Publications by authors named "Lili Chen"

599 Publications

Novel fabrication of dual nanoparticle loaded-co-polymeric dressing for effective healing efficiency in wound care after fracture surgery.

J Biomater Sci Polym Ed 2021 Aug 1:1-19. Epub 2021 Aug 1.

Orthopaedic Center, the First People's Hospital of Wenling, Wenling, PR China.

In the present study, curcumin loaded chitosan/poly ethylene glycol nanomaterial (CUR loaded CH/PEG/AgNPs) was fabricated and characterized for wound healing efficiency after fracture surgery. The interaction of functional groups and crystal nature were recorded under FTIR and XRD spectrometer and reveals that the stabilization and purity of NPs was mediated by OH/NH groups in chitosan. FESEM showed the presence of spherical and well dispersed particles. The average size of the particle was 13.48 nm. The CUR loaded CH/PEG/AgNPs showed higher swelling capacity (495.6 g/g) in phosphate buffer saline compared to water (140.2 g/g). The drug loading efficiency was higher in CUR loaded CH/PEG/AgNPs compared to CH/PEG films as recorded by the absorbance peak at 460 nm corresponds to curcumin in the composite. A dose dependent cytotoxicity of CUR loaded CH/PEG/AgNPs was noticed on Vero cells. The viability of Vero cells was increased to 96.5% at 100 μg/mL. A remarkable change in Vero cells such as condensed nuclei and membrane blabbing was noticed in cells treated with CUR loaded CH/PEG/AgNPs. A greater inhibition of and was noticed at 24 h and 48 h treated with CUR loaded CH/PEG/AgNPs. A greater healing effect by increasing the wound contraction (98% on day 12) was observed with CUR loaded CH/PEG/AgNPs compared to control. Histopathological examination demonstrated that CUR loaded CH/PEG/AgNPs showed complete tissue regeneration in wound excised rats. The results of this study conclude that CUR loaded CH/PEG/AgNPs could be promising candidate to prevent microbial infections in wound, healing wound rapidly and inhibit the proliferation of apoptotic cells. Thus, CUR loaded CH/PEG/AgNPs could be a potential therapeutic agent with broad spectrum applications in the future. HighlightsA new approach was used to develop curcumin-loaded chitosan/poly(ethylene glycol)/AgNPs.The CUR-loaded CH/PEG/AgNPs were confirmed to be crystals by XRD analysis.The prepared CH/PEG/AgNPs were spherical and averaged 13.48 nm in size.The growth of and were inhibited mostly by CH/PEG/AgNPs treatment.CUR loaded CH/PEG/AgNPs showed complete tissue regeneration in wound excised mice.
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http://dx.doi.org/10.1080/09205063.2021.1953237DOI Listing
August 2021

Chemotherapeutic potency stimulated by SNAI1-knockdown based on multifaceted nanomedicine.

J Control Release 2021 Jul 26;337:343-355. Epub 2021 Jul 26.

State Key Laboratory of Fine Chemicals, Dalian University of Technology, No. 2 Linggong Road, Dalian 116024, China; School of Bioengineering, Dalian University of Technology, No. 2 Linggong Road, Dalian 116024, China. Electronic address:

Molecular insights into tumorigenesis have uncovered intimate correlation of SNAI1 with tumor malignancy. Herein, to explore merits of SNAI1-knockdown in tumor therapy, we harnessed RNA interference tool (shSNAI1), together with chemotherapeutic doxorubicin. Owing to abundant hydroxyl groups, pullulan was attempted to be covalently conjugated with a multiple of functional moieties, including positively-charged oligoethylenimine components for electrostatic entrapment of polyanionic shSNAI1 and hydrophobic components for entrapment of lipophilic doxorubicin. Notably, the aforementioned covalent conjugations were tailored to be detachable in response to intracellular reducing microenvironment owing to redox disulfide linkage, thereby accounting for selective intracellular liberation of the therapeutic payloads. Moreover, the surface of nanomedicine was modified with hyaluronic acid, endowing not only excellent biocompatibilities but active tumor-targeting function due to its receptors (CD44) overexpressed on tumor cells. Subsequent investigations approved appreciably targeted co-delivery of shSNAI1 and doxorubicin into solid lung tumors via systemic administration and demonstrated critical contribution of SNAI1-knockdown in amplifying chemotherapeutic potencies.
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http://dx.doi.org/10.1016/j.jconrel.2021.07.039DOI Listing
July 2021

Normal-sized basal ganglia perivascular space related to motor phenotype in Parkinson freezers.

Aging (Albany NY) 2021 Jul 27;13(14):18912-18923. Epub 2021 Jul 27.

Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, Canada.

Changes in basal ganglia (BG) perivascular spaces (PVSs) are related to motor and cognitive behaviors in Parkinson's disease (PD). However, the correlation between the initial motor phenotype and PVSs distribution/burden in PD freezing of gait (FOG) remains unclear. In addition, the normal-sized PVSs (nPVSs) have not been well-studied. With high-resolution 7T-MRI, we studied nPVSs burden in BG, thalamus, midbrain and centrum semiovale. The numbers and volume of nPVSs were assessed in 10 healthy controls, 10 PD patients without FOG, 20 with FOG [10 tremor dominant (TD), 10 non-TD subtype]. Correlation analyses were further performed in relation to clinical parameters. In this proof of concept study, we found that the nPVS burden of bilateral and right BG were significantly higher in freezers. A negative correlation existed between the tremor score and BG-nPVSs count. A positive correlation existed between the levodopa equivalent daily dose and BG-nPVSs count. The nPVS burden correlated with the progression to FOG in PD, but the distribution and burden of nPVS differ in TD vs. non-TD subtypes. High resolution 7T-MRI is a sensitive and reliable tool to evaluate BG-nPVS, and may be a useful imaging marker for predicting gait impairment that may evolve into FOG in PD.
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http://dx.doi.org/10.18632/aging.203343DOI Listing
July 2021

The Psychological Impact of COVID-19 Pandemic on Health Care Workers: A Systematic Review and Meta-Analysis.

Front Psychol 2021 8;12:626547. Epub 2021 Jul 8.

Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.

The COVID-19 epidemic has generated great stress throughout healthcare workers (HCWs). The situation of HCWs should be fully and timely understood. The aim of this meta-analysis is to determine the psychological impact of COVID-19 pandemic on health care workers. We searched the original literatures published from 1 Nov 2019 to 20 Sep 2020 in electronic databases of PUBMED, EMBASE and WEB OF SCIENCE. Forty-seven studies were included in the meta-analysis with a combined total of 81,277 participants. The pooled prevalence of anxiety is 37% (95% CI 0.31-0.42, I = 99.9%) from 44 studies. Depression is estimated in 39 studies, and the pooled prevalence of depression is 36% (95% CI 0.31-0.41, I = 99.6%). There are 10 studies reported the prevalence of insomnia, and the overall prevalence of insomnia is 32% (95% CI 0.23-0.42, I = 99.5%). The subgroup analysis showed a higher incidence of anxiety and depression among women and the frontline HCWs compared to men and non-frontline HCWs respectively. The COVID-19 pandemic has caused heavy psychological impact among healthcare professionals especially women and frontline workers. Timely psychological counseling and intervention ought to be implemented for HCWs in order to alleviate their anxiety and improve their general mental health.
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http://dx.doi.org/10.3389/fpsyg.2021.626547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297953PMC
July 2021

Sequestration to lipid droplets promotes histone availability by preventing turnover of excess histones.

Development 2021 Jul 21. Epub 2021 Jul 21.

Department of Biology, University of Rochester, Rochester, NY, USA.

Because both dearth and overabundance of histones result in cellular defects, histone synthesis and demand are typically tightly coupled. In Drosophila embryos, histones H2B/H2A/H2Av accumulate on lipid droplets (LDs), cytoplasmic fat storage organelles. Without LD-binding, maternally provided H2B/H2A/H2Av are absent, but how LDs ensure histone storage is unclear. Using quantitative imaging, we uncover when during oogenesis these histones accumulate, and which step of accumulation is LD-dependent. LDs originate in nurse cells (NCs) and are transported to the oocyte. Although H2Av accumulates on LDs in NCs, the majority of the final H2Av pool is synthesized in oocytes. LDs promote intercellular transport of the histone-anchor Jabba and thus its presence in the ooplasm. Ooplasmic Jabba then prevents H2Av degradation, safeguarding the H2Av stockpile. Our findings provide insight into the mechanism for establishing histone stores during Drosophila oogenesis and shed light on the function of LDs as protein-sequestration sites.
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http://dx.doi.org/10.1242/dev.199381DOI Listing
July 2021

Value of Barthel, PLAN and NIHSS scores for predicting the death of patients with acute ischemic stroke during their 5-year follow-up.

J Clin Neurosci 2021 Aug 8;90:94-98. Epub 2021 Jun 8.

Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050031, China. Electronic address:

Objective: This study aimed to investigate the value of Barthel, PLAN, and NIHSS scores for predicting death in the 5-year follow-up after patients with AIS are discharged and find a simple and convenient predictive scale.

Methods: Data were prospectively collected from 678 patients with AIS. Patients' death after 5 years of follow-up was considered the final event. The predictors of death were examined through single-factor and multivariate analysis. The receiver operating characteristic curve (ROC) of the patients' Barthel, PLAN, and NIHSS scores was drawn, and the area under the curve (AUC) was calculated. Differences in the predictive power of the three scales were compared using MedCalc. The goodness of fit between predictive and actual models was evaluated with the Hosmer-Lemeshow method.

Results: Multivariate analysis suggested that the BI score was an independent predictor of death from AIS in the 5-year follow-up. The Barthel, PLAN, and NIHSS scale scores predicted the 5-year mortality AUC values of AIS were 0.687 [95% CI, (0.649-0.722)], 0.621 [95% CI, (0.583-0.659)], 0.637 [95% CI, (0.599-0.674)], the Hosmer-Lemeshow test revealed P > 0.05, indicating that the three models had a good fit. In pairwise comparison, the AUC value of the BI score was significantly greater than that of the NIHSS scores (Pc = 0.0189). BI and PLAN scores were very close to statistical significance (Pc = 0.0513). However, PLAN and NIHSS scores had no significant differences (Pc = 1.7493).

Conclusion: Simple BI scores had a high predictive value for the death of Chinese patients with AIS within 5 years.
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http://dx.doi.org/10.1016/j.jocn.2021.05.049DOI Listing
August 2021

Cholinesterase is Associated With Prognosis and Response to Chemotherapy in Advanced Gastric Cancer.

Pathol Oncol Res 2021 25;27:580800. Epub 2021 Mar 25.

Department of Oncology, Changzhou Tumor Hospital Affiliated to Soochow University, Changzhou, China.

Cholinesterase (CHE) is a routine serum biomarker in gastric cancer (GC). However, little research has been done on its clinical value in advanced GC. In addition, it is not clear whether it can be used as biomarker for the response and prognosis of advanced GC patients. Between Jan. 2013 and Dec. 2016, a total of 150 patients with advanced GC treated with first-line chemotherapy were admitted to Changzhou Tumor Hospital Affiliated to Soochow University. We retrospectively identified serum CHE level on the day before chemotherapy and at the end of chemotherapy and abstracted clinicopathologic features and treatment outcomes. Univariate and multivariate survival analyses were performed to assess the relationship between serum CHE levels and progression-free survival (PFS) and overall survival (OS). A total of 150 advanced GC patients were included and divided into serum level ≥5,000 IU/L and serum level <5,000 IU/L. CHE level lower than 5,000 IU/L was associated with poorer PFS (HR, 1.60; 95% CI, 1.141-2.243; = 0.006), poorer OS (HR, 1.76; 95% CI, 1.228-2.515; = 0.002) and trend of poorer response (HR, 0.56; 95% CI, 0.272-1.129; = 0.104). In univariate and multivariate logistic regression analysis, only liver metastasis and PS score were significantly associated with objective response ( < 0.05). The medium PFS was 8.0 months in patients with post-treatment CHE increased vs. 3.8 months in patients with CHE decreased after chemotherapy (HR, 1.82; 95% CI 1.28-2.57; = 0.0002). The medium OS was 13.1 months in patients with increased post-treatment CHE vs. 8.1 months in patients with decreased post-treatment CHE (HR, 1.87; 95% CI 1.29-2.71; = 0.0002). Advanced GC with CHE levels below 5,000 IU/L was significantly associated with poor PFS and OS. The results suggested that CHE analysis before chemotherapy was a promising prognostic marker for advanced GC.
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http://dx.doi.org/10.3389/pore.2021.580800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262142PMC
March 2021

AAPM Task Group 241: A medical physicist's guide to MRI-guided focused ultrasound body systems.

Med Phys 2021 Jul 5. Epub 2021 Jul 5.

National Cancer Institute, National Institutes of Health, Rockville, MD, USA.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a completely non-invasive technology that has been approved by FDA to treat several diseases. This report, prepared by the American Association of Physicist in Medicine (AAPM) Task Group 241, provides background on MRgFUS technology with a focus on clinical body MRgFUS systems. The report addresses the issues of interest to the medical physics community, specific to the body MRgFUS system configuration, and provides recommendations on how to successfully implement and maintain a clinical MRgFUS program. The following sections describe the key features of typical MRgFUS systems and clinical workflow and provide key points and best practices for the medical physicist. Commonly used terms, metrics and physics are defined and sources of uncertainty that affect MRgFUS procedures are described. Finally, safety and quality assurance procedures are explained, the recommended role of the medical physicist in MRgFUS procedures is described, and regulatory requirements for planning clinical trials are detailed. Although this report is limited in scope to clinical body MRgFUS systems that are approved or currently undergoing clinical trials in the United States, much of the material presented is also applicable to systems designed for other applications.
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http://dx.doi.org/10.1002/mp.15076DOI Listing
July 2021

A Diels-Alder polymer platform for thermally enhanced drug release toward efficient local cancer chemotherapy.

Sci Technol Adv Mater 2021 Jun 24;22(1):522-531. Epub 2021 Jun 24.

Research Center for Functional Materials, National Institute for Materials Science (NIMS), Tsukuba, Japan.

We reports a novel thermally enhanced drug release system synthesized via a dynamic Diels-Alder (DA) reaction to develop chemotherapy for pancreatic cancer. The anticancer prodrug was designed by tethering gemcitabine (GEM) to poly(furfuryl methacrylate) (PFMA) via -(3-maleimidopropionyloxy)succinimide as a linker by DA reaction (PFMA-L-GEM). The conversion rate of the DA reaction was found to be approximately 60% at room temperature for 120 h. The reversible deconstruction of the DA covalent bond in retro Diels-Alder (rDA) reaction was confirmed by proton nuclear magnetic resonance, and the reaction was significantly accelerated at 90 °C. A PFMA-LGEM film containing magnetic nanoparticles (MNPs) was prepared for thermally enhanced release of the drug via the rDA reaction. Drug release was initiated by heating MNPs by alternating magnetic field. This enables local heating within the film above the rDA reaction temperature while maintaining a constant surrounding medium temperature. The MNPs/PFMA-L-GEM film decreased the viability of pancreatic cancer cells by 49% over 24 h. Our results suggest that DA/rDA-based thermally enhanced drug release systems can serve as a local drug release platform and deliver the target drug within locally heated tissue, thereby improving the therapeutic efficiency and overcoming the side effects of conventional drugs used to treat pancreatic cancer.
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http://dx.doi.org/10.1080/14686996.2021.1939152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231351PMC
June 2021

Clinical significance of FBXW7 tumor suppressor gene mutations and expression in human colorectal cancer: a systemic review and meta-analysis.

BMC Cancer 2021 Jul 3;21(1):770. Epub 2021 Jul 3.

Department of General Surgery, Key Laboratory of Metabolism and Gastrointestinal Tumor, Key Laboratory of Laparoscopic Technology, Shandong Medicine and Health Key Laboratory of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, 250000, Shandong, China.

Background: Various studies investigating the clinical significance of FBXW7 mutation and/or expression have yielded inconclusive results in colorectal cancer (CRC) patients. Therefore, the present meta-analysis summarizes previous evidence and evaluates the clinical significance, including the prognostic role, of FBXW7 status in CRCs.

Methods: The meta-analysis was conducted by searching the databases of PubMed, China National Knowledge Infrastructure (CNKI), WANFANG data, Web of Science, Embase, and Web of Science. Pooled odds ratios (ORs) and hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated to assess the relationships between FBXW7 status and clinicopathological features and survival in CRC, respectively.

Results: Ten studies involving 4199 patients met the inclusion criteria and included in our meta-analysis. FBXW7 mutation/low expression was obviously correlated with advanced T stage (OR = 0.44, 95% CI: 0.27-0.74, P <  0.01) and lymph node metastasis (OR = 1.88, 95% CI: 1.40-2.53, P <  0.01), but was not associated with other parameters. Further investigation found that FBXW7 mutation/low expression predicted poor OS (HR = 1.25, 95% CI: 1.06-1.47, P <  0.01), but not DFS in CRC (HR = 1.04, 95% CI: 0.60-1.82, P = 0.88). Subgroup analysis found that FBXW7 status was obviously correlated with OS in cohorts recruited after 2009 (HR = 1.32, 95% CI: 1.17-1.50, P <  0.01), from eastern Asia (HR = 1.27, 95% CI: 1.04-1.55, P = 0.02), detected by immunohistochemistry/qRT-PCR (HR = 1.39, 95% CI: 1.22-1.59, P <  0.01), and analysed with multivariate method (HR = 1.47, 95% CI: 1.25-1.74, P <  0.01).

Conclusions: This study indicates that FBXW7 status, expression level especially, is associated with OS but not DFS in CRC. FBXW7 expression level may function as a prognostic biomarker in CRC.
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http://dx.doi.org/10.1186/s12885-021-08535-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254329PMC
July 2021

Development and Psychometric Assessment of the Problematic QQ Use Scale among Adolescents.

Int J Environ Res Public Health 2021 06 23;18(13). Epub 2021 Jun 23.

School of Psychology, Northwest Normal University, Lanzhou 730070, China.

The QQ social media platform is very popular among Chinese adolescents. As with other social media platforms (e.g., Facebook, Instagram, YouTube, etc.), there have been increasing reports that the use of QQ can be potentially problematic to a minority of users. However, unlike these other social media platforms, there is currently no scale to assess the risk of problematic QQ use. The present study developed the Problematic QQ Use Scale (PQQUS) among Chinese adolescents based on six core criteria of behavioral addiction (salience, tolerance, mood modification, loss of control, withdrawal, and conflict) that have been used in the development of other social media addiction scales. The scale was administered to a sample of 1008 Chinese school children to assess its psychometric properties, utilizing both classical test theory and item response theory. The analysis demonstrated that the PQQUS had good item discrimination indices relating to both CTT and IRT. The CFA results and Loevinger's -coefficient suggested the PQQUS had a unidimensional factor structure. The PQQUS had good internal reliability, good composite reliability, and good concurrent validity (based on correlations with measures of anxiety, depression, self-esteem, and life satisfaction). The invariance testing between boys and girls suggested this scale is a valid assessment tool for both groups. Overall, the PQQUS is a psychometrically robust tool for assessing problematic QQ use and will have a key role in further research on problematic QQ use among Chinese adolescents.
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http://dx.doi.org/10.3390/ijerph18136744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268458PMC
June 2021

TINCR inhibits the proliferation and invasion of laryngeal squamous cell carcinoma by regulating miR-210/BTG2.

BMC Cancer 2021 Jun 29;21(1):753. Epub 2021 Jun 29.

Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, No. 246 Xuefu Road, Harbin, 150086, China.

Background: Terminal differentiation-induced ncRNA (TINCR) plays an essential role in epidermal differentiation and is involved in the development of various cancers.

Methods: qPCR was used to detect the expression level of TINCR in tissues and cell lines of laryngeal squamous cell carcinoma (LSCC). The potential targets of TINCR were predicted by the bioinformation website. The expression of miR-210 and BTG2 genes were detected by qPCR, and the protein levels of BTG2 and Ki-67 were evaluated by western blot. CCK-8 assay, scratch test, and transwell chamber were used to evaluate the proliferation, invasion, and metastasis ability of LSCC cells. The relationships among TINCR, miR-210, and BTG2 were investigated by bioinformatics software and luciferase reporter assay. The in vivo function of TINCR was accessed on survival rate and tumor growth in nude mice.

Results: We used qRT-PCR to detect the expression of TINCR in laryngeal squamous cell carcinoma (LSCC) tissues and cells and found significantly lower levels in cancer tissues compared with adjacent tissues. Additionally, patients with high TINCR expression had a better prognosis. TINCR overexpression was observed to inhibit the proliferation and invasion of LSCC cells. TINCR was shown to exert its antiproliferation and invasion effects by adsorbing miR-210, which significantly promoted the proliferation and invasion of laryngeal squamous cells. Overexpression of miR-210 was determined to reverse the tumour-suppressive effects of TINCR. BTG2 (anti-proliferation factor 2) was identified as the target gene of miR-210, and BTG2 overexpression inhibited the proliferation and invasion of LSCC cells. BTG2 knockdown relieved the inhibitory effects of TINCR on the proliferation and invasion of LSCC. Finally, TINCR upregulation slowed xenograft tumour growth in nude mice and significantly increased survival compared with control mice.

Conclusion: The results of this study suggest that TINCR inhibits the proliferation and invasion of LSCC by regulating the miR-210/BTG2 pathway, participates in cell cycle regulation, and may become a target for the treatment of LSCC.
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http://dx.doi.org/10.1186/s12885-021-08513-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243464PMC
June 2021

Chemotherapy initiation with single-course methotrexate alone or combined with dactinomycin versus multi-course methotrexate for low-risk gestational trophoblastic neoplasia: a multi-centric randomized clinical trial.

Front Med 2021 Jun 28. Epub 2021 Jun 28.

Department of Gynecological Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006 s, China.

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.
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http://dx.doi.org/10.1007/s11684-021-0855-4DOI Listing
June 2021

Stable dual-emissive [email protected] metal-organic frameworks for visual and ratiometric sensing of Al and ascorbic acid.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Nov 10;261:120068. Epub 2021 Jun 10.

Key Laboratory of Functional Small Organic Molecule, Ministry of Education, College of Chemistry and Chemical Engineering, Jiangxi Normal University, 99 Ziyang Road, Nanchang 330022, China.

Encapsulation of fluorophore in metal organic framework (MOF) is an effective method to construct multi-emissive composites. Unfortunately, the small molecules loaded in MOF pores are easy to leak. To overcome this difficulty, fluorescin (FL) is proposed to be encapsulated tightly in the cage of the small tetrahedron of UiO-67, as one of the organic ligands coordinated with the central ion Zr. Finally, stable multi-emission fluorescence was successfully achieved, and Förster resonance energy transfer (FRET) occurred between FL and UiO-67. Ascorbic acid (AA) can dynamically quench the fluorescence of [email protected] nanoclusters (NCs) through internal filtering effect, photoinduced electron transfer (PET). The detection limit of the probe for AA was as low as 0.20 μM, and the detection range was 0.67 μM-0.36 mM. The probe was further employed to detect Al due to the coordination between Al and the carboxyl group in the [email protected] NCs. The detection limit for Al was 3.3 nM, and the linear range was 11 nM-5 μM agarose film and test paper were both prepared successfully for visual detection of AA and Al. This work provides new ideas for low-cost and convenient real-time detection method.
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http://dx.doi.org/10.1016/j.saa.2021.120068DOI Listing
November 2021

TRAF6/ERK/p38 pathway is involved in interleukin-17-mediated autophagy to promote osteoclast precursor cell differentiation.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 04;50(2):162-170

Department of Periodontology.

To investigate the effects of interleukin (IL)-17-mediated autophagy on the TNF receptor associated factor (TRAF6)/extracellular signal-regulated kinase (ERK)/p38 pathway and osteoclast differentiation. Mouse bone marrow-derived macrophages (BMM) were cultured with a medium containing 30 ng/mL macrophage colony stimulating factor and 50 ng/mL receptor activator of nuclear factor-kappa B ligard (RANKL), and IL-17 (0.01, 0.1, 1.0, 10 ng/mL) was added for intervention (IL-17 group). Tartrate-resistant acid phosphatase (TRAP) staining was used to observe TRAP positive multinucleated cells; phalloidin fluorescent staining was used to detect actin ring circumference; toluidine blue staining was used to analyze bone resorption lacuna formation. To further examine the mechanism of the effect of IL-17-mediated autophagy on the differentiation of osteoclasts, the control group used RANKL medium to culture mouse macrophage RAW264.7 cells, while the IL-17 group was treated with IL-17 (0.01, 0.1, 1.0, /mL). Western blot was used to detect the expression of autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3 (LC3) and osteoclast-related proteins c-fos and nuclear factor of activated T cell 1 (NFATc1) after treatment with different concentrations of IL-17. The expression of LC3, NFATc1, TRAF6/ERK/p38 signaling pathway related proteins were detected in IL-17 and autophagy inhibitor 3-MA group. The number of TRAP positive multinucleated cells, the circumference of the actin ring and the area of bone resorption lacuna in IL-17 group treated with IL-17 (0.01, 0.1, were significantly higher than those in the control group. In IL-17 treated RAW264.7 cells, the expression of c-fos, NFATc1, Beclin-1, LC3, TRAF6, p-ERK, and p-p38 was all significantly up-regulated (all 0.05). After treatment with the autophagy inhibitor 3-MA, the expression levels of LC3, NFATc1, TRAF6, p-ERK, and p-p38 all decreased significantly (all 0.05). IL-17 can promote the expression of autophagy proteins and enhance the differentiation ability of osteoclast precursor cells, and the TRAF6/ERK/p38 signaling pathway may be involved in this process.
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http://dx.doi.org/10.3724/zdxbyxb-2021-0099DOI Listing
April 2021

PLAU Promotes Cell Proliferation and Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma.

Front Genet 2021 20;12:651882. Epub 2021 May 20.

Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Plasminogen activator, urokinase (uPA) is a secreted serine protease whose Dysregulation is often accompanied by various cancers. However, the biological functions and potential mechanisms of PLAU in head and neck squamous cell carcinoma (HNSCC) remain undetermined. Here, the expression, prognosis, function, and coexpression genetic networks of PLAU in HNSCC were investigated by a series of public bioinformatics tools. A Higher PLAU level predicted a poorer clinical outcome. Meanwhile, functional network analysis implied that PLAU and associated genes mainly regulated cell-substrate adhesion, tissue migration, and extracellular matrix binding. The top 4 significantly associated genes are , , , and . Pathway enrichment analysis indicated that PLAU might activate the epithelial-to-mesenchymal transition (EMT) process, which could explain the poor prognosis in HNSCC. Besides, genes associated with PLAU were also enriched in EMT pathways. We further validated the bioinformatics analysis results by and experiments. Then, we found that much more PLAU was detected in HNSCC tissues, and the silencing of PLAU inhibit the proliferation, migration, and EMT process of CAL27 cell lines. Notably, the downregulation of PLAU decreased the expression of . Moreover, knockdown also inhibits cell proliferation and migration. experiment results indicated that PLAU inhibition could suppress tumor growth. Collectively, PLAU is necessary for tumor progression and can be a diagnostic and prognostic biomarker in HNSCC.
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http://dx.doi.org/10.3389/fgene.2021.651882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173099PMC
May 2021

Understanding the interactions between inorganic-based nanomaterials and biological membranes.

Adv Drug Deliv Rev 2021 Aug 2;175:113820. Epub 2021 Jun 2.

Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Guangzhou 510515, China. Electronic address:

The interactions between inorganic-based nanomaterials (NMs) and biological membranes are among the most important phenomena for developing NM-based therapeutics and resolving nanotoxicology. Herein, we introduce the structural and functional effects of inorganic-based NMs on biological membranes, mainly the plasma membrane and the endomembrane system, with an emphasis on the interface, which involves highly complex networks between NMs and biomolecules (such as membrane proteins and lipids). Significant efforts have been devoted to categorizing and analyzing the interaction mechanisms in terms of the physicochemical characteristics and biological effects of NMs, which can directly or indirectly influence the effects of NMs on membranes. Importantly, we summarize that the biological membranes act as platforms and thereby mediate NMs-immune system contacts. In this overview, the existing challenges and potential applications in the areas are addressed. A strong understanding of the discussed concepts will promote therapeutic NM designs for drug delivery systems by leveraging the NMs-membrane interactions and their functions.
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http://dx.doi.org/10.1016/j.addr.2021.05.030DOI Listing
August 2021

MicroRNA miR-92a-3p regulates breast cancer cell proliferation and metastasis via regulating B-cell translocation gene 2 (BTG2).

Bioengineered 2021 12;12(1):2033-2044

Department of Gynecology, Affiliated Hospital of Jining Medical University. Jining, Shandong, China.

MicroRNAs (miRNAs) dysregulation contributes to tumorigenesis, and it is reported that abnormal miR-92a-3p expression participates in multiple cancers' occurrence and progression. This study focuses on miR-92a-3p's functions and regulatory mechanism in breast cancer (BC). The current study proved miR-92a-3p expression was enhanced in BC tissues and cells, and its high expression was related to increased TNM stage and larger tumor size of BC patients. Functionally, transfection of miR-92a-3p mimics facilitated BC cell proliferation and metastasis, yet transfection of miR-92a-3p inhibitors functioned oppositely. In addition, BTG2 was verified as a direct miR-92a-3p target in BC cells. This research indicated that miR-92a-3p facilitates BC cell proliferation and metastasis through repressing BTG2 expression.
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http://dx.doi.org/10.1080/21655979.2021.1924543DOI Listing
December 2021

PS-341 alleviates chronic low-grade inflammation and improves insulin sensitivity through the inhibition of TM4 (UBAC2) degradation.

Nutr Metab (Lond) 2021 Jun 1;18(1):54. Epub 2021 Jun 1.

Department of Endocrinology, Huashan Hospital Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.

Background: The TM4 (UBAC2) protein, which contains 4 transmembrane domains and one ubiquitin binding domain, is mainly expressed in cell and nuclear membranes. The current research aimed to explore the role of TM4 in metabolic inflammation and to examine whether the ubiquitin-proteasome inhibitor PS-341 could regulate the function of TM4.

Methods: The metabolic phenotypes of TM4 knockout (KO) mice were studied. We next explored the association between the polymorphisms of TM4 and obesity in a Chinese Han population. TM4 expression in the visceral fat of obese patients who underwent laparoscopic cholecystectomy was also analysed. Finally, the effect of PS-341 on the degradation and function of the TM4 protein was investigated in vivo and in vitro.

Results: TM4 KO mice developed obesity, hepatosteatosis, hypertension, and glucose intolerance under a high-fat diet. TM4 counterregulated Nur77, IKKβ, and NF-kB both in vivo and in vitro. The TM4 SNP rs147851454 is significantly associated with obesity after adjusting for age and sex (OR 1.606, 95% CI 1.065-2.422 P = 0.023) in 3394 non-diabetic and 1862 type 2 diabetic adults of Han Chinese. TM4 was significantly downregulated in the visceral fat of obese patients. PS-341 induced TM4 expression through inhibition of TM4 degradation in vitro. In db/db mice, PS-341 administration led to downregulation of Nur77/IKKβ/NF-κB expression in visceral fat and liver, and alleviation of hyperglycaemia, hypertension, and glucose intolerance. The hyperinsulinaemic-euglycaemic clamp demonstrated that PS-341 improved the glucose infusion rate and alleviated insulin resistance in db/db mice.

Conclusions: PS-341 alleviates chronic low-grade inflammation and improves insulin sensitivity through inhibition of TM4 degradation.
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http://dx.doi.org/10.1186/s12986-021-00579-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170790PMC
June 2021

Propionate and Butyrate Produced by Gut Microbiota after Probiotic Supplementation Attenuate Lung Metastasis of Melanoma Cells in Mice.

Mol Nutr Food Res 2021 Jun 1:e2100096. Epub 2021 Jun 1.

The Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin, 130024, China.

Scope: The beneficial effects of probiotics in reducing gastrointestinal inflammation and in preventing colorectal cancer have been reported, but the mechanism underlying the immunomodulatory effect of probiotics in inhibiting extra-intestinal tumor progression remains unclear.

Methods And Results: This study shows that probiotic supplementation attenuate lung metastasis of melanoma cells in mice. Feeding mice with VSL#3 probiotics change the composition and proportion of gut microbiota. The changes in gut bacteria composition, such as in the abundance of Lachnospiraceae, Streptococcus, and Lachnoclostridium, are associated with the production of short-chain fatty acids in the gut. The concentrations of propionate and butyrate are upregulated in gut and blood after feeding VSL#3, and the increase in propionate and butyrate levels promotes the expression of chemokine (C-C motif) ligand 20 (CCL20) in lung endothelial cells and the recruitment of T helper 17 (Th17) cells to the lungs via the CCL20/chemokine receptor 6 axis. The recruitment of Th17 cells decreases the number of tumor foci in lungs and attenuates the lung metastasis of melanoma cells in mice.

Conclusions: The results provide new information on the role and mechanisms of action of probiotics in attenuating extra-intestinal tumor metastasis.
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http://dx.doi.org/10.1002/mnfr.202100096DOI Listing
June 2021

biocompatibility and bioactivity of calcium silicate‑based bioceramics in endodontics (Review).

Int J Mol Med 2021 07 20;48(1). Epub 2021 May 20.

Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

Calcium silicate‑based bioceramics have been applied in endodontics as advantageous materials for years. In addition to excellent physical and chemical properties, the biocompatibility and bioactivity of calcium silicate‑based bioceramics also serve an important role in endodontics according to previous research reports. Firstly, bioceramics affect cellular behavior of cells such as stem cells, osteoblasts, osteoclasts, fibroblasts and immune cells. On the other hand, cell reaction to bioceramics determines the effect of wound healing and tissue repair following bioceramics implantation. The aim of the present review was to provide an overview of calcium silicate‑based bioceramics currently applied in endodontics, including mineral trioxide aggregate, Bioaggregate, Biodentine and iRoot, focusing on their biocompatibility and bioactivity. Understanding their underlying mechanism may help to ensure these materials are applied appropriately in endodontics.
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http://dx.doi.org/10.3892/ijmm.2021.4961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136140PMC
July 2021

Interleukin-17 induces pyroptosis in osteoblasts through the NLRP3 inflammasome pathway in vitro.

Int Immunopharmacol 2021 Jul 15;96:107781. Epub 2021 May 15.

Department of Oral Medicine, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address:

Objective: Interleukin-17 (lL-17), a pro-inflammatory cytokine produced by Th17 cells, is also considered to play an important role in bone metabolism, but the exact mechanism of bone destruction remains unclear. In this study, we explored whether IL-17 could induce osteoblasts pyroptosis in vitro.

Methods: The murine primary osteoblasts were isolated from the calvarial bones of mice. The proliferation of osteoblasts was evaluated by cell counting kit-8 (CCK-8) assay. The mRNA levels of NOD-like receptor family pyrin domain containing 3 (NLRP3), apoptosis associated speck like protein containing a card (ASC), caspase-1, gasdermin-D (GSDMD), IL-1β and receptor activator of nuclear factor-kappa B ligand (RANKL) were measured by real-time quantitative PCR. Pyroptosis after IL-17 treatment was evaluated by lactate dehydrogenase (LDH) Release Assay Kit and the morphological characteristics of osteoblasts were observed via Scanning Electron Microscopy (SEM). Pyroptosis associated proteins, cleaved IL-1β and RANKL were evaluated through western blot. The release of IL-1β and RANKL was measured by ELISA. In addition, calcium nodule was tested by alizarin red staining.

Results: High concentration IL-17 (100 ng/mL) could affect the proliferation of osteoblasts, promote the gene expression of NLRP3, caspase-1, GSDMD, IL-1β and RANKL. In contrast to control group, osteoblasts treated with IL-17 had the appearance of numerous pores, swelling and rupture. Also, the release of LDH, IL-1β and RANKL increased in the presence of IL-17. However, inhibition of NLRP3 prevented activation of the NLRP3 inflammasome, thereby restoring osteoblasts morphology and function.

Conclusion: IL-17 induced osteoblasts pyroptosis, and the pyroptosis of osteoblasts may prompt the release of IL-1β and RANKL,which may further contribute to disruption of bone metabolism. Besides, the NLRP3 inflammasome pathway was involved in the pyroptosis of osteoblasts.
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http://dx.doi.org/10.1016/j.intimp.2021.107781DOI Listing
July 2021

Traditional Chinese medicine Bu-Shen-Jian-Pi-Fang attenuates glycolysis and immune escape in clear cell renal cell carcinoma: results based on network pharmacology.

Biosci Rep 2021 Jun;41(6)

Department of Surgery, PuDong branch of Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 1000 Shangnan road, Shanghai 200126, China.

Clear cell renal cell carcinoma (ccRCC) is the most common malignant type of kidney cancer. The present study aims to explore the underlying mechanism and potential targets of the traditional Chinese medicine Bu-Shen-Jian-Pi-Fang (BSJPF) in the treatment of ccRCC based on network pharmacology. After obtaining the complete composition information for BSJPF from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, we analyzed its chemical composition and molecular targets and then established a pharmacological interaction network. Twenty-four significantly differentially expressed genes and nine pathways mainly related to tumor proliferation were identified and screened. Functional enrichment analysis indicated that the potential targets might be significantly involved in glycolysis and the HIF-1 signaling pathway. To further confirm the effect of BSJPF on ccRCC cell proliferation, a BALB/c xenograft mouse model was constructed. Potential targets involved in regulating glycolysis and the tumor immune microenvironment were evaluated using RT-qPCR. VEGF-A expression levels were markedly decreased, and heparin binding-EGF expression was increased in the BSJPF group. BSJPF also inhibited tumor proliferation by enhancing GLUT1- and LDHA-related glycolysis and the expression of the immune checkpoint molecules PD-L1 and CTLA-4, thereby altering the immune-rejection status of the tumor microenvironment. In summary, the present study demonstrated that the mechanism of BSJPF involves multiple targets and signaling pathways related to tumorigenesis and glycolysis metabolism in ccRCC. Our research provides a novel theoretical basis for the treatment of tumors with traditional Chinese medicine and new strategies for immunotherapy in ccRCC patients.
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http://dx.doi.org/10.1042/BSR20204421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202066PMC
June 2021

Electrophoretic deposition of silk fibroin coatings with pre-defined architecture to facilitate precise control over drug delivery.

Bioact Mater 2021 Nov 28;6(11):4243-4254. Epub 2021 Apr 28.

Department of Dentistry-Biomaterials, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Philips van Leydenlaan 25, 6525, EX Nijmegen, the Netherlands.

The therapeutic precision and clinical applicability of drug-eluting coatings can be substantially improved by facilitating tunable drug delivery. However, the design of coatings which allows for precise control over drug release kinetics is still a major challenge. Here, a double-layered silk fibroin (SF) coating system was constructed by sequential electrophoretic deposition. A mixture of dissolved SF (SF) molecules and pre-made SF nanospheres at different ratios was deposited as under-layer. Subsequently, this underlayer was covered by a top-layer comprising SF (SF) molecules (rich in arginylglycylaspartic acid, RGD) to improve the cellular response of the resulting double-layered coatings. Additionally, model drug doxycycline was either pre-mixed with dissolved SF molecules or pre-loaded into pre-made SF nanospheres at the same amount before their mixing and deposition. The thickness and nanosphere content of the under-layer architecture were proportional to the deposition time and nanosphere concentration in precursor mixtures, respectively. The surface topography, wettability, degradation rate and adhesion strength were comparable within the double-layered coating system. As expected, RGD-rich SF top-layer improved cell adhesion, spreading and proliferation compared with SF top-layer. Furthermore, the amount and duration of drug release increased linearly with increasing nanosphere concentration at fixed deposition time, whereas drug release amount increased linearly with increasing deposition time. These results indicate that the dosage and kinetics of loaded drugs can be quantitatively tailored by altering nanosphere concentration and deposition time as main processing parameters. Overall, this study illustrates the strong potential of pre-defining coating architecture to facilitate control over drug delivery.
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http://dx.doi.org/10.1016/j.bioactmat.2021.03.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102429PMC
November 2021

Food colorants metabolized by commensal bacteria promote colitis in mice with dysregulated expression of interleukin-23.

Cell Metab 2021 Jul 13;33(7):1358-1371.e5. Epub 2021 May 13.

Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address:

Both genetic predisposition and environmental factors appear to play a role in inflammatory bowel disease (IBD) development. Genetic studies in humans have linked the interleukin (IL)-23 signaling pathway with IBD, but the environmental factors contributing to disease have remained elusive. Here, we show that the azo dyes Red 40 and Yellow 6, the most abundant food colorants in the world, can trigger an IBD-like colitis in mice conditionally expressing IL-23, or in two additional animal models in which IL-23 expression was augmented. Increased IL-23 expression led to generation of activated CD4 T cells that expressed interferon-γ and transferred disease to mice exposed to Red 40. Colitis induction was dependent on the commensal microbiota promoting the azo reduction of Red 40 and generation of a metabolite, 1-amino-2-naphthol-6-sulfonate sodium salt. Together these findings suggest that specific food colorants represent novel risk factors for development of colitis in mice with increased IL-23 signaling.
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http://dx.doi.org/10.1016/j.cmet.2021.04.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266754PMC
July 2021

A Web-Based Database on Exposure to Persistent Organic Pollutants in China.

Environ Health Perspect 2021 May 4;129(5):57701. Epub 2021 May 4.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, China.

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http://dx.doi.org/10.1289/EHP8685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096379PMC
May 2021

Meta-analysis of association of microRNAs genetic variants with susceptibility to rheumatoid arthritis and systemic lupus erythematosus.

Medicine (Baltimore) 2021 Apr;100(17):e25689

Department of Ultrasound, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi.

Background: An increasing body of studies has investigated that genetic polymorphisms in microRNA (miRNA) may be related to susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, some results remain controversial. Thus, a meta-analysis was embarked on assessing whether some miRNA polymorphisms are associated with the risk of RA and SLE.

Methods: Relevant studies were acquired on PubMed, Web of Science, Cochrane Library, CNKI, and Embase electronic databases from inception to December 2019. The strength of the association of miRNA polymorphisms with the risk of RA and SLE was assessed by odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Eligible 20 articles (36 studies) involving 5 miRNAs were enrolled in the meta-analysis. For RA, the polled result showed that there was no significant relationship between miR-146a rs2910164 and RA, but subgroup analysis based on ethnicity demonstrated that CC genotype may be a genetic protect factor for RA in Caucasians (CC vs CG+GG, OR = 0.825, 95% CI: 0.684-0.996, Pz = .045, Ph = .166). Besides, statistical significance of miR-499 rs3746444 (T/C) with susceptibility to RA was observed as well in the overall population, and the association was only significant in Caucasians but not Asians. For SLE, the associations of miR-146a rs2431697 T allele/T-carrier with increased risk of SLE were observed.

Conclusions: Our results highlight that miR-499 rs3746444 may contribute to RA susceptibility, particularly in Caucasians. In addition, CC genotype in miR-146a rs2910164 may act as a protector of RA in Caucasians. For SLE, miR-146a rs2431697 (C/T) is most likely to the increased the risk of SLE. These findings do not support the genetic association between miR-196a2 rs11614913 and RA/SLE susceptibility, as well as the association of miR-146a rs2910164, miR-146a rs57095329, miR-499 rs3746444 with SLE.
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http://dx.doi.org/10.1097/MD.0000000000025689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084041PMC
April 2021

Identification of Vitamin K3 and its analogues as covalent inhibitors of SARS-CoV-2 3CL.

Int J Biol Macromol 2021 Jul 24;183:182-192. Epub 2021 Apr 24.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

After the emergence of the pandemic, repurposed drugs have been considered as a quicker way of finding potential antiviral agents. SARS-CoV-2 3CL is essential for processing the viral polyproteins into mature non-structural proteins, making it an attractive target for developing antiviral agents. Here we show that Vitamin K3 screened from the FDA-Approved Drug Library containing an array of 1,018 compounds has potent inhibitory activity against SARS-CoV-2 3CL with the IC value of 4.78 ± 1.03 μM, rather than Vitamin K1, K2 and K4. Next, the time-dependent inhibitory experiment was carried out to confirm that Vitamin K3 could form the covalent bond with SARS-CoV-2 3CL. Then we analyzed the structure-activity relationship of Vitamin K3 analogues and identified 5,8-dihydroxy-1,4-naphthoquinone with 9.8 times higher inhibitory activity than Vitamin K3. Further mass spectrometric analysis and molecular docking study verified the covalent binding between Vitamin K3 or 5,8-dihydroxy-1,4-naphthoquinone and SARS-CoV-2 3CL. Thus, our findings provide valuable information for further optimization and design of novel inhibitors based on Vitamin K3 and its analogues, which may have the potential to fight against SARS-CoV-2.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064871PMC
July 2021

Chlamydia trachomatis Pgp3 protein regulates oxidative stress via activation of the Nrf2/NQO1 signal pathway.

Life Sci 2021 Jul 20;277:119502. Epub 2021 Apr 20.

Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, China. Electronic address:

Aim: Chlamydia trachomatis has evolved various strategies to alleviate oxidative stress of host cells to maintain their intracellular survival. However, the exact mechanism of anti-oxidative stress of C. trachomatis is still unclear. The activation of nuclear factor erythroid 2-related factor 2/quinone oxidoreductase (Nrf2/NQO1) signal pathway has been identified as an efficient antioxidant defensive mechanism used by host cells to counteract oxidative stress. Pgp3 is a pivotal virulence factor of C. trachomatis involved in intracellular survival. The aim of this study is to explore the role of Pgp3 on Nrf2/NQO1 signal pathway against oxidative stress.

Main Methods: After HeLa cells were stimulated with Pgp3 protein, Nrf2 location and the inclusion bodies of C. trachomatis were detected by indirect immunofluorescence, western blotting and Oxidative stress assay kits were used to separately determine the protein expression and the content of malondialdehyde (MDA), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) before and after the interference of Nrf-2 and NQO1.

Key Findings: Pgp3 promoted the nuclear translocation of Nrf2 to increase NQO1 expression and reduced oxidative stress induced by LPS to contribute to the survival of C. trachomatis. Inhibition of Nrf2/NQO1 signal pathway with Nrf2 inhibitor and down-regulation of NQO1 with siRNA-NQO1 suppressed oxidative stress resistance induced by Pgp3.

Significance: Here we found that Pgp3 alleviated oxidative stress to promote the infectivity of C. trachomatis through activation of Nrf2/NQO1 signal pathway, which provided a novel understanding of the effects of Pgp3 in the pathogenesis of C. trachomatis.
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http://dx.doi.org/10.1016/j.lfs.2021.119502DOI Listing
July 2021

Nomogram development and validation to predict hepatocellular carcinoma tumor behavior by preoperative gadoxetic acid-enhanced MRI.

Eur Radiol 2021 Apr 20. Epub 2021 Apr 20.

Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China.

Objectives: Pretreatment evaluation of tumor biology and microenvironment is important to predict prognosis and plan treatment. We aimed to develop nomograms based on gadoxetic acid-enhanced MRI to predict microvascular invasion (MVI), tumor differentiation, and immunoscore.

Methods: This retrospective study included 273 patients with HCC who underwent preoperative gadoxetic acid-enhanced MRI. Patients were assigned to two groups: training (N = 191) and validation (N = 82). Univariable and multivariable logistic regression analyses were performed to investigate clinical variables and MRI features' associations with MVI, tumor differentiation, and immunoscore. Nomograms were developed based on features associated with these three histopathological features in the training cohort, then validated, and evaluated.

Results: Predictors of MVI included tumor size, rim enhancement, capsule, percent decrease in T1 images (T1%), standard deviation of apparent diffusion coefficient, and alanine aminotransferase levels, while capsule, peritumoral enhancement, mean relaxation time on the hepatobiliary phase (T1), and alpha-fetoprotein levels predicted tumor differentiation. Predictors of immunoscore included the radiologic score constructed by tumor number, intratumoral vessel, margin, capsule, rim enhancement, T1%, relaxation time on plain scan (T1), and alpha-fetoprotein and alanine aminotransferase levels. Three nomograms achieved good concordance indexes in predicting MVI (0.754, 0.746), tumor differentiation (0.758, 0.699), and immunoscore (0.737, 0.726) in the training and validation cohorts, respectively.

Conclusion: MRI-based nomograms effectively predict tumor behaviors in HCC and may assist clinicians in prognosis prediction and pretreatment decisions.

Key Points: • This study developed and validated three nomograms based on gadoxetic acid-enhanced MRI to predict MVI, tumor differentiation, and immunoscore in patients with HCC. • The pretreatment prediction of tumor microenvironment may be useful to guide accurate prognosis and planning of surgical and immunological therapies for individual patients with HCC.
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http://dx.doi.org/10.1007/s00330-021-07941-7DOI Listing
April 2021
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