Publications by authors named "Leilei Chen"

152 Publications

Corrigendum: Total Flavonoids of Rhizoma Drynariae Promotes Differentiation of Osteoblasts and Growth of Bone Graft in Induced Membrane Partly by Activating Wnt/β-Catenin Signaling Pathway.

Front Pharmacol 2021 16;12:726831. Epub 2021 Jul 16.

First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.

[This corrects the article DOI: 10.3389/fphar.2021.675470.].
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http://dx.doi.org/10.3389/fphar.2021.726831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322677PMC
July 2021

MRI study of changes in knee bone marrow edema-like signal in asymptomatic amateur marathon runners before and after half-marathon running.

Clin Imaging 2021 May 18;80:150-157. Epub 2021 May 18.

Department of Radiology, The Affiliated Hospital of Hangzhou Normal University, No. 126, Wenzhou Road, Gongshu District, Hangzhou 310000, Zhejiang, China.

Objective: To evaluate the incidence of knee bone marrow edema-like signal and its changes before and after running a half marathon running in asymptomatic amateur marathon runners to explore the impact of the half marathon on knee bone marrow edema-like signal.

Methods: 50 asymptomatic amateur marathon runners (30 males, 20 females) were recruited. T1-weighted imaging (T1WI), fat-suppressed protein density weighted imaging (fs-PDWI) and three-dimensional double-echo steady-state (3D-DESS) sequence on the right knee were performed before and within 3 h after a half-marathon running. 20 healthy volunteers were recruited as control. According to the whole-organ magnetic resonance imaging score (WORMS) system, the involvement of bone marrow edema-like signal in 15 regions of knee was graded from 0 to 3. The results were classified and Mann Whitney U test was used for comparison between groups.

Results: The total incidence of bone marrow edema-like signal in amateur marathon group was 62%. Among them, the incidence of grade 1-3 was 48% (24/50), 12% (6/50), 2% (1/50), respectively, which was statistically significant compared with the controls (P = 0.007). There was no significant difference between gender before running (P = 0.172) and after running (P = 0.162). There was no significant difference before and after running (P > 0.05). However, 3 subjects showed new lesions, 8 subjects showed progression and 4 subjects showed decreased signal.

Conclusion: The occurrence of knee bone marrow edema-like signal in amateur marathon runners is more common. The lesions of bone marrow edema-like signal will show aggravation or improvement in a certain extent after the half marathon.
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http://dx.doi.org/10.1016/j.clinimag.2021.05.005DOI Listing
May 2021

LRRK2-NFATc2 Pathway Associated with Neuroinflammation May Be a Potential Therapeutic Target for Parkinson's Disease.

J Inflamm Res 2021 16;14:2583-2586. Epub 2021 Jun 16.

Institute of Brain Science and Disease, Qingdao University, Qingdao, People's Republic of China.

Neuroinflammation plays an important role in the pathogenesis of Parkinson's disease (PD). However, the molecular mechanisms involved in extracellular α‑synuclein-induced proinflammatory microglial responses through Toll-like receptor 2 (TLR2) are unclear. Leucine-rich repeat kinase 2 (LRRK2) is a serine/threonine kinase, and its mutations are closely related to autosomal dominant PD. Recently, Masliah et al characterized a novel-specific neuroinflammation cascade dependent on LRRK2-NFATc2 in microglia activated by neuron-released α-synuclein. LRRK2 selectively phosphorylated and induced nuclear translocation of NFATc2 to activate a neuroinflammation cascade. In this cascade, LRRK2 kinase was activated by neuron-released α-synuclein in microglia via TLR2. Further, NFATc2, as a kinase substrate for LRRK2, was directly phosphorylated, which accelerated nuclear translocation of NFATc2, where cytokine/chemokine gene expression including TNF-α and IL-6 is regulated by NFATc2 transcriptional activity, resulting in a neurotoxic inflammatory environment. Moreover, an abnormal increase of NFATc2 in nuclear was observed in the brains of patients and a mouse model of PD. Additionally, the administration of an LRRK2 inhibitor could ameliorate neuroinflammation, prevent neuronal loss, and improve motor function. Therefore, modulation of LRKK2-NFATc2 signaling cascade might be a potential therapeutic target for the treatment of PD.
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http://dx.doi.org/10.2147/JIR.S301531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217840PMC
June 2021

Total Flavonoids of Rhizoma Drynariae Promotes Differentiation of Osteoblasts and Growth of Bone Graft in Induced Membrane Partly by Activating Wnt/β-Catenin Signaling Pathway.

Front Pharmacol 2021 26;12:675470. Epub 2021 May 26.

First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.

Total flavonoids of Rhizoma drynariae (TFRD), a Chinese medicine, is widely used in the treatment of fracture, bone defect, osteoporosis and other orthopedic diseases, and has achieved good effects. Purpose of this trial was to explore efficacy of TFRD on bone graft's mineralization and osteoblasts' differentiation in Masquelet induced membrane technique in rats. Forty male Sprague-Dawley rats were randomly divided into high dose group (H-TFRD), middle dose group (M-TFRD), low dose group (L-TFRD) and control group (control). The critical size bone defect model of rats was established with 10 rats in each group. Polymethyl methacrylate (PMMA) spacer was implanted into the defect of right femur in rats. After the formation of the induced membrane, autogenous bone was implanted into the induced membrane. After 12 weeks of bone graft, bone tissues in the area of bone graft were examined by X-ray, Micro-CT, hematoxylin-eosin (HE) and Masson trichrome staining to evaluate the growth of the bone graft. The -catenin, c-myc, COL1A1, BMP-2 and OPN in bone graft were quantitatively analyzed by Western blot and Immunohistostaining. Osteoblasts were cultured in the medium containing TFRD. Cell Counting Kit-8 (CCK-8) method, Alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining, Western blot, RT-PCR and other methods were used to detect the effects of TFRD on the proliferation of osteoblasts and the regulation of Wnt/β-catenin signaling pathway. experiments showed that the growth and mineralization of bone graft in TFRD group was better. Moreover, the expression of Wnt/β-catenin and osteogenesis-related proteins in bone tissue of TFRD group was more than that in other groups. experiments indicated that osteoblasts proliferated faster, activity of ALP was higher, number of mineralized nodules and proteins related to osteogenesis were more in TFRD group. But blocking Wnt/β-catenin signaling pathway could limit these effects. Therefore, TFRD could promote mineralization of bone graft and differentiation of osteoblasts in a dose-dependent manner during growing period of the bone graft of induced membrane technique, which is partly related to the activation of Wnt/β-catenin signaling pathway.
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http://dx.doi.org/10.3389/fphar.2021.675470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188237PMC
May 2021

HNRNPM controls circRNA biogenesis and splicing fidelity to sustain cancer cell fitness.

Elife 2021 Jun 2;10. Epub 2021 Jun 2.

Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.

High spliceosome activity is a dependency for cancer cells, making them more vulnerable to perturbation of the splicing machinery compared to normal cells. To identify splicing factors important for prostate cancer (PCa) fitness, we performed pooled shRNA screens in vitro and in vivo. Our screens identified heterogeneous nuclear ribonucleoprotein M (HNRNPM) as a regulator of PCa cell growth. RNA- and eCLIP-sequencing identified HNRNPM binding to transcripts of key homeostatic genes. HNRNPM binding to its targets prevents aberrant exon inclusion and backsplicing events. In both linear and circular mis-spliced transcripts, HNRNPM preferentially binds to GU-rich elements in long flanking proximal introns. Mimicry of HNRNPM-dependent linear-splicing events using splice-switching-antisense-oligonucleotides was sufficient to inhibit PCa cell growth. This suggests that PCa dependence on HNRNPM is likely a result of mis-splicing of key homeostatic coding and non-coding genes. Our results have further been confirmed in other solid tumors. Taken together, our data reveal a role for HNRNPM in supporting cancer cell fitness. Inhibition of HNRNPM activity is therefore a potential therapeutic strategy in suppressing growth of PCa and other solid tumors.
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http://dx.doi.org/10.7554/eLife.59654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346284PMC
June 2021

Targeting RNA editing of antizyme inhibitor 1: A potential oligonucleotide-based antisense therapy for cancer.

Mol Ther 2021 May 8. Epub 2021 May 8.

Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, Singapore 117599, Singapore; NUS Center for Cancer Research, Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore 117594, Singapore; Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 4 Medical Drive, Singapore 117594, Singapore. Electronic address:

Dysregulated adenosine-to-inosine (A-to-I) RNA editing is implicated in various cancers. However, no available RNA editing inhibitors have so far been developed to inhibit cancer-associated RNA editing events. Here, we decipher the RNA secondary structure of antizyme inhibitor 1 (AZIN1), one of the best-studied A-to-I editing targets in cancer, by locating its editing site complementary sequence (ECS) at the 3' end of exon 12. Chemically modified antisense oligonucleotides (ASOs) that target the editing region of AZIN1 caused a substantial exon 11 skipping, whereas ECS-targeting ASOs effectively abolished AZIN1 editing without affecting splicing and translation. We demonstrate that complete 2'-O-methyl (2'-O-Me) sugar ring modification in combination with partial phosphorothioate (PS) backbone modification may be an optimal chemistry for editing inhibition. ASO3.2, which targets the ECS, specifically inhibits cancer cell viability in vitro and tumor incidence and growth in xenograft models. Our results demonstrate that this AZIN1-targeting, ASO-based therapeutics may be applicable to a wide range of tumor types.
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http://dx.doi.org/10.1016/j.ymthe.2021.05.008DOI Listing
May 2021

Corynoxine Protects Dopaminergic Neurons Through Inducing Autophagy and Diminishing Neuroinflammation in Rotenone-Induced Animal Models of Parkinson's Disease.

Front Pharmacol 2021 13;12:642900. Epub 2021 Apr 13.

Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.

Recent studies have shown that impairment of autophagy is related to the pathogenesis of Parkinson's disease (PD), and small molecular autophagy enhancers are suggested to be potential drug candidates against PD. Previous studies identified corynoxine (Cory), an oxindole alkaloid isolated from the Chinese herbal medicine (Miq.) Jacks, as a new autophagy enhancer that promoted the degradation of α-synuclein in a PD cell model. In this study, two different rotenone-induced animal models of PD, one involving the systemic administration of rotenone at a low dosage in mice and the other involving the infusion of rotenone stereotaxically into the pars compacta (SNpc) of rats, were employed to evaluate the neuroprotective effects of Cory. Cory was shown to exhibit neuroprotective effects in the two rotenone-induced models of PD by improving motor dysfunction, preventing tyrosine hydroxylase (TH)-positive neuronal loss, decreasing α-synuclein aggregates through the mechanistic target of the rapamycin (mTOR) pathway, and diminishing neuroinflammation. These results provide preclinical experimental evidence supporting the development of Cory into a potential delivery system for the treatment of PD.
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http://dx.doi.org/10.3389/fphar.2021.642900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078868PMC
April 2021

An in situ TEM nanoindentation-induced new nanostructure in cadmium zinc telluride.

Nanoscale 2021 Apr 6;13(15):7169-7175. Epub 2021 Apr 6.

Key Laboratory for Precision and Non-Traditional Machining Technology of Ministry of Education, Dalian University of Technology, Dalian 116024, China.

Phase transformations occurring in a solid govern the structural and physical properties significantly. Nevertheless, deformation-induced phase transition in a soft-brittle solid has not been demonstrated yet. Soft-brittle cadmium zinc telluride (CZT) based instruments have produced technological breakthroughs in the semiconductor industry, and therefore their phase transformations have been widely investigated during the past 60 years. In this study, in situ transmission electron microscopy (TEM) nanoindentation was performed on CZT, and it was found that no brittle fracture occurred at a peak load of 41.9 μN, corresponding to a stress of 1.75 GPa. A new nanostructure induced by in situ TEM nanoindentation was observed, consisting of a single crystal, slip bands, stacking faults, a superlattice, a new tetragonal phase, and Moiré fringes. The new tetragonal phase was formed by partial Cd and Te atoms in the (111[combining macron]) plane slipping along the [1[combining macron]21[combining macron]] orientation, which was elucidated by ab initio simulations. It belongs to a tetragonal crystal system, and the lattice distances along the X and Y axes were 0.382 and 0.376 nm, respectively. Our findings provide new insights into the deformation-induced phase transformation for a soft-brittle solid, and have application potential in solar cells, radiation detectors, and medical imaging, quantum, flexible electronic and optoelectronic devices.
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http://dx.doi.org/10.1039/d1nr00447fDOI Listing
April 2021

Safety and efficacy of low-dose ticagrelor in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Platelets 2021 Apr 4:1-8. Epub 2021 Apr 4.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

It remains unclear whether low-dose ticagrelor offers better safety and similar efficacy for Asian patients with acute coronary syndromes (ACS). We aimed to compare the safety and effectiveness of low-dose ticagrelor vs standard-dose ticagrelor in Chinese patients with ACS undergoing percutaneous coronary intervention (PCI). In this observational cohort study, a total of 2110 ACS patients who were event-free at 3 months after the index PCI were divided into standard-dose ticagrelor (90 mg twice daily) (n = 1830) or low-dose ticagrelor (45 mg twice daily) (n = 280) on a background of aspirin 100 mg once daily for at least another 9 months. The primary end point was type 2, 3, or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) criteria over a 1-year follow-up period post-PCI. Predictors of the primary end point were identified. Both Cox regression and propensity score matching analyses were used. The cumulative incidence of BARC type 2, 3, or 5 bleeding was lower in the low-dose ticagrelor group vs the standard-dose group either before (adjusted HR 0.24; 95% CI 0.07-0.77; = .016) or after matching (HR 0.25; 95% CI 0.08-0.85; = .026). A composite of cardiac death, myocardial infarction, or stroke was not significantly different between the two groups (0.4% vs 0.9%, respectively). By multivariate analysis, only low-dose ticagrelor was a protected predictor of BARC type 2, 3, or 5 bleeding either before (HR 0.28, 95% CI 0.09-0.89) or after matching (HR 0.24, 95% CI 0.07-0.82). A low-dose regimen of ticagrelor might provide better safety than standard-dose ticagrelor in Chinese patients with ACS undergoing PCI.
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http://dx.doi.org/10.1080/09537104.2021.1909717DOI Listing
April 2021

Commentary: LncRNA-T199678 Mitigates α-Synuclein-Induced Dopaminergic Neuron Injury via miR-101-3p.

Front Aging Neurosci 2021 12;13:650840. Epub 2021 Mar 12.

Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Institute of Brain Science and Disease, Qingdao University, Qingdao, China.

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http://dx.doi.org/10.3389/fnagi.2021.650840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994253PMC
March 2021

Influence of heart rate and coronary artery calcification on image quality and diagnostic performance of coronary CT angiography: comparison between 96-row detector dual source CT and 256-row multidetector CT.

J Xray Sci Technol 2021 ;29(3):529-539

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

Background: CT-derived fractional flow reserve (FFRCT) and diagnostic accuracy rely on good image quality during coronary CT angiography (CCTA).

Objective: To investigate whether heart rate (HR) and coronary artery calcium (CAC) score decrease image quality and diagnostic performance of two advanced CT scanners including 96-row detector dual source CT (DSCT) and 256-row multidetector CT (MDCT).

Methods: First, 79 patients who underwent CCTA (42 with DSCT and 37 with MDCT) and invasive coronary angiography (ICA) are enrolled. Next, coronary segments with excellent image quality are evaluated and the percentage is calculated. Then, diagnostic accuracy in detecting significant diameter stenosis is presented with ICA as the reference standard.

Results: Compared with the DSCT, the percentage of coronary segments with excellent image quality is lower (P = 0.010) while diagnostic accuracy on per-segment level is improved (P = 0.037) using MDCT. CAC score≥400 is the only independent factor influencing the percentage of coronary segments with excellent image quality [odds ratio (OR): DSCT, 3.096 and MDCT, 1.982] and segmental diagnostic accuracy (OR: DSCT, 2.630 and MDCT, 2.336) for both scanners. HR≥70 bpm (OR: 5.506) is the independent factor influencing the percentage of coronary segments with excellent image quality with MDCT.

Conclulsion: During CCTA, CAC score≥400 still decreases the proportion of coronary segments with excellent image quality and diagnostic accuracy with advanced CT scanners. HR≥70 bpm is another factor causing image quality decreasing with MDCT.
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http://dx.doi.org/10.3233/XST-210837DOI Listing
January 2021

Alpha-Synuclein Handling by Microglia: Activating, Combating, and Worsening.

Neurosci Bull 2021 May 20;37(6):751-753. Epub 2021 Mar 20.

Institute of Brain Science and Disease, Qingdao University, Qingdao, 266071, China.

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http://dx.doi.org/10.1007/s12264-021-00651-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099942PMC
May 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Non-EBV infection-associated hemophagocytic lymphohistiocytosis: a distinct subgroup where pathogen-directed therapy is essential and favorable outcomes are expected.

Leuk Lymphoma 2021 07 13;62(7):1657-1663. Epub 2021 Feb 13.

Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

EBV is the most prevalent cause of infection-associated hemophagocytic lymphohistiocytosis (IAHLH), non-EBV IAHLH is observed clinically but less documented. We conducted a retrospective research enrolled 36 cases from 1/1/2015 to 31/12/2019. Intriguingly, 92% cases were immunocompetent individuals prior to the onset of HLH. Clinically, the cardinal features were prolonged high fever, splenomegaly and hemophagocytosis. Bicytopenia occurred in most patients, besides, liver dysfunction was characterized by increased transaminase, bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (γ-GGT) and lactate dehydrogenase (LDH). Immunomodulatory agents should be added to control the overwhelming inflammatory storm without delay. Once a certain pathogen was identified as the causative factor of HLH, cytotoxic agents were withdrawn, specific pathogen-directed treatment was initiated. Further, glucocorticoids were tapered off when a stable state of HLH was achieved. After treatment, about 70% patients were fully recovered without relapse. All in all, non-EBV IAHLH is a special group of HLH with admirable outcome.
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http://dx.doi.org/10.1080/10428194.2021.1885657DOI Listing
July 2021

MNK1 and MNK2 enforce expression of E2F1, FOXM1, and WEE1 to drive soft tissue sarcoma.

Oncogene 2021 Mar 9;40(10):1851-1867. Epub 2021 Feb 9.

Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.

Soft tissue sarcoma (STS) is a heterogeneous disease that arises from connective tissues. Clinical outcome of patients with advanced tumors especially de-differentiated liposarcoma and uterine leiomyosarcoma remains unsatisfactory, despite intensive treatment regimens including maximal surgical resection, radiation, and chemotherapy. MAP kinase-interacting serine/threonine-protein kinase 1 and 2 (MNK1/2) have been shown to contribute to oncogenic translation via phosphorylation of eukaryotic translation initiation factor 4E (eIF4E). However, little is known about the role of MNK1/2 and their downstream targets in STS. In this study, we show that depletion of either MNK1 or MNK2 suppresses cell viability, anchorage-independent growth, and tumorigenicity of STS cells. We also identify a compelling antiproliferative efficacy of a novel, selective MNK inhibitor ETC-168. Cellular responsiveness of STS cells to ETC-168 correlates positively with that of phosphorylated ribosomal protein S6 (RPS6). Mirroring MNK1/2 silencing, ETC-168 treatment strongly blocks eIF4E phosphorylation and represses expression of sarcoma-driving onco-proteins including E2F1, FOXM1, and WEE1. Moreover, combination of ETC-168 and MCL1 inhibitor S63845 exerts a synergistic antiproliferative activity against STS cells. In summary, our study reveals crucial roles of MNK1/2 and their downstream targets in STS tumorigenesis. Our data encourage further clinical translation of MNK inhibitors for STS treatment.
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http://dx.doi.org/10.1038/s41388-021-01661-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946644PMC
March 2021

Construction project risk prediction model based on EW-FAHP and one dimensional convolution neural network.

PLoS One 2021 9;16(2):e0246539. Epub 2021 Feb 9.

Sichuan University of Science and Engineering, the Artificial Intelligence Key Laboratory of Sichuan Province, Zigong, China.

In order to solve the problem of low accuracy of traditional construction project risk prediction, a project risk prediction model based on EW-FAHP and 1D-CNN(One Dimensional Convolution Neural Network) is proposed. Firstly, the risk evaluation index value of construction project is selected by literature analysis method, and the comprehensive weight of risk index is obtained by combining entropy weight method (EW) and fuzzy analytic hierarchy process (FAHP). The risk weight is input into the 1D-CNN model for training and learning, and the prediction values of construction period risk and cost risk are output to realize the risk prediction. The experimental results show that the average absolute error of the construction period risk and cost risk of the risk prediction model proposed in this paper is below 0.1%, which can meet the risk prediction of construction projects with high accuracy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246539PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872238PMC
July 2021

"3G" Trial: An RNA Editing Signature to Guide Gastric Cancer Chemotherapy.

Cancer Res 2021 May 8;81(10):2788-2798. Epub 2021 Feb 8.

Cancer Science Institute of Singapore, National University of Singapore, Singapore.

Gastric cancer cases are often diagnosed at an advanced stage with poor prognosis. Platinum-based chemotherapy has been internationally accepted as first-line therapy for inoperable or metastatic gastric cancer. To achieve greater benefits, selection of patients eligible for this treatment is critical. Although gene expression profiling has been widely used as a genomic classifier to identify molecular subtypes of gastric cancer and to stratify patients for different chemotherapy regimens, its prediction accuracy can be improved. Adenosine-to-inosine (A-to-I) RNA editing has emerged as a new player contributing to gastric cancer development and progression, offering potential clinical utility for diagnosis and treatment. Using a systematic computational approach followed by both validations and validations in The Cancer Genome Atlas (TCGA), we conducted a transcriptome-wide RNA editing analysis of a cohort of 104 patients with advanced gastric cancer and identified an RNA editing (GCRE) signature to guide gastric cancer chemotherapy. RNA editing events stood as a prognostic and predictive biomarker in advanced gastric cancer. A GCRE score based on the GCRE signature consisted of 50 editing sites associated with 29 genes, predicting response to chemotherapy with a high accuracy (84%). Of note, patients demonstrating higher editing levels of this panel of sites presented a better overall response. Consistently, gastric cancer cell lines with higher editing levels showed higher chemosensitivity. Applying the GCRE score on TCGA dataset confirmed that responders had significantly higher levels of editing in advanced gastric cancer. Overall, this newly defined GCRE signature reliably stratifies patients with advanced gastric cancer and predicts response from chemotherapy. SIGNIFICANCE: This study describes a novel A-to-I RNA editing signature as a prognostic and predictive biomarker in advanced gastric cancer, providing a new tool to improve patient stratification and response to therapy.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2872DOI Listing
May 2021

Locally activated mitophagy contributes to a "built-in" protection against early burn-wound progression in rats.

Life Sci 2021 Jul 23;276:119095. Epub 2021 Jan 23.

Department of Plastic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China. Electronic address:

Aims: Deep burn-wounds undergo a dynamic progression in the initial or periburn area after insults, and the zone of stasis is the crucial region suffering the deterioration, considered as salvageable. Few studies explored the role of mitochondria in this process. This study is to clarify a possible "built-in" protection of mitophagy.

Main Methods: A classic "comb" scald rat model was established. Histological and blood-flow observation were processed based on hematoxylin-eosin staining and laser analysis. Oxidative and apoptotic status were analyzed by commercial kits. Transmission-electron microscope, immunofluorescence staining, and western blot were applied to detect the mitophagy in the zone of stasis and potential regulators. Adenovirus-based gene-silence contributed to determine the role of HIF-1α as a regulatory mediator.

Key Findings: We found that burn-caused typical ischemia and histological deterioration in the zone of stasis, in parallel with increases in oxidative stress and apoptosis. Mitochondrial damage was involved in the aforementioned changes. Furthermore, we detected mitophagy in burn-wounds, which was contradictory to the burn-wound conversion. HIF-1α expression was closely related to the level of mitophagy, while BNIP3 and PARKIN are involved downstream.

Significance: We demonstrate that burn-induced mitochondrial impairment contributes to the mobilization of injurious mechanisms in the zone of stasis and that mitophagy provides a beneficial way to protect against burn-wound progression via the elimination of damaged mitochondria. Our findings offer insights into mitochondrial quality control in burn-wound progression and suggest the novel concept that HIF-1α may be a therapeutic target due to its possible regulation on BNIP3- or PARKIN-mediated mitophagy.
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http://dx.doi.org/10.1016/j.lfs.2021.119095DOI Listing
July 2021

New insights into interaction of proteins in extracellular polymeric substances of activated sludge with ciprofloxacin using quartz crystal microbalance with dissipation.

Chemosphere 2021 Jan 25;263:128044. Epub 2020 Aug 25.

Department of Civil and Environmental Engineering, Ningbo University, Ningbo, 315211, China.

Proteins in extracellular polymeric substances play a vital role in adsorbing organic contaminants in biological wastewater treatment processes, but there is still lack of a fast and effective approach to monitor their interaction. Quartz crystal microbalance with dissipation (QCM-D) was used to investigate the binding and viscoelastic properties of ciprofloxacin (CIP) on extracellular proteins from activated sludge by a two-step sequential deposition method. A saturated viscoelastic monolayer of proteins was formed on the crystal by injecting 500 mg L extracellular proteins. Binding of CIP with the extracellular proteins film followed the pseudo-first-order kinetic equation and Langmuir model, with the maximum binding capacity of 172.4 mg g. The binding mass, energy dissipation, and reaction rate constant increased with increasing CIP concentration. A strong binding was obtained at pH 5, suggesting electrostatic interactions as the dominating binding mechanism. Cations inhibited CIP binding with extracellular proteins, probably due to cations competition. Two binding periods were distinguished according to the viscoelastic properties of CIP layer: viscous binding in the initial period and elastic towards binding saturation. Results highlighted QCM-D as an effective and real-time technique to evaluate the role of extracellular proteins in contaminants removal.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128044DOI Listing
January 2021

The Potential Use of RNA-based Therapeutics for Breast Cancer Treatment.

Curr Med Chem 2021 ;28(25):5110-5136

Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.

Breast cancer is one of the most lethal cancers in women worldwide, and the development of efficient treatments faces several challenges. Breast cancer is characterized by histological and functional heterogeneity in aspects such as tumorigenesis, metastasis, and drug resistance. RNA therapy has emerged as a highly attractive class of drugs for the treatment and prevention of breast cancer. It might play remarkable regulatory roles in the treatment of targeted cells by either increasing or silencing expressions of specific proteins, and such features of RNA-based drugs cause high selectivity and low risk of off-target effect in breast cancer. RNA therapy exerts anti-proliferative and pro-apoptotic effects upon cell culture systems, animal models, and in clinical trials in most studies. In this mini-review, we outline the classifications, mechanisms, advantages, and challenges of RNA therapy and highlight its application in breast cancer treatment. Additionally, we summarize the clinical trials of RNA-targeting therapies and the development of anti-tumor RNA drugs and provide future directions for RNA therapeutics in breast cancer.
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http://dx.doi.org/10.2174/0929867327666201117100336DOI Listing
August 2021

Apelin-13 Protects Dopaminergic Neurons against Rotenone-Induced Neurotoxicity through the AMPK/mTOR/ULK-1 Mediated Autophagy Activation.

Int J Mol Sci 2020 Nov 8;21(21). Epub 2020 Nov 8.

Institute of Brain Science and Disease, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Qingdao University, Qingdao 266071, China.

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Several brain-gut peptides are able to exert neuroprotective effects on the nigrostriatal dopaminergic system. Apelin-13 is a neuropeptide, conveying potential neuroprotective activities. However, whether, and how, apelin-13 could antagonize rotenone-induced neurotoxicity has not yet been elucidated. In the present study, rotenone-treated SH-SY5Y cells and rats were used to clarify whether apelin-13 has protective effects on dopaminergic neurons, both in vivo and in vitro. The results showed that apelin-13 could protect SH-SY5Y cells from rotenone-induced injury and apoptosis. Apelin-13 was able to activate autophagy, and restore rotenone induced autophagy impairment in SH-SY5Y cells, which could be blocked by the autophagy inhibitor 3-Methyladenine. Apelin-13 activated AMPK/mTOR/ULK-1 signaling, AMPKα inhibitor compound C, as well as apelin receptor blockage via siRNA, which could block apelin-13-induced signaling activation, autophagy activation, and protective effects, in rotenone-treated SH-SY5Y cells. These results indicated that apelin-13 exerted neuroprotective properties against rotenone by stimulating AMPK/mTOR/ULK-1 signaling-mediated autophagy via the apelin receptor. We also observed that intracerebroventricular injection of apelin-13 could alleviate nigrostriatal dopaminergic neuron degeneration in rotenone-treated rats. Our findings provide new insights into the mechanism by which apelin-13 might attenuate neurotoxicity in PD.
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http://dx.doi.org/10.3390/ijms21218376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664695PMC
November 2020

Regulatory Networks of LncRNA MALAT-1 in Cancer.

Cancer Manag Res 2020 15;12:10181-10198. Epub 2020 Oct 15.

Department of Medical Genetics, Harbin Medical University, Harbin 150081, People's Republic of China.

Long noncoding (lnc)RNAs are a group of RNAs with a length greater than 200 nt that do not encode a protein but play an essential role in regulating the expression of target genes in normal biological contexts as well as pathologic processes including tumorigenesis. The lncRNA metastasis-associated lung adenocarcinoma transcript (MALAT)-1 has been widely studied in cancer. In this review, we describe the known functions of MALAT-1; its mechanisms of action; and associated signaling pathways and their clinical significance in different cancers. In most malignancies, including lung, colorectal, thyroid, and other cancers, MALAT-1 functions as an oncogene and is upregulated in tumors and tumor cell lines. MALAT-1 has a distinct mechanism of action in each cancer type and is thus at the center of large gene regulatory networks. Dysregulation of MALAT-1 affects cellular processes such as alternative splicing, epithelial-mesenchymal transition, apoptosis, and autophagy, which ultimately results in the abnormal cell proliferation, invasion, and migration that characterize cancers. In other malignancies, such as glioma and endometrial carcinoma, MALAT-1 functions as a tumor suppressor and thus forms additional regulatory networks. The current evidence indicates that MALAT-1 and its associated signaling pathways can serve as diagnostic or prognostic biomarker or therapeutic target in the treatment of many cancers.
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http://dx.doi.org/10.2147/CMAR.S276022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575067PMC
October 2020

Characterization and comparison of collagen extracted from the skin of the Nile tilapia by fermentation and chemical pretreatment.

Food Chem 2021 Mar 25;340:128139. Epub 2020 Sep 25.

Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Guangdong Provincial Engineering Technology Research Center of Marine Food, Key Laboratory of Advanced Processing of Aquatic Product of Guangdong Higher Education Institution, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China.

Chemical pretreatment of collagen raw materials is time-consuming and environmentally hazardous. Collagen extraction after fermentation pretreatment has not been reported. We extracted and characterized acid-soluble collagen (ASC) and pepsin-soluble collagen (PSC) from Nile tilapia (Oreochromis niloticus) skin following fermentation and chemical treatments and comparatively evaluated the feasibility of fermentation. Fermentation-ASC (FASC) and fermentation-PSC (FPSC) yields (4.76 and 8.14 wt%, respectively) were slightly but not significantly higher than chemical-ASC (CASC) and chemical-PSC (CPSC) yields (4.27 and 7.60 wt%, respectively). All extracts were identified as type I collagens by SDS-PAGE and retained their triple helical structure well, as confirmed through Fourier transform infrared spectroscopy. All collagen microstructures under scanning electron microscopy were multi-layered aggregates. These collagens also had similar biochemical properties (i.e. denatured between 36.5 and 37.1 °C, high soluble at pH 1-4 and at <3% [w/v] NaCl). Therefore, fermentation method is a viable alternative for pretreating collagen extraction materials.
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http://dx.doi.org/10.1016/j.foodchem.2020.128139DOI Listing
March 2021

Axonal Iron Transport might Contribute to Iron Deposition in Parkinson's Disease.

Neurosci Bull 2021 02 22;37(2):275-277. Epub 2020 Sep 22.

Institute of Brain Science and Disease, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Qingdao University, Qingdao, 266071, China.

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http://dx.doi.org/10.1007/s12264-020-00585-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870726PMC
February 2021

Occurrence, distribution, and health risk assessment of 20 personal care products in indoor and outdoor swimming pools.

Chemosphere 2020 Sep 25;254:126872. Epub 2020 Apr 25.

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

The distribution of 20 personal care products (PCPs), including seven preservatives, six UV filters, five anticorrosion agents, and two antimicrobials, were determined in 40 swimming pools using solid phase extraction followed by liquid chromatography-tandem mass spectrometry. Among 14 targets detected, 1H-benzotriazole and triclocarban were observed in all samples. The detected concentrations of preservatives, UV filters, anticorrosion agents, and antimicrobials were in the ranges of not detected (nd)-179 ng L, nd-289 ng L, nd-58.4 ng L, and nd-56.9 ng L, respectively. The presence of preservatives, UV filters and antimicrobials in pool waters might be mainly brought in by human activities while anticorrosion agents were mainly from the source water. Furthermore, the concentrations of methylparaben, ethylparaben, 1H-benzotriazole, 5-methyl-1H-benzotriazole, 5-chloro-1H-benzotriazole, and 5,6-dimethyl-1H-benzotriazole in indoor pools were found higher than those in outdoor pools. The longer opening time and weaker light intensity for indoor pools might cause the difference. The redundancy analysis showed significantly negative correlations between the concentrations of parabens and the contents of residual chlorine in the pool waters. A higher chlorine residue may promote the decomposition of parabens. Health risk assessment showed that skin penetration would be the main approach for the intake of PCPs by swimmers while swimming. Compared with the non-athletic swimmers, the athletic swimmers might be more sensitive, but the health risks for both groups of swimmers could be negligible.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126872DOI Listing
September 2020

Effects of proximal fibular osteotomy on stress changes in mild knee osteoarthritis with varus deformity: a finite element analysis.

J Orthop Surg Res 2020 Sep 3;15(1):375. Epub 2020 Sep 3.

The Lab of Orthopaedics of Chinese Medicine of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China.

Background: Many previous studies lack sufficient quantitative evidences about changes in biomechanical properties of the knee in response to proximal fibular osteotomy (PFO). Therefore, the aim of this study was to compare the preoperative and postoperative effects of PFO on mechanical stresses in the knee joint and provide with a biomechanical basis for PFO in the treatment of mild knee osteoarthritis (KOA) with varus deformity.

Methods: A total of 10 patients suffering mild KOA with varus deformity were enrolled in this study. Their image data from computerized tomography (CT) and magnetic resonance imaging (MRI) were used for finite element models, and PFO models were established. Static structural analysis was carried out using ABAQUS to compare the von Mises stress distribution and values of the maximal von Mises stress of femoral cartilage, meniscuses, tibial cartilages, and tibial plateau before and after surgery.

Results: The stress distribution in the cortical bone of the tibial plateau showed that stresses were transferred from the anterior medial area to the posterior medial area after PFO. Values of the maximal von Mises stress in femoral cartilage, medial meniscus, medial tibial cartilage, and tibial plateau after surgery were significantly lower than the preoperative values, with statistically significant differences (P < 0.05). Postoperative values of the maximal von Mises stress of lateral meniscus and lateral tibial cartilage were significantly higher than the preoperative ones, with statistically significant differences (P < 0.05).

Conclusion: PFO could reduce the stresses in the medial compartment of the knee joint with stress pathways transferring from the anterior medial area to the posterior medial area of the tibial plateau. Therefore, PFO is recommended for the treatment of mild KOA with varus deformity featuring favorably pain-relieving effects.
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http://dx.doi.org/10.1186/s13018-020-01894-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469409PMC
September 2020

New insights into the structure-activity relationships of antioxidative peptide PMRGGGGYHY.

Food Chem 2021 Feb 29;337:127678. Epub 2020 Jul 29.

School of Life Sciences, Central South University, Changsha 410013, China. Electronic address:

The sequence and structure of antioxidant peptides play fundamental roles in their antioxidant functions. However, the structural mechanism of antioxidant peptides is still unclear. In this study, we used quantum calculations to reveal the antioxidant mechanism of the peptide PMRGGGGYHY. PMRGGGGYHY has multiple antioxidant active sites, and two tyrosine residues were determined to be the major active sites. Based on the structure-activity relationships of PMRGGGGYHY, the antioxidant activity of the modified peptide significantly improved by 4.8-fold to 9.73 ± 0.61 μmol TE/μmol. In addition, the removal of glycine residues from PMRGGGGYHY would increase the energy of the HOMOs and simplify the hydrogen bonding network, causing a significant increase in antioxidant activity. The intracellular ROS scavenging ability gradually decreased with decreasing glycine content. This same peptide has very different effects in vitro versus as a cellular antioxidant. This paper provides new insights into the structural mechanism and rational design/modification of novel antioxidant peptides.
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http://dx.doi.org/10.1016/j.foodchem.2020.127678DOI Listing
February 2021

RNA editing mediates the functional switch of COPA in a novel mechanism of hepatocarcinogenesis.

J Hepatol 2021 01 18;74(1):135-147. Epub 2020 Jul 18.

Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore; Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore. Electronic address:

Background & Aims: RNA editing introduces nucleotide changes in RNA sequences. Recent studies have reported that aberrant adenosine-to-inosine RNA editing is implicated in cancers. Until now, very few functionally important protein-recoding editing targets have been discovered. Here, we investigated the role of a recently discovered protein-recoding editing target COPA (coatomer subunit α) in hepatocellular carcinoma (HCC).

Methods: Clinical implication of COPA editing was studied in a cohort of 125 HCC patients. CRISPR/Cas9-mediated knockout of the editing site complementary sequence (ECS) was used to delete edited COPA transcripts endogenously. COPA editing-mediated change in its transcript or protein stability was investigated upon actinomycin D or cycloheximide treatment, respectively. Functional difference in tumourigenesis between wild-type and edited COPA (COPAvs. COPA) and the exact mechanisms were also studied in cell models and mice.

Results: ADAR2 binds to double-stranded RNA formed between edited exon 6 and the ECS at intron 6 of COPA pre-mRNA, causing an isoleucine-to-valine substitution at residue 164. Reduced editing of COPA is implicated in the pathogenesis of HCC, and more importantly, it may be involved in many cancer types. Upon editing, COPA switches from a tumour-promoting gene to a tumour suppressor that has a dominant-negative effect. Moreover, COPA may undergo protein conformational change and therefore become less stable than COPA. Mechanistically, COPA may deactivate the PI3K/AKT/mTOR pathway through downregulation of caveolin-1 (CAV1).

Conclusions: We uncover an RNA editing-associated mechanism of hepatocarcinogenesis by which downregulation of ADAR2 caused the loss of tumour suppressive COPA and concurrent accumulation of tumour-promoting COPA in tumours; a rapid degradation of COPA protein and hyper-activation of the PI3K/AKT/mTOR pathway further promote tumourigenesis.

Lay Summary: RNA editing is a process in which RNA is changed after it is made from DNA, resulting in an altered gene product. In this study, we found that RNA editing of a gene known as coatomer subunit α (COPA) is lower in tumour samples and discovered that this editing process changes COPA protein from a tumour-promoting form to a tumour-suppressive form. Loss of the edited COPA promotes the development of liver cancer.
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http://dx.doi.org/10.1016/j.jhep.2020.07.021DOI Listing
January 2021

Multimodal theranostics augmented by transmembrane polymer-sealed nano-enzymatic porous MoS nanoflowers.

Int J Pharm 2020 Aug 4;586:119606. Epub 2020 Jul 4.

Minhang Hospital and School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai 201203, China. Electronic address:

Developing an all-in-one multimodal theranostic platform that can synergistically integrate sensitive photoacoustic (PA) imaging, enhanced photothermal therapy (PTT) and photodynamic therapy (PDT) as well as the nano-enzyme activated chemodynamic therapy (CDT) presents a great challenge for the current nanomedicine design. Herein, a simple hydrothermal method was used to prepare porous molybdenum disulfide (MoS) nanoflowers. These nanoflowers were assembled by three dimensional (3D)-stacked MoS nanosheets with plentiful pores and large surfaces, which thus exhibited enhanced photothermal conversion via light trapping and peroxidase (POD)-like activity via active defects exposure. Consequently, this 3D-MoS nanostructure could be well-sealed by polyethylene glycol-polyethylenimine polymer modified with nucleolar translocation signal sequence of the LIM Kinase 2 protein (LNP) via strong electrostatic interaction, which not only benefited to stably deliver anticancer drug doxorubicin (DOX) into the tumor cells for pH/NIR-responsive chemotherapy, but also provided strong photoacoustic, photothermal performances and stimulated generation of reactive oxygen species (ROS) for imaging-guided PTT/PDT/CDT combined therapy. This work promised a simple all-in-one multimodal theranostic platform to augment the potential antitumoral therapeutic outcomes.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119606DOI Listing
August 2020

Can Clinical and Functional Outcomes Be Improved with an Intelligent "Internet Plus"-Based Full Disease Cycle Remote Ischemic Conditioning Program in Acute ST-elevation Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention? Rationale and Design of the i-RIC Trial.

Cardiovasc Drugs Ther 2020 Jun 30. Epub 2020 Jun 30.

Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, No.300 Guangzhou Road, Nanjing, 210029, China.

Background: Acute ST-elevation myocardial infarction (STEMI) is associated with a high incidence of complications as well as a considerable hospitalization rate and economic burden. Preliminary evidence suggests that remote ischemic conditioning (RIC) is a promising non-invasive intervention that may effectively and safely reduce myocardial infarct size, subsequent cardiac events and complications, and mortality. However, RIC's cardio-protective effect remains under debate, especially for single timepoint RIC programs. Adequately powered large-scale randomized controlled trials investigating clinical outcomes are thus needed to clarify the role of full disease cycle RIC programs.

Methods: The intelligent "Internet Plus"-based full disease cycle remote ischemic conditioning (i-RIC) trial is a pragmatic, multicenter, randomized controlled, parallel group, clinical trial. The term, intelligent "Internet Plus"-based full disease cycle, refers to smart devices aided automatic and real-time monitoring of remote ischemic pre-, per- or post-conditioning intervention for patients with STEMI undergoing percutaneous coronary intervention (PCI). Based on this perspective, 4700 STEMI patients from five hospitals in China will be randomized to a control and an intervention group. The control group will receive PCI and usual care, including pharmacotherapy, before and after PCI. The intervention group will receive pre-, per-, and post-operative RIC combined with long-term i-RIC over a one-month period in addition. A smartphone application, an automated cuff inflation/deflation device and "Internet Plus"-based administration will be used in the long-term phase. The primary outcome is the combined cardiac death or hospitalization for heart failure rate. Secondary outcomes include clinical and functional outcomes: major adverse cardiac and cerebrovascular events rate, all-cause mortality, myocardial reinfarction rate, readmission rate for heart failure and ischemic stroke rate, unplanned revascularization rate, plasma concentration of myocardial infarction-related key biomarkers, infarct size, cardiac function, cardiopulmonary endurance, health-related quality of life, total hospital length of stay, total medical cost, and compliance with treatment regime.

Discussion: The i-RIC trial is designed to test the hypothesis that clinical and functional outcomes can be improved with the i-RIC program in STEMI patients undergoing PCI. The concept of RIC is expected to be enhanced with this intelligent "Internet Plus"-based program focusing on the full disease cycle. If the i-RIC program results in superior improvement in primary and secondary outcomes, it will offer an innovative treatment option for STEMI patients and form the basis of future recommendations.

Clinical Trial Registration: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ): ChiCTR2000031550, 04 April 2020.
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http://dx.doi.org/10.1007/s10557-020-07022-9DOI Listing
June 2020
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