Publications by authors named "Xiao-Feng Li"

552 Publications

Evaluation of the digestion and transport profiles and potential immunocompetence of puerarin and its acylated derivatives.

Food Funct 2021 May 25. Epub 2021 May 25.

School of Food Sciences and Engineering, South China University of Technology, Guangzhou 510641, China.

Acylation has become one of the most widely used methods to improve the lipid solubility and bioavailability of flavonoids. In this study, puerarin acid esters (PAES) with different chain lengths were synthesized via biocatalytic acylation. This was the first study to evaluate the digestion and transport profiles and immunocompetence of PAES. The relationship between the digestion and transport profiles and potential immunocompetence of the acylated derivatives in Caco-2 cell monolayers was also explored. Puerarin and PAES remained stable in gastric phases, whereas different degrees of hydrolysis of PAES were found in the intestine. PAES with less than 12 carbon chains were positively correlated with the degree of hydrolysis, while those with more than 12 carbon chains showed higher resistance to hydrolysis by the artificial human digestive juice. The apparent permeability coefficients of puerarin, puerarin acetate, puerarin propanoate, puerarin butyrate, puerarin hexanoate, puerarin octanate and puerarin laurate were 1.62 ± 0.09, 1.70 ± 0.15, 1.89 ± 0.19, 1.86 ± 0.18, 2.29 ± 0.12, 4.06 ± 1.01 and 2.32 ± 0.88 × 10-6 cm s-1, respectively, in Caco-2 cell monolayers. The results of the immune factor assays indicated that puerarin propanoate, puerarin hexanoate and puerarin myristate could significantly promote the secretion of IL-6, TNF-α and IL-10. These findings suggested that a better absorption could be predicted after oral intake using PAES. Meanwhile, the concentration of esters and their metabolites (puerarin) found in the digestion and transport profiles directly affected their potential immunocompetence.
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http://dx.doi.org/10.1039/d1fo00555cDOI Listing
May 2021

Low-dose IL-2 therapy limits the reduction in absolute numbers of circulating regulatory T cells in rheumatoid arthritis.

Ther Adv Musculoskelet Dis 2021 28;13:1759720X211011370. Epub 2021 Apr 28.

Department of Rheumatology, the Second Hospital of Shanxi Medical University.

Background: Circulating regulatory T cells (Tregs) are responsible for mediating immune tolerance and maintaining immunological homeostasis. Decreases in Tregs may be involved in the onset of rheumatoid arthritis (RA). Low-dose interleukin-2 (IL-2) has been considered for the treatment of inflammatory diseases mediated by T cells. This study focused on the status of circulating CD4T subsets and the clinical feasibility of IL-2 therapies in patients with RA.

Methods: The subjects included 888 patients with RA and 100 healthy controls (HCs); 233 RA patients received IL-2 treatment with 0.5 million international units (MIU)/day from days 1 through 5. The demographic features, disease activity, and levels of CD4+T cells measured by modified flow cytometry were collected in all RA patients before and after treatment.

Results: RA patients had lower absolute Treg counts (but not Th17) compared with HCs, which was associated with disease activity; previously treated RA patients had the fewest circulating Tregs (0.05). Patients treated with low-dose IL-2 had a three-fold increase in absolute anti-inflammatory Treg counts, as well as a two-fold increase in the other CD4T subsets. Moreover, post-treatment levels of markers of disease activity in RA patients treated with IL-2 were significantly lower than the baseline values (0.001), with no apparent side effects.

Conclusion: Decreased absolute counts of circulating CD4T lymphocyte subsets were observed in patients with RA. Circulating Tregs, which mediate immune tolerance, may be involved in the pathogenesis and progression of RA; however, this was ameliorated by low-dose IL-2, without obvious side effects.

Plain Language Summary: • Circulating Tregs may be involved in the pathogenesis and progression of RA.• The absolute count of Tregs was significantly correlated with disease activity measures.• Low-dose IL-2 was able to effectively expade Tregs and help for RA patients' symptoms remission without evaluated side effects.
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http://dx.doi.org/10.1177/1759720X211011370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107675PMC
April 2021

Circular RNA circUbe2k promotes hepatic fibrosis via sponging miR-149-5p/TGF-β2 axis.

FASEB J 2021 Jun;35(6):e21622

Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, China.

Abundant regulatory genes and complex circuits involving non-coding RNAs (ncRNAs) monitor the formation and development of hepatic fibrosis (HF). Circular RNAs (circRNAs) are a class of RNAs generated from protein coding genes by back-splicing, playing crucial roles in various pathological processes, including HF. However, little is known about mechanisms of action of circRNAs, let alone in HF. In this study, we found circUbe2k enhanced in CCl -induced HF mice and LX-2 cells stimulated with TGF-β1, regulating the development of HF. Restraining the expression of circUbe2k inhibited α-SMA and Col1α1 expression in CCl -induced HF mice and in LX-2 cells stimulated with TGF-β1. Furthermore, inhibiting circUbe2k expression reduced hepatic stellate cells (HSCs) activation and proliferation in vivo and in vitro. Mechanistically, we demonstrated a direct interaction between circUbe2k and miR-149-5p, which results in the modulation of TGF-β2 expressions. Together, circUbe2k may act as a "catalyst" of HSCs activation and HF through the circUbe2k/miR-149-5p/TGF-β2 axis. Our results provide unprecedented evidence for a significant role for circUbe2k to serve as a potential biomarker for HF therapy.
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http://dx.doi.org/10.1096/fj.202002738RDOI Listing
June 2021

Decreased expression of CLCA2 and the correlating with immune infiltrates in patients with cervical squamous cell carcinoma: A bioinformatics analysis.

Taiwan J Obstet Gynecol 2021 May;60(3):480-486

Lanzhou University Second Hospital, Lanzhou, China. Electronic address:

Objective: Calcium-activated chloride channel 2 (CLCA2) is closely related to the invasion, metastasis, and prognosis of some common malignant tumors. The present study aimed to evaluate the role of CLCA2 in cervical squamous cell carcinoma (CESC) using bioinformatics analysis.

Materials And Methods: The mRNA sequencing data and the corresponding clinical data were obtained from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database respectively. Then univariate analysis of variance was used to analyze the differential mRNA expression of CLCA2 between normal, cervical Intraepithelial neoplasia (CIN), and CESC tissues and clinicopathological characteristics. The Gene Expression Profiling Interactive Analysis (GEPIA) was used to assess the association between CLCA2 and Disease-Free Survival (DFS), overall survival (OS). The Gene Set Enrichment Analysis (GSEA) was used to explore the associated signaling pathways. The Tumor Immune Estimation Resource (TIMER) was used to predict the potential biological roles of CLCA2 in tumor-immune of CESC.

Results: CLCA2 expression was significantly decreased in CESC tissues compared with normal and CIN tissues (P < 0.05). Meanwhile, obese patients had lower levels of CLCA2 expression than normal-weight CESC patients (P < 0.05). However, there was no significant difference in the expression level of CLCA2 in patients with different T stage, lymph node status, metastasis, and FIGO stage in CC(P > 0.05). The survival analysis indicated that for DFS, CESC with high CLCA2 expression was associated with better prognoses compared with those with low expression levels (P < 0.05). But for the OS, there was no difference. GSEA revealed that 4 pathways exhibited significant differential enrichment in the CLCA2 high-expression phenotype, including the P53 signaling pathway, the ERBB signaling pathway, the NOTCH signaling pathway, and the ubiquitin-mediated proteolysis. The TIMER reveals the expression of CLCA2 showed a significant inverse association with the number of B cells, Macrophage cells, and Dendritic Cell infiltration.

Conclusion: The present study indicates that CLCA2 expression may be a potential prognostic marker for patients with CESC.
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http://dx.doi.org/10.1016/j.tjog.2021.03.016DOI Listing
May 2021

The Hypoxia-Activated Prodrug TH-302: Exploiting Hypoxia in Cancer Therapy.

Front Pharmacol 2021 19;12:636892. Epub 2021 Apr 19.

Department of Nuclear Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China.

Hypoxia is an important feature of most solid tumors, conferring resistance to radiation and many forms of chemotherapy. However, it is possible to exploit the presence of tumor hypoxia with hypoxia-activated prodrugs (HAPs), agents that in low oxygen conditions undergo bioreduction to yield cytotoxic metabolites. Although many such agents have been developed, we will focus here on TH-302. TH-302 has been extensively studied, and we discuss its mechanism of action, as well as its efficacy in preclinical and clinical studies, with the aim of identifying future research directions.
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http://dx.doi.org/10.3389/fphar.2021.636892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091515PMC
April 2021

Convergent evolution of SARS-CoV-2 in human and animals.

Protein Cell 2021 Apr 30. Epub 2021 Apr 30.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China.

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http://dx.doi.org/10.1007/s13238-021-00847-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085470PMC
April 2021

Cytokinin-Controlled Gradient Distribution of Auxin in Root Tip.

Int J Mol Sci 2021 Apr 8;22(8). Epub 2021 Apr 8.

Institute of Cell Biology and MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.

The plant root is a dynamic system, which is able to respond promptly to external environmental stimuli by constantly adjusting its growth and development. A key component regulating this growth and development is the finely tuned cross-talk between the auxin and cytokinin phytohormones. The gradient distribution of auxin is not only important for the growth and development of roots, but also for root growth in various response. Recent studies have shed light on the molecular mechanisms of cytokinin-mediated regulation of local auxin biosynthesis/metabolism and redistribution in establishing active auxin gradients, resulting in cell division and differentiation in primary root tips. In this review, we focus our attention on the molecular mechanisms underlying the cytokinin-controlled auxin gradient in root tips.
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http://dx.doi.org/10.3390/ijms22083874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069370PMC
April 2021

Arrb2 causes hepatic lipid metabolism disorder via AMPK pathway based on metabolomics in alcoholic fatty liver.

Clin Sci (Lond) 2021 May;135(10):1213-1232

Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China.

Background And Aims: Alcoholic fatty liver (AFL) is an early form of alcoholic liver disease (ALD) that usually manifests as lipid synthesis abnormalities in hepatocytes. β-arrestin2 (Arrb2) is involved in multiple biological processes. The present study aimed to explore the role of Arrb2 in the regulation of lipid metabolism in AFL and the underlying mechanism and identify potential targets for the treatment of AFL.

Methods: The expression of Arrb2 was detected in liver tissues obtained from AFL patients and Gao-binge AFL model mice. In addition, we specifically knocked down Arrb2 in AFL mouse liver in vivo and used Arrb2-siRNA or pEX3-Arrb2 to silence or overexpress Arrb2 in AML-12 cells in vitro to explore the functional role and underlying regulatory mechanism of Arrb2 in AFL. Finally, we investigated whether Arrb2 could cause changes in hepatic lipid metabolites, thereby leading to dysregulation of lipid metabolism based on liquid chromatography-mass spectrometry (LC-MS) analysis.

Results: Arrb2 was up-regulated in the livers of AFL patients and AFL mice. The in vivo and in vitro results confirmed that Arrb2 could induce lipid accumulation and metabolism disorders. Mechanistically, Arrb2 induced hepatic metabolism disorder via AMP-activated protein kinase (AMPK) pathway. The results of LC-MS analysis revealed that hepatic lipid metabolites with the most significant differences were primary bile acids.

Conclusions: Arrb2 induces hepatic lipid metabolism disorders via AMPK pathway in AFL. On one hand, Arrb2 increases fatty acid synthesis. On the other hand, Arrb2 could increase the cholesterol synthesis, thereby leading to the up-regulation of primary bile acid levels.
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http://dx.doi.org/10.1042/CS20201363DOI Listing
May 2021

[Effect of astragaloside IV on the expression of NOD-like receptor protein 3 inflammasome in neonatal rats with hypoxic-ischemic brain damage].

Zhongguo Dang Dai Er Ke Za Zhi 2021 Apr;23(4):402-409

Integrated Traditional Chinese and Western Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China.

Objective: To study the effect of astragaloside IV (AS-IV) on NOD-like receptor protein 3 (NLRP3) inflammasome in neonatal rats with hypoxic-ischemic brain damage (HIBD).

Methods: A total of 24 Sprague-Dawley rats, aged 7 days, were randomly divided into a sham-operation group, an HIBD group, and an AS-IV treatment group, with 8 rats in each group. After 24 hours of modeling, brain tissue was collected for hematoxylin-eosin staining, yo-PRO-1 staining, and EthD-2 immunofluorescent staining in order to observe the cerebral protection effect of AS-IV in vivo. HT22 cells were used to prepare a model of oxygen-glycogen deprivation (OGD), and a concentration gradient (50-400 μmol/L) was established for AS-IV. CCK-8 assay was used to measure the viability of HT22 cells. RT-PCR and Western blot were used to observe the effect of different concentrations of AS-IV on the mRNA and protein expression of NLRP3, gasdermin D (GSDMD), caspase-1, and interleukin-1β (IL-1β).

Results: Yo-Pro-1 and EthD-2 staining showed that compared with the sham-operation group, the HIBD group had an increase in pyroptotic cells with a small number of necrotic cells, and the AS-IV group had reductions in both pyroptotic and necrotic cells. Compared with the sham-operation group, the HIBD group had significantly higher protein expression levels of NLRP3, IL-1β, caspase-1, and GSDMD ( < 0.05). Compared with the HIBD group, the AS-IV group had significant reductions in the protein expression levels of NLRP3, caspase-1, and GSDMD ( < 0.05). HT22 cell experiment showed that compared with the OGD group, the AS-IV group had inhibited mRNA and protein expression of NLRP3, GSDMD, caspase-1, and IL-1β, with the best therapeutic effect at the concentration of 200 μmol/L ( < 0.05).

Conclusions: AS-IV may alleviate HIBD in neonatal rats by inhibiting the expression of NLRP3, GSDMD, caspase-1, and IL-1β.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050542PMC
April 2021

Novel Dicistroviruses in an Unexpected Wide Range of Invertebrates.

Food Environ Virol 2021 Apr 10. Epub 2021 Apr 10.

Institute of Plant Virology, Ningbo University, Ningbo, China.

Dicistroviruses are members of a rapidly growing family of small RNA viruses. Related sequences have been discovered in many environmental samples, indicating that our knowledge about dicistrovirus diversity and host range is still limited. In this study, we performed a systematic search against the publicly available transcriptome database, and identified large numbers of dicistrovirus-like sequences in a wide variety of eukaryotic species. The origins of these sequences were 108 invertebrates (including 77 insect species belonging to 18 orders) and 11 plants, revealing new associations between dicistroviruses and hosts. Finally, 83 transcripts corresponding to nearly-complete viral genomes were retrieved from the RNA-seq data, of which most sequences showed limited similarity to known dicistroviruses and might present previously unreported virus species. Phylogenetic analysis suggested that horizontal virus transfer has occurred between diverse hosts and has important implications for dicistrovirus evolution. The results will provide new insight into the hidden diversity of the Dicistroviridae, and help us to better understand the viral evolution, host range and the possible way of transmission.
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http://dx.doi.org/10.1007/s12560-021-09472-2DOI Listing
April 2021

[Characteristics of clinical application of electroacupuncture therapy for peripheral neuropathy based on data mining].

Zhen Ci Yan Jiu 2021 Mar;46(3):240-7

Institute of Acupuncture-moxibustion and Massage, Hebei University of Chinese Medicine, Shijiazhuang 050200, China.

Objective: To investigate the application characteristics of electroacupuncture (EA) in the treatment of peripheral neuropathy, so as to provide a basis for clinical use of EA therapy.

Methods: Keywords of "electroacupuncture"peripheral neuropathy" "facial paralysis" "trigeminal neuralgia" "sciatica" "common peroneal nerve injury" "diabetic peripheral neuropathy" "intercostal neuralgia" "gluteal epithelial neuritis" "ulnar nerve injury" "median nerve paralysis" "postherpetic neuralgia", and "great occipital neuralgia" were used to search articles in both English and Chinese published from 1999 to 2019 in databases of CNKI, Wanfang, VIP, CBM, Ovid, PubMed and Embase and related books such as electroacupuncture, and neurology, followed by establishing a database of "Electroacupuncture Treatment of Peripheral Neuropathy". Then, the collected articles were put into statistical analysis after sorting, screening, input, checking, and data extracting by using data mining technology and statistical software EpiData.

Results: Of the searched 1 528 papers, 778 were eligible, involving 13 types of peripheral neuropathy which the facial paralysis and facial spasm were most frequently seen, followed by trigeminal neuralgia and sciatica, with an effective rate being above 90% for nearly all the 13 diseases. The acupoints employed were chiefly those close to the affected area and distribute along the nerve trunk.In addition, about the needling techniques, the penetration needling was frequently used, and the triple needling, quintuple needling and accompanied needling were also used. Regarding the related needle manipulations, the uniform reinforcing-reduction technique was most frequently used. The duration of EA was 30 min, with a highest stimulating frequency of 50 Hz. The acupoint injection was frequently supplemented, followed by moxibustion, and the treatment sessions were usually about 30 times.

Conclusion: EA therapy is frequently used in the treatment of peripheral neuropathy, and has some characteristics in acupoint selection, stimulating parameters and some additional needling techniques.
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http://dx.doi.org/10.13702/j.1000-0607.200638DOI Listing
March 2021

Longitudinal dynamics of antibody responses in recovered COVID-19 patients.

Signal Transduct Target Ther 2021 03 31;6(1):137. Epub 2021 Mar 31.

Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China.

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http://dx.doi.org/10.1038/s41392-021-00559-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009921PMC
March 2021

Molecular Diagnosis of Neurofibromatosis by Multigene Panel Testing.

Front Genet 2021 9;12:603195. Epub 2021 Mar 9.

Department of Dermatology, First Affiliated Hospital of Anhui Medical University, Hefei, China.

Neurofibromatosis (NF) is an autosomal genetic disorder for which early and definite clinical diagnoses are difficult. To identify the diagnosis, five affected probands with suspected NF from unrelated families were included in this study. Molecular analysis was performed using multigene panel testing and Sanger sequencing. Ultradeep sequencing was used to analyze the mutation rate in the tissues from the proband with mosaic mutations. Three different pathogenic variants of the gene were found in three probands who mainly complained of café-au-lait macules (CALMs), including one frameshift variant c.5072_5073insTATAACTGTAACTCCTGGGTCAGGGAGTACACCAA:p.Tyr1692Ilefs in exon 37, one missense variant c.3826C > T:p.Arg1276Ter in exon 28, and one splicing variant c.4110 + 1G > T at the first base downstream of the 3'-end of exon 30. One gene mosaic variant was found in a proband who complained of cutaneous neurofibroma with the frameshift variant c.495_498del:p.Thr165fs in exon 5, and ultradeep sequencing showed the highest mutation rate of 10.81% in cutaneous neurofibromas. A frameshift variant, c.36_39del:p.Ser12fs in exon 1 of the gene, was found in a proband who presented with skin plaques and intracranial neurogenic tumors. All of these pathogenic variants were heterozygous, one was not reported, and one not in Chinese before. This study expands the pathogenic variant spectrum of NF and demonstrates the clinical diagnosis.
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http://dx.doi.org/10.3389/fgene.2021.603195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985060PMC
March 2021

Decreased numbers and sex-based differences of circulating regulatory T cells in patients with seropositive undifferentiated arthritis.

Ther Adv Chronic Dis 2021 24;12:2040622320986721. Epub 2021 Feb 24.

Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

Aims: CD4 T cells play crucial roles as both mediators and regulators of the pathogenesis of rheumatoid arthritis (RA). However, the characteristics of CD4 T cell subpopulations in the earliest stage of RA development remain unclear. Hence, we determined the proportions and absolute counts of circulating CD4 T cell subsets in patients with seropositive undifferentiated arthritis (SUA), the early and preclinical stage of RA.

Methods: Peripheral blood samples and clinical information were collected from 177 patients with SUA, 104 patients with RA, and 120 healthy controls. All patients were newly diagnosed and untreated. Proportions and absolute counts of CD4 T cell subpopulations were determined by flow cytometric analysis.

Results: In patients with SUA, percentages and absolute counts of circulating regulatory T (Treg) cells were decreased significantly and Th17/Treg cell ratios were abnormally increased, whereas Th17 cell numbers were similar to those in healthy controls. In addition, sex-based differences in circulating Treg cells were observed, with female SUA patients having lower proportions and absolute counts of Treg cells than those in males. Moreover, female patients with SUA had higher erythrocyte sedimentation rates and 28-joint Disease Activity Scores than those in males.

Conclusion: Immune tolerance deficiency resulting from an abnormal reduction in circulating Treg cells might be the most crucial immunological event in the earliest stage of RA. The sex-specific disparity in Treg cells should also be considered for immunoregulatory and preventive strategies targeting early RA.
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http://dx.doi.org/10.1177/2040622320986721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925950PMC
February 2021

Osthole enhances the bone mass of senile osteoporosis and stimulates the expression of osteoprotegerin by activating β-catenin signaling.

Stem Cell Res Ther 2021 Feb 27;12(1):154. Epub 2021 Feb 27.

Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.

Introduction: Osthole has a potential therapeutic application for anti-osteoporosis. The present study verified whether osthole downregulates osteoclastogenesis via targeting OPG.

Methods: In vivo, 12-month-old male mice were utilized to evaluate the effect of osthole on bone mass. In vitro, bone marrow stem cells (BMSCs) were isolated and extracted from 3-month-old OPG mice and the littermates of OPG mice. Calvaria osteoblasts were extracted from 3-day-old C57BL/6J mice or 3-day-old OPG mice and the littermates of OPG mice.

Results: Osthole significantly increased the gene and protein levels of OPG in primary BMSCs in a dose-dependent manner. The deletion of the OPG gene did not affect β-catenin expression. The deletion of the β-catenin gene inhibited OPG expression in BMSCs, indicating that osthole stimulates the expression of OPG via activation of β-catenin signaling.

Conclusion: Osthole attenuates osteoclast formation by stimulating the activation of β-catenin-OPG signaling and could be a potential drug for the senile osteoporosis.
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http://dx.doi.org/10.1186/s13287-021-02228-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912492PMC
February 2021

Obacunone protects retinal pigment epithelium cells from ultra-violet radiation-induced oxidative injury.

Aging (Albany NY) 2021 02 1;13(8):11010-11025. Epub 2021 Feb 1.

Department of Ophthalmology, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huaian, China.

Ultra-violet (UV) radiation (UVR) causes significant oxidative injury to retinal pigment epithelium (RPE) cells. Obacunone is a highly oxygenated triterpenoid limonoid compound with various pharmacological properties. Its potential effect in RPE cells has not been studied thus far. Here in ARPE-19 cells and primary murine RPE cells, obacunone potently inhibited UVR-induced reactive oxygen species accumulation, mitochondrial depolarization, lipid peroxidation and single strand DNA accumulation. UVR-induced RPE cell death and apoptosis were largely alleviated by obacunone. Obacunone activated Nrf2 signaling cascade in RPE cells, causing Keap1-Nrf2 disassociation, Nrf2 protein stabilization and nuclear translocation. It promoted transcription and expression of antioxidant responsive element-dependent genes. Nrf2 silencing or CRISPR/Cas9-induced Nrf2 knockout almost reversed obacunone-induced RPE cytoprotection against UVR. Forced activation of Nrf2 cascade, by Keap1 knockout, similarly protected RPE cells from UVR. Importantly, obacunone failed to offer further RPE cytoprotection against UVR in Keap1-knockout cells. , intravitreal injection of obacunone largely inhibited light-induced retinal damage. Collectively, obacunone protects RPE cells from UVR-induced oxidative injury through activation of Nrf2 signaling cascade.
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http://dx.doi.org/10.18632/aging.202437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109142PMC
February 2021

A single-dose live attenuated chimeric vaccine candidate against Zika virus.

NPJ Vaccines 2021 Jan 29;6(1):20. Epub 2021 Jan 29.

Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, MD4 Level 5, 5 Science Drive 2, Singapore, 117597, Singapore.

The mosquito-borne Zika virus is an emerging pathogen from the Flavivirus genus for which there are no approved antivirals or vaccines. Using the clinically validated PDK-53 dengue virus vaccine strain as a backbone, we created a chimeric dengue/Zika virus, VacDZ, as a live attenuated vaccine candidate against Zika virus. VacDZ demonstrates key markers of attenuation: small plaque phenotype, temperature sensitivity, attenuation of neurovirulence in suckling mice, and attenuation of pathogenicity in interferon deficient adult AG129 mice. VacDZ may be administered as a traditional live virus vaccine, or as a DNA-launched vaccine that produces live VacDZ in vivo after delivery. Both vaccine formulations induce a protective immune response against Zika virus in AG129 mice, which includes neutralising antibodies and a strong Th1 response. This study demonstrates that VacDZ is a safe and effective vaccine candidate against Zika virus.
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http://dx.doi.org/10.1038/s41541-021-00282-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846741PMC
January 2021

The mA methylome of SARS-CoV-2 in host cells.

Cell Res 2021 04 28;31(4):404-414. Epub 2021 Jan 28.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, 100071, China.

The newly identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a global health emergency because of its rapid spread and high mortality. The molecular mechanism of interaction between host and viral genomic RNA is yet unclear. We demonstrate herein that SARS-CoV-2 genomic RNA, as well as the negative-sense RNA, is dynamically N-methyladenosine (mA)-modified in human and monkey cells. Combined RIP-seq and miCLIP analyses identified a total of 8 mA sites at single-base resolution in the genome. Especially, epidemic strains with mutations at these identified mA sites have emerged worldwide, and formed a unique cluster in the US as indicated by phylogenetic analysis. Further functional experiments showed that mA methylation negatively regulates SARS-CoV-2 infection. SARS-CoV-2 infection also triggered a global increase in host mA methylome, exhibiting altered localization and motifs of mA methylation in mRNAs. Altogether, our results identify mA as a dynamic epitranscriptomic mark mediating the virus-host interaction.
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http://dx.doi.org/10.1038/s41422-020-00465-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115241PMC
April 2021

The Gut Microbiota and Its Relevance to Peripheral Lymphocyte Subpopulations and Cytokines in Patients with Rheumatoid Arthritis.

J Immunol Res 2021 8;2021:6665563. Epub 2021 Jan 8.

Department of Rheumatology, The Second Hospital of Shanxi Medical University, Shanxi, China.

Growing experimental and clinical evidence suggests that a chronic inflammatory response induced by gut microbiome critically contribute to the development of rheumatoid arthritis (RA). Previous studies demonstrated the disturbance of lymphocyte subpopulations in RA patients. The purpose of this study was to explore the characteristics of gut microbiome and the associations between bacterium and lymphocyte subpopulations as well as cytokines in patients with RA. Fecal samples from 205 RA patients and 199 healthy controls (HCs) were collected for bacterial DNA extraction and 16S ribosomal RNA (rRNA) gene sequencing. The levels of peripheral lymphocyte subpopulation such as T, B, CD4T, CD8T, NK, T helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs) of these subjects were detected by flow cytometry combined with standard absolute counting beads. The serum levels of cytokines interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-17, tumour necrosis factor- (TNF-), and interferon- (INF-) were tested by flow cytometric bead array (CBA). Alpha and beta diversity of gut microbiome were explored by bioinformatics analysis. Spearman rank correlation test was used to explore the relationships between gut microbiome and lymphocyte subsets as well as serum cytokines. The diversity and relative abundance of intestinal microbiota in patients with RA were significantly different from those in HCs. Detailly, the abundant of phylum in RA patients was more than that in HCs, while was less than in HCs. There was increased relative abundance of genus as well as genus , more abundance of in patients with lower levels of T, B, CD4T, and Tregs. In addition, the relative abundances of , , , and were correlated with cytokines. Gut microbiome of RA patients was clearly different from that of HCs. Abnormal bacteria communities are associated with the altered levels of lymphocyte subpopulation and cytokines, which might be one of the pathogenesis of RA.
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http://dx.doi.org/10.1155/2021/6665563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810541PMC
January 2021

ACOX1, regulated by C/EBPα and miR-25-3p, promotes bovine preadipocyte adipogenesis.

J Mol Endocrinol 2021 03;66(3):195-205

Hubei Key Laboratory of Animal Embryo Engineering and Molecular Breeding, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China.

Acyl-coenzyme A oxidase 1 (ACOX1) is the first and rate-limiting enzyme in peroxisomal fatty acid β-oxidation of fatty acids. Previous studies have reported that ACOX1 was correlated with the meat quality of livestock, while the role of ACOX1 in intramuscular adipogenesis of beef cattle and its transcriptional and post-transcriptional regulatory mechanisms remain unclear. In the present study, gain-of-function and loss-of-function assays demonstrated that ACOX1 positively regulated the adipogenesis of bovine intramuscular preadipocytes. The C/EBPα-binding sites in the bovine ACOX1 promoter region at -1142 to -1129 bp, -831 to -826 bp, and -303 to -298 bp were identified by promoter deletion analysis and site-directed mutagenesis. Electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) further showed that these three regions are C/EBPα-binding sites, both in vitro and in vivo, indicating that C/EBPα directly interacts with the bovine ACOX1 promoter and inhibits its transcription. Furthermore, the results from bioinformatics analysis, dual luciferase assay, site-directed mutagenesis, qRT-PCR, and Western blotting demonstrated that miR-25-3p directly targeted the ACOX1 3'UTR (3'UTR). Taken together, our findings suggest that ACOX1, regulated by transcription factor C/EBPα and miR-25-3p, promotes adipogenesis of bovine intramuscular preadipocytes via regulating peroxisomal fatty acid β-oxidation.
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http://dx.doi.org/10.1530/JME-20-0250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052523PMC
March 2021

Precise diagnosis of three top cancers using dbGaP data.

Sci Rep 2021 Jan 12;11(1):823. Epub 2021 Jan 12.

Huaiyin Institute of Technology, Huaian, 223003, China.

The challenge of decoding information about complex diseases hidden in huge number of single nucleotide polymorphism (SNP) genotypes is undertaken based on five dbGaP studies. Current genome-wide association studies have successfully identified many high-risk SNPs associated with diseases, but precise diagnostic models for complex diseases by these or more other SNP genotypes are still unavailable in the literature. We report that lung cancer, breast cancer and prostate cancer as the first three top cancers worldwide can be predicted precisely via 240-370 SNPs with accuracy up to 99% according to leave-one-out and 10-fold cross-validation. Our findings (1) confirm an early guess of Dr. Mitchell H. Gail that about 300 SNPs are needed to improve risk forecasts for breast cancer, (2) reveal an incredible fact that SNP genotypes may contain almost all information that one wants to know, and (3) show a hopeful possibility that complex diseases can be precisely diagnosed by means of SNP genotypes without using phenotypical features. In short words, information hidden in SNP genotypes can be extracted in efficient ways to make precise diagnoses for complex diseases.
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http://dx.doi.org/10.1038/s41598-020-80832-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804208PMC
January 2021

Validation of Susceptibility Loci for Vitiligo Identified by GWAS in the Chinese Han Population.

Front Genet 2020 3;11:542275. Epub 2020 Dec 3.

Department of Dermatology of First Affiliated Hospital, Institute of Dermatology, Anhui Medical University, Hefei, China.

Forty-nine susceptible loci have been reported to be significantly associated with vitiligo by genome-wide association studies (GWASs) in European-derived whites. To date, some of these reported susceptibility loci have not yet been validated in the Chinese Han population. The purpose of this study was to examine whether the 16 reported susceptible loci in European-derived whites were associated with vitiligo in the Chinese Han population. Imputation was performed using our previous GWAS dataset by IMPUTE v2.2.2. The 16 imputed top single-nucleotide polymorphisms (SNPs) with suggestive signals, together with the reported SNPs, were genotyped in a total of 2581 patients and 2579 controls by the Sequenom MassARRAY system. PLINK 2.0 software was used to perform association analysis. The dbSNP database, HaploReg, and eQTL data were adopted to annotate the biological function of the SNPs. Finally, four SNPs from three loci were significantly associated with vitiligo, including rs3747517 ( = 1.29 × 10, OR = 0.87) in 2q24.2, rs4807000 ( = 7.78 × 10, OR = 0.66) and rs6510827 ( = 3.65 × 10, OR = 1.19) in 19p13.3, and rs4822024 ( = 6.37 × 10, OR = 0.67) in 22q13.2. According to the dbSNP database, rs3747517 is a missense variant of , rs4807000 and rs6510827 are located in , and rs4822024 is located 6 kb upstream of . Further bioinformatics analysis by HaploReg and eQTL found that rs4807000, rs6510827, and rs4822024 are involved in regulating gene expression. Our study revealed the strong association of 2q24.2 (rs3747517), 19p13.3 (rs4807000, rs6510827), and 22q13.2 (rs4822024) with the risk of vitiligo in the Chinese Han population, which implicates common factors for vitiligo across different ethnicities, and helps expand the understanding of the genetic basis of this disease.
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http://dx.doi.org/10.3389/fgene.2020.542275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744663PMC
December 2020

MiR-146a functions as a potential tumor suppressor in retinoblastoma by negatively regulate neuro-oncological ventral antigen-1.

Kaohsiung J Med Sci 2021 Apr 19;37(4):286-293. Epub 2020 Dec 19.

Department of Ophthalmology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai 'an City, Jiangsu, China.

MicroRNAs (miRNAs) are dysregulated in many tumors and have been found to play crucial roles in cancer biology. Retinoblastoma is a rare tumor that develops rapidly from a malignant tumor of immature cells in the retina known as photoreceptor progenitors. Our study aimed to explore the role of miR-146a in the pathology of retinoblastoma. Potential target gene of miR-146a was predicted by Targetscan. Reverse transcription quantitative polymerase chain reaction (RT-PCR) showed that miR-146a was downregulated and ventral nerve tumor antigen 1 (Neuro - oncological ventral antigen 1, NOVA1) was upregulated in retinoblastoma. Luciferase assay confirmed that miR-146a directly target NOVA1. MiR-146a knockdown and overexpression experiments were performed and found that miR-146a could regulate the expression of NOVA1. The miR-146a knockdown and overexpression experiments were conducted to investigate the biological function of miR-146a. MiR-146a was found inhibited the viability, proliferation and invasion of retinoblastoma cell by MTT, EdU, and transwell assays. Flow cytometry was performed for the apoptosis analysis and miR-146a increased the apoptosis of retinoblastoma cell was found. Above phenomenon can be rescued by overexpression of NOVA1. In conclusion, these results suggest that miR-146a acts as a tumor suppressor and can act as a potential therapeutic target for retinoblastoma in the future.
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http://dx.doi.org/10.1002/kjm2.12337DOI Listing
April 2021

Dynamic Hormone Control of Stress and Fertility.

Front Physiol 2020 17;11:598845. Epub 2020 Nov 17.

EPSRC Centre for Predictive Modelling in Healthcare, Living Systems Institute, College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, United Kingdom.

Neuroendocrine axes display a remarkable diversity of dynamic signaling processes relaying information between the brain, endocrine glands, and peripheral target tissues. These dynamic processes include oscillations, elastic responses to perturbations, and plastic long term changes observed from the cellular to the systems level. While small transient dynamic changes can be considered physiological, larger and longer disruptions are common in pathological scenarios involving more than one neuroendocrine axes, suggesting that a robust control of hormone dynamics would require the coordination of multiple neuroendocrine clocks. The idea of apparently different axes being in fact exquisitely intertwined through neuroendocrine signals can be investigated in the regulation of stress and fertility. The stress response and the reproductive cycle are controlled by the Hypothalamic-Pituitary-Adrenal (HPA) axis and the Hypothalamic-Pituitary-Gonadal (HPG) axis, respectively. Despite the evidence surrounding the effects of stress on fertility, as well as of the reproductive cycle on stress hormone dynamics, there is a limited understanding on how perturbations in one neuroendocrine axis propagate to the other. We hypothesize that the links between stress and fertility can be better understood by considering the HPA and HPG axes as coupled systems. In this manuscript, we investigate neuroendocrine rhythms associated to the stress response and reproduction by mathematically modeling the HPA and HPG axes as a network of interlocked oscillators. We postulate a network architecture based on physiological data and use the model to predict responses to stress perturbations under different hormonal contexts: normal physiological, gonadectomy, hormone replacement with estradiol or corticosterone (CORT), and high excess CORT (hiCORT) similar to hypercortisolism in humans. We validate our model predictions against experiments in rodents, and show how the dynamic responses of these endocrine axes are consistent with our postulated network architecture. Importantly, our model also predicts the conditions that ensure robustness of fertility to stress perturbations, and how chronodisruptions in glucocorticoid hormones can affect the reproductive axis' ability to withstand stress. This insight is key to understand how chronodisruption leads to disease, and to design interventions to restore normal rhythmicity and health.
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http://dx.doi.org/10.3389/fphys.2020.598845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718016PMC
November 2020

The expression, modulation and use of cancer-testis antigens as potential biomarkers for cancer immunotherapy.

Am J Transl Res 2020 15;12(11):7002-7019. Epub 2020 Nov 15.

Department of Respiratory Medicine, The Second Hospital of Jilin University Changchun, P. R. China.

Cancer-testis antigens (CTA) are tumor antigens, present in the germ cells of testes, ovaries and trophoblasts, which undergo deregulated expression in the tumor and malignant cells. CTA genes are either X-linked or autosomal, favourably expressed in spermatogonia and spermatocytes, respectively. CTAs trigger unprompted humoral immunity and immune responses in malignancies, altering tumor cell physiology and neoplastic behaviors. CTAs demonstrate varied expression profile, with increased abundance in malignant melanoma and prostate, lung, breast and epithelial cell cancers, and a relatively reduced prevalence in intestinal cancer, renal cell adenocarcinoma and malignancies of immune cells. A combination of epigenetic and non-epigenetic agents regulates CTA mRNA expression, with the key participation of CpG islands and CpG-rich promoters, histone methyltransferases, cytokines, tyrosine kinases and transcriptional activators and repressors. CTA triggers gametogenesis, in association with mutated tumorigenic genes and tumor repressors. The CTAs function as potential biomarkers, particularly for prostate, cervical, breast, colorectal, gastric, urinary bladder, liver and lung carcinomas, characterized by alternate splicing and phenotypic heterogeneity in the cells. Additionally, CTAs are prospective targets for vaccine therapy, with the MAGE-A3 and NYESO-1 undergoing clinical trials for tumor regression in malignant melanoma. They have been deemed important for adaptive immunotherapy, marked by limited expression in normal somatic tissues and recurrent up-regulation in epithelial carcinoma. Overall, the current review delineates an up-dated understanding of the intricate processes of CTA expression and regulation in cancer. It further portrays the role of CTAs as biomarkers and probable candidates for tumor immunotherapy, with a future prospect in cancer treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724325PMC
November 2020

Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection.

Cell Res 2021 01 1;31(1):25-36. Epub 2020 Dec 1.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases/National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China.

Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.
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http://dx.doi.org/10.1038/s41422-020-00444-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705443PMC
January 2021

Detection of a novel HLA-B allele, HLA-B*55:71, in a Chinese hematopoietic stem cell donor and platelet donor.

HLA 2021 Apr 10;97(4):366-368. Epub 2020 Dec 10.

Transfusion Medicine Institute, Liaoning Blood Center, Shenyang, China.

HLA-B*55:71 has one nucleotide change from HLA-B*55:02:01:01 where histidine (3) is changed to tyrosine.
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http://dx.doi.org/10.1111/tan.14160DOI Listing
April 2021

Two novel FUT1 alleles that cause para-Bombay phenotype in a Chinese individual.

Transfusion 2020 Dec 11;60(12):E55-E57. Epub 2020 Nov 11.

Key Laboratory of Blood Safety Research of Liaoning, Shenyang, China.

Background: Bombay and para-Bombay phenotypes, which arise from gene mutations of α-1,2-fucosyltransferase FUT1, are very rare in Chinese population. A para-Bombay phenotype Chinese individual with two novel FUT1 mutations was reported here.

Study Design And Methods: The peripheral blood and saliva samples of the proband and her family members were collected after informed consent. ABO and H blood group phenotyping was performed by haemagglutination methods. ABO genotype was determined by PCR-SSP kit. A, B, and H antigens in saliva were detected by a hemagglutination inhibition test. Fragments encompassing the full coding region of FUT1 and FUT2 genes were PCR amplified and sequenced. Allelic sequences were validated by cloning and sequencing individual colonies.

Results: The serologic reaction results of the proband revealed that A, B, and H antigen were absent on RBCs, but B and H antigen were presented in saliva, and the serum contains anti-H. The proband was assigned as B/O1 by ABO genotyping. Two new heterozygous mutations of FUT1 gene, c.508dupT and c.787A>C, were identified through direct sequencing of PCR-amplified products. TA cloning and sequencing confirmed that two novel mutations were on different alleles. FUT2 gene sequence of the proband is consistent with standard. The other family members of the proband showed normal phenotypes of ABO blood group and their genotypes are consistent with phenotypes.

Conclusion: Two novel FUT1 alleles, with the previously not reported mutations c.508dupT and c.787C, respectively, are responsible for the para-Bombay phenotype detected in the sample from the proband.
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http://dx.doi.org/10.1111/trf.16183DOI Listing
December 2020

lncRNA VIM‑AS1 promotes cell proliferation, metastasis and epithelial‑mesenchymal transition by activating the Wnt/β‑catenin pathway in gastric cancer.

Mol Med Rep 2020 Dec 11;22(6):4567-4578. Epub 2020 Oct 11.

Yulin Cancer Diagnosis and Treatment Center, The First Hospital of Yulin, Yulin, Shaanxi 719000, P.R. China.

The present study aimed to explore the biological functions and molecular mechanisms of the long non‑coding RNA VIM antisense RNA 1 (VIM‑AS1) in gastric cancer (GC). The expression of VIM‑AS1 was analyzed in tissues from patients with GC and GC cell lines by reverse transcription‑quantitative (RT‑q)PCR. The relationship between VIM‑AS1 expression and overall survival time of patients with GC was also assessed. To determine the biological functions of VIM‑AS1, Cell Counting Kit‑8 assay, colony formation assay, flow cytometry, wound healing assay and Transwell assay were employed. The targeting relationship among VIM‑AS1, microRNA (miR)‑8052 and frizzled 1 (FZD1) was verified by the dual luciferase reporter gene assay. The underlying molecular mechanism of VIM‑AS1 on GC was determined by RT‑qPCR and western blotting. In addition, tumor formation was detected in nude mice. The results of the present study demonstrated that VIM‑AS1 was highly expressed in GC tissues and cells. In addition, VIM‑AS1 expression was demonstrated to be closely related to the prognosis of patients with GC. Notably, silencing VIM‑AS1 inhibited the proliferation, migration and invasion, and enhanced apoptosis of AGS and HGC‑27 cells. Silencing VIM‑AS1 significantly increased the protein expression levels of cleaved caspase‑3, Bax and E‑cadherin, but decreased the protein expression levels of Bcl‑2, N‑cadherin, vimentin, matrix metalloproteinase (MMP)‑2, MMP‑9, β‑catenin, cyclin D1, C‑myc and FZD1. Additionally, silencing VIM‑AS1 inhibited tumor growth in nude mice. Cumulatively, the present study demonstrated that VIM‑AS1 may promote cell proliferation, migration, invasion and epithelial‑mesenchymal transition by regulating FDZ1 and activating the Wnt/β‑catenin pathway in GC.
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http://dx.doi.org/10.3892/mmr.2020.11577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646824PMC
December 2020

Type-IInterferon-Inducible SERTAD3 Inhibits Influenza A Virus Replication by Blocking the Assembly of Viral RNA Polymerase Complex.

Cell Rep 2020 11;33(5):108342

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

Influenza A virus (IAV) infection stimulates a type I interferon (IFN-I) response in host cells that exerts antiviral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). However, most ISGs are poorly studied for their roles in the infection of IAV. Herein, we demonstrate that SERTA domain containing 3 (SERTAD3) has a significant inhibitory effect on IAV replication in vitro. More importantly, Sertad3 mice develop more severe symptoms upon IAV infection. Mechanistically, we find SERTAD3 reduces IAV replication through interacting with viral polymerase basic protein 2 (PB2), polymerase basic protein 1 (PB1), and polymerase acidic protein (PA) to disrupt the formation of the RNA-dependent RNA polymerase (RdRp) complex. We further identify an 8-amino-acid peptide of SERTAD3 as a minimum interacting motif that can disrupt RdRp complex formation and inhibit IAV replication. Thus, our studies not only identify SERTAD3 as an antiviral ISG, but also provide the mechanism of potential application of SERTAD3-derived peptide in suppressing influenza replication.
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http://dx.doi.org/10.1016/j.celrep.2020.108342DOI Listing
November 2020