) from leaves of dandelion collected on the Qinghai-Tibet Plateau of PR China, were analysed using a polyphasic approach. All four isolates were aerobic, rod-shaped, non-motile, oxidase-negative, Gram-stain-positive and catalase-positive. According to four phylogenetic trees, strain pairs S-713/406 and S-531/1598 form two independent branches belonging to the genus , and are closest to , , , , and . Although sharing MK8-(H) as their major isoprenoid quinone, strains S-713 and S-531 contained C 9 (24.64 and 16.34 %) and iso-C (9.74 and 29.38 %), respectively, as their main fatty acids, with remarkable differences in their biochemical profiles but only slight ones in their optimal growth conditions. The chromosomes of strains S-713 and S-531 were 4 207 844 bp (G+C content, 73.0 mol%) and 4 809 817 bp (G+C content, 72.5 mol%), respectively. Collectively, the two strain pairs represent two separate novel species of the genus , for which the names sp. nov. and sp. nov. are proposed, with S-713 (=JCM 33698=CGMCC 4.7660) and S-531 (=JCM 33468=CGMCC 4.7659) as the respective type strains.
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http://dx.doi.org/10.1099/ijsem.0.004920DOI Listing
July 2021

Pharmacist-led, prescription intervention system-assisted feedback to reduce prescribing errors: A retrospective study.

J Clin Pharm Ther 2021 Jul 27. Epub 2021 Jul 27.

Department of Intensive Care Unit, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.

What Is Known And Objective: Prescribing errors are prevalent in hospital settings, with provision of feedback recommended to support prescribing by doctors. To evaluate the impact of a pharmacist-led prescription intervention system on prescribing error rates and to measure intervention efficiency.

Methods: All prescribers in Shandong Provincial Third Hospital received feedback from ward pharmacists using a pharmacist-led prescription intervention system. The prescribing error rate was calculated from Oct 2019 to December 2020. After the intervention was applied, the rates of PASS 1 (System pass), PASS 2 (Pharmacist pass) and PASS 3 (Pharmacist-doctor pass) events and the feedback time were calculated each month.

Results And Discussion: Irrational use of drugs was reduced and the prescription rate increased significantly. The error rate reduced from 6.94% to 1.96%, representing an estimated 71.76% decrease overall (p < 0.05). The PASS 1 rate gradually increased from 88% to 96% (p < 0.05), the PASS 2 rate gradually decreased from 5.06% to 2.04% (p < 0.05), the PASS 3 rate gradually decreased from 6.94% to 1.96% (p < 0.05).

What Is New And Conclusion: The pharmacist-led prescription intervention system has the potential to reduce prescribing errors and improve prescribing outcomes and patient safety.
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http://dx.doi.org/10.1111/jcpt.13491DOI Listing
July 2021

Genetic Depletion of Amylin/Calcitonin Receptors Improves Memory and Learning in Transgenic Alzheimer's Disease Mouse Models.

Mol Neurobiol 2021 Jul 27. Epub 2021 Jul 27.

Department of Medicine (Neurology), Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, T6G 2S2, Canada.

Based upon its interactions with amyloid β peptide (Aβ), the amylin receptor, a class B G protein-coupled receptor (GPCR), is a potential modulator of Alzheimer's disease (AD) pathogenesis. However, past pharmacological approaches have failed to resolve whether activation or blockade of this receptor would have greater therapeutic benefit. To address this issue, we generated compound mice expressing a human amyloid precursor protein gene with familial AD mutations in combination with deficiency of amylin receptors produced by hemizygosity for the critical calcitonin receptor subunit of this heterodimeric GPCR. These compound transgenic AD mice demonstrated attenuated responses to human amylin- and Aβ-induced depression of hippocampal long-term potentiation (LTP) in keeping with the genetic depletion of amylin receptors. Both the LTP responses and spatial memory (as measured with Morris water maze) in these mice were improved compared to AD mouse controls and, importantly, a reduction in both the amyloid plaque burden and markers of neuroinflammation was observed. Our data support the notion of further development of antagonists of the amylin receptor as AD-modifying therapies.
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http://dx.doi.org/10.1007/s12035-021-02490-yDOI Listing
July 2021

The sugar transporter system of strawberry: genome-wide identification and expression correlation with fruit soluble sugar-related traits in a Fragaria × ananassa germplasm collection.

Hortic Res 2020 Jul 27;7(1):132. Epub 2020 Jul 27.

Shanghai Key Laboratory of Protected Horticultural Technology, Forestry and Fruit Tree Research Institute, Shanghai Academy of Agricultural Sciences (SAAS), Shanghai, 201403, China.

Sugar from plant photosynthesis is a basic requirement for life activities. Sugar transporters are the proteins that mediate sugar allocation among or within source/sink organs. The transporters of the major facilitator superfamily (MFS) targeting carbohydrates represent the largest family of sugar transporters in many plants. Strawberry (Fragaria × ananassa Duchesne) is an important crop appreciated worldwide for its unique fruit flavor. The involvement of MFS sugar transporters (STs) in cultivated strawberry fruit sugar accumulation is largely unknown. In this work, we characterized the genetic variation associated with fruit soluble sugars in a collection including 154 varieties. Then, a total of 67 ST genes were identified in the v4.0 genome integrated with the v4.0.a2 protein database of F. vesca, the dominant subgenome provider for modern cultivated strawberry. Phylogenetic analysis updated the nomenclature of strawberry ST homoeologs. Both the chromosomal distribution and structural characteristics of the ST family were improved. Semi-RT-PCR analysis in nine tissues from cv. Benihoppe screened 34 highly expressed ST genes in fruits. In three varieties with dramatically differing fruit sugar levels, qPCR integrated with correlation analysis between ST transcript abundance and sugar content identified 13 sugar-correlated genes. The correlations were re-evaluated across 19 varieties, including major commercial cultivars grown in China. Finally, a model of the contribution of the sugar transporter system to subcellular sugar allocation in strawberry fruits was proposed. Our work highlights the involvement of STs in controlling strawberry fruit soluble sugars and provides candidates for the future functional study of STs in strawberry development and responses and a new approach for strawberry genetic engineering and molecular breeding.
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http://dx.doi.org/10.1038/s41438-020-00359-0DOI Listing
July 2020

The association between ECG criteria and Echo criteria for left ventricular hypertrophy in a general Chinese population.

Ann Noninvasive Electrocardiol 2021 Jul 26:e12880. Epub 2021 Jul 26.

Department of Cardiology, Tsinghua University, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Beijing, China.

Background: Several ECG criteria have been widely used for diagnosis of left ventricular hypertrophy (LVH) in clinical practice. However, their performance in a general Chinese population is limited.

Methods And Results: A multi-stage, stratified cluster sampling across China was performed and 7415 representative Chinese adults aged 18-85 years were analyzed. ECG was collected by using GE MAC 5500 machine. The association between five ECG-LVH criteria (i.e., Peguero-Lo Presti, Cornell, Cornell product, Sokolow-Lyon and Sokolow-Lyon product) and echocardiographic LVH (Echo-LVH) was assessed by Pearson's correlation, diagnostic statistics like predictive values, and receiver operating characteristics (ROC) curve. We found that the prevalence of the Echo-LVH was 11% while ECG-LVH ranged from 3% to 27%. All ECG-LVH criteria had high negative predictive value (NPV) (89%) and specificity (73-96%) but low positive predictive value (PPV) (12-24%) and sensitivity (4-29%). The newly Peguero-Lo Presti criteria had higher sensitivity (29%) but lower specificity (73%) and accuracy (68%) compared with other criteria. Cornell product had the best diagnostic performance (AUC: 0.59), as well as the highest specificity (96%) and accuracy (86%) but lowest sensitivity (4%). Among single-lead components of ECG criteria, R voltage and QRS duration performed relatively better than others. Hypertensive and older individuals had higher sensitivity but lower specificity and accuracy than their counterparts.

Conclusion: ECG-LVH criteria had high NPV to detect Echo-LVH. Though with higher sensitivity, Peguero-Lo Presti criteria did not have better diagnostic performance to detect Echo-LVH. R and QRS duration had stronger association with Echo-LVH among all single-lead components.
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http://dx.doi.org/10.1111/anec.12880DOI Listing
July 2021

PI3K/Akt pathway expression in children with different obesity degrees and its relationship with glucolipid metabolism and insulin resistance.

Am J Transl Res 2021 15;13(6):6592-6598. Epub 2021 Jun 15.

Department of Endocrinology, Zhuji People's Hospital of Zhejiang Province Zhuji 311800, Zhejiang, China.

Objective: This study investigated and analyzed the expression of PI3K/Akt pathway in children with different degree of obesity and its connection with glucolipid metabolism and insulin resistance (IR).

Methods: 157 children with simple obesity, who admitted to our hospital from March 2020 to September 2020, were enrolled as obesity group. These children were divided into mild-group (n=67), moderate-group (n=55) and severe-group (n=35) referring to their body mass index (BMI). Another 60 healthy children admitted to hospitalized were randomly chosen as control group. The expression of PI3K mRNA and Akt mRNA in peripheral blood mononuclear cells (PBMCs) of each group were detected by RT-PCR, and its connection with glucose and lipid metabolism, as well as IR was analyzed.

Results: Each group of children had insignificant difference in FBG (Fasting blood glucose) level (). The triglyceride (TG), total cholesterol (TC), Low-density lipoprotein (LDL), Fasting insulin (FINS) and Homeostasis model assessment insulin resistance (HOMA-IR) levels in each obesity group were substantially higher than those in control group (), and these levels decreased remarkably with the increase of obesity severity (). The high-density lipoprotein (HDL) level of children in each obesity group was notably lower than that of the control group (), and the level decreased remarkably with the ascending degree of obesity (). The levels of PI3K mRNA and Akt mRNA in PBMCs of children in each obesity group were obviously lower than those in control group (), and these index levels decreased much with the increasing worsen of children's obesity degree (). The relative expression of PI3K mRNA and Akt mRNA in children with simple obesity was negatively correlated with TG, TC, LDL, FINS and HOMA-IR (), positively correlated with HDL (), and was not associated with FBG level ().

Conclusion: The inhibition of PI3K/Akt signaling pathway in children with simple obesity is associated with the abnormal glucolipid metabolism and IR, which affects the occurrence and progression of obesity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290792PMC
June 2021

Identification of the SARS-CoV-2 Entry Receptor ACE2 as a Direct Target for Transcriptional Repression by Miz1.

Front Immunol 2021 7;12:648815. Epub 2021 Jul 7.

Department of Surgery, College of Medicine and University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL, United States.

Multiple lines of evidence have demonstrated that cigarette smoke or Chronic Obstructive Pulmonary Disease upregulates angiotensin-converting enzyme 2, the cellular receptor for the entry of the severe acute respiratory syndrome coronavirus 2, which predisposes individuals to develop severe Coronavirus disease 2019. The reason for this observation is unknown. We recently reported that the loss of function of Miz1 in the lung epithelium in mice leads to a spontaneous COPD-like phenotype, associated with upregulation of angiotensin-converting enzyme 2. We also reported that cigarette smoke exposure downregulates Miz1 in lung epithelial cells and in mice, and Miz1 is also downregulated in the lungs of COPD patients. Here, we provide further evidence that Miz1 directly binds to and represses the promoter of angiotensin-converting enzyme 2 in mouse and human lung epithelial cells. Our data provide a potential molecular mechanism for the upregulation of angiotensin-converting enzyme 2 observed in smokers and COPD patients, with implication in severe Coronavirus disease 2019.
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http://dx.doi.org/10.3389/fimmu.2021.648815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292894PMC
July 2021

Autosomal recessive hyper-IgE syndrome caused by DOCK8 gene mutation with new clinical features: a case report.

Authors:
Jing Yang Yan Liu

BMC Neurol 2021 Jul 23;21(1):288. Epub 2021 Jul 23.

Tong Ji Hospital, Tong Ji Medical College, Huazhong University of Science and Technology, jiefang Ave. No. 1095, Wuhan, 430030, China.

Background: Autosomal recessive hyper-IgE syndrome (AR-HIES) caused by DOCK8 gene is a rare immunodeficiency disease, the main clinical manifestations include recurrent Eczema-like rash, skin and lung abscesses, accompanied with increased serum IgE level. Here, we report a 7-year-old Chinese girl with a new clinic features caused by DOCK8 gene mutations.

Case Presentation: A 7-year-old girl was admitted to our hospital because of abnormal walking posture. The clinical manifestations of the patient included abnormal gait, eczema-like rash, fingertip abscess, high muscle tone, and facial paralysis. Among them, high muscle tone and facial paralysis are new clinic features which have not been reported previously. The blood eosinophils and serum IgE levels were significantly increased, and the lymphocyte subsets indicated a decrease of T lymphocytes. The magnetic resonance imaging (MRI) of her brain suggested myelin dysplasia and brain atrophy. Two novel compound heterozygous mutations (c.1868 + 2 T > C and c.5962-2A > G) of DOCK8 gene were identified by whole exome sequencing. By literature review, there are 11 mutations of DOCK8 gene in Chinese AR-HIES patients.

Conclusions: Two novel splice-site mutations(c.1868 + 2 T > C and c.5962-2A > G) of DOCK8 gene and new clinic features were found in a Chinese girl with AR-HIES, which extends our understanding of DOCK8 gene mutation spectrum and phenotype of AR-HIES in children.
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http://dx.doi.org/10.1186/s12883-021-02324-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299654PMC
July 2021

Dimethyl Sulfoxide-Free Cryopreservation of Human Umbilical Cord Mesenchymal Stem Cells Based on Zwitterionic Betaine and Electroporation.

Int J Mol Sci 2021 Jul 12;22(14). Epub 2021 Jul 12.

Department of Emerging Transfusion Technology, Institute of Health Service and Transfusion Medicine, Academy of Military Medical Sciences, Beijing 100850, China.

The effective cryopreservation of mesenchymal stem cells (MSCs) is indispensable to the operation of basic research and clinical transplantation. The prevalent protocols for MSC cryopreservation utilize dimethyl sulfoxide (DMSO), which is easily permeable and able to protect MSCs from cryo-injuries, as a primary cryoprotectant (CPA). However, its intrinsic toxicity and adverse effects on cell function remain the bottleneck of MSC cryopreservation. In this work, we cryopreserved human umbilical cord mesenchymal stem cells (UCMSCs) using zwitterionic betaine combined with electroporation without any addition of DMSO. Betaine was characterized by excellent compatibility and cryoprotective properties to depress the freezing point of pure water and balance the cellular osmotic stress. Electroporation was introduced to achieve intracellular delivery of betaine, intending to further provide comprehensive cryoprotection on UCMSCs. Compared with DMSO cryopreservation, UCMSCs recovered from the protocol we developed maintained the normal viability and functions and reduced the level of reactive oxygen species (ROS) that are harmful to cell metabolism. Moreover, the in vivo distribution of thawed UCMSCs was consistent with that of fresh cells monitored by a bioluminescence imaging (BLI) system. This work opens a new window of opportunity for DMSO-free MSC cryopreservation using zwitterionic compounds like betaine combined with electroporation.
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http://dx.doi.org/10.3390/ijms22147445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306716PMC
July 2021
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