Publications by authors named "Wang-Jia Li"

86 Publications

Significance of intra-nodular vessel sign in differentiating benign and malignant pulmonary ground-glass nodules.

Insights Imaging 2021 May 26;12(1):65. Epub 2021 May 26.

Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, China.

Background: The presence of pulmonary vessels inside ground-glass nodules (GGNs) of different nature is a very common occurrence. This study aimed to reveal the significance of pulmonary vessels displayed in GGNs in their diagnosis and differential diagnosis.

Results: A total of 149 malignant and 130 benign GGNs confirmed by postoperative pathological examination were retrospectively enrolled in this study. There were significant differences in size, shape, nodule-lung interface, pleural traction, lobulation, and spiculation (each p < 0.05) between benign and malignant GGNs. Compared with benign GGNs, intra-nodular vessels were more common in malignant GGNs (67.79% vs. 54.62%, p = 0.024), while the vascular categories were similar (p = 0.663). After adjusting the nodule size and the distance between the nodule center and adjacent pleura [radius-distance ratio, RDR], the occurrences of internal vessels between them were similar. The number of intra-nodular vessels was positively correlated with nodular diameter and RDR. Vascular changes were more common in malignant than benign GGNs (52.48% vs. 18.31%, p < 0.0001), which mainly manifested as distortion and/or dilation of pulmonary veins (61.19%). The occurrence rate, number, and changes of internal vessels had no significant differences among all the pre-invasive and invasive lesions (each p > 0.05).

Conclusions: The incidence of internal vessels in GGNs is mainly related to their size and the distance between nodule and pleura rather than the pathological nature. However, GGNs with dilated or distorted internal vessels, especially pulmonary veins, have a higher possibility of malignancy.
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http://dx.doi.org/10.1186/s13244-021-01012-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155149PMC
May 2021

Pulmonary Benign Ground-Glass Nodules: CT Features and Pathological Findings.

Int J Gen Med 2021 24;14:581-590. Epub 2021 Feb 24.

Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.

Background: Some pulmonary ground-glass nodules (GGNs) are benign and frequently misdiagnosed due to lack of understanding of their CT characteristics. This study aimed to reveal the CT features and corresponding pathological findings of pulmonary benign GGNs to help improve diagnostic accuracy.

Patients And Methods: From March 2016 to October 2019, patients with benign GGNs confirmed by operation or follow-up were enrolled retrospectively. According to overall CT manifestations, GGNs were classified into three types: I, GGO with internal high-attenuation zone; II, nodules lying on adjacent blood vessels; and other type, lesions without obvious common characteristics. CT features and pathological findings of each nodule type were evaluated.

Results: Among the 40 type I, 25 type II, and 14 other type GGNs, 24 (60.0%), 19 (76.0%), and 10 (71.4%) nodules were resected, respectively. Type I GGNs were usually irregular (25 of 40, 62.5%) with only one high-attenuation zone (38 of 40, 95.0%) (main pathological components: thickened alveolar walls with inflammatory cells, fibrous tissue, and exudation), which was usually centric (24 of 40, 60.0%), having blurred margin (38 of 40, 95.0%), and connecting to blood vessels (32 of 40, 80.0%). The peripheral GGO (main pathological component: a small amount of inflammatory cell infiltration with fibrous tissue proliferation) was usually ill-defined (28 of 40, 70.0%). Type II GGNs (main pathological components: focal interstitial fibrosis with or without inflammatory cell infiltration) lying on adjacent vessel branches were usually irregular (19 of 25, 76.0%) and well defined (16 of 25, 64.0%) but showed coarse margins (15 of 16, 93.8%). Other type GGNs had various CT manifestations but their pathological findings were similar to that of type II.

Conclusion: For subsolid nodules with CT features manifested in type I or II GGNs, follow-up should be firstly considered in further management.
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http://dx.doi.org/10.2147/IJGM.S298517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930605PMC
February 2021

Improvement of long-term clinical outcomes by successful PCI in the very elderly women with ACS.

BMC Cardiovasc Disord 2021 Mar 4;21(1):122. Epub 2021 Mar 4.

Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, No.95, Yongan Road, Xicheng District, Beijing, 100050, People's Republic of China.

Background: Whether very elderly women with acute coronary syndromes (ACS) should receive aggressive percutaneous coronary intervention (PCI) is still controversial. We assessed the effectiveness and long-term clinical outcomes of successful PCI in this population and identified prognostic factors which might contribute to the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) in the very elderly female PCI cohort.

Methods: Female ACS patients aged ≥ 80 years were consecutively enrolled (n = 729) into the study. All the patients were divided into female PCI group (n = 232) and medical group (n = 497). MACCE was followed up, including non-fatal myocardial infarction (MI), stroke, heart failure requiring hospitalization (HFRH), cardiovascular (CV) death, and the composite of them. After propensity score matching (1:1), the incidences of MACCE were compared between the two groups. Clinical and coronary artery lesion characteristics were compared between the female PCI patients with (n = 56) and without MACCE (n = 176). Multivariate Cox regression analysis was performed to identify risk factors which independently associated with MACCE in the female PCI patients. MACCE of male PCI patients, who aged ≥ 80 years and hospitalized in the same period (n = 264), was also compared with that of the female PCI patients.

Results: A total of 32% very elderly female ACS patients received PCI in the present study. (1) Compared to female medical group, PCI procedure significantly alleviated the risks of MACCE: non-fatal MI (6.2% vs. 20.2%, P < 0.001), HFRH (10.9% vs. 22.5%, P = 0.012), CV death (12.4% vs. 28.7%, P < 0.001) and the composite MACCE (24.0% vs. 44.2%, P < 0.001) during the median follow-up period of 36 months. (2) Between very elderly female and male PCI patients, there were no significant differences in occurrence of MACCE (P = 0.232) and CV death (P = 0.951). (3) Multivariate Cox analysis revealed that ST-segment elevation myocardial infarction (STEMI) (HR 1.944, 95% CI 1.11-3.403, P = 0.02) and elevated log- N-Terminal pro-brain natriuretic peptide (NT-proBNP) (HR 1.689, 95% CI 1.029-2.773, P = 0.038) were independently associated with the incidence of MACCE in the female PCI patients.

Conclusions: PCI procedure significantly attenuated the risk of MACCE and improved the long-term clinical outcomes in very elderly female ACS patients. Aggressive PCI strategy may be reasonable in this population.
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http://dx.doi.org/10.1186/s12872-021-01933-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934370PMC
March 2021

Analysis of potential factors contributing to refusal of invasive strategy after ST-segment elevation myocardial infarction in China.

Chin Med J (Engl) 2021 Jan 14;134(5):524-531. Epub 2021 Jan 14.

Department of Emergency Medicine and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.

Background: Reduced application of percutaneous coronary intervention (PCI) is associated with higher mortality rates after ST-segment elevation myocardial infarction (STEMI). We aimed to evaluate potential factors contributing to the refusal of PCI in STEMI patients in China.

Methods: We studied 957 patients diagnosed with STEMI in the emergency departments (EDs) of six public hospitals in China. The differences in baseline characteristics and 30-day outcome were investigated between patients who refused PCI and those who underwent PCI. Multivariable logistic regression was used to evaluate the potential factors associated with refusing PCI.

Results: The potential factors contributing to refusing PCI were older than 65 years (odds ratio [OR] 2.66, 95% confidence interval [CI] 1.56-4.52, P < 0.001), low body mass index (BMI) (OR 0.91, 95% CI 0.84-0.98, P = 0.013), not being married (OR 0.29, 95% CI 0.17-0.49, P < 0.001), history of myocardial infarction (MI) (OR 2.59, 95% CI 1.33-5.04, P = 0.005), higher heart rate (HR) (OR 1.02, 95% CI 1.01-1.03, P = 0.002), cardiac shock in the ED (OR 5.03, 95% CI 1.48-17.08, P = 0.010), pre-hospital delay (>12 h) (OR 3.31, 95% CI 1.83-6.02, P < 0.001) and not being hospitalized in a tertiary hospital (OR 0.45, 95% CI 0.27-0.75, P = 0.002). Compared to men, women were older, were less often married, had a lower BMI and were less often hospitalized in tertiary hospitals.

Conclusions: Patients who were older, had lower economic or social status, and had poorer health status were more likely to refuse PCI after STEMI. There was a sex difference in the potential predictors of refusing PCI. Targeted efforts should be made to improve the acceptance of PCI among patients with STEMI in China.
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http://dx.doi.org/10.1097/CM9.0000000000001171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929575PMC
January 2021

Lower respiratory tract samples are reliable for severe acute respiratory syndrome coronavirus 2 nucleic acid diagnosis and animal model study.

Zool Res 2021 Mar;42(2):161-169

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) continue to impact countries worldwide. At present, inadequate diagnosis and unreliable evaluation systems hinder the implementation and development of effective prevention and treatment strategies. Here, we conducted a horizontal and longitudinal study comparing the detection rates of SARS-CoV-2 nucleic acid in different types of samples collected from COVID-19 patients and SARS-CoV-2-infected monkeys. We also detected anti-SARS-CoV-2 antibodies in the above clinical and animal model samples to identify a reliable approach for the accurate diagnosis of SARS-CoV-2 infection. Results showed that, regardless of clinical symptoms, the highest detection levels of viral nucleic acid were found in sputum and tracheal brush samples, resulting in a high and stable diagnosis rate. Anti-SARS-CoV-2 immunoglobulin M (IgM) and G (IgG) antibodies were not detected in 6.90% of COVID-19 patients. Furthermore, integration of nucleic acid detection results from the various sample types did not improve the diagnosis rate. Moreover, dynamic changes in SARS-CoV-2 viral load were more obvious in sputum and tracheal brushes than in nasal and throat swabs. Thus, SARS-CoV-2 nucleic acid detection in sputum and tracheal brushes was the least affected by infection route, disease progression, and individual differences. Therefore, SARS-CoV-2 nucleic acid detection using lower respiratory tract samples alone is reliable for COVID-19 diagnosis and study.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995275PMC
March 2021

TM4SF19 aggravates LPS-induced attenuation of vascular endothelial cell adherens junctions by suppressing VE-cadherin expression.

Biochem Biophys Res Commun 2020 12 12;533(4):1204-1211. Epub 2020 Oct 12.

Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Laboratory Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address:

Atherosclerosis is a chronic vascular inflammatory disease that initially starts from an arterial intima lesion and endothelial barrier dysfunction. The purpose of this study was to investigate the role of TM4SF19, a recently identified member of the transmembrane 4L six superfamily, in vascular endothelial cell adherens junctions. We found TM4SF19 expression was significantly increased in atherosclerotic plaques and sera of patients with coronary heart disease (CHD) compared with healthy people by immunohistochemistry and ELISA. In vitro, human umbilical vein endothelial cells (HUVECs) were stimulated by lipopolysaccharides (LPS). TM4SF19 and VE-cadherin expression as well as cell adherens junctions were assessed. Additionally, LPS could upregulate TM4SF19 expression and downregulate VE-cadherin expression in HUVECs in a concentration dependent manner. Overexpression of TM4SF19 substantially aggravated LPS-induced reduction of VE-cadherin expression and attenuation of vascular endothelial cell adherens junctions. However, both the decreased VE-cadherin expression and weakened cell adherens junctions induced by LPS could be dramatically reversed when the expression of TM4SF19 was depressed. This study is the first to reveal the effect of TM4SF19 on endothelial cell adherens junctions. Meanwhile, our results also provide novel therapeutic strategies for atherosclerotic diseases.
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http://dx.doi.org/10.1016/j.bbrc.2020.08.078DOI Listing
December 2020

Aldehyde dehydrogenase 2 preserves mitochondrial morphology and attenuates hypoxia/reoxygenation-induced cardiomyocyte injury.

World J Emerg Med 2020 ;11(4):246-254

Department of Emergency Medicine and Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.

Background: Disturbance of mitochondrial fission and fusion (termed mitochondrial dynamics) is one of the leading causes of ischemia/reperfusion (I/R)-induced myocardial injury. Previous studies showed that mitochondrial aldehyde dehydrogenase 2 (ALDH2) conferred cardioprotective effect against myocardial I/R injury and suppressed I/R-induced excessive mitophagy in cardiomyocytes. However, whether ALDH2 participates in the regulation of mitochondrial dynamics during myocardial I/R injury remains unknown.

Methods: In the present study, we investigated the effect of ALDH2 on mitochondrial dynamics and the underlying mechanisms using the H9c2 cells exposed to hypoxia/reoxygenation (H/R) as an model of myocardial I/R injury.

Results: Cardiomyocyte apoptosis was significantly increased after oxygen-glucose deprivation and reoxygenation (OGD/R), and ALDH2 activation largely decreased the cardiomyocyte apoptosis. Additionally, we found that both ALDH2 activation and overexpression significantly inhibited the increased mitochondrial fission after OGD/R. Furthermore, we found that ALDH2 dominantly suppressed dynamin-related protein 1 (Drp1) phosphorylation (Ser616) and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation (Thr172) but not interfered with the expression levels of mitochondrial shaping proteins.

Conclusions: We demonstrate the protective effect of ALDH2 against cardiomyocyte H/R injury with a novel mechanism on mitochondrial fission/fusion.
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http://dx.doi.org/10.5847/wjem.j.1920-8642.2020.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517403PMC
January 2020

Simple synthesis of multifunctional photosensitizers for mitochondrial and bacterial imaging and photodynamic anticancer and antibacterial therapy.

J Mater Chem B 2020 Sep 22. Epub 2020 Sep 22.

School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.

Photosensitizers (PSs), a critical drug administered for successful photodynamic therapy (PDT), have been well researched regarding their anticancer or bactericidal capability with high precision and low invasiveness. Although traditional PSs have been explored either in photodynamic anticancer or in antibiosis, they usually require synthesis with multiple steps, harsh synthetic conditions, and a complicated purification process for a single targeted product. Therefore, developing new multifunctional PSs with a simple synthesis and reactant flexibility which combine mitochondrial and bacterial imaging, efficient photodynamic anticancer and antibacterial effects is of the utmost urgency and of great importance for clinical applications. Herein, a large structural investigation of isoquinolinium-based PSs synthesized by a simple Rh-catalysed annulation reaction with high yields is presented. These lipophilic cationic PSs have a tunable photophysical property. LIQ-6 was found to perform not only as an ideal mitochondria targeting probe but also an effective cancer cell killing PS, and moreover, a tracker for bacterial imaging and ablation. LIQ-6 can be used to image a wide range of cancer cells and to monitor the photo-induced cell apoptosis, and simultaneously, it can also image and be a photodynamic germicide for both Gram-positive and Gram-negative bacteria. Furthermore, LIQ-6 shows great effectiveness in the wound healing process, showing its ability to be an ideal PS in vivo as well. This contribution is believed to offer a new platform for the construction of a theragnostic system for future practical applications in biology and biomedicine.
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http://dx.doi.org/10.1039/d0tb01669aDOI Listing
September 2020

CT features and outcomes of newly developed pulmonary lesions in patients with Coronavirus Disease 2019 (COVID-19).

Int J Med Sci 2020 29;17(15):2373-2378. Epub 2020 Aug 29.

Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China, 40016.

: In patients with coronavirus disease 2019 (COVID-19) pneumonia, whether new pulmonary lesions will continue to develop after treatment was unknown. This study aimed to determine whether new pulmonary lesions will develop after treatment in patients with COVID-19 pneumonia, and investigate their CT features and outcomes. This retrospective study included 56 consecutive patients with confirmed COVID-19 pneumonia from January 20 to March 5, 2020. Their initial and follow-up CT images and clinical data were reviewed. The CT manifestations of primary and newly developed pulmonary lesions and their changes after treatment were mainly evaluated. Among the 56 patients (mean age: 48±15 years, 35 men) with COVID-19 pneumonia, 42 (75.0%) patients developed new pulmonary lesions during treatment. All new lesions developed before the nucleic acid test turned negative. Patients with new lesions were more likely to have lymphopenia (=0.041) or increased C-reactive protein (CRP) levels (0.001) than those without new lesions. Of the 42 patients, 30 (71.4%) patients developed new lesions once, and 12 (28.6%) twice or thrice, which usually appeared when primary lesions were progressing (37, 88.1%) and 1-15 days after treatment. The newly developed lesions were usually multiple (38, 90.5%), distributed in the previously involved (39, 92.9%) or uninvolved (27, 64.3%) lobes, and manifested as ground-glass opacities (GGOs) with consolidation (23, 54.8%) or pure GGOs (19, 45.2%). After their occurrence, the new lesions in most patients (32, 76.2%) showed direct absorption, whereas those in some patients (10, 23.8%) progressed before absorption. During treatment, most patients with COVID-19 pneumonia will develop new pulmonary lesions, which usually manifest as multiple GGOs distributed around the primary lesions or in previously uninvolved lobes, and are subsequently absorbed directly.
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http://dx.doi.org/10.7150/ijms.47587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484640PMC
September 2020

Mixed Lineage Kinase Domain-Like Protein Promotes Human Monocyte Cell Adhesion to Human Umbilical Vein Endothelial Cells Via Upregulation of Intercellular Adhesion Molecule-1 Expression.

Med Sci Monit 2020 Aug 13;26:e924242. Epub 2020 Aug 13.

Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (mainland).

BACKGROUND Atherosclerosis is a progressive inflammatory disease that involves a variety of inflammatory and proinflammatory factors, including intercellular adhesion molecule (ICAM)-1. ICAM-1 plays an important role in atherosclerosis by promoting cell adhesion. Mixed lineage kinase domain-like (MLKL), a critical regulator of necroptotic cell death, is indicated to play an important role in atherosclerosis. This study investigated the effects of MLKL on ICAM-1 expression and cell adhesion, thus providing a new direction for the research of atherosclerosis pathogenesis. MATERIAL AND METHODS siRNA-MLKL and pcDNA-MLKL were designed, and the expression of MLKL and ICAM-1 were estimated by real-time polymerase chain reaction at the mRNA level and Western blotting at the protein level. The adhesion of human monocyte cells (THP-1) to human umbilical vein endothelial cells (HUVECs) was examined under immunofluorescence microscopy, and the ability of cell adhesion was evaluated by ImageJ software. RESULTS Overexpression of MLKL greatly enhanced ICAM-1 expression in HUVECs and the adherence of THP-1 cells to HUVECs. Knockdown of MLKL by siRNA dramatically inhibited the expression of ICAM-1 and the adherence of THP-1 cells to HUVECs. MLKL could promote THP-1 adhesion to HUVECs by activating ICAM-1 expression in HUVECs. CONCLUSIONS MLKL can promote THP-1 cell adhesion to HUVECs through up-regulation of ICAM-1 expression in HUVECs. Thus, MLKL might be a useful target for reducing adhesion of monocytes to endothelial cells and atherosclerosis.
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http://dx.doi.org/10.12659/MSM.924242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446275PMC
August 2020

[Effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts on intestinal flora of vascular aging mice induced by high glucose and high lipid].

Zhongguo Zhong Yao Za Zhi 2020 Jun;45(12):2938-2946

Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment of Major Disease,Medical Experiment Center, China Academy of Chinese Medical Sciences Beijing 100700, China Guangdong Research Center for Integrative Medicine in Metabolic Diseases, Chinese Medicine Research Institute of Guangdong Pharmaceutical University Guangzhou 510006, China.

The aim of this paper was to observe the changes of intestinal flora in vascular aging mice, in order to explore the relationship between vascular aging and intestinal flora and the effects of extracts of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma on intestinal flora of vascular aging mice. A model of vascular aging in mice was induced through intrape-ritoneal injection with streptozotocin(STZ) combined with high-fat diet. Biochemical detection was performed on serum cholesterol(CHO), triglyceride(TG), high-density liptein cholesterol(HDL-C), low-density liptein cholesterol(LDL-C) and blood glucose(GLU). HE staining was used to detect mice thoracic aorta morphology, and the expressions of cyclin-dependent kinase inhibitor 2 A(p16) and cyclin-dependent kinase inhibitor 1 A(p21) protein in mice thoracic aorta were detected by Western blot. The 16 S rDNA gene of mice intestinal flora was detected by Illumina MiSeq high-throughput sequencing technology to explore the changes of intestinal flora in each group. The results demonstrated that the GLU level in low-dose and high-dose TCM groups decreased, but with unobvious changes in blood lipid indexes. Metformin could significantly decrease the levels of GLU(P<0.01), CHO and LDL-C in mice(P<0.05). Intravascular injury was not obvious in each drug group, and the expressions of p16 and p21 protein were significantly decreased(P<0.05). The intestinal flora of each group was mainly composed of Firmicutes(F) and Bacteroidetes(B) at the level of the phylum, but the B/F ratio was different from that of the youth group and the blank control group. The B/F ratio of the model group was significantly lower(P<0.01), and compared with the model group, the B/F ratio of the high-dose group and the metformin group was signi-ficantly higher(P<0.05). There were dominant and differential floras in the intestine of each group of mice. The results showed that extracts of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma could improve the intestinal flora structure and create a good intestinal environment by increasing the B/F ratio, which provides a new possible pathway for lowering blood glucose and blood lipids and delaying vascular aging.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200117.401DOI Listing
June 2020

Lipopolysaccharide Promotes Inflammatory Response via Enhancing IFIT1 Expression in Human Umbilical Vein Endothelial Cells.

DNA Cell Biol 2020 Jul 16;39(7):1274-1281. Epub 2020 Jun 16.

Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Atherosclerosis is an immune inflammatory disease and a major cause of mortality and morbidity worldwide. It is generally considered that a number of potent proinflammatory cytokines have a great influence on its pathogenesis, including IL-1β, IL-6, TNF-α, and NF-κB. A growing amount of empirical evidence indicates that the mechanism of cardiac dysfunction caused by lipopolysaccharide (LPS) is the activation of inflammation, but the exact mechanism in atherosclerosis is still unclear. Previous studies have shown that interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) participates in inflammation, but the effects and possible mechanism of action of IFIT1 on proinflammatory response remain largely unexplained. We found that LPS induced upregulation of IFIT1 expression in a time- and concentration-dependent manner in human umbilical vein endothelial cells (HUVECs). Overexpression of IFIT1 significantly upregulated LPS-induced expression of IL-1β, IL-6, TNF-α, and NF-κB in HUVECs. IFIT1-siRNA treatment dramatically decreased LPS-induced expression of IL-1β, IL-6, TNF-α, and NF-κB in HUVECs. The above results show that LPS induces expression of IL-1β, IL-6, TNF-α, and NF-κB through upregulating IFIT1 expression in HUVECs, and suggested that IFIT1 could act as potential therapeutic target to ameliorate atherosclerosis-related diseases.
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http://dx.doi.org/10.1089/dna.2020.5454DOI Listing
July 2020

Reference intervals for steroid hormones in healthy 6- to 15-year-old girls based on liquid chromatography-tandem mass spectrometry in China.

Chin Med J (Engl) 2020 May;133(10):1239-1241

Department of Endocrinology, Genetics, Metabolism, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.

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http://dx.doi.org/10.1097/CM9.0000000000000771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249713PMC
May 2020

CT Characteristics for Predicting Invasiveness in Pulmonary Pure Ground-Glass Nodules.

AJR Am J Roentgenol 2020 08 29;215(2):351-358. Epub 2020 Apr 29.

Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Rd, Yuanjiagang, Yuzhong District, Chongqing 40016, China.

The objective of our study was to investigate the differences in the CT features of atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IA) manifesting as a pure ground-glass nodule (pGGN) with the aim of determining parameters predictive of invasiveness. A total of 161 patients with 172 pGGNs (14 AAHs, 59 AISs, 68 MIAs, and 31 IAs) were retrospectively enrolled. The following CT features of each histopathologic subtype of nodule were analyzed and compared: lesion location, diameter, area, shape, attenuation, uniformity of density, margin, nodule-lung interface, and internal and surrounding changes. ROC curves revealed that nodule diameter and area (cutoff value, 10.5 mm and 86.5 mm; sensitivity, 87.1% and 87.1%; specificity, 70.9% and 65.2%) were significantly larger in IAs than in AAHs, AISs, and MIAs ( < 0.001), whereas the latter three were similar in size ( > 0.050). CT attenuation higher than -632 HU in pGGNs indicated invasiveness (sensitivity, 78.8%; specificity, 59.8%). As opposed to noninvasive pGGNs (AAHs and AISs), invasive pGGNs (MIAs and IAs) usually had heterogeneous density, irregular shape, coarse margin, lobulation, spiculation, pleural indentation, and dilated or distorted vessels (each, < 0.050). Multivariate analysis showed that mean CT attenuation and presence of lobulation were predictors for invasive pGGNs ( ≤ 0.001). The likelihood of invasiveness is greater in pGGNs with larger size (> 10.5 mm or > 86.5 mm), higher attenuation (> -632 HU), heterogeneous density, irregular shape, coarse margin, spiculation, lobulation, pleural indentation, and dilated or distorted vessels.
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http://dx.doi.org/10.2214/AJR.19.22381DOI Listing
August 2020

Biodegradable Magnesium-Based Implants in Orthopedics-A General Review and Perspectives.

Adv Sci (Weinh) 2020 Apr 28;7(8):1902443. Epub 2020 Feb 28.

Musculoskeletal Research Laboratory Department of Orthopaedics & Traumatology The Chinese University of Hong Kong Hong Kong SAR P. R. China.

Biodegradable Mg-based metals may be promising orthopedic implants for treating challenging bone diseases, attributed to their desirable mechanical and osteopromotive properties. This Review summarizes the current status and future research trends for Mg-based orthopedic implants. First, the properties between Mg-based implants and traditional orthopedic implants are compared on the following aspects: in vitro and in vivo degradation mechanisms of Mg-based implants, peri-implant bone responses, the fate of the degradation products, and the cellular and molecular mechanisms underlying the beneficial effects of Mg ions on osteogenesis. Then, the preclinical studies conducted at the low weight bearing sites of animals are introduced. The innovative strategies (for example, via designing Mg-containing hybrid systems) are discussed to address the limitations of Mg-based metals prior to their clinical applications at weight-bearing sites. Finally, the available clinical studies are summarized and the challenges and perspectives of Mg-based orthopedic implants are discussed. Taken together, the progress made on the development of Mg-based implants in basic, translational, and clinical research has laid down a foundation for developing a new era in the treatment of challenging and prevalent bone diseases.
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http://dx.doi.org/10.1002/advs.201902443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175270PMC
April 2020

Antitumour properties based on the self-assembly of camptothecin and carbamoylmannose conjugates.

Chem Biol Drug Des 2020 08 5;96(2):870-877. Epub 2020 May 5.

Key Laboratory of Medicinal Chemistry and Molecular Diagnosis (Ministry of Education), Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, China.

Camptothecin (CPT) and its analogues show potent antitumour activity. However, poor water solubility and severe side effects have restricted their applications in clinical practice. In this paper, a novel self-assembly based on camptothecin and carbamoylmannose conjugates (CPT-Man) was constructed. The self-assembly increased the water solubility of camptothecin to 0.64 mg/ml and antitumour activity. Moreover, CPT-Man could induce obvious cancer cell apoptosis. This work provides a new approach for exploring carbohydrate-modified antitumour properties by self-assembled CPT drugs.
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http://dx.doi.org/10.1111/cbdd.13698DOI Listing
August 2020

Magnesium and vitamin C supplementation attenuates steroid-associated osteonecrosis in a rat model.

Biomaterials 2020 04 31;238:119828. Epub 2020 Jan 31.

Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China; Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. Electronic address:

Magnesium (Mg)-based biometal attracts clinical applications due to its biodegradability and beneficial biological effects on tissue regeneration, especially in orthopaedics, yet the underlying anabolic mechanisms in relevant clinical disorders are lacking. The present study investigated the effect of magnesium (Mg) and vitamin C (VC) supplementation for preventing steroid-associated osteonecrosis (SAON) in a rat experimental model. In SAON rats, 50 mg/kg Mg, or 100 mg/kg VC, or combination, or water control was orally supplemented daily for 2 or 6 weeks respectively. Osteonecrosis was evaluated by histology. Serum Mg, VC, and bone turnover markers were measured. Microfil-perfused samples prepared for angiography and trabecular architecture were evaluated by micro-CT. Primary bone marrow cells were isolated from each group to evaluate their potentials in osteoblastogenesis and osteoclastogenesis. The mechanisms were tested in vitro. Histological evaluation showed SAON lesions in steroid treated groups. Mg and VC supplementation synergistically reduced the apoptosis of osteocytes and osteoclast number, and increased osteoblast surface. VC supplementation significantly increased the bone formation marker PINP, and the combination significantly decreased the bone resorption marker CTX. TNFα expression and oxidative injury were decreased in bone marrow in Mg/VC/combination group. Mg significantly increased the blood perfusion in proximal tibia and decreased the leakage particles in distal tibia 2 weeks after SAON induction. VC significantly elevated the osteoblast differentiation potential of marrow cells and improved the trabecular architecture. The combination supplementation significantly inhibited osteoclast differentiation potential of marrow cells. In vitro study showed promoting osteoblast differentiation effect of VC, and anti-inflammation and promoting angiogenesis effect of Mg with underlying mechanisms. Mg and VC supplementation could synergistically alleviate SAON in rats, indicating great translational potentials of metallic minerals for preventing SAON.
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http://dx.doi.org/10.1016/j.biomaterials.2020.119828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185815PMC
April 2020

Alternative processing technology for the preparation of carbonized Zingiberis Rhizoma by stir-frying with sand.

Pharm Biol 2020 Dec;58(1):131-137

School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People's Republic of China.

Carbonized ginger, a type of charry herb, has been used as a hemostatic medicine since ancient times. However, there are some serious problems such as inhomogeneous heating and emitting smoke during processing with traditional stir-frying method. To investigate the feasibility to obtain carbonized ginger by stir-frying with sand instead of stir-frying method. Dried-ginger (100 g) was processed by stir-frying for 30 min at 270 ± 10 °C, or by stir-frying with sand (1:10, w/w) for 8 min at 240 ± 5 °C. The HPLC fingerprint was established for two samples. The adsorption capacity and major components including tannins, gingerols, shogaols and gingerone were quantitated by UV and HPLC, respectively. The hemostatic effect by prothrombin time (PT) and activated partial thromboplastin time (APTT) was evaluated . The similarity of the two samples for HPLC fingerprints was >0.93. The sand-fried samples showed significantly higher adsorption capacity compared with the stir-fried samples (4.915 vs. 4.593 mg/g;  0.05) and higher contents of major components (4.698 vs. 3.930 mg/g, 1.352 vs. 1.144 mg/g, 2.419 vs. 2.095 mg/g, 0.666 vs. 0.568 mg/g and 1.083 vs. 0.911 mg/g for tannins, gingerone, 6-shogaol, 8-shogaol and 10-shogaol, respectively;  0.05); while no significant differences were seen for 6-gingerol, 8-gingerol and 10-gingerol ( 0.05). The PT and APTT values were similar between the stir-fried and sand-fried test groups and significantly lower compared to controls ( 0.05). The carbonizing process by stir-frying with sand is superior to the stir-frying method for carbonized ginger.
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http://dx.doi.org/10.1080/13880209.2019.1711431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006685PMC
December 2020

[Chemical constituents from fermented Noni juice].

Zhongguo Zhong Yao Za Zhi 2019 Sep;44(18):4015-4020

Key Laboratory of Tropical Medicinal Plant Chemistry of Ministry of Education,Hainan Normal University Haikou 571158,China Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province,College of Chemistry and Chemical Engineering,Hainan Normal University Haikou 571158,China.

The present work was launched to study the chemical constituents from fermented Noni juice. Ten compounds were isolated by using silicagel,Sephadex LH-20 and pre-HPLC. The structures of these compounds were identified by 1D and 2D NMR. Their structures were established as norimester( 1),cyclo( R-Pro-S-Phe)( 2),cyclo-( L-Pro-L-Leu)( 3),trans-cyclo-( D-tryptophanyl-Ltyrosyl)( 4),cyclo( L-Trp-N-methyl-L-Ala-)( 5),4-allyl-2-hydroxyphenyl 1-O-β-D-apiosyl-( 1 → 6)-β-D-glucopyranoside( 6),2-methoxy-4-vinylphenyl β-D-apiofuranosyl-( 1→6)-β-D-glucopyranoside( 7),( +)-lirioresinol A( 8),( ±)-syringaresinol( 9),and2-formyl-1 H-pyrrole-1-butanoic acid( 10). All compounds were tested for their antibacterial activity and α-glucosidase inhibitory activity. Compound 1 was a new compound. All compounds were isolated from fermented Noni juice for the first time. Compound 1 showed significant inhibitory activity against α-glucosidase [IC50 value of( 4. 22±0. 03) μmol·L-1].
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20190619.201DOI Listing
September 2019

Design, synthesis and antitumor activity of a novel PEG-A6-conjugated irinotecan derivative.

Bioorg Med Chem Lett 2020 01 3;30(2):126847. Epub 2019 Dec 3.

School of Pharmacy, Guilin Medical University, Guilin 541004, China; Department of Chemistry & Pharmaceutical Science, Guilin Normal College, Guangxi 541001, China. Electronic address:

A novel PEG-A6-conjugated irinotecan derivative 8 was designed and synthesized as antitumor agent by the PEGylation and A6-peptide modification of irinotecan. In vivo antitumor activity screening assay revealed that 8 exhibited better in vivo antiproliferation activity than irinotecan and its previous PEG-cRGD-conjugated derivative BGC0222 in MIA PaCa-2, NCI-H446, MDA-MB-231, HT-29 and NCI-N87 xenograft models, while the tumor of one in six mice in NCI-H446 assay and the tumors of two in six mice in MIA PaCa-2 assay completely subsided and disappeared within the 21-day period of 8-treatment, indicating that 8 should be a potential antitumor agent.
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http://dx.doi.org/10.1016/j.bmcl.2019.126847DOI Listing
January 2020

Ultrafast labeling and high-fidelity imaging of mitochondria in cancer cells using an aggregation-enhanced emission fluorescent probe.

Chem Commun (Camb) 2019 Dec 20;55(97):14681-14684. Epub 2019 Nov 20.

School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.

An aggregation-enhanced emission mitochondrial probe, LIQ-3, was developed for ultrafast labeling within one minute and for distinguishing cancer cells from normal cells. Furthermore, the probe revealed high-fidelity tracking of mitochondria in a three-dimensional localization with advantages that include a specific targeting capacity and a high signal-to-noise ratio.
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http://dx.doi.org/10.1039/c9cc07775hDOI Listing
December 2019

Primary solid lung cancerous nodules with different sizes: computed tomography features and their variations.

BMC Cancer 2019 Nov 7;19(1):1060. Epub 2019 Nov 7.

Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuanjiagang, Yuzhong district, Chongqing, China.

Background: The computed tomography (CT) features of small solid lung cancers and their changing regularity as they grow have not been well studied. The purpose of this study was to analyze the CT features of solid lung cancerous nodules (SLCNs) with different sizes and their variations.

Methods: Between February 2013 and April 2018, a consecutive cohort of 224 patients (225 nodules) with confirmed primary SLCNs was enrolled. The nodules were divided into four groups based on tumor diameter (A: diameter ≤ 1.0 cm, 35 lesions; B: 1.0 cm < diameter ≤ 1.5 cm, 60 lesions; C: 1.5 cm < diameter ≤ 2.0 cm, 63 lesions; and D: 2.0 cm < diameter ≤ 3.0 cm, 67 lesions). CT features of nodules within each group were summarized and compared.

Results: Most nodules in different groups were located in upper lobes (groups A - D:50.8%-73.1%) and had a gap from the pleura (groups A - D:89.6%-100%). The main CT features of smaller (diameter ≤ 1 cm) and larger (diameter > 1 cm) nodules were significantly different. As nodule diameter increased, more lesions showed a regular shape, homogeneous density, clear but coarse tumor-lung interface, lobulation, spiculation, spinous protuberance, vascular convergence, pleural retraction, bronchial truncation, and beam-shaped opacity (p < 0.05 for all). The presence of halo sign in all groups was similar (17.5%-22.5%; p > 0.05).

Conclusions: The CT features vary among SLCNs with different sizes. Understanding their changing regularity is helpful for identifying smaller suspicious malignant nodules and early determining their nature in follow-up.
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http://dx.doi.org/10.1186/s12885-019-6274-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836448PMC
November 2019

Genomic profiling in amyloid light-chain amyloidosis reveals mutation profiles associated with overall survival.

Amyloid 2020 Mar 22;27(1):36-44. Epub 2019 Oct 22.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Amyloid light chain (AL) amyloidosis is characterized by tissue deposition of amyloid fibres derived from immunoglobulin that can lead to irreversible organ damage. Information about genomic profiles of AL amyloidosis is lacking. In this study, we adopted a two-step strategy to investigate the mutational profile of AL amyloidosis bone marrow plasma cells (PCs) and their clinical implications. In step one, whole-exome sequencing was performed in bone marrow PCs and paired with normal tissue from 10 AL amyloidosis patients, by which we identified 10 significantly mutated genes (SMGs). In step two, we constituted a targeted gene sequencing (TGS) panel covering the frequently mutated genes identified in step one, genes reported in prior AL amyloidosis studies, and known cancer driver mutations. Then, we analysed an expanded cohort of AL amyloidosis patients ( = 48) with this panel comprising 98 genes. Four recurrent mutations were identified by TGS and verified by Sanger sequencing: (c. 844 C > T), (c. 1595 A > G), (c. 311 C > T) and (c. 35 G > A), among which the first three mutations were associated with inferior overall survival (OS). Additionally, we found that the number of mutations identified by the TGS panel of 98 genes could be a prognostic predictor for OS. In summary, we revealed genomic profiling in AL amyloidosis and found mutation profiles associated with OS.
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http://dx.doi.org/10.1080/13506129.2019.1678464DOI Listing
March 2020

Effect of Slab Thickness on the Detection of Pulmonary Nodules by Use of CT Maximum and Minimum Intensity Projection.

AJR Am J Roentgenol 2019 09 7;213(3):562-567. Epub 2019 May 7.

Department of Radiology, First Affiliated Hospital of Chongqing Medical University, 1 Youyi Rd, Yuanjiagang, Yuzhong, Chongqing 40016, China.

The purpose of this study was to investigate the effect of slab thickness on the detection of pulmonary nodules by use of maximum-intensity-projection (MIP) and minimum-intensity-projection (MinIP) to process CT images. Chest CT data of 221 patients with pulmonary nodules were retrospectively analyzed. Nodules were categorized into two groups according to density: solid nodules (SNs) and subsolid nodules (SSNs). Pulmonary nodules were independently evaluated by two radiologists using axial CT images with 1-mm and 5-mm section thickness and MIP and MinIP images. MIP images for SN detection and MinIP images for SSN detection were separately reconstructed with four (5, 10, 15, 20 mm) and three (3, 8, 15 mm) slab thicknesses. The numbers and locations of detected nodules were recorded, and interobserver agreement was assessed. For each reader, the differences in nodule detection rates were evaluated in different series of images. Among the different series of images, interobserver agreements for detecting nodules were all good to excellent (κ ≥ 0.687). For total SNs and SNs with a diameter < 5 mm, detection rates on 10-mm MIP images were significantly higher than in other series of images (reader 1, 84.5% and 83.8%; reader 2, 83.6% and 82.2%). For total SSNs and SSNs < 5 mm, detection rates on 3-mm MinIP images were significantly higher than those in other series of images, except for 1-mm (reader 1, 93.3% and 78.6%; reader 2, 95.0% and 81.0%). Ten-millimeter MIP images are extremely efficient for detecting SNs. Three-millimeter MinIP images are more useful for visualizing SSNs, the efficiency being comparable to that achieved by use of 1-mm axial images.
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http://dx.doi.org/10.2214/AJR.19.21325DOI Listing
September 2019

[Clinical effect of exogenous pulmonary surfactant in the treatment of severe neonatal infectious pneumonia: a multicenter prospective clinical trial].

Zhongguo Dang Dai Er Ke Za Zhi 2019 Apr;21(4):327-331

Department of Neonatology, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing 100021, China.

Objective: To study the clinical effect of calsurf, a domestic exogenous pulmonary surfactant, in the treatment of severe neonatal infectious pneumonia.

Methods: A total of 208 neonates with severe infectious pneumonia who hospitalized in 5 hospitals of China were enrolled. According to their parents' wishes on admission, these neonates were administered with conventional treatment (control group; n=81) and calsurf  treatment + conventional treatment (calsurf treatment group, n=127). The two groups were compared in terms of the degree of oxygen dependence on admission, blood gas parameters before and after treatment, lung ultrasound results, duration of mechanical ventilation, length of hospital stay, hospital costs, complications and prognosis.

Results: Compared with the control group on admission, the calsurf treatment group had significantly higher inhaled oxygen concentration and partial pressure of carbon dioxide and significantly lower arterial partial pressure of oxygen and oxygenation index (P<0.01). After 1 hour of treatment, both groups had significant improvements in the above indices (P<0.05), and the improvements were more significant in the calsurf treatment group (P<0.05). After 4-6 hours of calsurf administration, there was a significant reduction in the degree of pulmonary consolidation. The calsurf treatment group had significantly shorter duration of mechanical ventilation and length of hospital stay than the control group, while there was no significant difference in the incidence rate of complications between the two groups. The neonates of both groups had a good prognosis.

Conclusions: In neonates with severe infectious pneumonia, calsurf treatment can significantly improve oxygenation, reduce the degree of pulmonary consolidation, and shorten the duration of mechanical ventilation and length of hospital stay. Therefore, it should be considered in neonates with severe infectious pneumonia.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7389218PMC
April 2019

A new triterpenoid glucoside from .

Nat Prod Res 2020 Jul 28;34(13):1874-1878. Epub 2019 Jan 28.

Key Laboratory of Tropical Medicinal Plant Chemistry of Ministry of Education, Hainan Normal University, Haikou, P.R.China.

A new triterpenoid glucoside, leuctriterpencoside (), along with two known compounds () were isolated from The structure of the new compound was elucidated using comprehensive spectroscopic methods. Compound showed significant inhibitory activity against α-glucosidase (IC value of 0.85 ± 0.12 M).
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http://dx.doi.org/10.1080/14786419.2019.1566820DOI Listing
July 2020

Isorhamnetin suppresses PANC-1 pancreatic cancer cell proliferation through S phase arrest.

Biomed Pharmacother 2018 Dec 26;108:925-933. Epub 2018 Sep 26.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address:

Isorhamnetin, a flavonoid ingredient derived from Vernonia anthelmintica (L.) Willd., has shown a spectrum of antitumor activity. However, the chemopreventive potential of isorhamnetin on advanced pancreatic cancer and the underlying molecular mechanism remain unknown. In the current study, treatment of the advanced pancreatic adenocarcinoma cell line PANC-1 with isorhamnetin resulted in robust cell growth arrest. PI-annexin V double staining and Hoechst 33258 staining revealed that isorhamnetin moderately induced early apoptosis without morphological alterations of nuclei. Instead, isorhamnetin caused cell cycle S-phase arrest through downregulation of cyclin A. In addition, isorhamnetin decreased the phosphorylation levels of MEK and ERK in the Ras/MAPK pathway, which is involved in regulating cell proliferation, differentiation and apoptosis. Wound-healing experiments demonstrated isorhamnetin significantly reduced the migratory behavior of PANC-1 cells. Altogether, the present study suggests that isorhamnetin may be a potential agent for prevention of pancreatic carcinoma.
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http://dx.doi.org/10.1016/j.biopha.2018.09.105DOI Listing
December 2018

Design, synthesis and pharmacological evaluation of a novel PEG-cRGD-conjugated irinotecan derivative as potential antitumor agent.

Eur J Med Chem 2018 Oct 31;158:82-90. Epub 2018 Aug 31.

School of Pharmacy, Guilin Medical University, Guilin, 541004, China; Department of Chemistry & Pharmaceutical Science, Guilin Normal College, Guangxi, 541001, China; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, Guilin, 541004, China. Electronic address:

A novel PEG-cRGD-conjugated irinotecan derivative BGC0222 was designed and synthesized as antitumor agent. Antitumor activity screening assay indicated that BGC0222 exhibited better in vitro antiproliferation activity than irinotecan and NKTR-102 against HT29, MIA PaCa-2 and MCF-7 tumor cell lines, with IC of 1.83 ± 0.09 μM, 3.95 ± 0.16 μM and 0.68 ± 0.04 μM, respectively, while it displayed better in vivo antiproliferation activity than irinotecan and NKTR-102 in HT-29, MIA PaCa-2, NCI-H446, U-87 MG and MDA-MB-231 xenograft models. The action mechanism of BGC0222 was then investigated by integrin-binding competition (IBC) and chick chorioallantoic membrane (CAM) angiogenesis assays, which indicated that BGC0222 may exert antitumor activity by binding to αβ target and consequently inducing neovascularization effect. Pharmacokinetic analysis showed that BGC0222 could slowly and steadily release irinotecan, which was subsequently metabolized into 7-ethyl-10-hydroxycamptothecin (SN-38) in the whole blood.
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http://dx.doi.org/10.1016/j.ejmech.2018.08.091DOI Listing
October 2018

Steroid-associated osteonecrosis animal model in rats.

J Orthop Translat 2018 Apr 6;13:13-24. Epub 2018 Feb 6.

Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.

Objective: Established preclinical disease models are essential for not only studying aetiology and/or pathophysiology of the relevant diseases but more importantly also for testing prevention and/or treatment concept(s). The present study proposed and established a detailed induction and assessment protocol for a unique and cost-effective preclinical steroid-associated osteonecrosis (SAON) in rats with pulsed injections of lipopolysaccharide (LPS) and methylprednisolone (MPS).

Methods: Sixteen 24-week-old male Sprague-Dawley rats were used to induce SAON by one intravenous injection of LPS (0.2 mg/kg) and three intraperitoneal injections of MPS (100 mg/kg) with a time interval of 24 hour, and then, MPS (40 mg/kg) was intraperitoneally injected three times a week from week 2 until sacrifice. Additional 12 rats were used as normal controls. Two and six weeks after induction, animals were scanned by metabolic dual energy X-ray absorptiometry for evaluation of tissue composition; serum was collected for bone turnover markers, Microfil perfusion was performed for angiography, the liver was collected for histopathology and bilateral femora and bilateral tibiae were collected for histological examination.

Results: Three rats died after LPS injection, i.e., with 15.8% (3/19) mortality. Histological evaluation showed 100% incidence of SAON at week 2. Dual energy X-ray absorptiometry showed significantly higher fat percent and lower lean mass in SAON group at week 6. Micro-computed tomography (Micro-CT) showed significant bone degradation at proximal tibia 6 weeks after SAON induction. Angiography illustrated significantly less blood vessels in the proximal tibia and significantly more leakage particles in the distal tibia 2 weeks after SAON induction. Serum amino-terminal propeptide of type I collagen and osteocalcin were significantly lower at both 2 and 6 weeks after SAON induction, and serum carboxy-terminal telopeptide was significantly lower at 6 weeks after SAON induction. Histomorphometry revealed significantly lower osteoblast surface and higher marrow fat fraction and oedema area in SAON group. Hepatic oedema appeared 2 weeks after SAON induction, and lipid accumulation appeared in the liver of SAON rats 6 weeks after SAON induction.

Conclusion: The present study successfully induced SAON in rats with pulsed injection of LPS and MPS, which was well simulating the clinical feature and pathology. Apart from available large animal models, such as bipedal emus or quadrupedal rabbits, our current SAON small model in rats could be a cost-effective preclinical experimental model to study body metabolism, molecular mechanism of SAON and potential drugs developed for prevention or treatment of SAON.

The Translational Potential Of This Article: The present study successfully induced SAON in a small animal model in rats with pulsed injection of LPS and MPS. The evaluation protocols with typical histopathologic ON features and advanced evaluation approaches to identify the metabolic disorders of SAON could be used in future rat SAON studies. The SAON rat model is a suitable and cost-effective animal model to study molecular mechanism of SAON and potential drugs developed for prevention and treatment of SAON.
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http://dx.doi.org/10.1016/j.jot.2018.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892381PMC
April 2018

Aldehyde dehydrogenase 2 Glu504Lys variant predicts a worse prognosis of acute coronary syndrome patients.

J Cell Mol Med 2018 04 14;22(4):2518-2522. Epub 2018 Feb 14.

Department of Emergency Medicine and Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.

Aldehyde dehydrogenase 2 (ALDH2) Glu504Lys variant was an independent risk factor for acute coronary syndrome (ACS). However, there are lacking researches about the relationship between the variant and prognosis of ACS. In the prospective study, 377 ACS patients were grouped into the wild-type (*1/*1) and the mutation (*2/*2 + *1/*2) groups according to genotype detection. Compared with the wild-type group, incidences of major adverse cardiac events (MACE) and cardiac death were both higher in the mutation group (9.2% vs 21.0%, P = .002; 5.2% vs 12.2%, P = .026); the MACE-free and the cardiac-death-free cumulative survival rates were obviously lower in the mutation group. Moreover, the mutant genotypes were associated with significantly increased risk of MACE and cardiac death (HR 2.443, 95%CI: 1.390-4.296, P = .002; HR 2.727, 95%CI: 1.303-5.708, P = .008). These results suggested that ALDH2 Glu504Lys variant could predict a worse prognosis of ACS patients.
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http://dx.doi.org/10.1111/jcmm.13536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867093PMC
April 2018