Publications by authors named "Xiaoqing Chen"

351 Publications

Mutational Landscape of PI3K-AKT-mTOR Pathway in Breast Cancer: Implications for Targeted Therapeutics.

J Cancer 2021 27;12(14):4408-4417. Epub 2021 May 27.

Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Comprehensive analysis of PI3K-AKT-mTOR pathway gene alterations in breast cancer may be helpful for targeted therapy. We performed targeted sequencing using a panel of 520 cancer-related genes to investigate gene alterations in the PI3K-AKT-mTOR pathway from 589 consecutive Chinese women diagnosed with stage I-III breast cancer. Analyses of overall survival (OS) were performed using the publicly available clinical and genomic data from METABRIC. PI3K-AKT-mTOR pathway gene alterations were detected in 62.6% (369/589) of our cohort. The most commonly altered genes were (45%), (7.5%), (5.9 %), (2.7%), and (2%). Four mutations (E545K, H1047R, E542K, and H1047L) were detected in all the breast cancer molecular subtypes. Seven mutations (E545G, E418_L422delinsV, E726K, E110del, G1049R, G118D, and D350G) were only detected in HR subtypes. Two mutations (C420R and N345K) were only detected in non-triple-negative subtypes. Most cases with mutation were HR/HER2 subtype (77.3%), followed by triple-negative subtype (18.2%). In the METABRIC breast cancer dataset, no significant OS difference was observed between the -mutant and wild-type groups. However, patients with multiple mutations (mOS: 131 vs. 159 months, = 0.029), or mutations located in the domain had significantly shorter OS (mOS, 130 vs. 154 months, =0.020) than those without the mutations. Our study reveals the heterogeneity in PI3K-AKT-mTOR pathway among the breast cancer molecular subtypes in our cohort. Moreover, the number and specific sites of mutations have distinct prognostic impact.
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http://dx.doi.org/10.7150/jca.52993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176410PMC
May 2021

Crystalline ruthenium polypyridine nanoparticles: a targeted treatment of bacterial infection with multifunctional antibacterial, adhesion and surface-anchoring photosensitizer properties.

J Mater Chem B 2021 05;9(18):3808-3825

School of Life Sciences, Anhui Agricultural University, Hefei, 230036, China.

Photodynamic antibacterial therapy employs nanocomposites as an alternative to traditional antibiotics for the treatment of bacterial infections. However, many of these antibacterial materials are less effective towards bacteria than traditional drugs, either due to poor specificity or antibacterial activity. This can result in needless and excessive drug use in treatments. This paper describes a multifunctional drug delivery nanoparticle (MDD-NP), [email protected], based on the nanostructured-form of [Ru(bpy)2dppz] (PF6)2 (Sph-Ru), which has adhesive properties towards its microbial targets as well as surface-anchoring photosensitizer effects. The design and construction of MDD-NP is based on the adhesive properties of the outer layers of montmorillonite (MMT), which allows [email protected] to successfully reach its bacterial target; the outer layer of the E. coli. In addition, under 670 nm red irradiation therapy (R-IT), the surface-anchoring properties use the photosensitizer phthalocyanine zinc (PZ) to destroy the bacteria by producing reactive oxygen species (ROS) which causes cell lysis of E. coli. More importantly, [email protected] has no fluorescence response to live E. coli with intact cell membranes but selectively stained and demonstrated fluorescence during membrane damage of early-stage cells as well as exposure of nuclear materials at late-stage of cell lysis. [email protected] showed beneficial and synergistic anti-infective effects in vivo by inhibiting the E. coli infection-induced inflammatory response and eventually promoting wound healing in mice. This new strategy for high precision antibacterial therapy towards specific targets, provides an exciting opportunity for the application of multifunctional nanocomposites towards microbial infections.
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http://dx.doi.org/10.1039/d1tb00103eDOI Listing
May 2021

growth of ZIF-8 on gold nanoparticles/magnetic carbon nanotubes for the electrochemical detection of bisphenol A.

Anal Methods 2021 May;13(20):2338-2344

College of Chemistry and Chemical Engineering, Key Laboratory of Hunan Province for Water Environment and Agriculture Product Safety, Central South University, Changsha 410083, China.

We herein report a facile and scalable strategy for the fabrication of a metal-organic framework (MOF) based composite by in situ growing ZIF-8 on gold nanoparticle (AuNP) loaded magnetic carbon nanotubes (mCNTs). AuNPs were firstly loaded on PEI (polyethylenimine) modified mCNTs by electrostatic forces, and then AuNPs/mCNTs were encapsulated into the ZIF-8 frame through in situ self-assembling of zinc ions and 2-methylimidazole. The morphology, spectroscopy and structural properties of the AuNP/[email protected] nanocomposites were systematically characterized. The conductivity-strain tests revealed that the in situ insertion of AuNPs/mCNTs in ZIF-8 could not only shorten the electron transfer distance between active sites and mCNTs, but also increase the dispersion of mCNTs, which would benefit the electron and mass transfer. Besides, by adopting the AuNP/[email protected] nanocomposite-modified glassy carbon electrode (GCE) as the working electrode, a novel electrochemical sensor was successfully developed for the detection of bisphenol A (BPA). A linear range of BPA detection from 1 μM to 100 μM with a limit of detection of 690 nM was favorably obtained. Moreover, the developed sensor exhibited satisfactory reproducibility and superior stability with excellent anti-interference ability, and was successfully applied in the detection of BPA in real samples.
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http://dx.doi.org/10.1039/d1ay00324kDOI Listing
May 2021

Characterization of Frequently Mutated Cancer Genes and Tumor Mutation Burden in Chinese Breast Cancer.

Front Oncol 2021 21;11:618767. Epub 2021 Apr 21.

Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Objectives: Various genomic alterations and genomic signatures, including amplification, mutations in , , and , and tumor mutational burden (TMB), have become important biomarkers for treatment selection in breast cancer (BC). This study aimed to investigate the mutational features of Chinese early-stage BC patients.

Methods: Tumors and matched blood samples collected from 589 Chinese patients with early-stage BC were sequenced using a commercial gene panel consisting of 520 cancer-related genes to analyze all types of genomic alterations and estimate the TMB status.

Results: A total of 18 genes were found to be more frequently mutated (<0.05) or amplified (<0.05) in stage T3-4 tumors as compared with T1-2 tumors. A total of 18 genes were found to be differentially mutated (<0.05) or amplified (<0.05) in patients with lymph node metastasis than those without lymph node metastasis. Younger patients (≤35 years) were more frequently identified with mutations or gene amplifications in eleven genes (<0.05). TMB >10mutations/Mb were found in 5.7% of our cohort. Although the TMB was similar for various molecular subtypes between our cohort and the BC cohort of The Cancer Genome Atlas (TCGA) study, the TMB were statistically different for HR+/HER-, HR+/HER2+, and triple-negative subtypes between our cohort and African Americans in the TCGA study. As compared to the TCGA BC cohort, our cohort had a much earlier median age of diagnosis (48 vs. 58 years, <0.001), and had significantly lower frequency of triple-negative subtype (11.5% vs. 18.4%, <0.001) and invasive lobular BC (2.4% vs. 19.0%, <0.001). Further subgroup analyses revealed that mutation rates in various genes including , , and were distinct for patients who were younger (≤35 years), had triple-negative or invasive lobular BC in our cohort than in the TCGA cohort.

Conclusions: This study revealed distinct mutational features of various molecular subtypes of early-stage BC among Chinese patients. Moreover, we provide new insights into the differences in early-stage BC between the East and West.
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http://dx.doi.org/10.3389/fonc.2021.618767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096980PMC
April 2021

Microbiome analysis reveals gut microbiota alteration in mice with the effect of matrine.

Microb Pathog 2021 Jul 6;156:104926. Epub 2021 May 6.

College of Animal Science and VeterinaryMedicine, Xinyang Agriculture And Forestry University, Xinyang, China.

Mounting evidence revealed the negative effects of abuse of antibiotic including the induction of decreased immunity and dysbacteriosis. Matrine displayed multiple beneficial effects such as anti-inflammatory, antiviral and antibacterial, but studies of its influence on gut microbiota are still insufficient to report. Here, the present study was conducted to investigate the influence of matrine on the gut microbiota of mice and amoxicillin was used as a positive control. A total of 21 cecal samples were obtained from seven groups for high-throughput sequencing analysis based on V3-V4 variable region of 16S rRNA genes. Results revealed that the diversity and abundance of gut microbiota in mice gradually decreased with the increase of the concentration of amoxicillin, whereas matrine administration did not effect the intestinal microbial community structure. Additionally, amoxicillin and matrine supplementation also caused significant changes in the relative abundance of some intestinal bacteria. Specifically, the ratio of Klebsiella and Corynebacterium_1, Bacteroides and Parasutterella in the amoxicillin treated-group were increased as compared to the control group, whereas Muribaculaceae_unclassified, Alistipes and Lactobacillus were significantly decreased. Conversely, matrine administration significantly increased the proportion of beneficial bacteria such as Ruminiclostridium_9, Lachnospiraceae_NK4A136_group and Ruminococcaceae_unclassified. In conclusion, amoxicillin administration could change the microbial community composition and structure by increasing the proportion of pathogenic to beneficial bacteria, whereas matrine could increase the number of beneficial bacteria. Moreover, this study provides a theoretical basis for finding alternatives to antibiotics to decrease bacterial resistance and intestinal flora imbalance.
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http://dx.doi.org/10.1016/j.micpath.2021.104926DOI Listing
July 2021

Reovirus enhances cytotoxicity of natural killer cells against colorectal cancer via TLR3 pathway.

J Transl Med 2021 05 1;19(1):185. Epub 2021 May 1.

Center for Stem Cell and Tissue Engineering Research/School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550004, Guizhou, China.

Background: Cetuximab has been approved for use for first-line treatment of patients with wild-type KRAS metastatic colorectal cancer (CRC). However, treatment with cetuximab has shown limited efficacy as a CRC monotherapy. In addition, natural killer (NK) cell function is known to be severely attenuated in cancer patients. The goal of this study was to develop a new strategy to enhance antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by NK cells, in combination with cetuximab against CRC cells.

Methods: Ex vivo expanded NK cells were stimulated with reovirus, and reovirus-activated NK cells mediated ADCC assay were performed on CRC cells in combination with cetuximab. The synergistic antitumor effects of reovirus-activated NK cells and cetuximab were tested on DLD-1 tumor-bearing mice. Finally, Toll-like receptor 3 (TLR3) knockdown in NK cells, along with chemical blockade of TLR3/dsRNA complex, and inhibition of the TLR3 downstream signaling pathway, were performed to explore the mechanisms by which reovirus enhances NK cell cytotoxicity.

Results: We first confirmed that exposure of NK cells to reovirus enhanced their cytotoxicity in a dose-dependent manner.We then investigated whether reovirus-activated NK cells exposed to cetuximab-bound CRC cells exhibited greater anti-tumor efficacy than either monotherapy. Co-culture of CRC cell lines with reovirus-activated NK cells indicated that NK cytotoxicity was significantly higher in combination with cetuximab, regardless of KRAS mutation status or EGFR expression level. We also found that reovirus activation of NK cells, in conjunction with cetuximab, resulted in significantly stronger anti-tumor efficacy.Finally, TLR3 knockdown, inhibition of TLR3/dsRNA complex or TBK1/IKKε demonstrated that activation of NK cells by reovirus was dependent on TLR3 and its downstream signaling pathway.

Conclusions: This study demonstrated that combination treatment of reovirus-activated NK cells with cetuximab synergistically enhances their anti-tumor cytotoxicity, suggesting a strong candidate strategy for clinical treatment of CRC.
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http://dx.doi.org/10.1186/s12967-021-02853-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088708PMC
May 2021

Identification of Rab27a as a host factor for oncolytic herpes virus susceptibility to tumor cells.

Virus Res 2021 Jul 26;299:198425. Epub 2021 Apr 26.

Shenzhen International Institute for Biomedical Research, Shenzhen, 518110, Guangdong, China. Electronic address:

Oncolytic viruses are emerging as therapeutic agents in oncology. However, resistance of tumor cells to HSV oncolysis pose significant barriers to antitumor response. Thus, study on the mechanisms of therapeutic resistance to oHSV and finding strategies for overcoming these mechanisms are needed. In this study, Rab27a, a small GTPase involved in exosome biogenesis, was noticed to highly correlate with the susceptibility of tumor cells to oHSV. We found that i) lower abundance of Rab27a in oHSV resistant mouse tumor cells was shown when compared to that of sensitive tumor cells through deep-sequencing; ii) the resistance of human tumor cells to oHSV infection is associated with a downregulation of Rab27a expression and overexpression of Rab27a can promote the replication capacity of oHSV; iii) Interestingly, a stabilizer protein of Rab27a, KIBRA, highly accumulated in oHSV resistant tumor cells, which is in contrast with the expression pattern of Rab27a. Furthermore, knockdown of KIBRA expression reduced oHSV replication in oHSV resistant tumor cells. Consequently, Rab27a was found to be relevant with oHSV replication without cell type specificity, and low abundance of Rab27a contributes to oHSV resistance in both mouse and human tumor cells, which will give new insights in the identification of potential targets or biomarkers for oHSV cancer therapy.
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http://dx.doi.org/10.1016/j.virusres.2021.198425DOI Listing
July 2021

Characterization of AKT Somatic Mutations in Chinese Breast Cancer Patients.

Cancer Manag Res 2021 7;13:3055-3065. Epub 2021 Apr 7.

Department of Breast Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Guangzhou, Guangdong, People's Republic of China.

Purpose: This study aimed to investigate AKT gene mutation status in Chinese breast cancer patients.

Methods: The study included 411 breast cancer patients hospitalized in Guangdong Provincial People's Hospital (GDPH) from June 1, 2017 to September 27, 2018. Mastectomy or breast conserving surgery was performed, and tissue samples were subjected to next-generation sequencing (NGS) to determine AKT gene mutation status. Meanwhile, the expression of human epidermal growth factor receptor 2 (Her2), progesterone receptor (PR), and estrogen receptor (ER) was analyzed by immunohistochemistry staining. The Cancer Genome Atlas (TCGA) database was used for comparative studies.

Results: Patients in the GDPH cohort had an older age ( < 0.001), higher postmenopausal rate ( < 0.001), larger tumor size ( < 0.001), higher histologic type of infiltrating duct cancer ( < 0.001), higher metastatic rate ( < 0.001), higher expression of ER ( = 0.015) and HER2 ( < 0.001), and higher percentage of the HR/HER2 subtype ( < 0.001) than those in the TCGA cohort. The GDPH cohort displayed lower rates of overall AKT and AKT3 mutation ( < 0.001), but a higher AKT1 mutation rate ( < 0.0001) compared with the TCGA cohort. Notably, the NGS studies identified missense mutation and copy number amplification as the most common AKT variation type in the GDPH and TCGA cohorts, respectively. Specifically, E17K mutation in AKT1 was predominantly detected in GDPH cohort, while being absent in TCGA cohort. Moreover, in the GDPH cohort, AKT variation was correlated with a number of clinicopathological variables, including age over 50, HER2-, HR+/HER2-, and PR+.

Conclusion: Patients in the GDPH cohort had lower rates of AKT and AKT3 mutation and higher AKT1 mutation rate than those in the TCGA cohort, while harboring missense mutations detected predominantly as E17K mutation in AKT1. In GDPH cohort, there were correlations between AKT mutation and the clinicopathological characteristics of patients.
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http://dx.doi.org/10.2147/CMAR.S299624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039050PMC
April 2021

Rock glacier inventory, permafrost probability distribution modeling and associated hazards in the Hunza River Basin, Western Karakoram, Pakistan.

Sci Total Environ 2021 Aug 30;782:146833. Epub 2021 Mar 30.

Key Laboratory of Mountain Hazards and Earth Surface Process, Institute of Mountain Hazards and Environment, Chinese Academy of Sciences, Chengdu 610041, China; University of Chinese Academy of Sciences, Beijing 100049, China; China-Pakistan Joint Research Center on Earth Science, QAU, Islamabad, Pakistan.

The destabilization of rock glaciers and permafrost variations is of great importance to the safety of the population and infrastructure in the Karakoram region because of their effects on land stability and river obstructions. In this study, we compiled the first complete rock glacier inventory for the Hunza Basin, western Karakoram, of 616 rock glaciers with an area of 194 km between 2800 and 5700 m a.s.l. We categorized the rock glaciers as intact or relict, and their distributions and destabilization were further analyzed and used along with in situ climate and elevation dataset to model the permafrost probability distribution. The modeled areas where the permafrost zonation index (PZI) is 0.5-1.00 indicate that permafrost occurs over 85% of the catchment area and lies above 3525 m a.s.l., which closely matches the zero-degree isotherm of 3800 m a.s.l. Based on the sensitivity analysis of the independent variables, elevation is the most sensitive variable, followed by net radiation, for predicting the probabilities of the presence and absence of permafrost. The model distributions are quite precise, with median posterior areas under the curve of 0.98 and 0.96 for model training and testing, respectively. We analyzed the rock glacier destabilization for 68 rock glaciers that interacted with river channels, of which 50 blocked or diverted river channels. Destabilized rock glaciers can be closely linked to the 0 °C isotherm between 3400 and 4600 m a.s.l. The significant damage caused by periodic floods from the subsequent blockage of river channels by landslides can be attributed to variations in permafrost. Which demolished infrastructure, including a hydropower plant, suspension bridge and water supply system in Hassan-abad catchment. Quantification of rock glacier dynamics and permafrost in the region can further improve policies related to the reduction in disaster risk and mitigation of associated hazards.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146833DOI Listing
August 2021

Subconjunctival injections of dimethyl fumarate inhibit lymphangiogenesis and allograft rejection in the rat cornea.

Int Immunopharmacol 2021 Apr 3;96:107580. Epub 2021 Apr 3.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. Electronic address:

Corneal lymphangiogenesis induced by macrophages played a critical role in corneal allograft rejection (CGR). However, there are few Food and Drug Administration (FDA)-approved drugs that target lymphangiogenesis. The aim of our study is to evaluate the effects of dimethyl fumarate (DMF) on corneal allograft survival in rats. Penetrating corneal transplantation was performed in rats. Subconjunctival injections of dimethyl fumarate (20 µg) were administered at the end of the operation and postoperative day 3 to day 11. The clinical signs of corneal allografts were evaluated. Immunohistochemistry, quantitative real-time PCR (qPCR), flow cytometry and western blot were performed respectively. The effects and mechanism of DMF on RAW264.7 cells were determined by qPCR, enzyme-linked immunosorbent assay (ELISA), and western blot in vitro. The results showed that subconjunctival injections of DMF could significantly inhibit corneal lymphangiogenesis and CGR with decreased corneal macrophage infiltration compared with the vehicle group. Moreover, DMF could reduce the mRNA expression of monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and vascular endothelial growth factor-C (VEGF-C) in the corneal grafts and RAW264.7 macrophages by inhibiting NF-κB activation. Furthermore, compared with the vehicle group, the number of dendritic cells in the ipsilateral cervical lymph nodes of the DMF-treated group was decreased significantly. Collectively, our findings showed that DMF could suppress CGR by inhibiting the macrophage-induced corneal lymphoangiogenesis.
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http://dx.doi.org/10.1016/j.intimp.2021.107580DOI Listing
April 2021

Sub-thermionic, ultra-high-gain organic transistors and circuits.

Nat Commun 2021 03 26;12(1):1928. Epub 2021 Mar 26.

National Laboratory of Solid-State Microstructures, School of Electronic Science and Engineering and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, 210093, China.

The development of organic thin-film transistors (OTFTs) with low power consumption and high gain will advance many flexible electronics. Here, by combining solution-processed monolayer organic crystal, ferroelectric HfZrO gating and van der Waals fabrication, we realize flexible OTFTs that simultaneously deliver high transconductance and sub-60 mV/dec switching, under one-volt operating voltage. The overall optimization of transconductance, subthreshold swing and output resistance leads to transistor intrinsic gain and amplifier voltage gain over 5.3 × 10 and 1.1 × 10, respectively, which outperform existing technologies using organics, oxides and low-dimensional nanomaterials. We further demonstrate battery-powered, integrated wearable electrocardiogram (ECG) and pulse sensors that can amplify human physiological signal by 900 times with high fidelity. The sensors are capable of detecting weak ECG waves (undetectable even by clinical equipment) and diagnosing arrhythmia and atrial fibrillation. Our sub-thermionic OTFT is promising for battery/wireless powered yet performance demanding applications such as electronic skins and radio-frequency identification tags, among many others.
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http://dx.doi.org/10.1038/s41467-021-22192-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997979PMC
March 2021

Risk of Malnutrition Is Common in Patients with Coronavirus Disease 2019 (COVID-19) in Wuhan, China: A Cross-sectional Study.

J Nutr 2021 06;151(6):1591-1596

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

Background: The coronavirus disease 2019 (COVID-19) has quickly spread across the world. However, the nutritional status of COVID-19 patients has not yet been extensively examined.

Objectives: The aim of this study was to evaluate the nutritional status of COVID-19 patients and to identify factors independently associated with malnutrition risk.

Methods: In this single-center, cross-sectional study, we analyzed data from 760 hospitalized COVID-19 patients between 29 January 2020 and 15 March 2020. Based on the Nutrition Risk Screening (NRS) 2002 score, we divided patients into the normal nutrition group (NRS score <3) and the malnutrition risk group (NRS score ≥3). The associations of age, gender, symptoms, comorbidities, BMI, serum albumin and prealbumin concentrations, disease severity, activities of daily living (ADL) score, and clinical outcomes with malnutrition risk were analyzed. Multivariable logistic regression analysis was used to identify independent factors associated with malnutrition risk.

Results: Of patients with COVID-19, 82.6% were at risk of malnutrition. There were statistical differences in the age, incidence of fever, BMI, serum albumin and prealbumin concentrations, ADL score, and disease severity between the 2 groups. Multivariable logistic regression analysis revealed that age ≥65 y (vs. <65 y; OR: 5.40; P < 0.001), serum albumin <35 g/L (vs. ≥35 g/L; OR: 3.61; P < 0.001), serum prealbumin <150 mg/L (vs. ≥150 mg/L; OR: 2.88; P = 0.042), critical cases (vs. moderate cases; OR: 4.46; P < 0.001), ADL score 41-60 (vs. ADL score 100; OR: 4.50; P = 0.012), and ADL score ≤40 (vs. ADL score 100; OR: 9.49; P < 0.001) were significantly associated with the risk of malnutrition in COVID-19 patients.

Conclusions: This study showed that prevalence of malnutrition risk was high in COVID-19 patients. Older age, low serum albumin and prealbumin concentrations, ADL score <60, and disease severity were independent factors associated with malnutrition risk.
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http://dx.doi.org/10.1093/jn/nxab009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989444PMC
June 2021

Pegylated liposomal doxorubicin-induced hand-foot syndrome predicted by serum metabolomic profiling and prevented by calcium dobesilate.

J Am Acad Dermatol 2021 Mar 5. Epub 2021 Mar 5.

School of Biological Science and Medical Engineering, Beihang University, Beijing, China; Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, China. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.02.079DOI Listing
March 2021

Organic Molecule Assisted Growth of Perovskite Films Consisting of Square Grains by Surface-Confined Process.

Nanomaterials (Basel) 2021 Feb 12;11(2). Epub 2021 Feb 12.

Faculty of Materials and Manufacturing, Beijing University of Technology, Beijing 100124, China.

Organic-inorganic perovskite single crystals are promising in the field of optoelectronics due to their excellent optoelectronic properties. However, the ion transport of perovskite precursor is poor in confined spaces, which results in difficulty in the preparation of perovskite single-crystal films. Herein, MAPbBr films consisting of square grains were fabricated by the surface-confined process using the organic molecule PEAI (phenethylammonium iodide). Under the effect of oversaturation gradient, PEA is combined with the surface of perovskite grain from top to side, which constrains the lateral growth of grains and induces a downward growth of perovskite, leading to the formation of square grains. With the improvement of concentration PEAI, the perovskite film exhibits a decreased side length of grains (from 0.98 to 12.96 μm) and increased grain number and coverage, as well as crystallinity. The perovskite single crystalline grain films with PEAI showed double photoluminescence (PL) emission peaks due to the existence of iodine-rich perovskite. This work may provide a practical way to fabricate high-quality perovskite films for perovskite photoelectronic devices.
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http://dx.doi.org/10.3390/nano11020473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918920PMC
February 2021

Simultaneous Extraction and Self-Assembly of Plasmonic Colloidal Gold Superparticles for SERS Detection of Organochlorine Pesticides in Water.

Anal Chem 2021 03 2;93(10):4657-4665. Epub 2021 Mar 2.

College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China.

Rapid component separation and reliable surface-enhanced Raman scattering (SERS) detection of organochlorine pesticide (OCP) residues in real water samples remain major challenges because of sample complexity, trace content, and low molecular affinity for a metal surface. Here, we report a novel strategy of simultaneous extraction and fabrication of plasmonic colloidal gold superparticles (AuSPs) to perform rapid SERS detection of OCPs in environmental water. In this protocol, multiple components of OCPs in complex water were facilely diffused into dichloromethane (DCM) microdroplets and specifically bound to octadecylamine-modified gold nanoparticles (Au-ODAs), affording the SERS substrate through self-assembly of the OCP-trapped Au-ODA into AuSPs with the evaporation of DCM. SERS signals of the specifically prepared Au-ODA could be used as an internal standard to calibrate the absolute signal of OCPs, and multiplex detection could be achieved depending on their molecularly narrow Raman peaks. As for simultaneously sensing four kinds of OCPs (4,4'-DDT, α-endosulfan, tetradifon, and chlordane) in water, the established method showed strong anti-interference ability and comparable quantification ranges with a low limit of detection (LOD). The recoveries ranged from 90.20 to 109.4% for OCPs in farmland, river, and fishpond water, indicating that the established AuSP-based platform is reliable and applicable to the detection of OCPs in real water samples.
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http://dx.doi.org/10.1021/acs.analchem.1c00234DOI Listing
March 2021

Social-ecological system resilience of debris flow alluvial fans in the Awang basin, China.

J Environ Manage 2021 May 23;286:112230. Epub 2021 Feb 23.

Key Laboratory of Mountain Hazards and Earth Surface Processes, Chinese Academy of Sciences, Chengdu, 610041, China; Institute of Mountain Hazards and Environment, Chinese Academy of Sciences, Chengdu, 610041, China.

Debris flow alluvial fans (DFAFs) are vulnerable, although they can be used as a natural resource. The relationships between different factors related to DFAF systems and between these factors and systems are important both for identifying the risks and opportunities presented by DFAFs and for tracking system status. In this regard, resilience may be used to characterize the status of a DFAF. This study aimed to explore the processes and mechanisms of interactions among the social, economic, and ecological factors related to DFAF with respect to resilience, and to discuss potential problems in a representative DFAF. Based on the site condition and characteristics of the Awang DFAF (China) in the period 1996-2017, we formed a comprehensive indicator evaluation framework by analyzing disturbance, function, and feedback. We also established a model for evaluating resilience by integrating the analytic hierarchy process (AHP) - an entropy evaluation method (EEM) and set pair analysis (SPA). The results showed that the system of the studied DFAF was dynamically stable. The domination of the ecological system was subsequently superseded by social and economic resilience. While disturbance had direct and immediate effects, coping ability was cumulative and characterized by hysteresis at a particular response time. Overall, resilience fluctuated within an acceptable range rather than linearly increasing or decreasing. This analysis illuminated the dynamic processes of DFAFs and contributed to the understanding and planning of system trade-offs and degraded-land utilization.
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http://dx.doi.org/10.1016/j.jenvman.2021.112230DOI Listing
May 2021

Involvement of TFAP2A in the activation of GSDMD gene promoter in hyperoxia-induced ALI.

Exp Cell Res 2021 Apr 17;401(1):112521. Epub 2021 Feb 17.

Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address:

Oxygen therapy is a common treatment in neonatal intensive care units, but long-term continuous hyperoxia ventilation may induce acute lung injury (ALI). Gasdermin D (GSDMD)-mediated pyroptosis participates in various diseases including ALI, but the role of GSDMD in hyperoxia-induced ALI is yet understood. Here, we showed a significant increase in GSDMD after exposure to high oxygen. To elucidate the molecular mechanisms involved in GSDMD regulation, we identified the core promoter of GSDMD, -98 ~ -12 bp relative to the transcriptional start site (TSS). The results of mutational analysis, overexpression or siRNA interference, EMSA and ChIP demonstrated that E2F4 and TFAP2A positively regulate the transcriptional activity of the GSDMD by binding to its promoter. However, only TFAP2A showed a regulatory effect on the expression of GSDMD. Moreover, TFAP2A was increased in the lung tissues of rats exposed to hyperoxia and showed a strong linear correlation with GSDMD. Our results indicated that TFAP2A positively regulates the GSDMD expression via binding to the promoter region of GSDMD.
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http://dx.doi.org/10.1016/j.yexcr.2021.112521DOI Listing
April 2021

Comparative study of adalimumab versus conventional therapy in sight-threatening refractory Behçet's uveitis with vasculitis.

Int Immunopharmacol 2021 Apr 10;93:107430. Epub 2021 Feb 10.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510000, Guangdong Province, China. Electronic address:

Background: Anti-tumor necrosis factor-alpha was regarded as an option in treatment of non-infectious uveitis. However, few studies in the far easter region have concentrated on this therapy and current studies have not emphasized the elimination of retinal vasculitis. To compare the effectiveness of adalimumab (ADA) plus conventional therapy (CT) versus CT alone in treating patients with retinal vasculitis (RV) due to refractory Behçet's uveitis (BU).

Design: Retrospective cohort study.

Methods: Clinical records of BU patients with previously treated but poorly controlled RV were analyzed. Patients were allocated into two groups depending on ADA use. Each group was treated for no less than 6 months between February 2015 and September 2020. The primary outcome parameter was the RV score. Best-corrected visual acuity (BCVA), number of relapses, macular thickness and ocular complications were considered concomitantly.

Results: Forty-two patients (72 eyes) were included; 21 patients were in CT group, and 21 patients were in ADA group. Inflammatory parameters improved in both groups. The improvement in the fluorescein angiography (FA) score and anterior chamber inflammation were significantly better in ADA group than in CT group (P < 0.05). The relapse time was significantly lower in ADA group than in CT group (P = 0.01). Daily glucocorticoid dose tapers were more evident in ADA group than in CT group (P < 0.05). Adverse events were detected in 7 patients (5 had upper respiratory tract infection and 2 had gastrointestinal discomfort) in ADA group; in CT group, upper respiratory infection and recurrent gum swelling were observed in 1 patient each.

Conclusion: Our results indicate that ADA plus CT outperforms CT alone in patients with RV due to refractory BU. More agile ADA use in these patients should be considered to achieve optimal treatment.
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http://dx.doi.org/10.1016/j.intimp.2021.107430DOI Listing
April 2021

AIEgen modulated per-functionalized flower-like IRMOF-3 frameworks with tunable light emission and excellent sensing properties.

Chem Commun (Camb) 2021 Mar 5;57(19):2392-2395. Epub 2021 Feb 5.

College of Chemistry and Chemical Engineering, The Hunan Provincial Key Laboratory of Water Environment and Agriculture Product Safety, Central South University, Changsha 410083, Hunan, China.

A series of functional IRMOF-3 frameworks with solid-state luminescence and tuneable light emission (from 490 to 608 nm) have been synthesized by per-functionalizing AIE-active Schiff-bases with zinc. These precursor AIE-active ligands endowed the functional frameworks with boosted fluorescence emission efficiencies (from 0.16% to 1.03%). IRMOF-3-h revealed a flower-like morphology attributed to the formation of J-aggregates, and could be used as a fluorescent probe for sensitive detection of copper(ii) (135 pM) and thiols (subnanomole).
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http://dx.doi.org/10.1039/d0cc08403dDOI Listing
March 2021

Efficacy of Huanglian root decoction on kidney injury in rat's model of metabolic syndrome.

J Tradit Chin Med 2021 02;41(1):117-124

Division of Nephrology, the 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou 350025, China.

Objective: To evaluate the efficacy of Huanglian root decoction (, HLD) on kidney injury in rat's model of metabolic syndrome (MetS), and investigate the possible mechanism.

Methods: A fructose-induced MetS rat model and human renal tubular epithelial cell-line model were used to compare the efficacy of HLD with that of berberine and tauroursodeoxycholic acid (TUDCA). Blood pressure, biochemical parameters, histopathological changes and the expression levels of oxidative stress markers were evaluated in the animal model at the end of an 8-week treatment regimen. Oxidative stress markers and molecules of the signal pathway of endoplasmic reticulum (ER) stress were evaluated in the human cell-line model.

Results: Levels of fasting insulin, systolic blood pressure and diastolic blood pressure were significantly decreased in rats in the Huanglian group compared to those in the MetS group (P < 0.05). Rats treated with HLD and TUDCA exhibited a significant reduction in blood levels of malondialdehyde compared to those in rats in the MetS group (P < 0.05). Significant increases in glutathione peroxidase in human tubular epithelial cells was found in the Huanglian group compared to that in the MetS group (14.02 vs 18.31, P < 0.05). The mRNA expression of protein kinase RNA-like endoplasmic reticulum kinase and eukaryotic translation initiation factor 2 α decreased significantly in Huanglian groups compared with that in the MetS group.

Conclusion: HLD has therapeutic efficacy on kidney injury in the MetS rat's model, and is non-inferior to berberine and TUDCA.
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http://dx.doi.org/10.19852/j.cnki.jtcm.20201228.002DOI Listing
February 2021

The construction of NiFeS/g-CN composites with high photocatalytic activity towards the degradation of refractory pollutants.

Dalton Trans 2021 Feb;50(7):2436-2447

School of Chemistry and Chemical Engineering, Central South University, Changsha 410083, People's Republic of China.

In this work, a novel NiFe layered double hydroxide-derived sulfide (NiFeSx)-modified g-C3N4 nanosheet photocatalyst (NiFeSx/g-C3N4) was synthesized, and its morphology, structure and visible light absorption capacity were simultaneously characterized by XRD, SEM, TEM, FT-IR, XPS, UV-Vis DRS, PL techniques and EIS Nyquist plots. Furthermore, it was discovered that at an optimum mass ratio of 3% (NiFeSx to g-C3N4), 3% NiFeSx/g-C3N4 composites exhibited the best degradation efficiency toward tetracycline hydrochloride refractory pollutants. The degradation rate of tetracycline hydrochloride by 3% NiFeSx/g-C3N4 composites was 92.54% under 70 min of visible light illumination, which was about 2.61 times higher than that of pure g-C3N4. The improved degradation activity may be attributed to the synergistic effect between the two constituents of as-synthesized composites, and the formed heterojunction reduced the efficiency of photogenerated carriers. More importantly, this work also gives some inspiration to synthesize some similar photocatalysts for a targeted environmental remediation.
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http://dx.doi.org/10.1039/d0dt04096gDOI Listing
February 2021

Elevated IL-38 inhibits IL-23R expression and IL-17A production in thyroid-associated ophthalmopathy.

Int Immunopharmacol 2021 Feb 28;91:107300. Epub 2020 Dec 28.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 510000, PR China. Electronic address:

IL-23/IL-23R and PGE/EP2+EP4 have been recognized as crucial signals that promote Th17 differentiation in many autoimmune diseases, including thyroid-associated ophthalmopathy (TAO). However, the interactive role of IL-23R in IL-23/Th17 signaling and PGE/Th17 signaling has not been clarified in TAO. Furthermore, the role of IL-38, a novel anti-inflammatory cytokine, has not been explored in TAO. Thus, we aimed to investigate the roles of IL-23R and IL-38 in the pathogenesis of TAO. Activated peripheral blood mononuclear cells (PBMCs) were cultured with or without IL-23 and PGE. The results showed that IL-23R and IL-17A were upregulated to different degrees and reached the highest levels with both stimuli, indicating that IL-23 induced PBMCs to secrete PGE, which further boosted the proportion of IL-23R+CD4+T cells to promote IL-17A secretion. Pretreatment with antagonists aimed at EP2/EP4 receptors diminished PGE-induced upregulation of IL-23R and IL-17A. IL-38 in TAO patients was increased. Activated orbital fibroblasts (OFs) and PBMCs were pretreated with different concentrations of IL-38. IL-23R and IL-17A expression in circulating PBMCs and IL-6 and IL-8 in resident OFs were suppressed by IL-38 at relatively low concentrations. Our findings suggest that the feedback loop of IL-23/IL-23R/PGE/EP2+EP4/IL-23R/IL-17A plays a significant role in the pathogenesis of TAO and that IL-23R is one of the key targets. Increased IL-38 in TAO could not only inhibit the expression of IL-23R and IL-17A in PBMCs but also suppress inflammation in OFs. Therapies targeting IL-23R may be effective, and IL-38 could be a potential therapeutic approach for TAO.
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http://dx.doi.org/10.1016/j.intimp.2020.107300DOI Listing
February 2021

Integrating amino acid oxidase with photoresponsive probe: A fast quantitative readout platform of amino acid enantiomers.

Talanta 2021 Mar 18;224:121894. Epub 2020 Nov 18.

College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, Hunan, China; Key Laboratory of Hunan Province for Water Environment and Agriculture Product Safety Central South University, Changsha, 410083, Hunan, China. Electronic address:

Low-cost, high-throughput, broadly useful photoresponsive enantiomeric excess (ee) sensing of amino acids remains challenging to date. Herein, based on the selective oxidation reaction of amino acid oxidase (AAO) to amino acid enantiomers (D/L-AA) and the oxidation reaction of substrate (HO) with aromatic boronic ester, we put forward a photoresponsive strategy for the determination of D/L-AA at a certain concentration. In this scheme, the substrate HO produced by the enzyme-catalyzed reaction was determined by sensitive fluorescent and colorimetric response of ethyl-3-(3-(benzothiazol-2-yl)-5-methyl-2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)phenyl)-2-cyanoacrylate (HBT-PB) to reflect the enantiomeric content at a certain concentration. The photoresponsive probe HBT-PB was readily available and inexpensive with sensitive long-wavelength red fluorescence and colorimetric light response to HO, the detection limit (LOD) was estimated as 2.91 μM. The operation of the sensing method was simple and data collection and processing are straightforward. The practicability of the scheme was favorably confirmed by accurate and scientific analysis of methionine and Dopa samples. As a result, the scheme was not only suitable for high-throughput screening but also adaptable to low-cost and sensitive RGB colorimetric analysis platform (LOD of methionine and Dopa was calculated as 9.23 μM and 8.34 μM respectively) with modern plate readers, and possessed extremely high enantioselectivity and wide applicability which benefited from the specificity and efficiency of enzyme catalytic reaction.
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http://dx.doi.org/10.1016/j.talanta.2020.121894DOI Listing
March 2021

Polysaccharides from natural resources exhibit great potential in the treatment of ulcerative colitis: A review.

Carbohydr Polym 2021 Feb 7;254:117189. Epub 2020 Nov 7.

Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China. Electronic address:

The incidence of ulcerative colitis (UC) is high. Despite the availability of various therapeutic agents for the treatment of UC, the routine treatment has limitations and serious side effects. Therefore, a new drug that safely and effectively treats UC is urgently needed. Polysaccharides from natural resources have recently become a hot topic of study for their therapeutic effects on UC. These effects are associated with the regulation of inflammatory cytokines, intestinal flora, and immune system and protection of the intestinal mucosa. This review focuses on the recent advances of polysaccharides from natural resources in the treatment of UC. The mechanisms and practicability of polysaccharides, including pectin, guar gum, rhamnogalacturonan, chitosan, fructan, psyllium, glycosaminoglycan, algal polysaccharides, polysaccharides from fungi and traditional Chinese medicine, and polysaccharide derivatives, are discussed in detail. The good efficacy and safety of polysaccharides make them promising drugs for treating UC.
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http://dx.doi.org/10.1016/j.carbpol.2020.117189DOI Listing
February 2021

Global metabolic profiling of hemorrhagic shock and resuscitation.

Biomed Chromatogr 2021 Apr 12;35(4):e5044. Epub 2021 Jan 12.

Institute of Translation Medicine, Shanghai University, Shanghai, China.

Hemorrhagic shock (HS) is a medical emergency during trauma. Significant loss of tissue perfusion may result in cellular hypoxia, organ damage and death. The primary treatment of HS is control of the source of bleeding as soon as possible and fluid replacement (crystalloid solutions and blood transfusion). Metabolomics can identify novel biomarkers for various functional and organic diseases. Therefore, systematic exploration of the biological mechanisms of HS and blood transfusion enables the optimization of treatments for HS to reduce the occurrence of organ damage. In this study, a global metabolic profiling strategy is applied to evaluate metabolic changes in the HS rat model. A serum metabolic network with 58 significant metabolites was constructed for HS and resuscitation. Our investigation will offer insights into the pathogenesis.
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http://dx.doi.org/10.1002/bmc.5044DOI Listing
April 2021

Apremilast Regulates the Teff/Treg Balance to Ameliorate Uveitis PI3K/AKT/FoxO1 Signaling Pathway.

Front Immunol 2020 17;11:581673. Epub 2020 Nov 17.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Autoimmune uveitis (AU), being one of the sight-threatening ocular inflammatory disorders, has been widely regarded by ophthalmologists and immunologists as a great challenge. Apremilast, a phosphodiesterase-4 inhibitor (PDE4i), which was approved by the U.S. Food and Drug Administration (FDA) for the treatment of active psoriatic arthritis in 2014, has been attracting researchers, who are exploring its efficiency and mechanism on uveitis. In this study, we used an experimental autoimmune uveitis (EAU), a representative model for human AU, to investigate the effect of apremilast on regulating anti-inflammatory mediators. Our study demonstrated that apremilast treatment resulted in a decrease in vascular leakage, macular edema, and inflammatory cell infiltration in the retina, corresponding to decreased clinical and pathological scores. Specifically, apremilast decreased the proportion and population of Th17 cells and increased the proportion and population of T regulatory (Treg) cells. Mechanistically, apremilast may regulate Th17 and Treg cells by inhibiting the phosphorylation of the phosphoinositide 3-kinase (PI3K)/protein kinase B(AKT)/Forkhead box O1 (FoxO1) signaling pathway. These findings suggested that apremilast alleviated EAU by regulating Th17 and Treg through the PI3K/AKT/FoxO1 pathway.
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http://dx.doi.org/10.3389/fimmu.2020.581673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705241PMC
November 2020

CYP2C19 is involved in the effect of Wuzhi tablet ( extract) and its constituents on the pharmacokinetics of intravenous voriconazole.

Pharmazie 2020 11;75(11):559-564

Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Guangdong Pharmaceutical University, Guangdong Academy of Medical Sciences, Guangzhou, China; Department of Clinical Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China;, Email:

The co-administration of voriconazole (VCZ) and Wuzhi tablet (WZ) is frequently prescribed for solid organ transplantation patients in China. However, the pharmacokinetic interactions between VCZ and WZ as well as its bioactive constituents, such as schisandrin A and schisandrol B, remain unknown. Therefore, the effects of WZ and the two lignans on the metabolism of VCZ and the potential role of cytochromeP450 (CYP450), especially cytochrome P450 2C19 (CYP2C19), were investigated. The results showed that WZ extensively inhibited the activities of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. Noteworthy, 2.5 mg/mL WZ almost completely inhibited the activity of 2C19, and the inhibition ratio reached 78.6±3% and 63.5±4.6% for schisandrin A and schisandrol B at concentrations 100 μM, respectively. In addition, rats were treated with a single or consecutive 14 day oral dose of WZ (250 mg/kg), schisandrol B (10 mg/kg) and schisandrin A (10 mg/ kg). In rats treated with WZ, the AUC value for intravenous VCZ dosing was increased by 80.2% (single dose, < 0.05) and 66.4% (dosage for 14 day, < 0.05) and the C was increased by 10.5% ( < 0.05) and (20.6%, < 0.05), respectively, much greater than that when VCZ (28 mg/kg) was given alone. Unexpectedly, the AUC and C values after schisandrol B and schisandrin A treatment were significantly increased. However, the mRNA expression of liver CYP2C19 and the protein expression of liver CYP2C19 were surprisingly increased after treatment with WZ, schisandrol B and schisandrin A in rats. Therefore, attention should be paid to when WZ and VCZ are administered concomitantly, as dosage adjustment might become necessary. Further clinical study is warranted to validate the interaction between WZ and VCZ.
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http://dx.doi.org/10.1691/ph.2020.0635DOI Listing
November 2020

Dose-dependent effect of human milk on Bronchopulmonary dysplasia in very low birth weight infants.

BMC Pediatr 2020 11 16;20(1):522. Epub 2020 Nov 16.

Department of Neonatology, The Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, 210004, Jiangsu, China.

Background And Aim: Human milk has potential protective effects against bronchopulmonary dysplasia (BPD). However, studies on the association between the dose of human milk and BPD in China are limited. This study aimed to evaluate the dose-dependent effects of human milk on BPD and other neonatal morbidities in very low birth weight (VLBW) infants.

Methods: This retrospective cohort study of preterm infants was conducted on preterm infants of gestational age ≤ 34 weeks and birth weight < 1500 g admitted to the multicenter clinical research database for breastfeeding quality improvement in Jiangsu province. The multivariate analysis was performed to compare the effect outcomes of daily graded doses [1-24 mL/(kg · day), 25-49 mL/(kg · day), and ≥ 50 mL/(kg · day) of body weight] of human milk on neonatal outcomes throughout the first 4 weeks of life versus a reference group receiving no human milk. The models were adjusted for potential confounding variables.

Results: Of 964 included infants, 279 (28.9%) received exclusive preterm formula, 128 (13.3%) received 1-24 ml/(kg · day), 139 (14.4%) received 25-49 ml/(kg · day), and 418 (43.4%) received ≥50 ml/(kg · day) human milk for the first 4 weeks of life. Compared with infants receiving exclusive formula, those receiving the highest volume of human milk daily [≥50 mL/(kg · day)] had lower incidences of BPD [27.5% in ≥50 mL/(kg · day) vs 40.1% in 0 mL/(kg · day) human milk, P = 0.001)], moderate and severe BPD [8.9% in ≥50 mL/(kg · day) vs 16.1% in 0 mL/(kg · day), P = 0.004], necrotizing enterocolitis [NEC; 3.8% in ≥50 mL/(kg · day) vs 10.8% in 0 mL/(kg · day), P = 0.001], late-onset sepsis [LOS; 9.3% in ≥50 mL/(kg · day) vs 19.7% in 0 mL/(kg · day), P <0.01], and extrauterine growth retardation [EUGR; 38.5% in ≥50 mL/(kg · day) vs 57.6% in 0 mL/(kg · day), P <0.01)]. The logistic regression indicated that those receiving ≥50 ml/kg · day human milk had lower odds of BPD [adjusted odds ratio (AOR) 0.453; 95% confidence interval (CI): 0.309, 0.666], moderate and severe BPD (AOR 0.430; 95% CI: 0.249, 0.742), NEC (AOR 0.314; 95% CI: 0.162, 0. 607), LOS (AOR 0.420; 95% CI: 0.263, 0.673), and EUGR (AOR 0.685; 95% CI: 0.479, 0.979).

Conclusions: A daily threshold amount of ≥50 ml/(kg · day) human milk in the first 4 weeks of life was associated with lower incidence of BPD as well as NEC, LOS, and EUGR in VLBW infants.

Trial Registration: ClinicalTrials.gov Identifier: NCT03453502 . Registration date: March 5, 2018. This study was retrospectively registered.
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http://dx.doi.org/10.1186/s12887-020-02394-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666971PMC
November 2020

Engeletin ameliorates pulmonary fibrosis through endoplasmic reticulum stress depending on lnc949-mediated TGF-β1-Smad2/3 and JNK signalling pathways.

Pharm Biol 2020 Dec;58(1):1105-1114

Department of Cellular and Genetic Medicine, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, China.

Context: Pulmonary fibrosis (PF) is a highly heterogeneous and lethal pathological process having no effective drug. Engeletin exerts multiple biological activities including anti-inflammatory and lung repair. Whether engeletin has therapeutic effects on PF remains unclear.

Objective: Examining effect and mechanism of engeletin on PF and

Materials And Methods: L929 cells (1 × 10/well) were treated with TGF-β1 (5 ng/mL). Sixty male C57BL/6 mice were divided into three groups and given saline or single intratracheal instillation bleomycin (5 mg/kg) or both bleomycin and intraperitoneally injected engeletin (25 mg/kg).

Results: Histological staining showed engeletin inhibited myofibrobasts activation and improved alveolar structure. Engeletin elevated forced vital capacity from 12 induced by bleomycin to 17. CCK-8 assay reported IC value of engeletin was 270 μg/mL. Real-time cellular analysis showed engeletin reduced proliferation and migration of myofibroblasts by 2.5- and 2-fold. Engeletin blocked α-SMA, vimentin, and collagen expression. RNA sequencing revealed PERK-ATF4 signalling pathway relating to ER stress involved in anti-fibrotic function of engeletin. Engeletin reduced ATF4, CHOP and BIP expression. Chemical inhibitors of smad2/3- (SB431542) and JNK- (SP600125) signalling pathways blocked expression of long noncoding RNA (lncRNA) - lnc949. Engeletin inhibited phosphorylation of smad2/3 and JNK leading to lower level of lnc949. Knockdown lnc949 inhibited ATF4, CHOP and BIP expression.

Conclusions: We reported gene expression profiling of engeletin through RNA-seq; and identified lnc949-mediated TGF-β1-Smad2/3 and JNK were upstream signalling pathways of ER stress induced by engeletin. Our results showed engeletin remedies pulmonary fibrogenesis and may be a new drug candidate.
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http://dx.doi.org/10.1080/13880209.2020.1834590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671710PMC
December 2020

Author Correction: Farnesoid X receptor activation inhibits TGFBR1/TAK1-mediated vascular inflammation and calcification via miR-135a-5p.

Commun Biol 2020 Nov 6;3(1):659. Epub 2020 Nov 6.

Experimental Center, Shandong University of Traditional Chinese Medicine, 250355, Jinan, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s42003-020-01414-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648068PMC
November 2020