Publications by authors named "Ting Yan"

236 Publications

Rufinamide (RUF) suppresses inflammation and maintains the integrity of the blood-brain barrier during kainic acid-induced brain damage.

Open Life Sci 2021 25;16(1):845-855. Epub 2021 Aug 25.

Department of Clinical Skills Training Center of ZhuJiang Hospital, ZhuJiang Hospital of Southern Medical University, Guangzhou 510282, China.

Rufinamide (RUF) is a structurally unique anti-epileptic drug, but its protective mechanism against brain injury remains unclear. In the present study, we validated how the RUF protected mice with kainic acid (KA)-induced neuronal damage. To achieve that, a mouse epilepsy model was established by KA intraperitoneal injection. After Nissl staining, although there was a significant reduction in Nissl bodies in mice treated with KA, 40, 80, and 120 mg/kg, RUF significantly reduced KA-induced neuronal damage, in a dose-dependent manner. Among them, 120 mg/kg RUF was most pronounced. Immunohistochemistry (IHC) and western blot analysis showed that RUF inhibited the IBA-1 overexpression caused by KA to block microglia cell overactivation. Further, RUF treatment partially reversed neuroinflammatory cytokine (IL-1β, TNFα, HMGB1, and NLRP3) overexpression in mRNA and protein levels in KA mice. Moreover, although KA stimulation inhibited the expression of tight junctions, RUF treatment significantly upregulated expression of tight junction proteins (occludin and claudin 5) in both mRNA and protein levels in the brain tissues of KA mice. RUF inhibited the overactivation of microglia, suppressed the neuroinflammatory response, and reduced the destruction of blood-brain barrier, thereby alleviating the excitatory nerve damage of the KA-mice.
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http://dx.doi.org/10.1515/biol-2021-0090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389504PMC
August 2021

Synergistic mechanism of Ni(OH)/NiMoS heterostructure electrocatalyst with crystalline/amorphous interfaces for efficient hydrogen evolution over all pH ranges.

J Colloid Interface Sci 2021 Aug 18;606(Pt 2):1004-1013. Epub 2021 Aug 18.

Research Institute of Comprehensive Energy Industry Technology, College of Chemistry & Chemical Engineering, Yan'an University, Yan'an 716000, Shaanxi, China. Electronic address:

Designing and fabricating efficient electrocatalysts is a practical step toward the commercial application of the efficient hydrogen evolution reaction (HER) over all pH ranges. Herein, novel [email protected](OH)-NiMoS heterostructure with interface between crystalline Ni(OH) and amorphous NiMoS was rationally designed and fabricated on Ti mesh (denoted as [email protected](OH)-NiMoS). Acid etching and calcination experiments helped in accurate elucidation of the synergistic mechanism as well as the vital role on crystalline Ni(OH) and amorphous NiMoS. In acidic solutions, the HER performance of [email protected](OH)-NiMoS was mainly attributed to the amorphous NiMoS. In neutral, alkaline, and natural seawater solutions, the HER performance was mainly determined by the synergistic interface behaviors between the Ni(OH) and NiMoS. The crystalline Ni(OH) accelerated water dissociation kinetics, while the amorphous NiMoS provided abundant active sites and allowed for fast electron transfer rates. To deliver current densities of 10 mA·cm in acidic, neutral, alkaline, and natural seawater solutions, the [email protected](OH)-NiMoS required overpotentials of 138, 198, 180 and 371 mV, respectively. This paper provides general guidelines for designing efficient electrocatalyst with crystalline/amorphous interfaces for efficient hydrogen evolution over all-pH ranges.
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http://dx.doi.org/10.1016/j.jcis.2021.08.090DOI Listing
August 2021

Application of a novel phage vB_SalS-LPSTLL for the biological control of Salmonella in foods.

Food Res Int 2021 09 4;147:110492. Epub 2021 Jun 4.

Key Laboratory of Environment Correlative Dietology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China; State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China; Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY, USA. Electronic address:

Salmonella is one of the most common foodborne pathogens around the world. Phages are envisioned as a new strategy to control foodborne pathogenic bacteria and food safety. A Salmonella specific lytic phage vB_SalS-LPSTLL (LPSTLL) was selected for food applications on the basis of lytic range, lytic efficiency, functional stability and characteristics. Phage LPSTLL was able to lyse 11 Salmonella serotypes, which represents the broadest range reported Salmonella phages, and was able to suppress the growth of Salmonella enterica in liquid culture over nine hours. LPSTLL exhibited rapid reproductive activity with a short latent period and a large burst size in one-step growth experiment. LPSTLL remained active over a pH range of 3.0 to 12.0, and at incubation temperatures up to 60 °C for 60 min, indicating wide applicability for food processing and storage. Significant reductions of viable Salmonella were observed in diverse foods (milk, apple juice, chicken and lettuce) with reductions up to 2.8 log CFU/mL recorded for milk. Sensory evaluation indicated that treatment with phage LPSTLL did not alter the visual or tactile quality of food matrices. Genome analysis of LPSTLL indicated the absence of any virulence or antimicrobial resistance genes. Genomic comparisons suggest phage LPSTLL constitutes a novel member of a new genus, the LPSTLLvirus with the potential for Salmonella biocontrol in the food industry.
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http://dx.doi.org/10.1016/j.foodres.2021.110492DOI Listing
September 2021

ZNF326 promotes colorectal cancer epithelial-mesenchymal transition.

Pathol Res Pract 2021 Sep 22;225:153554. Epub 2021 Jul 22.

Department of Pathology, College of Basic Medical Science, and the First Affiliated Hospital of China Medical University, Shenyang, China. Electronic address:

Zinc-finger protein 326 (ZNF326) activity has been reported in different tumors, but its expression and possible mechanism of action in colorectal cancer are not known. In this study, we applied immunohistochemistry to detect the expression of ZNF326 in colorectal tissues. Next, we used a ZNF326 expression plasmid and small interfering (si) RNA-ZNF326 (siZNF326) to transfect colorectal cancer cell lines in order to determine the effect of ZNF326 on cell migration and as well as its potential role in promoting epithelial-mesenchymal transition (EMT). A higher ZNF326 expression in the nuclei of colorectal tumor cells compared to normal mucosa was observed (70.3%, 109/155 specimens vs. 23.2%, 36/155 specimens). A high ZNF326 expression level was positively correlated with tumor differentiation, tumor-node-metastasis (TNM) staging, and lymph node metastasis. Transfection of cancer cell lines (SW480 and SW620) with a ZNF326-overexpression vector promoted colorectal cancer cell invasion and altered the expression of EMT-related proteins. Vimentin, N-cadherin, Snail, and Slug were upregulated, whereas E-cadherin and zonula occludens-1 (ZO-1) were downregulated. In contrast, downregulation of ZNF326 expression using siRNA-ZNF326 in cancer cell lines (CL187 and RKO) resulted in the opposite findings. ZNF326 overexpression also upregulated the expression of latent transforming growth factor beta binding protein 4 (LTBP4) and p-Smad2/3. In conclusion, ZNF326 promoted the EMT and invasiveness of colorectal cancer cells. These findings are likely due to LTBP4 and p-Smad2/3 upregulation and, in turn, transforming growth factor beta (TGF-β) signaling activation.
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http://dx.doi.org/10.1016/j.prp.2021.153554DOI Listing
September 2021

Near-infrared emissive polymer-coated IR-820 nanoparticles assisted photothermal therapy for cervical cancer cells.

J Biophotonics 2021 Jul 31:e202100117. Epub 2021 Jul 31.

State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, School of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, China.

Photothermal therapy (PTT) has attracted wide attention due to its noninvasiveness and its thermal ablation ability. As photothermal agents are crucial factor in PTT, those with the characteristics of biocompatibility, non-toxicity and high photothermal stability have attracted great interest. In this work, new indocyanine green (IR-820) was utilized as a photothermal agent and near-infrared (NIR) fluorescence imaging nanoprobe. To improve the biocompatibility, poly(styrene-co-maleic anhydride) (PSMA) was utilized to encapsulate the IR-820 molecules to form novel [email protected] nanoparticles (NPs). Then, the optical and thermal properties of [email protected] NPs were studied in detail. The [email protected] NPs showed excellent photothermal stability and biocompatibility. The cellular uptaking ability of the [email protected] NPs was further confirmed in HeLa cells by the NIR fluorescent confocal microscopic imaging technique. The [email protected] NPs assisted PTT of living HeLa cells was conducted under 793 nm laser excitation, and a high PTT efficiency of 73.3% was obtained.
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http://dx.doi.org/10.1002/jbio.202100117DOI Listing
July 2021

Safe and Effective Treatment for Anemic Patients With Chronic Kidney Disease: An Updated Systematic Review and Meta-Analysis on Roxadustat.

Front Pharmacol 2021 2;12:658079. Epub 2021 Jul 2.

Department of Pharmacy, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.

Roxadustat is a new oral drug for anemia in chronic kidney disease (CKD). This study aimed to synthesize the evidence from randomized controlled trial (RCT)-based studies that estimated the efficacy and safety of roxadustat in anemia patients with non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD. We searched the PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for related published studies. Moreover, we manually searched relevant pharmaceutical company websites and two international clinical trial registers to search for published and unpublished RCTs comparing roxadustat with erythropoietin-stimulating agents (ESAs) or placebo. Fifteen RCTs (seven for DD-CKD patients, eight for NDD-CKD patients) were included in the meta-analysis, with 10,189 patients, 4,810 DD-CKD patients, and 5,379 NDD-CKD patients enrolled. Compared with ESAs (epoetin alfa or darbepoetin alfa) and placebo, roxadustat raised the hemoglobin level [weighted mean difference (WMD): 0.82 g/dL; 95% confidence interval (CI): 0.43-1.21], transferrin level (WMD: 0.5 g/L; 95% CI: 0.34-0.65), and TIBC level (WMD: 41.79 μg/dL; 95% CI: 38.67-44.92) and lowered the hepcidin level (WMD: -37.38 ng/ml; 95% CI: -46.63- -28.12) in both the DD-CKD and NDD-CKD patients with renal anemia. Roxadustat improved hemoglobin response and lowered the ferritin and TAST levels in the NDD-CKD patients but not in the DD-CKD patients. Furthermore, there was no difference between the treatment-emergent adverse events (TEAEs) of roxadustat and that of ESAs or placebo. But the incidence of serious TEAEs in the roxadustat group was significantly higher with NDD-CKD patients (OR: 1.15; 95% CI: 1.02-1.29). This study confirmed that roxadustat therapy could alleviate the anemia of DD-CKD and NDD-CKD patients by raising the hemoglobin level and regulating iron metabolism, but increased serious incidences of treatment-emergent adverse events (TEAEs) in NDD-CKD patients.
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http://dx.doi.org/10.3389/fphar.2021.658079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283176PMC
July 2021

AKT1 is positively regulated by G-quadruplexes in its promoter and 3'-UTR.

Biochem Biophys Res Commun 2021 07 18;561:93-100. Epub 2021 May 18.

Key Laboratory of Saline-alkali Vegetation Ecology Restoration, Ministry of Education, College of Life Science, Northeast Forestry University, Harbin, 150040, China. Electronic address:

AKT1 plays a key role in cell growth and survival, and its activation in cancers is mediated by different mechanisms. In this study, we investigated the potential of G-quadruplex (G4) formation by multiple consecutive G-tracts in the AKT1 promoter and its 3'-UTR. In circular dichroism analyses, synthetic oligonucleotides based on these G-tract regions showed molar ellipticity peaks at specific wavelengths of G4 structures. We verified G4 forming potential of these oligonucleotides using dimethyl sulfate footprinting, gel-shift and immunostaining assays. In reporter assays, mutations of the G-tracts in either the promoter or the 3'-UTR of AKT1 reduced expression mediated by these G-rich regions, suggesting positive regulation of AKT1 gene expression by these G4 structures. Furthermore, SP1 bound to its consensus sites regardless of the presence of G4 motifs in the AKT1 promoter, and both the G4 motifs and SP1 binding sites were needed to reach the strongest promoter strength.
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http://dx.doi.org/10.1016/j.bbrc.2021.05.029DOI Listing
July 2021

HLA-DPB1 rs9277535 polymorphism is associated with rheumatoid arthritis risk in a Chinese Han population.

Aging (Albany NY) 2021 04 19;13(8):11696-11704. Epub 2021 Apr 19.

Department of Orthopedics, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou 213003, China.

We used a custom-by-design 48-Plex single nucleotide polymorphism scan™ kit to investigate the relationship between susceptibility to rheumatoid arthritis (RA) and HLA-DPB1 rs9277535 polymorphism in 805 RA patients and 1095 healthy controls from the Chinese Han population. Blood plasma levels of HLA-DPB1 were also examined using enzyme-linked immunosorbent assays in 170 RA patients and 170 matched control individuals. Quantitative reverse transcription PCR (qRT-PCR) was used to evaluate relative HLA-DPB1 mRNA levels in these blood samples as well. The results indicated that some HLA-DPB1 rs9277535 polymorphisms decreased RA susceptibility. Stratified analysis indicated that risk of RA decreased specifically in women and those who were at least 55 years old. In addition, the AG and GG+AG genotypes were associated with CRP status, ACPA status, and ESR in RA patients when the AA genotype was used as the reference group. Furthermore, average HLA-DPB1 plasma levels were increased in RA patients, and HLA-DPB1 plasma levels and mRNA expression were lower in those with the GG genotype than in those with the AA genotype. These results indicate that HLA-DPB1 rs9277535 polymorphism is associated with a decreased risk of RA in the Chinese population.
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http://dx.doi.org/10.18632/aging.202864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109103PMC
April 2021

Has Potential to Be a Prognosis Marker for Cervical Squamous Cell Carcinoma and an Index for Tumor Microenvironment Change.

Front Mol Biosci 2021 1;8:583028. Epub 2021 Apr 1.

Department of Gynecology, Guizhou Provincial People's Hospital, Medical College of Guizhou University, Guiyang, China.

The tumor microenvironment (TME) has an essential role in the development of cervical squamous cell carcinoma (CSCC); however, the dynamic role of the stromal and immune cells is still unclear in TME. We downloaded data from The Cancer Genome Atlas (TCGA) database and applied ESTIMATE and CIBERSORT algorithms to measure the quantity of stromal and immune cells and the composition of tumor-infiltrating immune cell (TIC) in 253 CSCC cases. The protein-protein interaction (PPI) network and Cox regression analysis presented the differentially expressed genes (DEGs). Then, C-C chemokine receptor type 7 () was screened out as a prognostic marker by the univariate Cox and intersection analysis of PPI. Further analysis showed a positive correlation between the expression of and the survival of CSCC patients. The result of the Gene Set Enrichment Analysis (GSEA) of genes in the high expression group displayed a predominant enrichment in immune-related pathways. An enrichment in metabolic activities was observed in the low expression group. CIBERSORT analysis showed a positive correlation between Plasma cells, CD8 T cells, and regulatory T cells and the expression, suggesting that might play a crucial role in maintaining the immunological dominance status for TME. Therefore, the expression level of might help predict the survival of CSCC cases and be an index that the status of TME transitioned from immunological dominance to metabolic activation, which presented a new insight into the treatment of CSCC.
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http://dx.doi.org/10.3389/fmolb.2021.583028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047428PMC
April 2021

Transcriptome Analysis of Ivosidenib-Mediated Inhibitory Functions on Non-Small Cell Lung Cancer.

Front Oncol 2021 30;11:626605. Epub 2021 Mar 30.

Department of Respiratory and Critical Care Medicine, The First Hospital, Shanxi Medical University, Taiyuan, China.

Ivosidenib is an isocitrate dehydrogenase mutant inhibitor that the US Food and Drug Administration recently approved for the treatment of leukemia. Studies suggested that ivosidenib may inhibit the progression of non-small cell lung cancer (NSCLC). In the present study, we explored RNAs and their potential regulatory mechanisms by which ivosidenib treats NSCLC cells. We used MTT assays, Transwell assays, and flow cytometry to measure the anti-tumor effects of ivosidenib in NSCLC cells. We performed whole transcriptome sequencing to determine differentially expressed mRNAs (DE-mRNAs) and non-coding RNAs (ncRNA). We used GO and KEGG pathway enrichment analyses to identify the functions and potential mechanisms. According to miRNA target interactions, we constructed a competing endogenous network. Ivosidenib inhibited the proliferation, invasion, and migration of NSCLC cells and inhibited tumor growth . We identified 212 DE-mRNAs, four DE-miRNAs, and 206 DE-lncRNAs in ivosidenib-treated NSCLC cells compared to untreated NSCLC cells. DE-mRNAs were significantly enriched in the cancer-associated pathways, including the TGF-β signaling pathway, the PI3K-Akt signaling pathway, the Jak-STAT signaling pathway, the MAPK signaling pathway, the Rap1 signaling pathway, and cell adhesion molecules. Based on the competing endogenous RNA hypothesis, we constructed lncRNA-miRNA-mRNA networks to elucidate the regulatory relationships between mRNA and ncRNA. We found that qRT-PCR results showed corresponding expression trends of differential genes with sequencing data. Our results provide insights into the molecular basis of ivosidenib suppression of NSCLC.
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http://dx.doi.org/10.3389/fonc.2021.626605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042334PMC
March 2021

Feasibility of modified radical mastectomy with nipple-areola preservation combined with stage I prosthesis implantation using air cavity-free suspension hook in patients with breast cancer.

World J Surg Oncol 2021 Apr 10;19(1):108. Epub 2021 Apr 10.

Department of Second Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, China.

Background: Mastoscopic surgery is proven to have lower incidence of postoperative complications and better postoperative recovery than traditional breast cancer surgery. This study aimed to examine the feasibility of mastoscopic modified radical mastectomy (MRM) with skin nipple-areola preservation under air cavity-free suspension hook and stage I silicone prosthesis implantation (SMALND) compared with routine MRM.

Methods: This was a retrospective study of patients who underwent MRM for breast cancer at the Shengjing Hospital Affiliated to China Medical University between January 1, 2019, and June 30, 2019. Surgical outcomes, complications, satisfaction, and quality of life (Functional Assessment of Cancer Therapy-Breast [FACT-B] [Chinese version]) were compared between the two groups.

Results: A total of 87 patients were enrolled, with 30 underwent SMALND and 57 underwent routine MRM. The intraoperative blood loss in the SMALND group was lower than in the control group (165.3±44.1 vs. 201.4±52.7 ml, P=0.001), the operation time was longer (220.5±23.9 vs. 155.6±9.2 min, P<0.001), daily axillary drainage volume was smaller (20.2±3.6 vs. 24.1±3.0 ml, P<0.001), daily subcutaneous drainage volume was smaller (15.5±2.3 vs. 19.3±3.5 ml, P<0.001), the discharge time was shorter (7.5±1.6 vs. 9.0±1.8 days, P<0.001), and FACT-B scores were higher (83.8±5.6 vs. 72.1±4.6, P<0.001). The overall satisfaction was higher in the SMALND group than in the controls (76.7% vs. 54.4%, P=0.041). Compared with the controls, the occurrence rates of nipple and flap necrosis, upper limb edema, and paraesthesia in the SMALND group were lower within 6 months (all P<0.05).

Conclusions: Compared with traditional MRM, SMALND had better surgical outcomes, higher satisfaction, higher quality of life, and lower complication rates.
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http://dx.doi.org/10.1186/s12957-021-02220-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037831PMC
April 2021

Cancer Stem Cell Initiation by Tumor-Derived Extracellular Vesicles.

Methods Mol Biol 2021 Mar 24. Epub 2021 Mar 24.

Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, Japan.

Cancer stem cells (CSCs) are capable of continuous proliferation and self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis, and cancer recurrence. CSCs are considered derived from normal stem cells affected by the inflammatory microenvironment. Stem cells, are considered to be induced into progenitor cells, which differentiate into various normal phenotypes depending on the normal niche. We hypothesized that CSCs could be derived from stem cells in the cancer-inducing niche, which is a condition of chronic inflammation rich in growth factors, interleukins, chemokines, etc. Exosomes are considered to be the key mediators responsible for the cell-to-cell communications carrying proteins, nucleic acids, metabolites, etc., to shuttle between cells. If these cells are in the environment of chronic inflammation, the exosomes should be reflecting the conditions. In this chapter, we detail the method of CSC initiation using extracellular vesicles (EVs) derived from cancer cell. The stem cells treated with the EVs acquired characteristics of CSCs showing spheroids expressing stemness markers in the suspension culture and high tumorigenicity in Balb/c nude mice. EVs might perform as suitable inducer for initiating CSCs from stem cells or progenitor cells. The model of CSCs and the procedure of their establishment with EVs will help study the exact effect of EVs in the cancer-inducing niche and tumor microenvironment.
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http://dx.doi.org/10.1007/7651_2021_371DOI Listing
March 2021

Exosomal miR-10b-5p mediates cell communication of gastric cancer cells and fibroblasts and facilitates cell proliferation.

J Cancer 2021 21;12(7):2140-2150. Epub 2021 Feb 21.

Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

Tumor microenvironment interacts with gastric cancer (GC) cells and affects tumor development. The communication between GC cells and fibroblasts has not been clearly studied and understood. MiR-10b-5p was found highly expressed in tissue and serum samples of patients with advanced stages (stage III+IV) than that in early stage patients (stage I+II). The expression determination of serum exosomal microRNA was also shown with high expression of miR-10b-5p in GC patients with advanced stages. Dual-luciferase activity assays indicated that miR-10b-5p targeted in GC cells and in fibroblasts. The silence of miR-10b-5p up-regulated the expression of PTEN and repressed PI3K/Akt/mTORC1 signaling in GC cells. Clonogenic assay and MTT assay demonstrated that miR-10b-5p inhibitor could significantly reduce the colony formation and cell viability of GC cells. And the incubation of exosomal miR-10b-5p could increase the proliferation of GC cells. Immunohistochemistry staining revealed that high expression of α-SMA was detected in GC tissues with advanced stages. The overexpression of miR-10b-5p down-regulated KLF11 expression and elevated TGFβR1 expression in fibroblasts. In addition, miR-10b-5p inhibitor blocked the secretion of TGFβ1 in GC cells and the directional migration of fibroblasts. Therefore, up-regulated exosomal miR-10b-5p is involved in the interaction of GC cells and fibroblasts in tumor microenvironment participating in the regulation of TGFβ signaling pathway.
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http://dx.doi.org/10.7150/jca.47817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974515PMC
February 2021

Host sunflower-induced silencing of parasitism-related genes confers resistance to invading Orobanche cumana.

Plant Physiol 2021 03;185(2):424-440

Key Laboratory of Forage and Endemic Crop Biotechnology, Ministry of Education, School of Life Sciences, Inner Mongolia University, Hohhot 010070, P. R. China.

Orobanche cumana is a holoparasitic plant that attaches to host-plant roots and seriously reduces the yield of sunflower (Helianthus annuus L.). Effective control methods are lacking with only a few known sources of genetic resistance. In this study, a seed-soak agroinoculation (SSA) method was established, and recombinant tobacco rattle virus vectors were constructed to express RNA interference (RNAi) inducers to cause virus-induced gene silencing (VIGS) in sunflower. A host target gene HaTubulin was systemically silenced in both leaf and root tissues by the SSA-VIGS approach. Trans-species silencing of O. cumana genes were confirmed for 10 out of 11 target genes with silencing efficiency of 23.43%-92.67%. Knockdown of target OcQR1, OcCKX5, and OcWRI1 genes reduced the haustoria number, and silencing of OcEXPA6 caused further phenotypic abnormalities such as shorter tubercles and necrosis. Overexpression of OcEXPA6 caused retarded root growth in alfalfa (Medicago sativa). The results demonstrate that these genes play an important role in the processes of O. cumana parasitism. High-throughput small RNA (sRNA) sequencing and bioinformatics analyses unveiled the distinct features of target gene-derived siRNAs in O. cumana such as siRNA transitivity, strand polarity, hotspot region, and 21/22-nt siRNA predominance, the latter of which was confirmed by Northern blot experiments. The possible RNAi mechanism is also discussed by analyzing RNAi machinery genes in O. cumana. Taken together, we established an efficient host-induced gene silencing technology for both functional genetics studies and potential control of O. cumana. The ease and effectiveness of this strategy could potentially be useful for other species provided they are amenable to SSA.
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http://dx.doi.org/10.1093/plphys/kiaa018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133596PMC
March 2021

Bilateral multifocality, a marker for aggressive disease, is not an independent prognostic factor for papillary thyroid microcarcinoma: A propensity score matching analysis.

Clin Endocrinol (Oxf) 2021 Jul 14;95(1):209-216. Epub 2021 Mar 14.

Department of Thyroid, Parathyroid, Breast and Hernia Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Context: Multifocality and bilaterality are common in patients with papillary thyroid microcarcinoma (PTMC). However, their clinical behaviours and prognostic implications remain controversial.

Objective: To investigate the relationship between multifocality and classically aggressive characteristics and outcomes in patients with PTMC.

Methods: Clinical data of 3005 patients with PTMC were retrospectively reviewed at a tertiary medical centre. The role of unilateral and bilateral multifocality in aggressive characteristics and clinical outcomes of PTMC was evaluated using propensity score matching (PSM).

Results: A total of 573 patients had bilateral multifocal disease (B-MFD), 272 had unilateral multifocal disease (U-MFD), and 2160 had unifocal disease (UFD). Univariate analysis showed that patients in the multifocal disease (MFD) groups showed significantly different characteristics compared to patients in the UFD group in terms of age, chronic lymphocytic thyroiditis (CLT), follicular variant PTMC, tumour diameter, aggressive growth, including extrathyroidal extension (ETE), central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM), and TNM stage, and underwent radioactive iodine (RAI) therapy. Further stratified analysis revealed that patients in the B-MFD group reflected the differences between the MFD and UFD groups. However, those in the U-MFD group showed slight differences only in sex, CLT and cell subtypes, compared to the UFD group. In addition, PSM indicated differences in ETE, CLNM and LLNM between the B-MFD and UFD groups (p < .001), while only ETE differed between the U-MFD and UFD groups (p < .001). After a median follow-up period of 60 months, no difference was observed in recurrence-free survival between the UFD and B-MFD (p = .294) or U-MFD (p = .603) groups using PSM.

Conclusion: This propensity score matching analysis provides strong evidence that bilateral multifocality, rather than unilateral multifocality, should be considered as an aggressive marker at presentation, and neither is an independent prognostic factor for clinical outcome in PTMC.
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http://dx.doi.org/10.1111/cen.14455DOI Listing
July 2021

Systematic Transcriptome Analysis Reveals the Inhibitory Function of Cinnamaldehyde in Non-Small Cell Lung Cancer.

Front Pharmacol 2020 9;11:611060. Epub 2021 Feb 9.

Department of Respiratory and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, China.

Cinnamaldehyde (CA) is the main component extracted from the traditional Chinese medicine cinnamon. Recent studies revealed that CA has antiviral and anti-tumor effects. However, the effect and mechanism of CA on non-small cell lung cancer (NSCLC) through whole transcriptome sequencing integrated analysis have not been systematically investigated. In this study, whole transcriptome sequencing was used to identify differentially expressed messenger RNAs (mRNAs), micro RNAs (miRNAs), and long non-coding RNAs (lncRNAs) that were influenced by CA and screen regulatory pathways. The results showed that CA significantly inhibited proliferation, invasion, and migration, whereas it induced the apoptosis of NSCLC cells. CA inhibited tumor growth . Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that these differentially expressed mRNAs were potentially implicated in the CA-suppressing malignant phenotypes of NSCLC. According to the competing endogenous RNA (ceRNA) hypothesis, a ceRNA network was constructed, including 13 mRNAs, 6 miRNAs, and 11 lncRNAs. Kyoto Encyclopedia of Genes and Genomes analysis of the 13 mRNAs in the ceRNA network showed that suppressors of cytokine signaling 1 (SOCS1), BTG anti-proliferation factor 2 (BTG2), and Bruton tyrosine kinase (BTK) were significantly enriched in the JAK/STAT signaling pathway, RNA degradation, and nuclear factor-κB (NF-κB) signaling pathway related to cancer. These findings indicated that SOCS1, BTG2, and BTK play an essential role in CA against NSCLC. Meanwhile, based on the ceRNA network, three lncRNAs (long intergenic non-protein coding RNA 1504 [LINC01504], LINC01783, and THUMPD3 antisense RNA 1 [THUMPD3-AS1]) and three miRNAs (has-miR-155-5p, has-miR-7-5p, and has-miR-425-5p) associated with SOCS1, BTG2, and BTK may be important in CA against NSCLC. Taken together, the present study demonstrated the activity of CA against lung cancer and its potential use as a therapeutic agent.
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http://dx.doi.org/10.3389/fphar.2020.611060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900626PMC
February 2021

Polymorphisms of 5-hydroxytryptamine receptor type 3B gene and clinical characteristics for vomiting after breast surgery in chinese han female population.

J Clin Pharm Ther 2021 Aug 19;46(4):936-941. Epub 2021 Feb 19.

Department of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, China.

What Is Known And Objective: The 5-hydroxytryptamine type 3B receptor (HTR3B) is involved in postoperative vomiting. We aimed to investigate whether genomic variations of rs1176744 and rs1672717 in HTR3B are associated with postoperative vomiting (POV) in the Chinese Han female population after surgery.

Methods: Five hundred and sixty-eight female patients classified as ASA I-II undergoing breast surgery under standard general anaesthesia were enrolled in the study. Episodes of POV in the first 24 h after surgery were recorded. Targeted single nucleotide polymorphisms (SNPs) in the HTR3B gene were identified by genotyping using the SNPscan technique. Univariate and multivariate analyses were conducted to investigate the association between SNPs and POV.

Results: We eventually analysed 407 subjects undergoing breast surgery under general anaesthesia. Of these, 104(25.6%) patients suffered POV within 24 h after surgery. In the multivariate logistic regression analysis, we found that age≥50 years (p = 0.012) and longer duration of surgery (p = 0.019) were independent risk factors for POV. Simultaneously, in the dominant model of rs1672717, compared with the AA genotype, GG+GA carriers suffered more POV (OR=1.669, p = 0.038). However, the use of atropine reduced the incidence of POV in our study (p = 0.019).

What Is New And Conclusion: Our investigation demonstrated that polymorphism of rs1672717 (HTR3B) may be a genetic risk factor for developing POV.

Trial Registration: clinicaltrials.gov identifier: NCT03705026.
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http://dx.doi.org/10.1111/jcpt.13386DOI Listing
August 2021

Altered Complexity of Spontaneous Brain Activity in Schizophrenia and Bipolar Disorder Patients.

J Magn Reson Imaging 2021 08 11;54(2):586-595. Epub 2021 Feb 11.

College of Information and Computer, Taiyuan University of Technology, Taiyuan, Shanxi, China.

Background: Schizophrenia (SC) and bipolar disorder (BP) share elements of symptoms and the underlying neural mechanisms for both remain unclear. Recently, the complexity of spontaneous functional MRI (fMRI) signals in brain activity has been investigated in SC and BP using multiscale sample entropy (MSE) with inconsistent results.

Purpose: To perform MSE analysis across five time scales to assess differences in resting-state fMRI signal complexity in SC, BP, and normal controls (NC).

Study Type: Retrospective.

Population: Fifty SC, 49 BP, and 49 NC.

Field Strength/sequence: A 3 T, T2* weighted echo planar imaging (EPI) sequence.

Assessment: The mean MSEs of all gray matter (GM) and of 12 regions of interest (ROIs) were extracted using masks across the five scales. The regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) in these ROIs were also determined and the relationship between the three measures was investigated. The correlations between cognitive assessment scores and MSE values were also explored.

Statistical Tests: Bonferroni correction, One-way ANOVA, Spearman rank correlation coefficient (r), Gaussian random field (GRF) correction.

Results: There were decreased GM MSE values in the patient groups (F = 9.629, P < 0.05). SC and BP patients demonstrated lower complexity than NCs in the calcarine fissure, precuneus, inferior occipital gyrus, lingual gyrus and cerebellum, and higher complexity in the median cingulate, thalamus, hippocampus, middle temporal gyrus and middle frontal gyrus. There were significant differences between SC and BP patients in the precuneus (F = 4.890, P < 0.05) and inferior occipital gyrus (F = 5.820, P < 0.05). Calcarine fissure, cingulate, temporal gyrus, occipital gyrus, hippocampus, precuneus, frontal gyrus, and lingual gyrus MSE values were significantly correlated with both ReHo (r > 0.282, P < 0.05) and ALFF (r > 0.278, P < 0.05). Furthermore, median temporal MSE (r = -0.321, P < 0.05) on scale 3 and (r = -0.307, P < 0.05) on scale 4 and median cingulate MSE (r = -0.337, P < 0.05) on scale 5 was significantly negatively correlated with cognitive assessment scores.

Data Conclusion: These data highlight different patterns of brain signal intensity complexity in SC and BP.

Level Of Evidence: 1 TECHNICAL EFFICACY: Stage 1.
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http://dx.doi.org/10.1002/jmri.27541DOI Listing
August 2021

Improvement of host-induced gene silencing efficiency via polycistronic-tRNA-amiR expression for multiple target genes and characterization of RNAi mechanism in Mythimna separata.

Plant Biotechnol J 2021 07 7;19(7):1370-1385. Epub 2021 Feb 7.

Key Laboratory of Forage and Endemic Crop Biotechnology, Ministry of Education, School of Life Sciences, Inner Mongolia University, Hohhot, China.

Host-induced gene silencing (HIGS) emerged as a new strategy for pest control. However, RNAi efficiency is reported to be low in Lepidoptera, which are composed of many important crop pests. To address this, we generated transgenic plants to develop HIGS effects in a maize pest, Mythimna separata (Lepidoptera, Noctuidae), by targeting chitinase encoding genes. More importantly, we developed an artificial microRNA (amiR) based PTA (polycistronic-tRNA-amiR) system for silencing multiple target genes. Compared with hpRNA (hairpin RNA), transgenic expression of a PTA cassette including an amiR for the gut-specific dsRNA nuclease gene MsREase, resulted in improved knockdown efficiency and caused more pronounced developmental abnormalities in recipient insects. When target gene siRNAs were analysed after HIGS and direct dsRNA/siRNA feeding, common features such as sense polarity and siRNA hotspot regions were observed, however, they differed in siRNA transitivity and major 20-24nt siRNA species. Core RNAi genes were identified in M. separata, and biochemical activities of MsAGO2, MsSID1 and MsDcr2 were confirmed by EMSA (electrophoretic mobility shift assay) and dsRNA cleavage assays, respectively. Taken together, we provide compelling evidence for the existence of the RNAi mechanism in M. separata by analysis of both siRNA signatures and RNAi machinery components, and the PTA system could potentially be useful for future RNAi control of lepidopteran pests.
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http://dx.doi.org/10.1111/pbi.13555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313139PMC
July 2021

Experimental data on the adsorption of water by branches and leaves as affected by different the morphological characteristics of plants.

Data Brief 2021 Feb 23;34:106689. Epub 2020 Dec 23.

China National Institute of Standardization, 100191, Beijing, China.

We determined 116 globally important woody tree species, classified them based on the differences between plant life-forms, leaf textures and trichomes on leaves and measured the indices of some plant morphological traits in the Guizhou karstic regions of China. The water adsorbed on the upper surfaces of branches and leaves and the water adsorbed on the upper and lower surfaces of branches and leaves (WW and WW) of these species was measured. The ratios of the weight of adsorbed water on the upper surfaces of branches and leaves to the weight of branches and leaves (RWW) and the ratios of the weight of adsorbed water on the upper and lower surfaces of branches and leaves to the weight of branches and leaves (RWW) were calculated. The adsorption of water and morphological trait indices follow the approximately normal distributions. The weight of branches and leaves (weight), total leaf area (TLA) and mean leaf area (MLA) significantly impacted the adsorption of water by branches and leaves. The different rates of the adsorption of water for 116 tree species can explain the interspecific variation in rainfall interception. Interpretation of these data is provided in Effects of the morphological characteristics of plants on rainfall interception and kinetic energy[J]. Journal of Hydrology, 2020: 125807. https://doi.org/10.1016/j.jhydrol.2020.125807.
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http://dx.doi.org/10.1016/j.dib.2020.106689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779717PMC
February 2021

Who Can You Count On? Understanding The Determinants of Reliability.

J Surv Stat Methodol 2020 Nov 3;8(5):903-931. Epub 2019 Oct 3.

Westat, MD, USA.

Using reinterview data from the PATH Reliability and Validity (PATH-RV) study, we examine the characteristics of questions and respondents that predict the reliability of the answers. In the PATH-RV study, 524 respondents completed an interview twice, five to twenty-four days apart. We coded a number of question characteristics and used them to predict the gross discrepancy rates (GDRs) and kappas for each question. We also investigated respondent characteristics associated with reliability. Finally, we fitted cross-classified models that simultaneously examined a range of respondent and question characteristics. Although the different models yielded somewhat different conclusions, in general factual questions (especially demographic questions), shorter questions, questions that did not use scales, those with fewer response options, and those that asked about a noncentral topic produced more reliable answers than attitudinal questions, longer questions, questions using ordinal scales, those with more response options, and those asking about a central topic. One surprising finding was that items raising potential social desirability concerns yielded more reliable answers than items that did not raise such concerns. The respondent-level models and cross-classified models indicated that five adult respondent characteristics were associated with giving the same answer in both interviews-education, the Big Five trait of conscientiousness, tobacco use, sex, and income. Hispanic youths and non-Hispanic black youths were less likely to give the same answer in both interviews. The cross-classified model also found that more words were associated with less reliable answers. The results are mostly consistent with earlier findings but are nonetheless important because they are much less model-dependent than the earlier work. In addition, this study is the first to incorporate such personality traits as needed for cognition and the Big Five personality factors and to examine the relationships among reliability, item nonresponse, and response latency.
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http://dx.doi.org/10.1093/jssam/smz034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750889PMC
November 2020

EGCG inhibits pressure overload-induced cardiac hypertrophy via the PSMB5/Nmnat2/SIRT6-dependent signalling pathways.

Acta Physiol (Oxf) 2021 04 7;231(4):e13602. Epub 2021 Jan 7.

Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.

Aim: Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, exerts multiple protective effects against cardiovascular diseases, including cardiac hypertrophy. However, the molecular mechanism underlying its anti-hypertrophic effect has not been clarified. This study revealed that EGCG could inhibit pressure overload-induced cardiac hypertrophy by regulating the PSMB5/Nmnat2/SIRT6-dependent signalling pathway.

Methods: Quantitative real-time polymerase chain reaction and western blotting were used to determine the expression of mRNA and protein respectively. A fluorometric assay kit was used to determine the activity of SIRT6, a histone deacetylase. Luciferase reporter gene assay and electrophoretic mobility shift assay were employed to measure transcriptional activity and DNA binding activity respectively.

Results: EGCG could significantly increase Nmnat2 protein expression and enzyme activity in cultured neonatal rat cardiomyocytes stimulated with angiotensin II (Ang II) and heart tissues from rats subjected to abdominal aortic constriction. Nmnat2 knockdown by RNA interference attenuated the inhibitory effect of EGCG on cardiac hypertrophy. EGCG blocked NF-κB DNA binding activity induced by Ang II, which was dependent on Nmnat2 and the subsequent SIRT6 activation. Moreover the activation of PSMB5 (20S proteasome subunit β-5, chymotrypsin-like) was required for EGCG-induced Nmnat2 protein expression. Additionally, we demonstrated that EGCG might interact with PSMB5 and inhibit the activation of the proteasome.

Conclusions: These findings serve as the first evidence that the effect of EGCG against cardiac hypertrophy may be, at least partially, attributed to the modulation of the PSMB5/Nmnat2-dependent signalling pathway, suggesting the therapeutic potential of EGCG in the prevention and treatment of cardiac hypertrophy.
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http://dx.doi.org/10.1111/apha.13602DOI Listing
April 2021

Six novel lignanoids with complex structures from Sigesbeckia glabrescens Makino with their cytotoxic activities.

Fitoterapia 2021 Jan 8;148:104799. Epub 2020 Dec 8.

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address:

Six new lignanoids, Glalignin A-E (1-5) and Glaneolignin A (6), together with four analogues, (+)-isolariciresinol (7), (+)-syringaresinol (8), dihydrodehydrodiconiferyl alcohol (9) and tribulusamide A (10), were obtained from the aerial parts of Sigesbeckia glabrescens Makino and also isolated for the first time from the Sigesbeckia genus. The structures of these compounds were elucidated by the interpretation of HRESIMS, 1D NMR, 2D NMR data and chemical evidence. The cytotoxic activities of the compounds were evaluated by testing their inhibition in several tumor cells using the MTT assay. New compound 2 and 5 displayed cytotoxicity against the human cancer cell lines human lung adenocarcinoma cells (A549) with IC values of 32.89 ± 6.83 and 35.86 ± 6.83 μM.
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http://dx.doi.org/10.1016/j.fitote.2020.104799DOI Listing
January 2021

Effect of miR-515-5p on Proliferation and Drug Sensitivity of Retinoblastoma Cells.

Cancer Manag Res 2020 24;12:12087-12098. Epub 2020 Nov 24.

Department of Ophthalmology, Laoshan Branch of the Affifiliated Hospital of Qingdao University, Qingdao, Shandong 266100, People's Republic of China.

Background: Retinoblastoma (RB) is a common malignancy in children eyes. Aberrant microRNA (miR) expression is observed in many cancer cases. miR-515-5p is reported to be concerned with the course of many cancers. This study explores the role of miR-515-5p in proliferation and drug sensitivity of RB cells.

Methods: Human RB cell lines (WERI-RB1, SO-RB50 and Y79) and human retinal pigment epithelial cell line ARPE-19 were utilized in this study. Drug-resistant cells SO-RB50/VCR and SO-RB50/CBP were constructed for the following experiments. The expressions of miR-515-5p and Notch1 in RB cells were detected. Notch1 was significantly upregulated in RB cells while miR-515-5p was notably downregulated. Then, the binding relationship between miR-515-5p and Notch1 was predicted and verified.

Results: miR-515-5p negatively regulated Notch1 expression. In vitro and in vivo experiments revealed that overexpressed miR-515-5p inhibited RB cell proliferation and enhanced drug sensitivity. Functional rescue experiment suggested that miR-515-5p regulated RB cell proliferation and drug sensitivity via inhibiting Notch1 expression.

Conclusion: It could be concluded that overexpressed miR-515-5p suppressed proliferation and drug resistance of RB cells by targeting Notch1 expression, indicating that miR-515-5p might constitute a promising therapy target for RB.
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http://dx.doi.org/10.2147/CMAR.S271165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700094PMC
November 2020

Sex Differences in Anatomical Rich-Club and Structural-Functional Coupling in the Human Brain Network.

Cereb Cortex 2021 03;31(4):1987-1997

College of Information and Computer, Taiyuan University of Technology, Taiyuan 030024, China.

Structural and functional differences between the brains of female and male adults have been well documented. However, potential sex differences in the patterns of rich-club organization and the coupling between their structural connectivity (SC) and functional connectivity (FC) remain to be determined. In this study, functional magnetic resonance imaging and diffusion tensor imaging techniques were combined to examine sex differences in rich-club organization. Females had a stronger SC-FC coupling than males. Moreover, stronger SC-FC coupling in the females was primarily located in feeder connections and non-rich-club nodes of the left inferior frontal gyrus and inferior parietal lobe and the right superior frontal gyrus and superior parietal gyrus, whereas higher coupling strength in males was primarily located in rich-club connections and rich-club node of the right insula, and non-rich-club nodes of the left hippocampus and the right parahippocampal gyrus. Sex-specific patterns in correlations were also shown between SC-FC coupling and cognitive function, including working memory and reasoning ability. The topological changes in rich-club organization provide novel insight into sex-specific effects on white matter connections that underlie a potential network mechanism of sex-based differences in cognitive function.
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http://dx.doi.org/10.1093/cercor/bhaa335DOI Listing
March 2021

Author Correction: Multi-region sequencing unveils novel actionable targets and spatial heterogeneity in esophageal squamous cell carcinoma.

Nat Commun 2020 Nov 12;11(1):5870. Epub 2020 Nov 12.

Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research on Esophageal Cancer, Shanxi Medical University, 030001, Taiyuan, PR China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41467-020-19641-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665205PMC
November 2020

Clinical features of patients undergoing hemodialysis with COVID-19.

Semin Dial 2021 01 29;34(1):57-65. Epub 2020 Oct 29.

Department of Urology, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.

Hemodialysis patients are susceptible to coronavirus disease 2019 (COVID-19). The aim of this study was to describe the epidemiological, clinical characteristics, and mortality-related risk factors for those who undergoing hemodialysis with COVID-19. We conducted a retrospective study. A total of 49 hemodialysis patients with COVID-19 (Group 1) and 74 uninfected patients (Group 2) were included. For patients in Group 1, we found the median age was 62 years (36-89 years), 59.3% were male, and the median dialysis vintage was 26 months. Twenty-eight patients (57%) had three or more comorbidities and two patients (4%) died. The most common symptoms were fever (32.7%) and dry cough (46.9%), while nine patients (18.4%) were asymptomatic. Blood routine tests indicated lymphocytopenia, the proportion of lymphocyte subsets was generally reduced, and chest CT scans showed ground-glass opacity (45.8%) and patchy shadowing (35.4%). However, these findings were not specific to hemodialysis patients with COVID-19, and similar manifestations could be found in patients without SARS-CoV-2 infection. In conclusion, for hemodialysis patients with COVID-19, lymphocytopenia and ground-glass opacities or patchy opacities were common but not specific to them, early active treatment and interventions against nosocomial infection can significantly reduce the mortality and the risk of SARS-CoV-2 infection.
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http://dx.doi.org/10.1111/sdi.12928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894471PMC
January 2021

PWP1 Promotes the Malignant Phenotypes of Lung Cancer Cells by Interacting with DVL2 and Merlin.

Onco Targets Ther 2020 8;13:10025-10037. Epub 2020 Oct 8.

Department of Pathology, College of Basic Medical Science, and First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.

Purpose: The significance of periodic tryptophan protein 1 (PWP1) expression in human cancer and its molecular mechanism of action have not been reported so far.

Materials And Methods: Immunohistochemistry was performed to analyze the expression of PWP1 in non-small cell lung cancer (NSCLC) tissues and statistical analysis was applied to analyze the relationship between PWP1 expression and the clinicopathological factors. The effects of PWP1 on NSCLC proliferation and invasion were determined by colony formation, transwell and MTT assays. Western blot analysis (WB), dual-luciferase reporter gene assays and immunofluorescence staining were performed to demonstrate whether PWP1 stimulates Wnt pathway and inhibits Hippo pathway. Co-immunoprecipitation (Co-ip) assays were used to confirm the potential role of PWP1 in Wnt and Hippo signaling pathways.

Results: PWP1 expression in NSCLC was higher than that in normal bronchial epithelium and normal submucosal glands. In addition, PWP1 expression had a positive correlation with poor differentiation, high pathological tumor-node-metastasis (TNM) stage, and lymph node metastasis. Kaplan-Meier database demonstrated that the overall survival time of patients with high PWP1 expression was significantly shorter than that of patients with low PWP1 expression. Mechanistically, we found that PWP1 could interact with DVL2 to upregulate β-catenin (thereby activating the Wnt pathway), whereas PWP1 could interact with Merlin (NF2) to downregulate p-MST1 (thereby inhibiting the Hippo signaling pathway). The effects of PWP1 on promoting the Wnt pathway or inhibiting the Hippo pathway were offset in DVL2- or Merlin-knockdown cells transiently overexpressing PWP1.

Conclusion: PWP1 expression in NSCLC was correlated with poor prognosis. PWP1 enhanced the activity of the Wnt pathway by interacting with DVL2, whereas PWP1 inhibited the activity of the Hippo pathway by interacting with Merlin. Together, these two effects promoted the detrimental biological behaviors of NSCLC cells.
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http://dx.doi.org/10.2147/OTT.S263815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553635PMC
October 2020

ARHGAP36 regulates proliferation and migration in papillary thyroid carcinoma cells.

J Mol Endocrinol 2021 01;66(1):1-10

Department of Thyroid, Parathyroid, Breast and Hernia Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.

The diagnosis and treatment of recurrence and metastasis in papillary thyroid carcinoma (PTC) are still clinical challenges. One of the key factors is the lack of specific diagnostic markers and therapeutic targets for recurrence and metastasis. Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful approach to find specific biomarkers by dissecting expression profiling in human cancers at the resolution of individual cells. Here, we investigated cell profiles of the primary tumor and lymph node metastasis and paracancerous normal tissues in one PTC patient using scRNA-seq, and compared individual cell gene expression differences. The transcriptomes of 11,805 single cells were profiled, and malignant cells exhibited a profound transcriptional overlap between primary and metastatic lesions, but there were differences in the composition and quantity of non-malignant cells. ARHGAP36 was one of the genes that were highly expressed in almost all of the primary and metastatic malignant cells without non-malignant or normal follicular cells and was then confirmed by immunostaining in a sample cohort. Compared with the paracancerous normal tissue, the expression of ARHGAP36 in primary and metastatic carcinoma tissues was significantly higher as assayed by qRT-PCR. ARHGAP36 knockdown significantly inhibited the proliferation and migration of PTC cells in vitro and involved several proliferation and migration-associated signaling pathways by RNA seq. Our study demonstrated that ARHGAP36 is exclusively expressed in the malignant cells of primary PTC, as well as metastatic lesions, and regulates their proliferation and migration, meaning it can be used as a potential diagnostic marker and therapeutic target molecule.
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http://dx.doi.org/10.1530/JME-20-0230DOI Listing
January 2021
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