Publications by authors named "Ping Sun"

729 Publications

Natural molecule Munronoid I attenuates LPS-induced acute lung injury by promoting the K48-linked ubiquitination and degradation of TAK1.

Biomed Pharmacother 2021 Jun 12;138:111543. Epub 2021 Apr 12.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Immunology, Shenzhen University School of Medicine, Shenzhen 518060, PR China. Electronic address:

Acute lung injury (ALI) is a severe lung disease with limited therapeutic strategies. Munronoid I, a limonoid, which is extracted and purified from Munronia sinica, exhibits effective anti-neoplastic activities. In this study, we attempted to determine the anti-inflammatory effects of Munronoid I using both the lipopolysaccharide (LPS)-induced in vivo murine ALI models and in vitro assays. Our results demonstrated that Munronoid I treatment ameliorated LPS-induced ALI and inflammation in mice. Moreover, it also significantly inhibited LPS-induced pathological injuries, infiltration of inflammatory cells, and production of IL-1β and IL-6. Furthermore, the in vitro assay showed that Munronoid I could inhibit the LPS-induced expression of inflammatory mediators such as iNOS, COX2, and production of pro-inflammatory cytokines by suppressing the activation of NF-κB signaling pathway in mouse peritoneal macrophages. Munronoid I reduced the LPS-, tumor necrosis factor alpha (TNF-α)- or interleukin 1 beta (IL-1β)-induced transforming growth factor beta-activated kinase 1 (TAK1) phosphorylation and protein expression. Furthermore, the Munronoid I also promoted K48-linked ubiquitination and proteasomal degradation of TAK1. Taken together, these results demonstrated that Munronoid I exhibited anti-inflammatory activities both in vitro and in vivo, which might be a potential therapeutic candidate for the treatment of ALI and pulmonary inflammation.
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http://dx.doi.org/10.1016/j.biopha.2021.111543DOI Listing
June 2021

An N6-Methyladenosine-Related Gene Set Variation Score as a Prognostic Tool for Lung Adenocarcinoma.

Front Cell Dev Biol 2021 8;9:651575. Epub 2021 Jul 8.

Department of Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.

N6-methyladenosine (m6A) is the most prevalent type of RNA modification, and we hypothesized that patterns of m6A-related genes may be useful for estimating risk of lung adenocarcinoma (LUAD). An m6A-related gene set variation score (m6A-GSVS) was generated using RNA-sequencing data from LUAD patients in The Cancer Genome Atlas (TCGA). We investigated the association of m6A-GSVS with stemness, tumor mutational burden (TMB), expression of three immune checkpoints, levels of tumor-infiltrating lymphocytes (TILs), and patient prognosis. We found that m6A-GSVS was higher in LUAD than in healthy lung tissue, and it strongly correlated with stemness and TMB. Activated CD4 + T cells were more numerous in LUAD samples that had higher m6A-GSVS than in those with lower scores. Biological processes and pathways, including "Cell cycle," "DNA replication," and "RNA degradation," were significantly enriched in samples with high scores. Furthermore, m6A-GSVS was an independent prognostic indicator in LUAD. In conclusion, we proposed an m6A-GSVS in LUAD. It is a putative indicator for evaluating the ability to RNA m6A, an independent prognostic indicator and associated with tumor stemness.
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http://dx.doi.org/10.3389/fcell.2021.651575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295598PMC
July 2021

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

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

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

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

The epidemic of Q fever in 2018 to 2019 in Zhuhai city of China determined by metagenomic next-generation sequencing.

PLoS Negl Trop Dis 2021 Jul 15;15(7):e0009520. Epub 2021 Jul 15.

Department of Infectious Diseases, the Fifth Affiliated Hospital of Sun Yat-Sen University (SYSU), Zhuhai, China.

Q fever is a worldwide zoonosis caused by Coxiella burnetii (Cb). From January 2018 to November 2019, plasma samples from 2,382 patients with acute fever of unknown cause at a hospital in Zhuhai city of China were tested using metagenomic next-generation sequencing (mNGS). Of those tested, 138 patients (5.8%) were diagnosed with Q fever based on the presence of Cb genomic DNA detected by mNGS. Among these, 78 cases (56.5%) presented from Nov 2018 to Mar 2019, suggesting an outbreak of Q fever. 55 cases with detailed clinical information that occurred during the outbreak period were used for further analysis. The vast majority of plasma samples from those Cb-mNGS-positive patients were positive in a Cb-specific quantitative polymerase chain reaction (n = 38) and/or indirect immunofluorescence assay (n = 26). Mobile phone tracing data was used to define the area of infection during the outbreak. This suggested the probable infection source was Cb-infected goats and cattle at the only official authorized slaughterhouse in Zhuhai city. Phylogenic analysis based on genomic sequences indicated Cb strains identified in the patients, goat and cattle were formed a single branch, most closely related to the genomic group of Cb dominated by strains isolated from goats. Our study demonstrates Q fever was epidemic in 2018-2019 in Zhuhai city, and this is the first confirmed epidemic of Q fever in a contemporary city in China.
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http://dx.doi.org/10.1371/journal.pntd.0009520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282036PMC
July 2021

Clinical evaluation of xenogeneic collagen matrix versus free gingival grafts for keratinized mucosa augmentation around dental implants: A randomized controlled clinical trial.

J Clin Periodontol 2021 Jul 4. Epub 2021 Jul 4.

Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang, Hangzhou, China.

Aim: To evaluate the outcomes of an apically repositioned flap (ARF) plus xenogeneic collagen matrix (XCM) in augmenting keratinized mucosa width (KMW) around dental implants when compared with ARF plus free gingival grafts (FGG).

Materials And Methods: Twenty-six participants with at least one site with KMW ≤2 mm were randomized into FGG or XCM group. Clinical examinations were performed at baseline and at 2 and 6 months after surgery, including KMW, keratinized mucosa thickness, gingival index (GI), and probing depth (PD). Post-operative pain and patient satisfaction were also evaluated.

Results: At 6 months, FGG attained a greater increase of KMW and thicker mucosa than XCM (4.1 ± 1.6 mm vs. 1.8 ± 1.0 mm, p < .001; 1.7 ± 0.6 mm vs. 1.2 ± 0.3 mm, p < .01). Regarding GI, PD, post-operative pain, aesthetic outcomes, and patient satisfaction, no significant difference could be detected. Moreover, the operation time of XCM group was shorter (60 ± 9 min vs. 39 ± 8 min, p < .001).

Conclusions: FGG could result in greater increase of KMW than XCM, though both could increase KMW, maintain peri-implant health, and attain comparable aesthetic outcomes. The use of XCM was associated with reduced operation time.
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http://dx.doi.org/10.1111/jcpe.13518DOI Listing
July 2021

Notopterol Attenuates Estrogen Deficiency-Induced Osteoporosis Repressing RANKL Signaling and Reactive Oxygen Species.

Front Pharmacol 2021 3;12:664836. Epub 2021 Jun 3.

Department of Orthopaedic Surgery, First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.

Integrity of the skeleton is sustained through the balanced activities of osteoblasts and osteoclasts in bone remodeling unit. The balance can be disrupted by excessive osteoclasts activation commonly seen in osteoporosis. Notopterol (NOT) is a main component of Notopterygium incisum which exerts a wide spectrum effect on biomedical pharmacology. In our study, we found NOT serves as an inhibitor in regulating RANKL-activated osteoclasts formation and bone resorption function by calculating tartrate resistant acid phosphatase (TRAcP) staining and hydroxyapatite resorption assays. Furthermore, RANKL-mediated signaling pathways including MAPK, NF-κB and calcium ossification were hampered, whereas ROS scavenging enzymes in Nrf2/Keap1/ARE signaling pathways were promoted by NOT. In addition, the activation of the essential transcription factor NFATc1 in RANKL-mediated osteoclastogenesis was almost totally suppressed by NOT. What is more, NOT diminished the loss of bone mass in preclinical model of OVX mice by blocking osteoclastogenesis determined by bone histomorphometry, TRAcP staining and H&E staining. Conclusively, our findings demonstrated that NOT could arrest osteoclastogenesis and bone resorptive activity by attenuating RANKL-mediated MAPK, NF-κB, calcium and NFATc1 signaling transduction pathways and enhancing ROS scavenging enzymes in Nrf2/Keap1/ARE pathways , and prohibit bone loss induced by OVX . Taken together, NOT may be identified to be a natural and novel treatment for osteolytic diseases.
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http://dx.doi.org/10.3389/fphar.2021.664836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210423PMC
June 2021

Extrinsic factors, endocrine mechanisms, and behavioral indicators of migratory restlessness in wintering whooper swans (Cygnus cygnus).

Sci Rep 2021 Jun 16;11(1):12636. Epub 2021 Jun 16.

Research Institute of Forest Ecology, Environment and Protection, Key Laboratory of Forest Protection of National Forestry and Grassland Administration, Chinese Academy of Forestry, Beijing, 100091, China.

Extrinsic factors, endocrine mechanisms, and behavioral indicators of migratory restlessness were studied in wintering whooper swans (Cygnus cygnus) in the Sanmenxia Swan National Wetland Park in western Henan Province, central China. First, the fecal glucocorticoid metabolite (FGM) concentration was established and related to mean air temperature or photo period (day length) using simple linear or non-linear regression models. After a model selection procedure, the best fitted model revealed that an increase of FGM concentration was associated with an increase in the squared mean air temperature (R = 0.88). Other models showed an increasing FGM concentration to correspond with increasing values of day length, squared day length, and mean air temperature-however without statistical support. In a second step, behavioral frequencies of seven behaviors were condensed into three behavioral principal components (PCs) using principal components analysis. Behavioral PCs largely corresponded to three activity phases described for wintering whooper swans in central China and were correlated with the FGM concentration using Spearman's rank-order correlations. Results revealed a significant correlation between FGM and behavioral PC2 (positive factor loadings from vigilance and preening, negative loading from foraging). Finally, we tested for an effect of behavioral PCs on changes in winter home range size using a set of multiple linear regression models. Results of averaged model parameter estimates showed only the behavioral PC3 (positive factor loadings from fighting and calling, negative loading from locomotion) had a marginal significant effect on home range size. Results confirmed findings of previous studies on migratory restlessness in whooper swans. However, due to the small sample size (N = 15 weeks) the effect of PC3 on home range size was weak and should be viewed with caution.
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http://dx.doi.org/10.1038/s41598-021-92031-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209029PMC
June 2021

[Retracted] MicroRNA-200c inhibits the metastasis of non-small cell lung cancer cells by targeting ZEB2, an epithelial-mesenchymal transition regulator.

Mol Med Rep 2021 Aug 10;24(2). Epub 2021 Jun 10.

Department of Chemotherapy, Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell Transwell assay data in the article (featured in Figs. 2C and 4C) were strikingly similar to data appearing in different form in other articles by different authors at different research institutions, which were already under consideration for publication or had already been published elsewhere at the time of the present article's submission [C. Lai , 'MicroRNA‑133a inhibits proliferation and invasion, and induces apoptosis in gastric carcinoma cells via targeting fascin actin‑bundling protein 1', Mol Med Rep 12: 1473‑1478, 2015; and Y. Shi , 'MicroRNA‑204 inhibits proliferation, migration, invasion and epithelial‑mesenchymal transition in osteosarcoma cells via targeting Sirtuin 1', Oncol Rep 34: 399‑406, 2015]. Owing to the fact that the contentious data in the above article had already appeared in different form in other articles prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. The authors did not reply to indicate whether or not they agreed with the retraction of the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in 13: 3349-3355, 2016; DOI: 10.3892/mmr.2016.4901].
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http://dx.doi.org/10.3892/mmr.2021.12212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201453PMC
August 2021

Tanshinones inhibit NLRP3 inflammasome activation by alleviating mitochondrial damage to protect against septic and gouty inflammation.

Int Immunopharmacol 2021 Aug 4;97:107819. Epub 2021 Jun 4.

The Fifth Affiliated Hospital, Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, PR China. Electronic address:

Tanshinones, the active ingredients derived from the roots of Salvia miltiorrhiza, have been widely used as traditional medicinal herbs for treating human diseases. Although tanshinones showed anti-inflammatory effects in many studies, large knowledge gaps remain regarding their underlying mechanisms. Here, we identified 15 tanshinones that suppressed the activation of NLRP3 inflammasome and studied their structure-activity relationships. Three tanshinones (tanshinone IIA, isocryptotanshinone, and dihydrotanshinone I) reduced mitochondrial reactive-oxygen species production in lipopolysaccharide (LPS)/nigericin-stimulated macrophages and correlated with altered mitochondrial membrane potentials, mitochondria complexes activities, and adenosine triphosphate and protonated-nicotinamide adenine dinucleotide production. The tanshinones may confer mitochondrial protection by promoting autophagy and the AMP-activated protein kinase pathway. Importantly, our findings demonstrate that dihydrotanshinone I improved the survival of mice with LPS shock and ameliorated inflammatory responses in septic and gouty animals. Our results suggest a potential pharmacological mechanism whereby tanshinones can effectively treat inflammatory diseases, such as septic and gouty inflammation.
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http://dx.doi.org/10.1016/j.intimp.2021.107819DOI Listing
August 2021

An evaluation of memory and attention in BRCA mutation carriers using an online cognitive assessment tool.

Cancer 2021 Jun 2. Epub 2021 Jun 2.

Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada.

Background: The objective of this study was to evaluate the impact of various surgical, hormonal, and lifestyle factors on memory and attention in women with a BRCA1 or BRCA2 mutation.

Methods: BRCA mutation carriers enrolled in a longitudinal study were invited to complete an online brain health assessment tool designed to screen for cognitive deficits. Four measures of memory and executive attention were assessed individually, and an overall score was compiled adjusting for age. Exposures, including preventive surgery, hormone use, and lifestyle factors, were captured by questionnaire. Performance on each of the 5 subtasks was analyzed according to various exposures. Analysis of covariance was used to compare overall scores.

Results: In total, 880 women completed the online cognitive assessment. The average age of the participants was 54 years (range, 23-86 years). The mean overall test score was 54.4 (range, 0-93). The individual subtask scores declined with age at test completion (P < .0001) and increased with level of education (P ≤ .01). Women who underwent a preventive oophorectomy had a significantly higher overall score compared with women who did not undergo this surgery (55.5 vs 50.5; P = .01). Reconstructive breast surgery was also associated with a higher overall score (56.5 vs 52.3; P = .005). Chemotherapy and hormone-replacement therapy were not predictive of the overall score.

Conclusions: These findings are reassuring to high-risk women who undergo early surgical menopause for their cancer predisposition. Further studies are needed to evaluate cognitive function over time when memory deficits become more prevalent.
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http://dx.doi.org/10.1002/cncr.33654DOI Listing
June 2021

Human Salivary Histatin-1-Functionalized Gelatin Methacrylate Hydrogels Promote the Regeneration of Cartilage and Subchondral Bone in Temporomandibular Joints.

Pharmaceuticals (Basel) 2021 May 19;14(5). Epub 2021 May 19.

Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam (VU), Amsterdam Movement Science, 1081 LA Amsterdam, The Netherlands.

The avascular structure and lack of regenerative cells make the repair of osteochondral defects in the temporomandibular joint (TMJ) highly challenging in the clinic. To provide a viable treatment option, we developed a methacrylated gelatin (Gel-MA) hydrogel functionalized with human salivary histatin-1 (Hst1). Gel-MA is highly biocompatible, biodegradable, and cost-effective. Hst1 is capable of activating a series of cell activities, such as adhesion, migration, differentiation, and angiogenesis. To evaluate the efficacy of Hst1/Gel-MA, critical-size osteochondral defects (3 mm in diameter and 3 mm in depth) of TMJ in New Zealand white rabbits were surgically created and randomly assigned to one of the three treatment groups: (1) control (no filling material); (2) Gel-MA hydrogel; (3) Hst1/Gel-MA hydrogel. Samples were retrieved 1, 2, and 4 weeks post-surgery and subjected to gross examination and a series of histomorphometric and immunological analyses. In comparison with the control and Gel-MA alone groups, Hst1/Gel-MA hydrogel was associated with significantly higher International Cartilage Repair Society score, modified O'Driscoll score, area percentages of newly formed bone, cartilage, collagen fiber, and glycosaminoglycan, and expression of collagen II and aggrecan. In conclusion, Hst1/Gel-MA hydrogels significantly enhance bone and cartilage regeneration, thus bearing promising application potential for repairing osteochondral defects.
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http://dx.doi.org/10.3390/ph14050484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159088PMC
May 2021

Biogeographic Role of the Kuroshio Current Intrusion in the Microzooplankton Community in the Boundary Zone of the Northern South China Sea.

Microorganisms 2021 May 20;9(5). Epub 2021 May 20.

Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystem, College of the Environment and Ecology, Xiamen University, Xiamen 361102, China.

Kuroshio Current intrusion (KCI) has significant impacts on the oceanographic conditions and ecological processes of the Pacific-Asian marginal seas. Little is known to which extent and how, specifically, the microzooplankton community can be influenced through the intrusion. Here, we focused on ciliates that often dominated the microzooplankton community and investigated their communities using high-throughput sequencing of 18S rRNA gene transcripts in the northern South China Sea (NSCS), where the Kuroshio Current (KC) intrudes frequently. We first applied an isopycnal mixing model to assess the fractional contribution of the KC to the NSCS. The ciliate community presented a provincial distribution pattern corresponding to more and less Kuroshio-influenced stations. Structural equation modeling revealed a significant impact of the KCI on the community, while environmental variables had a marginal impact. KCI-sensitive OTUs were taxonomically diverse but mainly belonged to classes and , suggesting the existence of core ciliates responding to the KCI. KCI-sensitive OTUs were grouped into two network modules that showed contrasting abundance behavior with the KC fraction gradient, reflecting differential niches (i.e., winner and loser) in the ciliate community during the Kuroshio intrusion scenarios. Our study showed that the Kuroshio intrusion, rather than environmental control, was particularly detrimental to the oligotrophic microzooplankton community.
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http://dx.doi.org/10.3390/microorganisms9051104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161332PMC
May 2021

Discovery of dronedarone and its analogues as NLRP3 inflammasome inhibitors with potent anti-inflammation activity.

Bioorg Med Chem Lett 2021 Aug 29;46:128160. Epub 2021 May 29.

Key Laboratory of Molecular Target & Clinical Pharmacology and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 511436, China. Electronic address:

Inhibiting NLRP3 inflammasome activation is a prospective therapeutic strategy for uncontrolled inflammatory diseases. It is the first time that dronedarone, a multiply ion channel blocker, was identified as a NLRP3-inflammasome inhibitor with an IC value of 6.84 μM against IL-1β release. A series of novel 5-amide benzofuran derivatives were designed and synthesized as NLRP3-inflammasome inhibitors. Compound 8c showed slightly increased activity (IC = 3.85 μM) against IL-1β release. Notably, treatment with 8c could significantly inhibit NLRP3-mediated IL-1β release and ameliorate peritoneal inflammation in a mouse model of sepsis. Collectively, 8c is a promising lead compound for further chemical development as a NLRP3 inhibitor with anti-inflammation effects.
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http://dx.doi.org/10.1016/j.bmcl.2021.128160DOI Listing
August 2021

Sintilimab Plus Platinum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results From a Randomized, Double-Blind, Phase 3 Trial (ORIENT-12).

J Thorac Oncol 2021 May 25. Epub 2021 May 25.

Medical Science and Strategy Oncology, Innovent Biologics Inc., Suzhou, People's Republic of China.

Introduction: The standard chemotherapy for squamous NSCLC (sqNSCLC) includes platinum plus gemcitabine. Sintilimab, an anti-programmed cell death protein 1 antibody, plus platinum and gemcitabine (GP) has revealed encouraging efficacy as first-line therapy for sqNSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to further compare the efficacy and safety of sintilimab with placebo, both in combination with GP.

Methods: ORIENT-12, a randomized, double-blind, phase 3 study, was conducted at 42 centers in the People's Republic of China (ClinicalTrials.gov, number NCT03629925). Patients with locally advanced or metastatic sqNSCLC and without EGFR-sensitive mutations or ALK rearrangements were enrolled in the study. The stratification factors included clinical stage, choice of platinum, and programmed death-ligand 1 tumor proportion score. The patients, investigators, research staff, and sponsor team were masked to treatment assignment. Eligible patients were randomized 1:1, using an integrated web-response system, to receive sintilimab 200 mg or placebo plus GP every 3 weeks for four or six cycles, followed by sintilimab or placebo as maintenance therapy until disease progression or 2 years. The primary end point was progression-free survival (PFS), assessed by an independent radiographic review committee.

Results: Between September 25, 2018 and July 26, 2019, a total of 543 patients were screened, of whom 357 patients were randomized to the sintilimab-GP group (n = 179) and the placebo-GP group (n = 178). After a median follow-up period of 12.9 months, sintilimab-GP continued to reveal a meaningful improvement in PFS than placebo-GP (hazard ratio = 0.536 [95% confidence interval: 0.422-0.681], p < 0.00001). Treatment-emergent adverse events of grade 3 or worse occurred in 86.6% patients in the sintilimab-GP group and in 83.1% in the placebo-GP group. The incidence of treatment-emergent adverse event leading to death was 4.5% and 6.7% in the two treatment groups, respectively.

Conclusions: Regarding PFS, sintilimab plus GP reveals clinical benefit than GP alone as first-line therapy in patients with locally advanced or metastatic sqNSCLC. The toxicity was acceptable, and no new unexpected safety signals were observed.
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http://dx.doi.org/10.1016/j.jtho.2021.04.011DOI Listing
May 2021

Fat-restricted low-glycemic index diet controls weight and improves blood lipid profile: A pilot study among overweight and obese adults in Southwest China.

Medicine (Baltimore) 2021 May;100(21):e26107

Health Management Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology.

Abstract: Evidence from trials demonstrating the benefits and risks of low-glycemic index and fat-restricted diets in weight loss and blood lipid profile changes is unclear. This study aimed to assess the implemented and effects of a fat-restricted low-glycemic index diet on weight control and blood lipid profile changes in in overweight/obese Southwest Chinese individualst.This prospective pilot study enrolled overweight/obese subjects at the People's Hospital of Sichuan Province between February and July 2019. The daily energy intake was reduced by 300 to 500 kcal according to the participant's weight and activity level, with low-glycemic index carbohydrate- and fat-energy ratios < 45% and 25% to 30%, respectively. Participants received guidance for 3 months by telephone follow-up, internet interaction, or WeChat. Changes in weight, body composition, and blood profile were measured.A total of 254 patients were finally analyzed, including 101 males and 153 females. After adjusting for potential confounders, weight (P < .001), body mass index (P < .001), waist circumference (P < .001), waist-hip ratio (P < .001), body fat percentage (P < .001), visceral fat area (P < .001), basal metabolism (P = .002), cholesterol (P < .001), and triglycerides (P < .001) were significantly reduced after the 3-month intervention. The above indexes showed no significant differences between men and women.Regardless of gender, fat-restricted low-glycemic index diet might be helpful for controlling weight and lowering blood cholesterol and triglycerides in overweight/obese individuals in Southwest China.
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http://dx.doi.org/10.1097/MD.0000000000026107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154408PMC
May 2021

Characterization of functional chocolate formulated using oleogels derived from β-sitosterol with γ-oryzanol/lecithin/stearic acid.

Food Chem 2021 Oct 6;360:130017. Epub 2021 May 6.

School of Food Science and Biological Engineering, Hefei University of Technology, Hefei 230009, PR China; Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan 750021, PR China. Electronic address:

With an aim to prepare the functional chocolate, corn oil was used as the base oil and β-sitosterol was combined with oryzanol/stearic acid/lecithin to prepare respective oleogels (GO, SO, and LO). Oleogels (12%) were prepared by adding compound oleogelators at different ratios [GO-2:3, SO-1:4, and LO-4:1 (w/w)] in corn oil. The microstructure, interaction, thermodynamic, crystalline, and rheological behavior of formulated oleogels were studied by microscopic observation, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and rotational rheometer, respectively. The results showed that GO had the strongest gel forming ability and the densest gel crystallization network. Moreover, chocolate prepared with GO (cocoa butter and oleogels-1:1) had the similar texture, crystal structure, rheological, and sensory properties to that of dark chocolate. This study provides the possibility for the wider application of oleogel prepared with lower saturated and trans-fatty acids in the chocolate industry.
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http://dx.doi.org/10.1016/j.foodchem.2021.130017DOI Listing
October 2021

A self-healing, recyclable, and degradable fire-retardant gelatin-based biogel coating for green buildings.

Soft Matter 2021 May;17(20):5231-5239

Institute of Safety Science and Engineering, School of Mechanical and Automotive Engineering, South China University of Technology, Wushan Road 381, Guangzhou 510641, P. R. China. and Key Laboratory of Polymer Processing Engineering of Ministry of Education, South China University of Technology, Wushan Road 381, Guangzhou, 510641, P. R. China.

Wood is one of the oldest building materials and commonly employed in construction. However, the inherent fire hazard of wood restricts its practical application. Application of fire retardant coatings has been proved to be a highly efficient method for improving the fire retardancy of structural materials during combustion. However, developing sustainable, renewable and environmentally-friendly coatings is challenging because of the dependence on traditional flame retardants. In this study, a self-healable, fully-recyclable and biodegradable biogel coating was proposed, derived entirely from natural and food-safe constituents, which has rarely been demonstrated for wood safety. A uniform and strongly-adhesive coating could be obtained on wood surfaces via a facile preparation process without compromising the inherent mechanical properties of wood. Meanwhile, the coating showed excellent self-healing properties after damage, full degradability and good recyclability when disposed. Remarkably, biogel-coated wood exhibited enhanced fire-retardant properties, reflected by a 24.0% decrease in peak heat release rate and 17.2% reduction in total heat release with a 350 μm thick coating, along with a sixfold enhancement in ignition delay time and self-extinguishing behavior. We merged all merits in one fire-retardant coating which can be easily reproduced, and is low cost and scalable, making the biogel-coated wood a promising candidate for widespread application in green buildings.
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http://dx.doi.org/10.1039/d1sm00435bDOI Listing
May 2021

Physiological and Transcriptomic Analysis Provide Insight into Low Temperature Enhancing Hypericin Biosynthesis in .

Molecules 2021 Apr 15;26(8). Epub 2021 Apr 15.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.

Hypericin (Hyp), well-known as an antidepressant, is mainly extracted from . Although Hyp accumulation and biomass are greater at lower compared to higher temperature, the regulation mechanism has not been reported. Here, the physiological characteristics and transcriptome of grown at 15 and 22 °C were determined and analyzed by HPLC and de novo sequencing. The results showed that the stomatal density and opening percentages were 1.1- and 1.4-fold more, and the Hyp content was 4.5-fold greater at 15 °C compared to 22 °C. A total of 1584 differentially expressed genes (DEGs) were observed at 15 versus 22 °C, with 749 characterized genes, 421 upregulated (UR) and 328 downregulated (DR). Based on biological functions, 150 genes were associated with Hyp biosynthesis, plant growth and the stress response, including photosynthesis, carbohydrate metabolism, fatty acids metabolism, cytochrome P450 (CYPs), morpho-physiological traits, heat shock proteins (HSPs), cold-responsive proteins (CRPs) and transcription factors (TFs). The differential expression levels of the master genes were confirmed by qRT-PCR and almost consistent with their Reads Per kb per Million (RPKM) values. This physiological and transcriptomic analyses provided insight into the regulation mechanisms of low temperature enhancing Hyp biosynthesis in .
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http://dx.doi.org/10.3390/molecules26082294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071384PMC
April 2021

The Screen Project: Guided Direct-To-Consumer Genetic Testing for Breast Cancer Susceptibility in Canada.

Cancers (Basel) 2021 Apr 15;13(8). Epub 2021 Apr 15.

Women's College Research Institute, Women's College Hospital, Toronto, ON M5S 1B2, Canada.

There is limited information of the outcomes of direct-to-consumer testing for BRCA1 and BRCA2 mutations. The Screen Project was initiated in 2017 to offer BRCA1 and BRCA2 genetic screening to all Canadians over the age of 18 who wish to know their mutation status. Patients enrolled in the study from 2017 to 2019 and were followed for one year after the receipt of a genetic test result. Study subjects registered online and were sent a saliva sample kit, which was shipped to the reference laboratory. Pre-test genetic counselling and counselling for mutation-negative subjects was optional and at the individual's discretion. There were 1269 tested individuals between March 2017 and January 2019. A total of 1157 (93%) were women and 87 (7%) were men. Sixty-six percent had a first- or second-degree relative with breast or ovarian cancer. Of the 1269 tested individuals, 30 (2.4%) had a pathogenic mutation in BRCA1 or BRCA2 (20 women and 10 men). Seventy-five percent of the female mutation carriers underwent a bilateral mastectomy and/or salpingo-oophorectomy within a year of receiving a positive result. Genetic counselling was available at no cost to all participants but was requested by only 5% of the non-carriers. The study subjects expressed a high degree of satisfaction with the process.
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http://dx.doi.org/10.3390/cancers13081894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071125PMC
April 2021

Two Cu(II) coordination polymers: Heterogeneous catalytic Knoevenagel condensation reaction and treatment activity on atherosclerosis via regulating the expression of the COX-2 in vascular endothelial cells.

J Inorg Biochem 2021 Jul 21;220:111464. Epub 2021 Apr 21.

Department of Chemistry, Capital Medical University, Beijing, China.

By altering auxiliary nitrogen-donor ligands, two novel coordination polymers (CPs) containing Cu(II) formulated as [Cu(L)(trz)(HO)]·2HO (1) (Htrz = 1,2,4-triazole and HL = 5-(4-carboxybenzyloxy)isophthalic acid) and [Cu(HL)(Hbiz)] (2, Hbiz = benzimidazole) have been produced under the hydrothermal conditions. The complex 2 with both acidic and basic sites was investigated as heterogeneous catalyst, which reveals highly efficient catalytic property of the Knoevenagel condensation reaction. Dynamic changes of coagulation parameters during atherosclerosis was also explored via detecting activated partial thromboplastin time (APTT) and prothrombin time (PT), and the results showed that compared with CP 2, CP 1 has a stronger improvement on the coagulation parameters during atherosclerosis. Then, the high-sensitivity C-reactive protein and matrix metalloproteinase-1 released by the atherosclerotic segment was detected with enzyme linked immunosorbent assay (ELISA) detection, which also revealed that CP 1 could obviously decrease the inflammatory mediator released by the atherosclerotic segment, but not CP 2. And, the cyclooxygenase-2 (COX-2) relative expression level in vascular endothelial cells was detected via the real time RT-PCR. The results of the real time reverse transcription-polymerase chain reaction (RT-PCR) indicated that CP 1 has stronger activity on inhibiting the Notch signaling pathway than CP 2. Finally, we got this information, CP 1 has excellent application values on the coagulation parameters during atherosclerosis via regulating the expression of the COX-2 in vascular endothelial cells.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111464DOI Listing
July 2021

Genetic deletion of endothelial microRNA-15a/16-1 promotes cerebral angiogenesis and neurological recovery in ischemic stroke through Src signaling pathway.

J Cereb Blood Flow Metab 2021 Apr 28:271678X211010351. Epub 2021 Apr 28.

Pittsburgh Institute of Brain Disorders and Recovery, Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Cerebral angiogenesis is tightly controlled by specific microRNAs (miRs), including the miR-15a/16-1 cluster. Recently, we reported that endothelium-specific conditional knockout of the miR-15a/16-1 cluster (EC-miR-15a/16-1 cKO) promotes post-stroke angiogenesis and improves long-term neurological recovery by increasing protein levels of VEGFA, FGF2, and their respective receptors VEGFR2 and FGFR1. Herein, we further investigated the underlying signaling mechanism of these pro-angiogenic factors after ischemic stroke using a selective Src family inhibitor AZD0530. EC-miR-15a/16-1 cKO and age- and sex-matched wild-type littermate (WT) mice were subjected to 1 h middle cerebral artery occlusion (MCAO) and 28d reperfusion. AZD0530 was administered daily by oral gavage to both genotypes of mice 3-21d after MCAO. Compared to WT, AZD0530 administration exacerbated spatial cognitive impairments and brain atrophy in EC-miR-15a/16-1 cKO mice following MCAO. AZD0530 also attenuated long-term recovery of blood flow and inhibited the formation of new microvessels, including functional vessels with blood circulation, in the penumbra of stroked cKO mice. Moreover, AZD0530 blocked the Src signaling pathway by downregulating phospho-Src and its downstream mediators (p-Stat3, p-Akt, p-FAK, p-p44/42 MAPK, p-p38 MAPK) in post-ischemic brains. Collectively, our data demonstrated that endothelium-targeted deletion of the miR-15a/16-1 cluster promotes post-stroke angiogenesis and improves long-term neurological recovery via activating Src signaling pathway.
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http://dx.doi.org/10.1177/0271678X211010351DOI Listing
April 2021

Nomograms for Predicting Axillary Lymph Node Status Reconciled With Preoperative Breast Ultrasound Images.

Front Oncol 2021 7;11:567648. Epub 2021 Apr 7.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

Introduction: The axillary lymph node (ALN) status of breast cancer patients is an important prognostic indicator. The use of primary breast mass features for the prediction of ALN status is rare. Two nomograms based on preoperative ultrasound (US) images of breast tumors and ALNs were developed for the prediction of ALN status.

Methods: A total of 743 breast cancer cases collected from 2016 to 2019 at the Second Affiliated Hospital of Harbin Medical University were randomly divided into a training set (n = 523) and a test set (n = 220). A primary tumor feature model (PTFM) and ALN feature model (ALNFM) were separately generated based on tumor features alone, and a combination of features was used for the prediction of ALN status. Logistic regression analysis was used to construct the nomograms. A receiver operating characteristic curve was plotted to obtain the area under the curve (AUC) to evaluate accuracy, and bias-corrected AUC values and calibration curves were obtained by bootstrap resampling for internal and external verification. Decision curve analysis was applied to assess the clinical utility of the models.

Results: The AUCs of the PTFM were 0.69 and 0.67 for the training and test sets, respectively, and the bias-corrected AUCs of the PTFM were 0.67 and 0.67, respectively. Moreover, the AUCs of the ALNFM were 0.86 and 0.84, respectively, and the bias-corrected AUCs were 0.85 and 0.81, respectively. Compared with the PTFM, the ALNFM showed significantly improved prediction accuracy ( < 0.001). Both the calibration and decision curves of the ALNFM nomogram indicated greater accuracy and clinical practicality. When the US tumor size was ≤21.5 mm, the Spe was 0.96 and 0.92 in the training and test sets, respectively. When the US tumor size was greater than 21.5 mm, the Sen was 0.85 in the training set and 0.87 in the test set. Our further research showed that when the US tumor size was larger than 35 mm, the Sen was 0.90 in the training set and 0.93 in the test set.

Conclusion: The ALNFM could effectively predict ALN status based on US images especially for different US tumor size.
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http://dx.doi.org/10.3389/fonc.2021.567648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058421PMC
April 2021

Preparation of EDTA-modified magnetic attapulgite chitosan gel bead adsorbent for the removal of Cu(II), Pb(II), and Ni(II).

Int J Biol Macromol 2021 Jul 23;182:1138-1149. Epub 2021 Apr 23.

Department of Environmental Engineering, Peking University, The Key Laboratory of Water and Sediment Sciences, Ministry of Education, Beijing 100871, China.

Attapulgite (ATP) has a unique porous layered chain structure and is an excellent environment-friendly decolorizer. However, its high viscosity makes it difficult to separate. First, it was combined with magnetic FeO nanoparticles to obtain FeO-ATP that is easy to recycle and reuse. Then, FeO-ATP nanoparticles were embedded in chitosan (CS) gel beads, and glutaraldehyde was used for cross-linking and curing. Lastly, ethylenediaminetetraacetic acid (EDTA) was successfully connected to FeO-ATP/CS gel beads through amidation reaction, which further increased the capability of the adsorbent to adsorb heavy metal ions. The prepared magnetic composite adsorbent is a sphere with a rough surface and porous structure. The maximum adsorption capacity of the prepared FeO-ATP/EDTA/CS adsorbent for Pb(II), Cu(II), and Ni(II) is 368.32, 267.94, and 220.31 mg g, respectively. After 5 times of repeated use, FeO-ATP/EDTA/CS still showed good adsorption capacity for Cu(II), Pb(II), and Ni(II). FeO-ATP/EDTA/CS has a large adsorption capacity for heavy metal ions, a wide pH applicability, good reuse, and rapid magnetic separation. In addition, Cu(II) loaded FeO-ATP/EDTA/CS also showed good catalytic degradation performance for bisphenol A. This study prepared a new type of adsorbent with good adsorption performance and provided a promising method for the treatment of wastewater.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.132DOI Listing
July 2021

Characteristics of Chinese Families in Which Children and Both Parents Are Diagnosed with Malignant Tumors: A Retrospective Study.

Chin Med Sci J 2021 Mar;36(1):27-34

Department of Cancer Prevention, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.

Objective To characterize Chinese families in which both parents and at least one child are diagnosed with malignant diseases and provide reference for cancer screening or early detection in people whose both parents are diagnosed with cancer. Methods Medical records of all clients to the center of cancer screening and prevention of the National Cancer Center/Cancer Hospital between January 2008 and February 2018 were screened to select families in which both parents and at least one child were diagnosed with malignant diseases. The cancer profiles of fathers, mothers, sons and daughters, their age distribution at diagnosis, and similarity of cancers between two generations were analyzed. The proportions of each cancer in males and females of the cohort were compared with corresponding data from the National Cancer Center Registry of China (NCCRC) in 2013. Results Totally 135 families were identified from records of 33 200 clients. Proportion of lung cancer in fathers (40/135, 29.6%) and in mothers (38/135, 28.1%) were higher than the national data (23.9% in males and 14.9% in females, respectively). The proportion of breast cancer in daughters (35/109, 32.1%) was higher than that of mothers (14/135, 10.4%) and the national data (17.1%). In 71 father-son pairs of cancer, 46.5% (33/71) were of the same systematic disease, and 16.9% (12/71) were of the same cancer. These two indexes were 31.2% (=34) and 10.1% (=11), respectively in the 109 father-daughter pairs of cancer, 36.6% (=26) and 8.5% (=6) respectively in the 71 mother-son pairs of cancer, and 31.2% (=34) and 20.2% (=20) respectively in the 109 mother-daughter pairs of cancer. Sons were more likely to suffer from cancers originated from the same system as father's cancer than daughters (=4.299, <0.05), and daughters were more likely to suffer from the same cancer as their mother's cancer than sons (=4.506, <0.05). The age (mean ± standard deviation) of the daughters (52.4±12.7) and the sons (59.4±10.9) at diagnosis were significantly younger than the fathers (65.5±12.2) and the mothers (65.7 ±12.5) (all <0.001). Conclusions For people whose both parents are diagnosed as cancer, screening or early detection examinations should cover a full range of cancers rather than the cancers their father and mother have suffered, or cancers stemmed from the same system as their parent's cancers. We suggest screening or early detection program for these special population start earlier than that for the general population, with emphasis on cancers derived from digestive system for males and women-specific cancers, i.e., breast cancer, ovarian cancer, cervical cancer and uterine cancer for females.
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http://dx.doi.org/10.24920/003789DOI Listing
March 2021

Discovery of chalcone analogues as novel NLRP3 inflammasome inhibitors with potent anti-inflammation activities.

Eur J Med Chem 2021 Jul 1;219:113417. Epub 2021 Apr 1.

Key Laboratory of Molecular Target & Clinical Pharmacology and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 511436, China. Electronic address:

NLRP3 inflammasome activation plays a critical role in inflammation and its related disorders. Herein we report a hit-to-lead effort resulting in the discovery of a novel and potent class of NLRP3 inflammasome inhibitors. Among these, the most potent lead 40 exhibited improved inhibitory potency and almost no toxicity. Further mechanistic study indicated that compound 40 inhibited the NLRP3 inflammasome activation via suppressing ROS production. More importantly, treatment with 40 showed remarkable therapeutic effects on LPS-induced sepsis and DSS-induced colitis. This study encourages further development of more potent inhibitors based on this chemical scaffold and provides a chemical tool to identify its cellular binding target.
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http://dx.doi.org/10.1016/j.ejmech.2021.113417DOI Listing
July 2021

Remediation of Chromium-Contaminated Soil Based on WHX-1 Immobilized on Biochar: Cr(VI) Transformation and Functional Microbial Enrichment.

Front Microbiol 2021 25;12:641913. Epub 2021 Mar 25.

College of Environmental Science and Engineering, Ocean University of China, Qingdao, China.

Microorganisms are applied to remediate chromium (Cr)-contaminated soil extensively. Nevertheless, the microbial loss and growth inhibition in the soil environment restrain the application of this technology. In this study, a Cr(VI)-reducing strain named WHX-1 was screened, and the microbial aggregates system was established via immobilizing the strain on biochar to enhance the Cr(VI)-reducing activity of this strain. The mechanism of the system on Cr(VI) transformation in Cr-contaminated soil was illuminated. Pot experiments indicated that the microbial aggregates system improved the physicochemical characteristics of Cr-contaminated soil obviously by increasing organic carbon content and cation exchange capacity, as well as decreasing redox potential and bulk density of soil. Moreover, 94.22% of Cr(VI) was transformed into Cr(III) in the pot, and the content of residue fraction Cr increased by 63.38% compared with control check (CK). Correspondingly, the physiological property of planted on the Cr-contaminated soil was improved markedly and the main Cr(VI)-reducing microbes, spp., were enriched in the soil with a relative abundance of 28.43% in the microbial aggregates system. Considering more active sites of biochar for microbial aggregation, it was inferred that WHX-1 could be immobilized by biochar, and more Cr(VI) was transformed into residue fraction. Cr stress was decreased and the growth of plants was enhanced. This study would provide a new perspective for Cr-contaminated soil remediation.
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http://dx.doi.org/10.3389/fmicb.2021.641913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027096PMC
March 2021

[Apoptosis of Endothelial Cells Induced by Anti-Platelet Integrin β3 Antibody].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Apr;29(2):567-573

Department of pathoanatomy, College of Basic Medical Sciences, Jinzhou Medical University, Jinzhou 121000, Liaoning province,

Objective: To investigate the damaging of human umbilical vein endothelial cells (HUVEC) induced by antiplatelet integrin β3 antibodies in vitro.

Methods: The serum from 36 chronic ITP patients were collected, flow cytometry and monoclonal antibody specific immobilization of platelet antigen (MAIPA) assay were used to collect antiplatelet integrin β3 antibodies from the serum of the patients. After HUVEC were treated by ITP patient serum (PS) containing anti-integrin β3 antibodies, the cell damage was detected by Lactate dehydrogenase (LDH) assay, cell apoptosis was detected by flow cytometry, the expression of apoptosis-related gene Bax was detected by Reverse transcription-Quantitative real-time PCR (RT-qPCR), and expression of Apoptosis-related signaling pathway protein Akt and related protein Bax were detected by Western blot. HUVEC were treated by PS combined with Akt activator SC79, the cells damage were detected by LDH assay, apoptosis of the cells were detected by flow cytometry, the expression of apoptosis-related gene Bax was detected by RT-qPCR.

Results: Among 36 cases of serum from the chronic ITP patients, 5 patients' serum containing anti-integrin β3 antibodies were collected. After HUVEC was treated by PS, the viability of LDH was significant increased(P<0.05), so as for the apoptosis of the cells(P<0.05), the expression of gene and protein of Bax was increased up-regulated(P<0.05), the protein expression of pAkt was down-regulated(P<0.05). Comparing with HUVEC cultured with PS alone, the viability of LDH of HUVEC treated by PS combined with SC79 was significantly reduced(P<0.05), so as for the apoptosis of the cells(P<0.05), and gene expression of Bax was significantly decreased(P<0.05).

Conclusion: Anti-integrin β3 serum can cause the damage and apoptosis of HUVEC through Akt signaling pathway,the apoptotic effects of anti-integrin β3 antibodies to HUVEC was effectively reversed by SC79.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.02.041DOI Listing
April 2021

Ubiquitin-specific peptidase 39 promotes human glioma cells migration and invasion by facilitating ADAM9 mRNA maturation.

Mol Oncol 2021 Apr 2. Epub 2021 Apr 2.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Immunology, School of Medicine, Shenzhen University, China.

Glioma cells are characterized by high migration and invasion ability; however, the molecular mechanism behind both processes still remains to be investigated. Several studies have demonstrated that ubiquitin-specific protease 39 (USP39) plays an oncogenic role in various cancer types. Here, we investigated the expression and function of USP39 in patients with glioma. Oncomine database analysis revealed that high USP39 expression was significantly correlated with poor overall survival in patients with glioma. Knockdown of USP39 in U251 and U87 cell lines significantly inhibited their migration and invasion in vitro. Gene expression profiling of glioma cells transduced with short hairpin RNA (shRNA) against USP39 revealed that disintegrin and metalloproteinase domain-containing protein 9 (ADAM9), a molecule previously related to tumor cell migration and invasion, was significantly downregulated. Furthermore, USP39 induced ADAM9 messenger RNA (mRNA) maturation and decreased the expression of integrin β1. Additionally, overexpression of ADAM9 inhibited the migration and invasion of glioma cells caused by USP39 depletion in vitro. USP39 promoted the invasion of glioma cells in vivo and reduced the overall survival of the mice. Altogether, our data show that USP39 induces mRNA maturation and elevates the expression of ADAM9 in glioma cells and may thus be considered potential target for treating patients with glioma.
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http://dx.doi.org/10.1002/1878-0261.12958DOI Listing
April 2021

SSAO/VAP-1 in Cerebrovascular Disorders: A Potential Therapeutic Target for Stroke and Alzheimer's Disease.

Int J Mol Sci 2021 Mar 25;22(7). Epub 2021 Mar 25.

Neurovascular Research Laboratory, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain.

The semicarbazide-sensitive amine oxidase (SSAO), also known as vascular adhesion protein-1 (VAP-1) or primary amine oxidase (PrAO), is a deaminating enzyme highly expressed in vessels that generates harmful products as a result of its enzymatic activity. As a multifunctional enzyme, it is also involved in inflammation through its ability to bind and promote the transmigration of circulating leukocytes into inflamed tissues. Inflammation is present in different systemic and cerebral diseases, including stroke and Alzheimer's disease (AD). These pathologies show important affectations on cerebral vessels, together with increased SSAO levels. This review summarizes the main roles of SSAO/VAP-1 in human physiology and pathophysiology and discusses the mechanisms by which it can affect the onset and progression of both stroke and AD. As there is an evident interrelationship between stroke and AD, basically through the vascular system dysfunction, the possibility that SSAO/VAP-1 could be involved in the transition between these two pathologies is suggested. Hence, its inhibition is proposed to be an interesting therapeutical approach to the brain damage induced in these both cerebral pathologies.
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http://dx.doi.org/10.3390/ijms22073365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036996PMC
March 2021

In Silico Network Analysis of Ingredients of Cornus officinalis in Osteoporosis.

Med Sci Monit 2021 Apr 2;27:e929219. Epub 2021 Apr 2.

Department of Endocrinology, The First Affiliated Hospital/School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China (mainland).

BACKGROUND Cornus officinalis (CO), also known as 'Shanzhuyu', is one of the most common traditional Chinese herbs used against osteoporosis. Although previous studies have found that CO has beneficial effects in alleviating osteoporosis, its mechanisms remain unclear. MATERIAL AND METHODS In this study, we applied system bioinformatic approaches to investigate the possible therapeutic mechanisms of CO against osteoporosis. We collected the active ingredients of CO and their targets from the TCMSP, BATMAN-TCM, and ETCM databases. Next, we obtained the osteoporosis targets from differentially expressed mRNAs from the Gene Expression Omnibus (GEO) gene series (GSE35958). Next, the shared genes of the CO pharmacological targets and osteoporosis-related targets were selected to construct the protein-protein interaction network, based on the results from the STRING database. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out by using the clusterProfiler package in R software. RESULTS In all, there were 58 unique CO compounds and 518 therapeutic targets. Based on the GO and KEGG enrichment results of 98 common genes, we selected the top 25 terms, based on the terms' P values. We found that the anti-osteoporotic effect of CO may mostly involve the regulation of calcium metabolism and reactive oxygen species, and the estrogen signaling pathway and osteoclast differentiation pathway. CONCLUSIONS We found the possible mechanisms of CO in treating osteoporosis may be based on multiple targets and pathways. We also provided a theoretical basis and promising direction for investigating the exact anti-osteoporotic mechanisms of CO.
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http://dx.doi.org/10.12659/MSM.929219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023278PMC
April 2021
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