Publications by authors named "Dai Li"

434 Publications

Study on Corrosion Mechanism of Different Concentrations of NaSO Solution on Early-Age Cast-In-Situ Concrete.

Materials (Basel) 2021 Apr 16;14(8). Epub 2021 Apr 16.

Shanxi Qinhan Hengsheng New Building Materials Science and Technology Ltd., Xianyang 712000, China.

The deterioration of early-age concrete performance caused by SO internal diffusion in concrete is a critical factor of concrete durability. In this study, the mechanical properties, heat of hydration, and pore structure of early-age cast-in-situ concrete with different sodium sulfate (NaSO) concentrations were studied. The mechanism of SO internal corrosion was evaluated by measuring the dynamic elastic modulus, compressive strength, and heat of hydration rate. Scanning electron microscopy, energy dispersive spectroscopy, X-ray computed tomography, X-ray diffraction, thermogravimetry-derivative thermogravimetry, and differential scanning calorimetry were applied to analyze microstructural variations and complex mineral assemblages of concrete samples. The results indicated that during the hardening process of cast-in-situ concrete, NaSO first promoted and then hindered the hydration rate of cement, and also hindered the early strength development of the cement. As the concentration of NaSO solution increases, the corrosion products of ettringite (AFt) and gypsum (Gyp) gradually increase, causing cross cracks in the concrete. The proportion of small and medium pores first increases and then decreases, and the large pores first decrease and then increase. The mechanical properties of concrete gradually decrease and diminish the mechanical properties of the concrete (thereby accelerating the damage to the concrete).
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http://dx.doi.org/10.3390/ma14082018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073549PMC
April 2021

Self-Powered Cathodic Photoelectrochemical Aptasensor Comprising a Photocathode and a Photoanode in Microfluidic Analysis Systems.

Anal Chem 2021 May 28;93(18):7125-7132. Epub 2021 Apr 28.

Department of Pediatric Surgery, Shandong Provincial Hospital Affliated to Shandong University, Jinan, Shandong 250021, P. R. China.

An intriguing self-powered cathodic photoelectrochemical (PEC) microfluidic aptasensor with enhanced cathodic photocurrent response is proposed for sensitive detection of prostate-specific antigen (PSA). The self-powered system is constructed by a cadmium sulfide-sensitized zinc oxide nanorod array (CdS/ZnO NA) as a photoanode with an iodide-doped bismuth oxychloride flower-array (I:BiOCI) as a photocathode, which can generate the electrical output under visible light irradiation with no external power supply. In addition, the p-type semiconductor I:BiOCI with a special internal electric field between the iodide ion layer and the [BiO] layer could increase the cathodic photocurrent response by facilitating the separation of electron/hole pairs under visible light excitation. It is worth noting that dissolved oxygen as an electron acceptor can be reduced by the photogenerated electron to form a superoxide radical (O) in the self-powered cathodic PEC system. The further enhanced cathodic photocurrent response can be achieved by eliminating O that reacts with the luminol anion radical (L) to produce chemiluminescence emission, which serves as an inner excitation light source. What is more exciting is that the integration of the photoanode and the photocathode into a microfluidic chip could realize automatic sample injection and detection. On this basis, the proposed aptasensor presents excellent reproducibility and high sensitivity for detecting PSA and exhibits a good linearity range (50 fg·mL to 50 ng·mL) with a low detection limit (25.8 fg·mL), which opens up a new horizon of potential for sensitively detecting other kinds of disease markers.
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http://dx.doi.org/10.1021/acs.analchem.1c01038DOI Listing
May 2021

Tip of the Iceberg: Roles of CircRNAs in Cancer Glycolysis.

Onco Targets Ther 2021 7;14:2379-2395. Epub 2021 Apr 7.

State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China.

Warburg effect reflects that tumor cells tend to generate energy by aerobic glycolysis rather than oxidative phosphorylation (OXPHOS), thus promoting the development of malignant tumors. As a kind of non-coding RNA, circular RNA (circRNA) is characterized by a closed ring structure and emerges as a regulator of cancer metabolism. Mounting studies revealed that circRNA can regulate the cancer metabolism process through affecting the expression of glycolysis relevant enzymes, transcription factors (TFs), and signaling pathways. In this review, we comprehensively analyzed and concluded the mechanism of circRNA regulating glycolysis, hoping to deepen the cognition of the cancer metabolic regulatory network and to reap huge fruits in targeted cancer treatment.
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http://dx.doi.org/10.2147/OTT.S297140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039208PMC
April 2021

NMR Methods for Determining Lipid Turnover via Stable Isotope Resolved Metabolomics.

Metabolites 2021 Mar 29;11(4). Epub 2021 Mar 29.

Center for Environmental and Systems Biochemistry, University of Kentucky, 789 S. Limestone St, Lexington, KY 40536, USA.

Lipids comprise diverse classes of compounds that are important for the structure and properties of membranes, as high-energy fuel sources and as signaling molecules. Therefore, the turnover rates of these varied classes of lipids are fundamental to cellular function. However, their enormous chemical diversity and dynamic range in cells makes detailed analysis very complex. Furthermore, although stable isotope tracers enable the determination of synthesis and degradation of complex lipids, the numbers of distinguishable molecules increase enormously, which exacerbates the problem. Although LC-MS-MS (Liquid Chromatography-Tandem Mass Spectrometry) is the standard for lipidomics, NMR can add value in global lipid analysis and isotopomer distributions of intact lipids. Here, we describe new developments in NMR analysis for assessing global lipid content and isotopic enrichment of mixtures of complex lipids for two cell lines (PC3 and UMUC3) using both C glucose and C glutamine tracers.
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http://dx.doi.org/10.3390/metabo11040202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065598PMC
March 2021

Network pharmacology integrated with molecular docking reveals the common experiment-validated antipyretic mechanism of bitter-cold herbs.

J Ethnopharmacol 2021 Jun 26;274:114042. Epub 2021 Mar 26.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. Electronic address:

Ethnopharmacological Relevance: Bitter-cold herbs have been used to clearing heat and expelling damp in clinical practice in China for thousands of years.

Aim Of The Study: This study aimed to investigate the common molecular mechanism of bitter-cold herbs through network pharmacology analysis, molecular docking and experimental validation in vivo.

Materials And Methods: Network pharmacological analysis integrated with molecular docking was employed to identify the active compounds and core action targets of the bitter-cold herbs. Then, the yeast-induced pathological model was established, and the antipyretic effect of the herbs was evaluated by checking rectal temperatures of the mice hourly. Lastly, the protein expression of core targets was examined to reveal the antipyretic mechanism.

Results: A total of 52 lead compounds from the four bitter-cold herbs, Phellodendri Chinensis Cortex (PCC), Sophorae Flavescentis Radix (SFR), Gentianae Radix Et Rhozima (GRER) and Coptidis Rhizoma (CR), and 248 compounds-related targets were screened out with PTGS2 ranking the first. The results from molecular docking showed that 22 compounds adopted the same orientation as aspirin and had an excellent stability in the active site pocket of PTGS2. Furthermore, these herbs exerted potential therapeutic effects through 38 related pathways. On the other hand, the outcome of animal experiments showed that they could significantly attenuate the yeast-induced mice fever with dose-dependent relationship. Further experimental results demonstrated that administration of yeast suspension raised protein expression of PTGS2 significantly, which was evidently inhibited in the high or low-dose groups of GRER as well as in the low-dose group of SFR (P < 0.01) though a higher expression of PTGS2 was shown in the low-dose group of CR compared with FM group (P < 0.01).

Conclusions: The bitter-cold herbs can alleviate fever response and their antipyretic effect may mainly be attributed to regulating the expression of PTGS2 after the formation of ligand-receptor/PTGS2 complexes, and their active compounds might be nominated as antipyretic lead-ligand candidates.
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http://dx.doi.org/10.1016/j.jep.2021.114042DOI Listing
June 2021

Fibroblasts in cancer dormancy: foe or friend?

Cancer Cell Int 2021 Mar 26;21(1):184. Epub 2021 Mar 26.

State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Cancer dormancy is defined that the residual cancer cells could enter into a state of quiescence and patients remain asymptomatic for years or even decades after anti-tumor therapies. Fibroblasts, which represent a predominant cell type in tumor microenvironment, play a pivotal role in determining the ultimate fate of tumor cells. This review recapitulates the pleiotropic roles of fibroblasts which are divided into normal, senescent, cancer-associated fibroblasts (CAFs) and circulation CAFs in tumor dormancy, relapse, metastasis and resistance to therapy to help the treatment of cancer metastasis.
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http://dx.doi.org/10.1186/s12935-021-01883-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995785PMC
March 2021

Upregulation of Serum miR-629 Predicts Poor Prognosis for Non-Small-Cell Lung Cancer.

Dis Markers 2021 2;2021:8819934. Epub 2021 Mar 2.

Department of Respiratory and Critical Care Medicine, Beijing Jishuitan Hospital, Beijing 100000, China.

Non-small-cell lung cancer (NSCLC) is one of the most common types of cancer worldwide. Accumulating evidence has suggested that aberrant expression of microRNAs (miRNAs) is involved in the carcinogenesis and progression of NSCLC. The current study is aimed at investigating the clinical significance of serum miR-629 in NSCLC. The expression levels of serum miR-629 in patients with NSCLC, patients with nonmalignant lung diseases, and healthy controls were assessed by real-time quantitative polymerase chain reaction. Our results showed that serum miR-629 levels were significantly upregulated in NSCLC patients compared to the controls. Serum miR-629 exhibited better performance for discriminating NSCLC patients from healthy controls, compared to the traditional biomarkers CYFRA 21-1 and CEA. In addition, a high serum miR-629 level was positively correlated with adverse clinicopathological parameters including lymph node metastasis, differentiation, and clinical stage. Serum miR-629 was dramatically reduced in the NSCLC cases receiving surgical treatment. Moreover, the patients in the high serum miR-629 group suffered poorer overall survival and disease-free survival than those in the low serum miR-629 group. In conclusion, serum miR-629 might serve as a potential prognostic biomarker for NSCLC.
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http://dx.doi.org/10.1155/2021/8819934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946467PMC
March 2021

Correction to: The prevalence of obstructive sleep apnea in interstitial lung disease: a systematic review and meta-analysis.

Sleep Breath 2021 Mar 23. Epub 2021 Mar 23.

Department of Respiratory and Critical Care Medicine, Beijing Jishuitan Hospital, The Fourth Medical College of Peking University, No. 31, Xinjiekou East Street, Beijing, 100035, China.

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http://dx.doi.org/10.1007/s11325-021-02354-8DOI Listing
March 2021

1,2,4-Oxadiazole-Based Bio-Isosteres of Benzamides: Synthesis, Biological Activity and Toxicity to Zebrafish Embryo.

Int J Mol Sci 2021 Feb 27;22(5). Epub 2021 Feb 27.

College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China.

To discover new compounds with broad spectrum and high activity, we designed a series of novel benzamides containing 1,2,4-oxadiazole moiety by bioisosterism, and 28 benzamides derivatives with antifungal activity were synthesized. These compounds were evaluated against four fungi: , , , and . The results indicated that most of the compounds displayed good fungicidal activities, especially against . For example, (84.4%), (83.6%), (83.3%), (83.1%), (83.3%), and (83.6%) were better than pyraclostrobin (81.4%) at 100 mg/L. In addition, the acute toxicity of to zebrafish embryo was 20.58 mg/L, which was classified as a low-toxicity compound.
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http://dx.doi.org/10.3390/ijms22052367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956408PMC
February 2021

Assessment of Carbon Density in Natural Mountain Forest Ecosystems at Northwest China.

Int J Environ Res Public Health 2021 02 21;18(4). Epub 2021 Feb 21.

State Key Laboratory of Desert and Oasis Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences (CAS), Urumqi 830011, China.

The natural mountain forests in northwest China are recognized as a substantial carbon pool and play an important role in local fragile ecosystems. This study used inventory data and detailed field measurements covering different forest age groups (young, middle-aged, near-mature, mature, old-growth forest), structure of forest (tree, herb, litter and soil layer) and trees (leaves, branches, trunks and root) to estimate biomass, carbon content ratio, carbon density and carbon storage in Altai forest ecosystems. The results showed that the average biomass of the Altai Mountains forest ecosystems was 126.67 t·hm, and the descending order of the value was tree layer (120.84 t·hm) > herb layer (4.22 t·hm) > litter layer (1.61 t·hm). Among the tree parts, trunks, roots, leaves and branches accounted for 50%, 22%, 16% and 12% of the total tree biomass, respectively. The average carbon content ratio was 0.49 (range: 0.41-0.52). The average carbon density of forest ecosystems was 205.72 t·hm, and the carbon storage of the forest ecosystems was 131.35 Tg (standard deviation: 31.01) inside study area. Soil had the highest carbon storage (65.98%), followed by tree (32.81%), herb (0.78%) and litter (0.43%) layers. Forest age has significant effect on biomass, carbon content ratio, carbon density and carbon storage. The carbon density of forest ecosystems in study area was spatially distributed higher in the south and lower in north, which is influenced by climate, topography, soil types and dominant tree species.
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http://dx.doi.org/10.3390/ijerph18042098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926412PMC
February 2021

Distinguishable Prognostic miRNA Signatures of Head and Neck Squamous Cell Cancer With or Without HPV Infection.

Front Oncol 2020 10;10:614487. Epub 2021 Feb 10.

State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Since their discovery in the 1990's, microRNAs (miRNA) have opened up new vistas in the field of cancer biology and are found to have fundamental roles in tumorigenesis and progression. As head and neck squamous cell carcinoma (HNSCC) with positive human papillomavirus (HPV+) is significantly distinct from its HPV negative (HPV-) counterpart in terms of both molecular mechanisms and clinical prognosis, the current study aimed to separately develop miRNA signatures for HPV+ and HPV- HNSCC as well as to explore the potential functions. Both signatures were reliable for the prediction of prognosis in their respective groups. Then Enrichment analysis was performed to predict the potential biological functions of the signatures. Importantly, combining previous studies and our results, we speculated that HPV+ HNSCC patients with low signature score had better immunity against the tumors and enhanced the sensitivity of therapies leading to improved prognosis, while HPV- HNSCC patients with high signature score acquired resistance to therapeutic approaches as well as dysregulation of cell metabolism leading to poor prognosis. Hence, we believe that the identified signatures respectively for HPV+ and HPV- HNSCC, are of great significance in accessing patient outcomes as well as uncovering new biomarkers and therapeutic targets, which are worth further investigation through molecular biology experiments.
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http://dx.doi.org/10.3389/fonc.2020.614487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902765PMC
February 2021

A Prussian Blue Nanoparticles-based Fluorescent Nanoprobe for Monitoring MicroRNA-92a and MicroRNA-21.

Anal Sci 2021 Feb 12. Epub 2021 Feb 12.

Academy of Military Medical Sciences, Academy of Military Sciences.

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http://dx.doi.org/10.2116/analsci.20P455DOI Listing
February 2021

Breastfeeding practice in China from 2013 to 2018: a study from a national dynamic follow-up surveillance.

BMC Public Health 2021 Feb 10;21(1):329. Epub 2021 Feb 10.

Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.

Background: Breastfeeding is important for the physical and psychological health of the mother and child. Basic data on breastfeeding practice in China are out-of-date and vary widely. This study aimed to evaluate the progress of breastfeeding practice in China, as well as to explore the bottlenecks in driving better practice.

Methods: This was an observational study. We used data from the Under-5 Child Nutrition and Health Surveillance System in China for the period 2013-2018. The prevalence of early initiation of breastfeeding (EIBF) and exclusive breastfeeding (EBF) were calculated for each year for subgroups of China. The Cochran-Armitage test was used to explore the time trends. The annual percent of change (APC) were calculated by log-linear regression followed by exp transformation.

Results: The prevalence of EIBF increased significantly from 44.57% (95% CI: 44.07, 45.07) in 2013 to 55.84% (95% CI: 55.29, 56.38) in 2018 (P < 0.001), with an APC of 4.67% (95% CI: 3.51, 5.85). And the prevalence of EBF increased rapidly from 16.14% (95% CI: 15.10, 17.18) to 34.90% (95% CI: 33.54, 36.26) (P < 0.001), with an APC of 14.90% (95% CI: 9.97, 20.04). Increases were observed in both urban and rural areas, with urban areas showing greater APCs for EIBF (6.05%; 95% CI: 4.22, 7.92 v.s. 2.26%; 95% CI: 1.40, 3.12) and EBF (18.21%; 95% CI: 11.53, 25.29 v.s. 9.43%; 95% CI: 5.52, 13.49). The highest EBF prevalence was observed in the East, but the Central area showed the highest APC. The prevalence of EBF decreased with increasing age within the first 6 months, especially after 3 months.

Conclusion: The prevalence of both EIBF and EBF in China are improving in recent years. The rural and West China could be the key areas in the future actions. More efforts should be made to protect and promote breastfeeding to achieve near- and long-term goals for child health.
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http://dx.doi.org/10.1186/s12889-021-10211-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874457PMC
February 2021

Core transcriptional networks in Williams syndrome: IGF1-PI3K-AKT-mTOR, MAPK and actin signaling at the synapse echo autism.

Hum Mol Genet 2021 Apr;30(6):411-429

Center for Integrated Neuroscience and Human Behavior, Brain Institute, Department of Pediatrics, University of Utah, Salt Lake City, UT 84112, USA.

Gene networks for disorders of social behavior provide the mechanisms critical for identifying therapeutic targets and biomarkers. Large behavioral phenotypic effects of small human deletions make the positive sociality of Williams syndrome (WS) ideal for determining transcriptional networks for social dysfunction currently based on DNA variations for disorders such as autistic spectrum disorder (ASD) and schizophrenia (SCHZ). Consensus on WS networks has been elusive due to the need for larger cohort size, sensitive genome-wide detection and analytic tools. We report a core set of WS network perturbations in a cohort of 58 individuals (34 with typical, 6 atypical deletions and 18 controls). Genome-wide exon-level expression arrays robustly detected changes in differentially expressed gene (DEG) transcripts from WS deleted genes that ranked in the top 11 of 12 122 transcripts, validated by quantitative reverse transcription PCR, RNASeq and western blots. WS DEG's were strictly dosed in the full but not the atypical deletions that revealed a breakpoint position effect on non-deleted CLIP2, a caveat for current phenotypic mapping based on copy number variants. Network analyses tested the top WS DEG's role in the dendritic spine, employing GeneMANIA to harmonize WS DEGs with comparable query gene-sets. The results indicate perturbed actin cytoskeletal signaling analogous to the excitatory dendritic spines. Independent protein-protein interaction analyses of top WS DEGs generated a 100-node graph annotated topologically revealing three interacting pathways, MAPK, IGF1-PI3K-AKT-mTOR/insulin and actin signaling at the synapse. The results indicate striking similarity of WS transcriptional networks to genome-wide association study-based ASD and SCHZ risk suggesting common network dysfunction for these disorders of divergent sociality.
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http://dx.doi.org/10.1093/hmg/ddab041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101356PMC
April 2021

DNMT3b SUMOylation Mediated MMP-2 Upregulation Contribute to Paclitaxel Induced Neuropathic Pain.

Neurochem Res 2021 May 6;46(5):1214-1223. Epub 2021 Feb 6.

Department of Anesthesiology, Changhai Hospital, Naval Medical University, Changhai Rd.168, Shanghai, 200433, China.

Paclitaxel is a common chemotherapeutic agent in cancer treatment, while it often causes chemotherapy-induced peripheral neuropathy (CIPN), which manifested as hyperalgesia and allodynia, and its mechanism remains largely unknown. The previous study has shown that matrix metalloproteinase-2 (MMP-2) plays a pivotal role in spinal nerve ligation (SNL) induced neuropathic pain, but its function in CIPN and exact molecular mechanisms underlying upregulation is not explored. Our present study revealed that MMP-2 is also upregulated in paclitaxel induced neuropathic pain (NP), and knockdown it by siRNA can ameliorate mechanical allodynia. Since DNA methylation is closely related to gene transcription, we explored the methylation status of the MMP-2 gene and demonstrated that MMP-2 upregulation is related to the reduced methylation level of its promoter. DNA methylation is mediated by DNA methyltransferases (DNMTs), and previous studies suggested that three main types of DNMTs can undergo SUMOylation. Our next study revealed that SUMO1 modification of DNMT3b is significantly enhanced. Intrathecal administration of SUMOylation inhibitor, ginkgolic acid (GA), could reverse enhanced SUMO1 modification of DNMT3b and upregulation of MMP-2 in the model rats. Further investigation suggested that DNMT3b binding activity to the promoter region of the MMP-2 gene is significantly decreased in paclitaxel treated rats, and the administration of GA can reverse these effects, which is also accompanied by changes in the promoter methylation status of the MMP-2 gene. Our study demonstrates that MMP-2 up-regulation mediated by DNMT3b SUMOylation is essential for paclitaxel induced NP development, which brings us new therapeutic options for CIPN.
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http://dx.doi.org/10.1007/s11064-021-03260-xDOI Listing
May 2021

The prevalence of obstructive sleep apnea in interstitial lung disease: a systematic review and meta-analysis.

Sleep Breath 2021 Jan 6. Epub 2021 Jan 6.

Department of Respiratory and Critical Care Medicine, Beijing Jishuitan Hospital, The Fourth Medical College of Peking University, No. 31, Xinjiekou East Street, Beijing, 100035, China.

Purpose: To evaluate the overall prevalence of obstructive sleep apnea (OSA) in interstitial lung disease (ILD).

Methods: We performed a systematic search of the academic literature while adhering to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines on four scientific databases including EMBASE, CENTRAL, Scopus, and MEDLINE. We performed a meta-analysis to evaluate the prevalence and severity of OSA. Severity was defined by apnea-hypopnea index (AHI) as mild (AHI ≥ 5 to < 15/h), moderate (AHI ≥ 15 to < 30/h), and severe (AHI ≥ 30/h).

Results: From 1397 studies, we found 10 eligible studies with 569 patients with ILD (mean age: 65.3 ± 6.0 years). Among these patients, 332 (61%) suffered from OSA with 32% categorized as mild, 17% moderate, and 9% severe.  CONCLUSION: This systematic review and meta-analysis provides preliminary evidence regarding the high prevalence of OSA in ILD.
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http://dx.doi.org/10.1007/s11325-020-02282-zDOI Listing
January 2021

Knowledge, attitude and practice concerning healthcare-associated infections among healthcare workers in Wuhan, China: cross-sectional study.

BMJ Open 2021 01 5;11(1):e042333. Epub 2021 Jan 5.

Department of Nosocomial Infection Management, Wuhan University Zhongnan Hospital, Wuhan, Hubei, China

Objectives: To assess the knowledge, attitude and practice (KAP) concerning healthcare-associated infections (HAIs) among healthcare givers and to identify the factors influencing KAP.

Design: This was a hospital-based, cross-sectional study.

Setting: Two public hospitals in Wuhan, central China.

Participants: Participants were recruited among healthcare workers (HCWs) of one general hospital and one children's hospital in Wuhan city between 1 June and 30 September 2019.

Primary And Secondary Outcome Measures: The outcomes were KAPs concerning HAIs.

Results: Data from 455 HCWs were included in the final data analysis. The mean scores of KAP and total KAP were 15.67±3.32, 25.00±2.75, 43.44±5.15 and 84.76±6.72, respectively. The following factors were significantly associated with the total KAP score concerning HAIs, explaining 61% of the variance (p<0.001): gender (β=2.36, 95% CI 1.11 to 4.40), age (β=6.65, 95% CI 5.07 to 7.74), position (β=7.02, 95% CI 3.88 to 8.45), type of employment (β=-1.08, 95% CI -2.08 to -0.07), with HAI education within last year (β=-2.98, 95% CI -4.23 to -1.72), with invasive operation authority (β=-4.22, 95% CI -5.46 to -2.99), antibacterial drug training (β=-4.38, 95% CI -5.45 to -3.31) and with antibacterial drug training and clinical consultation (β=-4.35, 95% CI -5.38 to -3.32).

Conclusion: The controllable factors identified in this study can be used by hospital managers to implement measures that improve KAP among HCWs. Moreover, these measures should be customised, based on uncontrollable factors to suit the specific characteristics of medical staff and to improve KAP. Training programmes should be designed for medical workers to increase their awareness of HAIs and to foster positive attitudes and practices.
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http://dx.doi.org/10.1136/bmjopen-2020-042333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786794PMC
January 2021

The anti-angiogenesis role of FBXW7 in diabetic retinopathy by facilitating the ubiquitination degradation of c-Myc to orchestrate the HDAC2.

J Cell Mol Med 2021 Feb 25;25(4):2190-2202. Epub 2020 Dec 25.

Aier Eye Hospital of Wuhan University, Wuhan, China.

Diabetic retinopathy (DR) is the most prevalently occurring microvascular complication in diabetic patients that triggers severe visual impairments. The anti-angiogenesis role of FBXW7 has been identified in breast cancer. Therefore, this study intends to decipher the mechanism of FBXW7 in angiogenesis of DR. DR model was induced on mice using high-glucose (HG) and high-fat diet, and retinal microvascular endothelial cells (RMECs) isolated from normal mice were induced with HG, followed by evaluation of FBXW7, Ki67, HIF-1α and VEGF expression by immunofluorescence, immunohistochemistry or Western blot analysis. After gain- and loss-of-function assays in normal and DR mice, angiogenesis was assessed by CD31 fluorescence staining and Western blot analysis. After ectopic expression and silencing experiments in HG-induced RMECs, RMEC proliferation, migration and angiogenesis were, respectively, determined by EdU, Transwell and in vitro angiogenesis assays. The impact of FBXW7 on the ubiquitination of c-Myc was studied by cycloheximide chase assay and proteasome inhibition, and the binding of c-Myc to HDAC2 promoter by dual-luciferase reporter gene experiment. DR mice and HG-induced RMECs possessed down-regulated FBXW7 and up-regulated Ki67, HIF-1α and VEGF. Silencing FBXW7 enhanced angiogenesis in normal mouse retinal tissue, but overexpressing FBXW7 or silencing c-Myc diminished angiogenesis in DR mouse retinal tissue. Overexpressing FBXW7 or silencing c-Myc depressed proliferation, migration and angiogenesis in HG-induced RMECs. FBXW7 induced c-Myc ubiquitination degradation, and c-Myc augmented HDAC2 expression by binding to HDAC2 promoter. Conclusively, our data provided a novel sight of anti-angiogenesis role of FBXW7 in DR by modulating the c-Myc/HDAC2 axis.
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http://dx.doi.org/10.1111/jcmm.16204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882985PMC
February 2021

Selective Trafficking of Light Chain-Conjugated Nanoparticles to the Kidney and Renal Cell Carcinoma.

Nano Today 2020 Dec 2;35. Epub 2020 Nov 2.

Transplantation Research Center, Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Specific delivery platforms for drugs to the kidney and diagnostic agents to renal cell carcinoma (RCC) constitute urgent but unfulfilled clinical needs. To address these challenges, we engineered nanocarriers that interact selectively for the first time with proximal tubule epithelial cells (PTECs) in the kidney and with RCC through the interplay between lambda light chains (LCs) attached to PEGylated polylactic-co-glycolic acid (PLGA) nanoparticles and the membrane protein megalin. Systemic administration of these light chain-conjugated nanoparticles (LC-NPs) to mice resulted in their specific retention by megalin-expressing PTECs for seven days. Repetitive dosing of LC-NPs demonstrated no renal toxicity. LC-NPs also localized selectively to megalin-expressing RCC tumors in mice. Moreover, we confirmed that both the primary tumor and lymph node metastases of human RCC express megalin, reinforcing the potential of LC-NPs for clinical use. Thus, LC-NPs can contribute potentially to improving the management of both non-oncologic and oncologic renal disorders.
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http://dx.doi.org/10.1016/j.nantod.2020.100990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685247PMC
December 2020

Direct Tumor Killing and Immunotherapy through Anti-SerpinB9 Therapy.

Cell 2020 11;183(5):1219-1233.e18

Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address:

Cancer therapies kill tumors either directly or indirectly by evoking immune responses and have been combined with varying levels of success. Here, we describe a paradigm to control cancer growth that is based on both direct tumor killing and the triggering of protective immunity. Genetic ablation of serine protease inhibitor SerpinB9 (Sb9) results in the death of tumor cells in a granzyme B (GrB)-dependent manner. Sb9-deficient mice exhibited protective T cell-based host immunity to tumors in association with a decline in GrB-expressing immunosuppressive cells within the tumor microenvironment (TME). Maximal protection against tumor development was observed when the tumor and host were deficient in Sb9. The therapeutic utility of Sb9 inhibition was demonstrated by the control of tumor growth, resulting in increased survival times in mice. Our studies describe a molecular target that permits a combination of tumor ablation, interference within the TME, and immunotherapy in one potential modality.
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http://dx.doi.org/10.1016/j.cell.2020.10.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927154PMC
November 2020

Targeting Glutaminolysis: New Perspectives to Understand Cancer Development and Novel Strategies for Potential Target Therapies.

Front Oncol 2020 26;10:589508. Epub 2020 Oct 26.

Department of General, Visceral, Tumor and Transplantation Surgery, University Hospital Cologne, Cologne, Germany.

Metabolism rewiring is an important hallmark of cancers. Being one of the most abundant free amino acids in the human blood, glutamine supports bioenergetics and biosynthesis, tumor growth, and the production of antioxidants through glutaminolysis in cancers. In glutamine dependent cancer cells, more than half of the tricarboxylic/critic acid (TCA) metabolites are derived from glutamine. Glutaminolysis controls the process of converting glutamine into TCA cycle metabolites through the regulation of multiple enzymes, among which the glutaminase shows the importance as the very first step in this process. Targeting glutaminolysis glutaminase inhibition emerges as a promising strategy to disrupt cancer metabolism and tumor progression. Here, we review the regulation of glutaminase and the role of glutaminase in cancer metabolism and metastasis. Furthermore, we highlight the glutaminase inhibitor based metabolic therapy strategy and their potential applications in clinical scenarios.
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http://dx.doi.org/10.3389/fonc.2020.589508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649373PMC
October 2020

Distributed Economic MPC for Dynamically Coupled Linear Systems With Uncertainties.

IEEE Trans Cybern 2020 Nov 10;PP. Epub 2020 Nov 10.

In this article, we propose a novel economic model-predictive control (MPC) algorithm for a group of disturbed linear systems and implement it in a distributed manner. The system consists of multiple subsystems interacting with each other via dynamics and aims to optimize an economic objective. Each subsystem is subject to constraints both on states and inputs as well as unknown but bounded disturbances. First, we divide the computation of control inputs into several local optimization problems based on each subsystem's local information. This is done by introducing compatibility constraints to confine the difference between the actual information and the previously published reference information of each subsystem, which is the key feature of the proposed distributed algorithm. Then, to ensure the satisfaction of both state and input constraints under disturbances, constraints are tightened on the state and the input of nominal systems by considering explicitly the effect of uncertainties. Moreover, based on an overall optimal steady state, a dissipativity constraint and a terminal constraint are designed and incorporated in the local optimization problems to establish recursive feasibility and guarantee stability for the resulting closed-loop system. Finally, the efficiency of the distributed economic MPC algorithm is demonstrated in a building temperature control case study.
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http://dx.doi.org/10.1109/TCYB.2020.3030021DOI Listing
November 2020

Measurement of red blood cell size based on a lensless imaging system.

Biotechnol Appl Biochem 2020 Nov 2. Epub 2020 Nov 2.

Faculty of Automation and Information Engineering, Xi'an University of Technology, Xi'an, People's Republic of China.

The variability in the size of red blood cells (RBCs) is an important additional diagnostic parameter for diseases, which has been established as a part of the complete blood count (CBC). The CBC can be performed using an automated flow cytometer, but it is too bulky and expensive for point-of-care testing. A miniaturized lensless imaging system is a competitive modality for a CBC, that is small and inexpensive. There are two challenges in developing a lensless imaging system for taking the CBC, which make the measurement of the RBC size very difficult: the diffraction effect and the low resolution. In this paper, the RBC radius measurement is replaced with a diffraction ring radius measurement. The diffraction ring radius is much larger than the RBC radius. This feature can improve the imaging resolution. Based on Fresnel diffraction, the relationship between the radius of RBCs and the diffraction fringes is analyzed. Finally, a complete measurement algorithm for determining the RBC size based on the lensless imaging system is given, which can be used to measure the variability in the size of RBCs. In our experiment, the maximum error is less than 6.74%.
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http://dx.doi.org/10.1002/bab.2057DOI Listing
November 2020

Mass spectrometry-based metabolomics investigation on two different indica rice grains (Oryza sativa L.) under cadmium stress.

Food Chem 2021 May 26;343:128472. Epub 2020 Oct 26.

State key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China. Electronic address:

Cadmium is a toxic environmental pollutant that is readily absorbed by rice grains and poses serious threats to human health. The selection and breeding of rice varieties with low cadmium accumulation is one of the most economical and ecological methods to reduce cadmium exposure. In this study, two different indica rice grains under cadmium stress were subjected to mass spectrometry-based metabolomics analysis for the first time. When the cadmium concentration increased in rice grains, most carbohydrates and amino acids were down-regulated, except myoinositol that can prevent cadmium toxicity, which was up-regulated. d-Mannitol and l-cysteine were up-regulated with the increase of cadmium concentration in low-cadmium-accumulating rice. Also, organic acids were activated especially 13-(S)-hydroperoxy-9(Z),11(E),15(Z)-octadecatrienoicacid that is related to the alpha-linolenic acid metabolism and jasmonic acid production. The determination of biomarkers and characterization of metabolic pathways might be helpful for the selection of rice varieties with low cadmium accumulation.
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http://dx.doi.org/10.1016/j.foodchem.2020.128472DOI Listing
May 2021

Exogenous IGF-1 alleviates depression-like behavior and hippocampal mitochondrial dysfunction in high-fat diet mice.

Physiol Behav 2021 Feb 31;229:113236. Epub 2020 Oct 31.

Department of Psychology, Tianjin Anding Hospital, Tianjin 300074, China; Department of Geriatrics, Tianjin Medical University General Hospital; Tianjin Geriatrics Institute, Tianjin 300052, China. Electronic address:

Background: Some evidence suggests that depression is more common in obese patients. This fact gives us a hint that obesity might be a promoter of depression, though a conclusion can not be drawn. The aim of the study was: (1) to confirm whether obesity induced by high-fat diet (HFD) promotes depression-like behaviors in mice, (2) to explore the protective role of insulin-like growth factor-1 (IGF-1) in such behavioral disorder of the animals and (3) to reveal whether mitochondrial mechanism was involved in such protective effect of the reagent.

Methods: C57BL/6 J mice were fed with HFD to establish a model of obesity. Then, the animals were separately or simultaneously treated with PEG-IGF-1, 666-15 (CREB blocker) and SR-18292 (PGC-1α blocker). After that, depression-like behaviors were assessed using sucrose preference test and tail suspension test. In hippocampus, respiratory control ratio, ATP generation and red/green fluorescence ratio were adopted to reveal mitochondrial function. Also in hippocampus, expressions of p-CREB and PGC-1α were measured using western blotting.

Results: HFD mice showed depression-like behaviors compared with control mice. Such diet also caused mitochondrial dysfunction and inhibition of CREB/PGC-1α signal pathway in hippocampus of these animals. After PEG-IGF-1 intervention, all the abnormalities mentioned above can be partly reversed. After 666-15 or SR-18292 treatment, such protective effect of PEG-IGF-1 can be attenuated, and the mice suffered from the re-deterioration of behavioral and mitochondrial abnormalities in hippocampus.

Conclusion: IGF-1 alleviated depression-like behaviors and mitochondrial dysfunction through the activation of CREB/PGC-1α signal pathway in HFD mice.
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http://dx.doi.org/10.1016/j.physbeh.2020.113236DOI Listing
February 2021

Biokinetics and biotransformation of paralytic shellfish toxins in different tissues of Yesso scallops, Patinopecten yessoensis.

Chemosphere 2020 Dec 23;261:128063. Epub 2020 Aug 23.

CAS Key Laboratory of Marine Ecology and Environmental Sciences, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China.

Paralytic shellfish toxins (PSTs) are a group of natural toxic substances often found in marine bivalves. Accumulation, anatomical distribution, biotransformation and depuration of PSTs in different tissues of bivalves, however, are still not very well understood. In this study, we investigated biokinetics and biotransformation of PSTs in six different tissues, namely gill, mantle, gonad, adductor muscle, kidney, and digestive gland, in Yesso scallops Patinopecten yessoensis exposed to a toxic strain of dinoflagellate Alexandrium pacificum. High daily accumulation rate (DAR) was recorded at the beginning stage of the experiment. Most of the PSTs in toxic algae ingested by scallops were retained and the toxicity level of PSTs in scallops exceeded the regulatory limit within 5 days. At the late stage of the experiment, however, DAR decreased obviously due to the removal of PSTs. Fitting results of the biokinetics model indicated that the amount of PSTs transferred from digestive gland to mantle, adductor muscle, gonad, kidney, and gill in a decreasing order, and adductor muscle, kidney, and gonad had higher removal rate than gill and mantle. Toxin profile in digestive gland was dominated by N-sulfocarbamoyl toxins 1/2 (C1/2), closely resembled that of the toxic algae. In contrast, toxin components in kidney were dominated by high-potency neosaxitoxin (NEO) and saxitoxin (STX), suggesting that the kidney be a major organ for transformation of PSTs.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128063DOI Listing
December 2020

NFATc2-dependent epigenetic upregulation of CXCL14 is involved in the development of neuropathic pain induced by paclitaxel.

J Neuroinflammation 2020 Oct 18;17(1):310. Epub 2020 Oct 18.

Department of Anesthesiology, Changhai Hospital, Naval Medical University, 168 Changhai Road, Shanghai, 200433, China.

Background: The major dose-limiting toxicity of paclitaxel, one of the most commonly used drugs to treat solid tumor, is painful neuropathy. However, the molecular mechanisms underlying paclitaxel-induced painful neuropathy are largely unclarified.

Methods: Paw withdrawal threshold was measured in the rats following intraperitoneal injection of paclitaxel. The qPCR, western blotting, protein or chromatin immunoprecipitation, ChIP-seq identification of NFATc2 binding sites, and microarray analysis were performed to explore the molecular mechanism.

Results: We found that paclitaxel treatment increased the nuclear expression of NFATc2 in the spinal dorsal horn, and knockdown of NFATc2 with NFATc2 siRNA significantly attenuated the mechanical allodynia induced by paclitaxel. Further binding site analysis utilizing ChIP-seq assay combining with gene expression profile revealed a shift of NFATc2 binding site closer to TTS of target genes in dorsal horn after paclitaxel treatment. We further found that NFATc2 occupancy may directly upregulate the chemokine CXCL14 expression in dorsal horn, which was mediated by enhanced interaction between NFATc2 and p300 and consequently increased acetylation of histone H4 in CXCL14 promoter region. Also, knockdown of CXCL14 in dorsal horn significantly attenuated mechanical allodynia induced by paclitaxel.

Conclusion: These results suggested that enhanced interaction between p300 and NFATc2 mediated the epigenetic upregulation of CXCL14 in the spinal dorsal horn, which contributed to the chemotherapeutic paclitaxel-induced chronic pain.
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http://dx.doi.org/10.1186/s12974-020-01992-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570122PMC
October 2020

Clinical analysis of conformal and intensity-modulated radiotherapy in patients with recurrent ovarian cancer.

Sci Rep 2020 10 14;10(1):17172. Epub 2020 Oct 14.

Department of Radiotherapy, Xi'an Gao Xin Hospital, Xi'an, Shaan'xi, China.

We aimed to provide evidence for radiotherapy treatment regimens in patients with clinically recurrent ovarian cancer. We analyzed the survival and prognostic factors in 43 patients who were treated for recurrent ovarian cancer at 58 tumor sites using three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) during January 2006-December 2017. t years 1, 2, and 3, overall survival (OS) rate was 82.4%, 68.4%, and 57.9%; local control (LC) rate was 100%, 100% and 80%; recurrence free survival (RFS) rate was 86.8%, 66.6%, and 61.1%; and disease-free survival (DFS) rate was 79.7%, 56.7%, and 46.8%, respectively. The radiotherapy technique was determined to be an independent prognostic factor for survival; the survival rate of patients was significantly improved with IMRT compared to 3D-CRT (P = 0.035). Radiotherapy dose was an independent prognostic factor; survival rate improved when patients were treated with a radiation dose ≥ 60 Gy as compared to < 60 Gy (P = 0.046). Elective nodal prophylactic radiation therapy (ENRT) did not lead to a significant improvement in survival when compared to involved-field radiation therapy (IFRT). The toxicities of 3D-CRT and IMRT were tolerable. One patient (2.3%) had grade 3 acute gastrointestinal (GI) toxicity, 2 (4.6%) grade 3 late GI toxicity, 5 (11.6%) grade 3 hematological toxicity, and 2 (4.6%) had grade 4 hematological toxicity. IMRT improved LC and OS in patients with recurrent ovarian cancer after surgery and multiple chemotherapy; toxicities were tolerable. The IMRT technique and radiotherapy dose of ≥ 60 Gy had independent prognostic significance for the survival of such patients.
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http://dx.doi.org/10.1038/s41598-020-74356-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560837PMC
October 2020

Method for evaluating the human bioequivalence of acarbose based on pharmacodynamic parameters.

J Int Med Res 2020 Oct;48(10):300060520960317

National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.

Objective: To explore a method for evaluating the bioequivalence of acarbose based on pharmacodynamic parameters using a single-dose, randomized-sequence, three-way crossover study of acarbose test (T) and reference (R) formulations.

Methods: Baseline-adjusted, pre-dose value deduction, and direct comparison methods were used to evaluate the geometric T/R ratios and 90% confidence intervals (CIs) of the ln-transformed pharmacodynamic parameters to identify the most suitable evaluation system. Twelve participants were randomly divided into three groups to receive treatment in the following sequences: TRR, RTR, and RRT, each including a 7-day washout period between treatment periods. The serum glucose concentration (baseline) was determined. Pharmacodynamic parameters, including the maximum reduction in serum glucose concentrations (ΔC) and difference of the AUC of glucose between before and after acarbose exposure (ΔAUEC), were tested.

Results: Using the direct comparison method, the geometric mean ratios of C, AUEC, and AUEC were 94.13%, 97.82% and 99.76%, respectively. The 90% CIs of the geometric T/R ratios for C, AUEC and AUEC all fell between 80% and 125%. Conversely, ΔC and ΔAUEC were less reliable measures of acarbose bioequivalence.

Conclusions: Pre-dose value deduction and direct comparison methods can be initially considered suitable for assessing acarbose bioequivalence.
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http://dx.doi.org/10.1177/0300060520960317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556174PMC
October 2020

Interleukin-35 promotes progression of prostate cancer and inhibits anti-tumour immunity.

Cancer Cell Int 2020 7;20:487. Epub 2020 Oct 7.

Department of Interventional Therapy, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Huan Hu West Road, Tianjin, 300060 China.

Background: Interleukin-35 (IL-35) has been reported to play an important role in the progression of cancers. The role of IL-35 in prostate cancer (PCA) is not well understood. In this study, we investigated the effects of IL-35 on PCA and its immunoregulatory effect on PCA.

Methods: The protein and mRNA expression of IL-35 in PCA cells was detected by western blot and RT-PCR. The invasion and migration of cells were detected using transwell and wound-healing assays. A CCK-8 assay was conducted to observe cell proliferation. In vivo, IL-35 plasma concentration was test by enzyme-linked immunosorbent assay. The role of IL-35 in tumour cell proliferation and angiogenesis of mice was detected by immunohistochemical stains. The mouse survival and tumour volumes were calculated, and lung metastasis rate was detected by HE staining. The modulatory effects of IL-35 on myeloid-derived inhibitory cells (MDSCs), regulatory T cells (Tregs), CD4+ T cells and CD8+ T cells from PCA mice were investigated by immunohistochemical stains and flow cytometry.

Results: High levels of IL-35 significantly promoted the migration, invasion and cell proliferation of PCA cells in vitro. IL-35 was associated with tumour growth, metastasis and poor prognosis in PCA mice. Additionally, high levels of IL-35 significantly increased the proportions of MDSCs and Tregs and decreased the proportions of CD4+ and CD8+ T cells in the spleen, blood and tumour microenvironment. The IL-35 neutralizing antibody played the opposite role.

Conclusions: IL-35 contributed to the progression of PCA through promoting cell proliferation and tumour angiogenesis. IL-35 might limit the anti-tumour immune response by upregulating the proportions of Tregs and MDSCs and by reducing the proportions of CD4+ and CD8+ T cells. IL-35 might serve as a novel therapeutic target for PCA.
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http://dx.doi.org/10.1186/s12935-020-01583-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541216PMC
October 2020