Publications by authors named "Haiyang Yu"

379 Publications

Photo-assisted self-interference cancellation for in-band full-duplex radio-over-fiber system.

Appl Opt 2021 Apr;60(11):3021-3030

An optical approach to cancel the radio frequency self-interference for an in-band full-duplex radio-over-fiber system is proposed and experimentally demonstrated based on two Mach-Zehnder modulators and a balanced photodetector (BPD). The cancellation depth is larger than 50 dB and 24 dB for the single frequency and for a wideband signal, respectively. The application of the BPD eliminates the common mode noise and reduces no system flexibility because signal transmission is in one optical fiber by polarization multiplexing technology, instead of two fibers in the traditional self-interference cancellation system with a BPD. In addition, with no electrical delay and attenuation applied, the operational frequency band and cancellation depth are not confined by electronic devices.
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http://dx.doi.org/10.1364/AO.419023DOI Listing
April 2021

Hypoxic acclimation improves cardiac redox homeostasis and protects heart against ischemia-reperfusion injury through upregulation of O-GlcNAcylation.

Redox Biol 2021 Apr 30;43:101994. Epub 2021 Apr 30.

Laboratory of Mitochondria and Metabolism, Department of Anesthesiology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, 610041, China; Laboratory of Anesthesia and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, 610041, China. Electronic address:

Ischemia-reperfusion (I/R) injury is detrimental to cardiovascular system. Alteration in glucose metabolism has been recognized as an important adaptive response under hypoxic conditions. However, the biological benefits underlying this metabolic phenotype remain to be elucidated. This study was designed to investigate the impact of hypoxic acclimation (HA) on cardiac I/R injury and the antioxidative mechanism(s). Male adult mice were acclimated in a hypoxic chamber (10% oxygen [O]) for 8 h/day for 14 days, and then subjected to cardiac I/R injury by ligation of left anterior descending coronary artery for 30 min and reperfusion for 24 h or 7 days. Our results showed that HA attenuated oxidative stress and reduced infarct size in the I/R hearts. This cardioprotective effect is coupled with an elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification partially due to inflammatory stimulation. Hyperglycosylation activated glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme in the pentose phosphate pathway, resulting in an upregulation of NADPH/NADP and GSH/GSSG couples and enhancement of redox homeostasis in the heart. Pharmacological suppression of O-GlcNAcylation totally abolished the influence of HA on the G6PDH activity, redox balance and post-I/R damage in the hearts and cultured cardiomyocytes, whereby augmentation of O-GlcNAcylation further enhanced the benefits, suggesting a central role of O-GlcNAcylation in HA-initiated antioxidative and cardioprotective effects. These findings, therefore, identified HA as a promising anti-I/R strategy for the heart and proposed O-GlcNAc modification of G6PDH as a therapeutic target in ischemic heart disease.
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http://dx.doi.org/10.1016/j.redox.2021.101994DOI Listing
April 2021

Enhanced anti-PD-1 therapy in hepatocellular carcinoma by tumor vascular disruption and normalization dependent on combretastatin A4 nanoparticles and DC101.

Theranostics 2021 3;11(12):5955-5969. Epub 2021 Apr 3.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.

Anti-programmed cell death protein 1 (PD-1) therapy has shown promising efficacy in hepatocellular carcinoma (HCC), but its response rates in advanced HCC are lower than 20%. A critical reason for this is the imbalance between CD8 T cells and tumor burden. Here, a novel concept of vascular disruption and normalization dependent on a polymeric vascular disrupting agent (VDA) poly (-glutamic acid)--methoxy poly (ethylene glycol)/combretastatin A4 (CA4-NPs) + a vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) inhibitor DC101 is applied to improve anti-PD-1 therapy, wherein CA4-NPs reduce tumor burden and DC101 simultaneously increases the number of intratumoral CD8 T cells, successfully regulating the abovementioned imbalance in an H22 tumor model. Blood vessel density, tumor cell proliferation, and necrosis were evaluated to reveal the effects on reducing tumor burden by CA4-NP treatment. Pericyte coverage of blood vessels, tumor blood vessel perfusion, tumor hypoxia, and intratumoral immune cells were examined to verify their role in vascular normalization and immune cell homing of DC101. Furthermore, the effects of CA4-NPs + DC101 on reducing tumor burden and increasing the number of immune cells were studied. Finally, tumor suppression, intratumoral CD8 T cell activation, and the synergistic effects of anti-PD-1 combined with CA4-NPs + DC101 were verified. The tumor inhibition rate of anti-PD-1 antibody combined with CA4-NPs + DC101 reached 86.4%, which was significantly higher than that of anti-PD-1 (16.8%) alone. Importantly, the Q value reflecting the synergy between CA4-NPs + DC101 and anti-PD-1 was 1.24, demonstrating a strong synergistic effect. Furthermore, CA4-NPs + DC101 improved anti-PD-1 therapy by increasing the number of intratumoral CD8 T cells (anti-PD-1, 0.31% vs triple drug combination, 1.18%). These results reveal a novel approach to enhance anti-PD-1 therapy with VDAs + VEGF/VEGFR2 inhibitors in HCC.
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http://dx.doi.org/10.7150/thno.58164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058708PMC
April 2021

Structurally diverse triterpenes obtained from the fruits of Mill. as inflammation inhibitors by NF-κB signaling pathway.

Food Funct 2021 Apr 22. Epub 2021 Apr 22.

Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, 301617, Tianjin, China. zhwwxzh@ tjutcm.edu.cn and Institute of TCM, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, 301617, Tianjin, China.

Twenty-nine triterpenes were obtained from the fruits of Ziziphus jujuba Mill. through various chromatography methods, and their stereo-structures were confirmed by spectroscopic methods. Among them, 2α,3β,20-trihydroxylupane-28-oic acid (1) was identified as a new compound, and the 1H and 13C NMR data of 7, 8 and 23, as well as the 13C NMR data of 17 are reported here for the first time. Meanwhile, the nitric oxide (NO) inhibitory activities of all compounds were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. As results, compounds 2, 7, 10-13, 15, 16, 18-21, 26-29 were found to play important roles in suppressing NO production at 5 μM. The structure-activity relationships (SARs) on NO inhibition indicated that the ursolic and oleanolic acid skeletons, p-coumaroyl group substitution, six-membered A ring, and deoxygenation (loss of C[double bond, length as m-dash]O) in the C ring showed a more positive effect on the NO inhibitory activity of triterpenes, while the reduction of the A ring C[double bond, length as m-dash]O to OH was a negative factor. Moreover, it was found that compounds 15 and 19 could suppress the phosphorylation of IκBα and NF-κB/p65 to prevent it from shifting into the nucleus and downregulate the expression of inflammatory factors, such as iNOS, IL-6 and TNF-α. Our investigations revealed that the NO inhibitory effects of the active triterpenes obtained from Z. jujuba were mediated, at least in part, through the NF-κB signaling pathway.
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http://dx.doi.org/10.1039/d1fo00117eDOI Listing
April 2021

LncRNA SNHG16 contributes to osteosarcoma progression by acting as a ceRNA of miR-1285-3p.

BMC Cancer 2021 Apr 6;21(1):355. Epub 2021 Apr 6.

Department of Orthopedic, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.

Background: The long non-coding (lnc) RNA activated by small nucleolar RNA host gene 16 (SNHG16), which has been reported to play a vital role in a number of different types of cancer, is a novel lncRNA. However, following an osteosarcoma (OS) study, the expression pattern, biological roles, clinical values and potential molecular mechanism of SNHG16 remain unclear. In the current study, we aimed to examine its expression and possible function in osteosarcoma (OS).

Method: Cell proliferation was measured by colony formation assay and Cell Counting Kit-8 (CCK-8) in vitro, and xenograft transplantation assay in vivo. Meanwhile, we used transwell chambers to test cell migration and invasion was evaluated. Cell cycle and apoptosis was evaluated by flow cytometry assay. Immunoblotting and qPCR analysis was carried out to detect protein and gene expression, respectively. Luciferase reporter assay was used to predict the potential downstream genes.

Results: The present study demonstrated that SNHG16 is highly expressed in both the tissues of patients with OS, as well as OS cell lines, and its expression level was positively correlated with clinical stage and poor overall survival. Functional assays revealed that the depletion of SNHG16 inhibits OS growth, OS cell progression and promotes apoptosis both in vivo and in vitro. In addition, the present study revealed that microRNA-1285-3p expression levels can be decreased by SNHG16 acting as a 'sponge', and that this pathway takes part in OS tumor growth in vivo, and OS cell proliferation, invasion, migration and apoptosis in vitro.

Conclusions: The results from the present study demonstrate the role of lncRNA SNHG16 in OS progression, which is SNHG16 might exert oncogenic role in osteosarcoma (OS) by acting as a ceRNA of miR-1285-3p, and it may become a novel target in OS therapy.
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http://dx.doi.org/10.1186/s12885-021-07933-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022398PMC
April 2021

Regulation of PINX1 expression ameliorates lipopolysaccharide-induced lung injury and alleviates cell senescence during the convalescent phase through affecting the telomerase activity.

Aging (Albany NY) 2021 Mar 26;13(7):10175-10186. Epub 2021 Mar 26.

Intensive Care Unit, Qingdao Hospital of Traditional Chinese Medicine (Hiser Hospital), Qingdao 266033, Shandong Province, China.

PIN2/TERF1-interacting telomerase inhibitor 1 (PINX1) is necessary for telomerase reverse transcriptase (TERT) elements to bind at telomeres and non-telomere sites. We aimed to investigate the role of PINX1 and TERT in lipopolysaccharide (LPS)-induced lung injury during acute stage and convalescent phase. Lung injury rat model was induced, and the expression of PINX1 and TERT in serum and lung tissues was examined using RT-qPCR on day 0 (D0), D3, and D14, respectively. The pathologic changes of lung tissues on D3 and D14 were detected using hematoxylin and eosin staining after TERT overexpression, PINX1 overexpression, or PINX1 silencing in lung injury rats. Results revealed that TERT was persistently reduced on D3 and D14, while PINX1 was decreased on D3 but increased on D14. TERT overexpression and PINX1 silencing led to the most serious lung damage, the highest levels of inflammatory factors and apoptosis on D3, while the best recovery was observed on D14. Simultaneously, PINX1 overexpression presented the opposite effects at acute stage and convalescent phase. Co-immunoprecipitation (co-IP) assay verified the connection between PINX1 and TERT. Taken together, these findings demonstrated that regulation of PINX1 expression ameliorates lung injury and alleviates cell senescence during the convalescent phase through affecting the telomerase activity.
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http://dx.doi.org/10.18632/aging.202779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064186PMC
March 2021

Biochanin A Attenuates Ovariectomy-Induced Cognition Deficit Antioxidant Effects in Female Rats.

Front Pharmacol 2021 16;12:603316. Epub 2021 Mar 16.

Departments of Neuroscience and Behavioral Medicine and Psychiatry, Rockefeller Neurosciences Institute, West Virginia University Health Sciences Center, Morgantown, WV, United States.

Impairment of memory and cognition is one of the major symptoms in women with postmenopausal disorders due to estrogen deficiency, which accounts for the much higher prevalence of Alzheimer's disease in females. Biochanin A (BCA), a natural phytoestrogen, has been reported to protect neurons against ischemic brain injury. However, the neuroprotective effects of BCA in the postmenopausal-like model of ovariectomized (OVX) rats remain to be investigated. All the rats except for the sham group underwent the resection of bilateral ovaries. Seven days after the OVX surgery, rats were randomly divided into six groups: sham, OVX, OVX + BCA (5 mg/kg), OVX + BCA (20 mg/kg), OVX + BCA (60 mg/kg), and OVX + estradiol (E2; 0.35 mg/kg), which were administrated daily by gavage for 12 weeks. Learning and memory were examined using the Morris water-maze test before the end of the experiment. Morphological changes of the rat hippocampus were observed by HE staining and electron microscopy. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in the hippocampus were measured. The effect of BCA on cell viability was measured in the presence of hydrogen peroxide (HO) using CCK8. Flow cytometry was used to measure neuronal apoptosis and reactive oxygen species (ROS) induced by HO. Expression of Bcl-2, Bax, and Caspase-3 was determined by Western blotting using hippocampal tissues and primary cultures of hippocampal neurons. Chronic treatment with BCA mimicked the ability of E2 to reverse the deficit of learning and memory in the Morris water-maze test in OVX rats. BCA normalized OVX-induced morphological changes as revealed by HE staining and electron microscopy. In addition, BCA significantly decreased the levels of MDA, the biomarker of oxidative damage, and increased the activity of the intracellular antioxidant enzymes SOD and GSH-Px in OVX rats. Further, in primary cultures of hippocampal neurons, BCA reversed HO-induced decreases in cell viability and accumulation of ROS. Finally, BCA reversed OVX- or HO-induced increases in Bax and Caspase-3 and decreases in Bcl-2 in the hippocampus and primary cultures of hippocampal neurons. These results suggest that BCA improves memory through its neuroprotective properties in the brain under the circumstance of estrogen deficiency and can be used for treatment of memory loss in postmenopausal women.
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http://dx.doi.org/10.3389/fphar.2021.603316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010695PMC
March 2021

Determination of Trimethylamine -oxide and Betaine in Serum and Food by Targeted Metabonomics.

Molecules 2021 Mar 2;26(5). Epub 2021 Mar 2.

State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

Trimethylamine -oxide (TMAO), as a gut-derived metabolite, has been found to be associated with enhanced risk for atherosclerosis and cardiovascular disease. We presented a method for targeted profiling of TMAO and betaine in serum and food samples based on a combination of one-step sample pretreatment and proton nuclear magnetic resonance spectroscopy. The key step included a processing of sample preparation using a selective solid-phase extraction column for retention of basic metabolites. Proton signals at 3.29 and 3.28 were employed to quantify TMAO and betaine, respectively. The developed method was examined with acceptable linear relationship, precision, stability, repeatability, and accuracy. It was successfully applied to detect serum levels of TMAO and betaine in TMAO-fed mice and high-fructose-fed rats and also used to determine the contents of TMAO and betaine in several kinds of food, such as fish, pork, milk, and egg yolk.
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http://dx.doi.org/10.3390/molecules26051334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958608PMC
March 2021

The Bdkrb2 gene family provides a novel view of viviparity adaptation in Sebastes schlegelii.

BMC Ecol Evol 2021 03 17;21(1):44. Epub 2021 Mar 17.

MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, China.

Background: Black rockfish (Sebastes schlegelii) is a viviparous teleost. We proposed that the rockfish ovarian wall had a similar function to the uterus of mammals previously. In the present study, the well-developed vascular system was observed in the ovarian wall and the exterior surface of the egg membrane. In gestation, adaptation of the ovary vasculature to the rising needs of the embryos occurs through both vasodilation and neovascularization. Bdkrb2, encoding a receptor for bradykinin, plays a critical role in the control of vasodilatation by regulating nitric oxide production.

Results: Eight Bdkrb2 genes were identified in the black rockfish genome. These genes were located on chromosome 14, which are arranged in a tandem array, forming a gene cluster spanning 50 kb. Protein structure prediction, phylogenetic analysis, and transcriptome analysis showed that eight Bdkrb2 genes evolved two kinds of protein structure and three types of tissue expression pattern. Overexpression of two Bdkrb2 genes in zebrafish indicated a role of them in blood vessel formation or remodeling, which is an important procedure for the viviparous rockfish getting prepared for fertilization and embryos implantation.

Conclusions: Our study characterizes eight Bdrkb2 genes in the black rockfish, which may contribute to preparation for fertilization and embryo implantation. This research provides a novel view of viviparity adaptation and lays the groundwork for future research into vascular regulation of ovarian tissue in the breeding cycle in black rockfish.
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http://dx.doi.org/10.1186/s12862-021-01774-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968187PMC
March 2021

Micromodel Studies of Surfactant Flooding for Enhanced Oil Recovery: A Review.

ACS Omega 2021 Mar 24;6(9):6064-6069. Epub 2021 Feb 24.

State Key Laboratory of Petroleum and Prospecting, China University of Petroleum (Beijing), Beijing 102249, China.

Micromodels have been widely used to visualize surfactant flooding, which provides new insights into understanding pore-scale events during displacement. In this review, recent advances in micromodel studies of surfactant flooding are briefly summarized. The mechanisms of surfactant flooding as demonstrated by micromodel studies are presented, as well as pore-scale findings that cannot be captured by traditional coreflood methods.
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http://dx.doi.org/10.1021/acsomega.0c05750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948245PMC
March 2021

Reasonable driving speed limits based on recognition time in a dynamic low-visibility environment related to fog-A driving simulator study.

Accid Anal Prev 2021 May 8;154:106060. Epub 2021 Mar 8.

School of Civil and Hydraulic Engineering, Hefei University of Technology, Hefei 230009, Anhui, PR China. Electronic address:

To determine a reasonable speed limit and ensure traffic safety in a dynamic low-visibility environment with fog, a driving simulator study was conducted. A total of 31 young participants were recruited, and each completed 5 driving simulator trials under varying visibility conditions and speed levels during the daytime. The combined coupling effect of the visibility and driving speed on drivers' recognition times was explored, and a quantitative model of the recognition time, visibility, and driving speed was established. A determination method and suggested value of a reasonable driving speed limit in dynamic low-visibility conditions were proposed based on the stopping sight distance model. The results show that there are significant differences in the recognition times of drivers under different visibility and speed conditions. The reasonable driving speed limit values in dynamic low-visibility conditions should be based on visibility changes. When the stopping sight distance is 75 m and the visibility is less than 35 m, the speed limit should be 20 km/h. When the visibility is between 35 m and 60 m, the speed limit should be 30 km/h. When the visibility is between 60 m and 140 m, the speed limit should be 50 km/h. When the visibility is greater than 140 m, the speed limit should be 60 km/h. These research results can provide a theoretical reference for the formulation of a VSL in a dynamic low-visibility environment related to fog and reduce crash risk in conditions of inadequate visibility in fog.
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http://dx.doi.org/10.1016/j.aap.2021.106060DOI Listing
May 2021

Synergistic Therapy for Cervical Cancer by Codelivery of Cisplatin and JQ1 Inhibiting Plk1-Mutant Trp53 Axis.

Nano Lett 2021 Mar 11;21(6):2412-2421. Epub 2021 Mar 11.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.

JQ1, a specific inhibitor of bromodomain-containing protein 4 (BRD4), could have great potential in the treatment of cervical cancer. However, its clinical application is limited by its short plasma half-life and limited antitumor efficacy. In this work, cisplatin (CDDP) was first utilized as the stabilizer and cooperator in the nanosystem (mPEG--P(Glu--Phe)-CDDP/JQ1, called PGP-CDDP/JQ1) to break through the efficiency limitation of JQ1. The PGP-CDDP/JQ1 had a combination index (CI) of 0.21, exerting a strong cytotoxic synergistic effect. experiments revealed that PGP-CDDP/JQ1 had a significantly higher tumor inhibition effect (tumor inhibition rate: 85% vs 14%) and plasma stability of JQ1 (area under the curve (AUC): 335.97 vs 16.88 μg × h/mL) than free JQ1. The mechanism underling the synergism of JQ1 with CDDP in PGP-CDDP/JQ1 was uncovered to be inhibiting Plk1-mutant Trp53 axis. Thus, this study provides an optional method for improving the clinical application of JQ1 in cervical cancer.
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http://dx.doi.org/10.1021/acs.nanolett.0c04402DOI Listing
March 2021

Digital Workflow for a Scleroderma Patient with Microstomia: A Clinical Report.

J Prosthodont 2021 Feb 27. Epub 2021 Feb 27.

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

Making impressions in patients with microstomia is often rather problematic due to their restricted mouth opening. Herein, this report describes a novel digital workflow for making impressions with computer-aided design and computer-aided manufacturing (CAD/CAM) custom sectional trays for a 58-year-old female patient with scleroderma and microstomia. CAD/CAM custom sectional trays were made based on digital dentition models from another case with similar arch scale. After the sectional impressions were obtained, the sectional casts were scanned and digitally aligned to form the final dentition models. The removable partial dentures were designed on the final digital models and printed using a 3D printer. This procedure was executed with a successful prosthetic outcome that included good fit and acceptable esthetics. The patient also reported a high level of satisfaction.
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http://dx.doi.org/10.1111/jopr.13351DOI Listing
February 2021

Inhibition of HMGB1 reduced high glucose-induced BMSCs apoptosis via activation of AMPK and regulation of mitochondrial functions.

J Physiol Biochem 2021 May 26;77(2):227-235. Epub 2021 Feb 26.

State Key Laboratory of Oral Disease, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, 14 S Renmin Rd. 3rd Sec, Chengdu, Sichuan, 610041, People's Republic of China.

High mobility group box-1 (HMGB1) participates actively in oxidative stress damage, and the latter relates closely to diabetes and diabetic complications including osteoporosis, though the underlying mechanisms are elusive. This study aimed to investigate the effect of high glucose on bone marrow stromal cells (BMSCs) apoptosis and the role of HMGB1 in this process. BMSCs were isolated from 2-week-old Sprague-Dawley rats and cultured in medium containing normal glucose (NG), high glucose (HG), high glucose + glycyrrhizin (HMGB1 inhibitor, HG+GL), and high glucose + glycyrrhizin + dorsomorphin (AMPK inhibitor, HG+GL+Dm), respectively. Cell apoptosis, expression of HMGB1, AMPK, apoptotic markers, and mitochondrial functions were detected. By these approaches, we demonstrated that HG treatment significantly upregulated the expression of HMGB1 in BMSCs, which could be attenuated by GL treatment. Inhibiting HMGB1 by GL improved AMPK activation, decreased mitochondrial ROS levels, increased mitochondrial membrane potential, normalized mitochondrial fission/fusion balance, and consequently reduced apoptosis of BMSCs under HG condition. The addition of AMPK inhibitor dorsomorphin hampered this protective effect. Taken together, our data show that inhibition of HMGB1 can be an effective approach to alleviate HG-induced BMSCs apoptosis by activation of AMPK pathway and relieving mitochondrial dysfunction.
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http://dx.doi.org/10.1007/s13105-021-00784-2DOI Listing
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

Determination of Hardness and Fracture Toughness of Y-TZP Manufactured by Digital Light Processing through the Indentation Technique.

Biomed Res Int 2021 12;2021:6612840. Epub 2021 Feb 12.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

Objective: The purpose of the study was to determine the hardness and fracture toughness of dental yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) manufactured by digital light processing (DLP) technology to study its clinical prospects.

Methods: The experimental group was DLP-manufactured zirconia, and the control group was milled zirconia. The hardness was investigated under a range of test loads (0.49 N, 0.98 N, 1.96 N, 4.90 N, 9.81 N, 29.42 N, 49.03 N, 98.07 N, and 196.1 N). Meyer's law was applied to describe the indentation size effect (ISE). Meanwhile, the PSR model and MPSR model were utilized to generate true hardness values. The cracks were observed to be induced by indentation under loads above 49.03 N, while the cracks showed the radial-median type under the load of 196.1 N, under which the fracture toughness was calculated.

Results: The true hardness of DLP-manufactured zirconia was 1189 HV based on the PSR model and 1193 HV based on the MPSR model, a bit lower than that of milled zirconia. The fracture toughness was 3.43 ± 0.29 MPa√m, which showed no statistical difference with the milled zirconia.

Conclusion: The dental zirconia manufactured by the DLP 3D printing technique is similar to that manufactured by the conventional milling process in hardness and fracture toughness, thus having a promising future of clinical use.
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http://dx.doi.org/10.1155/2021/6612840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896846PMC
February 2021

Oral delivery of carrier-free dual-drug nanocrystal self-assembled microspheres improved NAD bioavailability and attenuated cardiac ischemia/reperfusion injury in mice.

Drug Deliv 2021 Dec;28(1):433-444

Laboratory of Plastic Surgery and Burns, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, P. R. China.

Nicotinamide riboside (NR), as a dietary supplement, can be converted to nicotinamide adenine dinucleotide (NAD) in cells to support mitochondrial energy metabolism. However, the efficacy of oral administrated NR is limited due to its quick degradation in circulation and low bioavailability in targeted organs. In this study, we fabricated nanocrystal self-assembled microspheres by Nano Spray Dryer for oral delivery of NR. The structure of NR and resveratrol (RES) nanocrystal self-assembled microspheres (NR/RESms) is confirmed by the morphology, chemical structure, and crystallization. The NR/RESms displayed restricted NR release at the gastric acid-mimic condition (<15% in the first 8 hours), while achieved accelerated NR release in an enteric-mimic environment (>46% within 8 hours). Oral administration of NR/RESms for 8 hours significantly elevated NAD levels in serum (169.88 nM versus 30.93 nM in the NR group,  < .01; and 66.89 nM in the NR + RES group,  < .05), and enhanced NAD abundance in multiple organs in mice, exhibiting an improved oral NAD bioavailability. In addition, without any serious adverse effects on major organs, oral delivery of NR/RESms attenuated myocardial infarction (15.82% versus 19.38% in the I/R + NR group and 20.76% in the I/R + NR + RES group) in a cardiac ischemia/reperfusion (I/R) injury mouse model. Therefore, our data supported that the NR/RESms is a promising candidate as NAD booster for oral administration.
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http://dx.doi.org/10.1080/10717544.2021.1886198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899691PMC
December 2021

Mimicking efferent nerves using a graphdiyne-based artificial synapse with multiple ion diffusion dynamics.

Nat Commun 2021 02 16;12(1):1068. Epub 2021 Feb 16.

Institute of Photoelectronic Thin Film Devices and Technology, Key Laboratory of Optoelectronic Thin Film Devices and Technology of Tianjin, College of Electrical Information and Optical Engineering, School of Materials Science and Engineering, National Institute for Advanced Materials, Nankai University, Tianjin, P. R. China.

A graphdiyne-based artificial synapse (GAS), exhibiting intrinsic short-term plasticity, has been proposed to mimic biological signal transmission behavior. The impulse response of the GAS has been reduced to several millivolts with competitive femtowatt-level consumption, exceeding the biological level by orders of magnitude. Most importantly, the GAS is capable of parallelly processing signals transmitted from multiple pre-neurons and therefore realizing dynamic logic and spatiotemporal rules. It is also found that the GAS is thermally stable (at 353 K) and environmentally stable (in a relative humidity up to 35%). Our artificial efferent nerve, connecting the GAS with artificial muscles, has been demonstrated to complete the information integration of pre-neurons and the information output of motor neurons, which is advantageous for coalescing multiple sensory feedbacks and reacting to events. Our synaptic element has potential applications in bioinspired peripheral nervous systems of soft electronics, neurorobotics, and biohybrid systems of brain-computer interfaces.
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http://dx.doi.org/10.1038/s41467-021-21319-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886898PMC
February 2021

TCM nonpharmacological interventions for ankylosing spondylitis: A protocol for systematic review and network meta-analysis.

Medicine (Baltimore) 2021 Feb;100(6):e24279

Clinical College of Traditional Chinese Medicine, Gansu University of Traditional Chinese Medicine.

Background: Ankylosing spondylitis (AS) is a common infammatory rheumatic disease that affects the axial skeleton. Traditional Chinese medicine (TCM) nonpharmacological interventions are gaining an increasing popularity for AS. Nevertheless, the evidence of efficacy and safety of random controlled trials (RCTs) remains controversial. This study aims to evaluate the efficacy and acceptability of different TCM nonpharmacological therapies by systematic review and network meta-analysis.

Methods: According to the strategy, the authors will retrieve a total of 7 electronic databases by December 2020, including PubMed, the Cochrane Library, EMbase, China National Knowledge Infrastructure, China Biological Medicine, Chongqing VIP, and Wan-fang databases After a series of screening, 2 researchers will use Aggregate Data Drug Information System and Stata software to analyze the data extracted from the randomized controlled trials of TCM nonpharmacological interventions for AS. The primary outcome will be the improvement of Pain intensity and functional status/disability and the secondary outcomes will include lobal improvement, health-related quality of life, satisfaction with treatment, and adverse events. Both classical meta-analysis and network meta-analysis will be implemented to investigate direct and indirect evidences on this topic. The quality of the evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation instrument.

Results: This study will provide a reliable evidence for the selection of TCM nonpharmacological therapies in the treatment of AS.

Conclusion: This study will generate evidence for different TCM nonpharmacological therapies for AS and provide a decision-making reference for clinical research.

Ethics And Dissemination: This study does not require ethical approval. The results will be disseminated through a peer-reviewed publication.

Osf Registration Number: DOI 10.17605/OSF.IO/FHD2U.
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http://dx.doi.org/10.1097/MD.0000000000024279DOI Listing
February 2021

Radiomics Analysis of MR Imaging with Gd-EOB-DTPA for Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma: Investigation and Comparison of Different Hepatobiliary Phase Delay Times.

Biomed Res Int 2021 7;2021:6685723. Epub 2021 Jan 7.

Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Purpose: To investigate whether the radiomics analysis of MR imaging in the hepatobiliary phase (HBP) can be used to predict microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC).

Method: A total of 130 patients with HCC, including 80 MVI-positive patients and 50 MVI-negative patients, who underwent MR imaging with Gd-EOB-DTPA were enrolled. Least absolute shrinkage and selection operator (LASSO) regression was applied to select radiomics parameters derived from MR images obtained in the HBP 5 min, 10 min, and 15 min images. The selected features at each phase were adopted into support vector machine (SVM) classifiers to establish models. Multiple comparisons of the AUCs at each phase were performed by the Delong test. The decision curve analysis (DCA) was used to analyze the classification of MVI-positive and MVI-negative patients.

Results: The most predictive features between MVI-positive and MVI-negative patients included 9, 8, and 14 radiomics parameters on HBP 5 min, 10 min, and 15 min images, respectively. A model incorporating the selected features produced an AUC of 0.685, 0.718, and 0.795 on HBP 5 min, 10 min, and 15 min images, respectively. The predictive model for HBP 5 min, 10 min and 15 min showed no significant difference by the Delong test. DCA indicated that the predictive model for HBP 15 min outperformed the models for HBP 5 min and 10 min.

Conclusions: Radiomics parameters in the HBP can be used to predict MVI, with the HBP 15 min model having the best differential diagnosis ability.
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http://dx.doi.org/10.1155/2021/6685723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810556PMC
January 2021

Cyclosporine A Promotes Bone Remodeling in LPS-Related Inflammation via Inhibiting ROS/ERK Signaling: Studies and .

Oxid Med Cell Longev 2021 7;2021:8836599. Epub 2021 Jan 7.

State Key Laboratory of Oral Disease, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

In some inflammatory diseases of bone, osteogenesis and osteoclasis are uncoupled and the balance is usually tipped resulting in bone destruction. The underlying mechanism of osteogenic dysfunction in inflammation still needs further study. This study is aimed at investigating the effects of cyclosporine A (CsA) on bone remodeling in lipopolysaccharide- (LPS-) related inflammation. , an alveolar bone defect model was established using 10-week-old C57BL/6J mice. The mice were divided into phosphate-buffered saline (PBS), LPS, and LPS+CsA groups. After 3 weeks, micro-CT analysis and histomorphometric evaluation were conducted. , murine osteoblasts were treated with vehicle medium, LPS, LPS+CsA, LPS+extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor (LPS+PD98059), and LPS+antioxidant (LPS+EUK134). Cell proliferation, osteogenic behaviors, oxidative stress, and ERK signaling were determined. By these approaches, LPS inhibited bone remodeling and promoted oxidative stress accumulation in alveolar bone defects. When animals were treated with CsA, all LPS-induced biochemical changes ameliorated with a marked protective effect. , the reactive oxygen species (ROS) levels in mitochondria increased in LPS-treated osteoblasts, with decreased expression of osteogenic differentiation genes. The CsA, PD98059, and EUK134 presented remarkable protective effects against LPS treatment. CsA effectively enhanced bone remodeling and attenuated oxidative stress caused by LPS via inhibiting ROS/ERK signaling. Taken together, the protective effect of CsA and the inhibitory effect of ERK signaling on the maintenance of mitochondrial function and reduction of ROS levels hold promise as a potential novel therapeutic strategy for inflammatory diseases in bones.
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http://dx.doi.org/10.1155/2021/8836599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810558PMC
January 2021

Computer-assisted tooth preparation template and predesigned restoration: a digital workflow.

Int J Comput Dent 2020 ;23(4):351-362

This article introduces a new, fully digital workflow for the preparation of a guiding template and the procedure of the clinical operation in which it is put to use. A step-by-step technique is described including the virtual CAD of the preparation, the design of the template, the restoration based on the contours of the virtual preparation, the tooth preparation guided by the template, and the bonding of the predesigned restoration. The design and manufacture of all the templates and restorations are completed before the clinical operation.
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January 2021

Polygonum multiflorum: Recent updates on newly isolated compounds, potential hepatotoxic compounds and their mechanisms.

J Ethnopharmacol 2021 May 21;271:113864. Epub 2021 Jan 21.

State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, PR China. Electronic address:

Ethnopharmacological Relevance: Polygonum multiflorum Thunb.(PM), (known as Heshouwu () in China) is one of the most important and well mentioned Chinese medicinal herbs in the literature for its use in blackening hair, nourishing liver and kidney, anti-aging, anti-hyperlipidemia, antioxidant, anti-inflammatory, anticancer, hepatoprotection, cardio-protection and improving age-related cognitive dysfunction. The purpose of this review is to give a comprehensive and recent update on PM: new compounds or isolated for the first time, potential hepatotoxic compounds and their mechanisms. Moreover, future perspectives and challenges in the future study of this plant are conversed which will make a new base for further study on PM.

Materials And Methods: A comprehensive review of relevant published literature on PM using the scientific databases SCOPUS, PubMed, and Science Direct was done.

Results: PM is broadly produced in many provinces of China and well known in other Eastern Asian Countries for its ethno-medical uses. Previous phytochemical investigation of PM had led to the isolation of more than 175 compounds including recently isolated 70 new compounds. Most of the new compounds isolated after 2015 are majorly dianthrone glycosides and stilbene glycosides. Processing has also a significant effect on chemical composition, pharmacological activities, and toxicity of PM. PM-induced liver injury is increasing after the first report in Hong Kong in 1996. Hepatotoxicity of PM was constantly reported in Japan, Korea, China, Australia, Britain, Italy, and other countries although its toxicity is related to idiosyncratic hepatotoxicity. More interestingly, although there is indispensable interest to predict idiosyncratic hepatotoxicity of PM and understand its mechanisms, the responsible hepatotoxic compounds and mechanisms of liver damage induced by PM are still not clear. There is a big controversy on the identification of the most responsible constituent. Anthraquinone and stilbene compounds in PM, mainly emodine and TSG are mentioned in the literature to be the main responsible hepatotoxic compounds. However, comparing the two compounds, which one is the more critical toxic agent for PM-induced hepatotoxicity is not well answered. Affecting different physiological and metabolic pathways such as oxidative phosphorylation and TCA cycle pathway, metabolic pathways, bile acid excretion pathway and genetic polymorphisms are among the mechanisms of hepatotoxicity of PM.

Conclusion: Deeper and effective high throughput experimental studies are still research hotspots to know the most responsible constituent and the mechanism of PM-induced hepatotoxicity.
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http://dx.doi.org/10.1016/j.jep.2021.113864DOI Listing
May 2021

Silencing long non-coding RNA HNF1A-AS1 inhibits growth and resistance to TAM of breast cancer cells via the microRNA-363/SERTAD3 axis.

J Drug Target 2021 Jan 21:1-31. Epub 2021 Jan 21.

Third Affiliated Hospital of Zhengzhou University(Henan Maternal and Child Health Care Hospital) , No. 7, Kangfuqian street, Erqi District, Zhengzhou, 450052, Henan,P.R. China.

Long non-coding RNAs (lncRNAs) can exert effects on drug resistance of cancer cells. This study investigated the role of lncRNA HNF1A-antisense 1 (HNF1A-AS1) in growth and Tamoxifen (TAM) sensitivity of breast cancer (BC) cells. HNF1A-AS1 expression was promoted in BC cells and tissues. BC cells with HNF1A-AS1 silencing were constructed to detect cell proliferation. TAM resistant cell line with HNF1A-AS1 silencing and parent cell line with overexpressed HNF1A-AS1 were constructed to measure drug resistance. Silencing HNF1A-AS1 reduced proliferation and TAM resistance of BC cells. The downstream microRNAs (miRs) of HNF1A-AS1 and its targets were figured out and their functions in TAM resistance of BC cells were identified. HNF1A-AS1 sponged miR-363 to promote SERTAD3 expression. Downregulation of miR-363 or upregulation of SERTAD3 stimulated TAM resistance of BC cells. The findings were reproduced in experiments. It could be concluded that silencing HNF1A-AS1 inhibited growth and drug resistance to TAM of BC cells through the miR-363/SERTAD3 axis and the inactivation of the TGF-β/Smad pathway.
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http://dx.doi.org/10.1080/1061186X.2021.1878362DOI Listing
January 2021

Effects of statins on cytokines levels in gingival crevicular fluid and saliva and on clinical periodontal parameters of middle-aged and elderly patients with type 2 diabetes mellitus.

PLoS One 2021 8;16(1):e0244806. Epub 2021 Jan 8.

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

Objective: To analyze the effect of statins on cytokines levels in gingival crevicular fluid (GCF) and saliva and on clinical periodontal parameters of middle-aged and elderly patients with type 2 diabetes mellitus (T2DM).

Methods: Systemically healthy controls (C group, n = 62), T2DM patients not taking statins (D group, n = 57) and T2DM patients taking statins (S group, n = 24) were recruited. In each group, subjects (40-85 years) were subclassified into the h (periodontal health)group, the g (gingivitis)group or the p (periodontitis) group according to different periodontal conditions. 17 cytokines in gingival crevicular fluid (GCF) and saliva samples of each subject were measured utilizing the Luminex technology kit. Further, HbA1c (glycated hemoglobin), FPG (fasting plasma glucose), PD (probing depth), CAL (clinical attachment level), BOP (bleeding on probing), GI (gingival index) and PI (periodontal index) were recorded. Data distribution was tested through the Shapiro-Wilk test, upon which the Kruskal-Wallis test was applied followed by Mann-Whitney U test and Bonferroni's correction.

Results: Levels of IFN-γ, IL-5, IL-10 and IL-13 in the saliva of the Dh group were significantly lower than those in the Ch group, while factor IL-4 was higher (p<0.05). Levels of MIP-3α, IL-7 and IL-2 in GCF of the Dh group were considerably higher than those in the Ch group (p<0.05), while that of IL-23 was considerably lower. Compared with the Cg group, levels of IFN-γ, IL-4, IL-5, IL-6, IL-10 and IL-13 were significantly lower in the saliva of the Dg group (p<0.05). Lower levels of IFN-γ, IL-5 and IL-10 were detected in the Sg group than those in the Cg group (p<0.05). At the same time, levels of IL-1β, IL-6, IL-7, IL-13, IL-17, IL-21 and MIP-3α in the gingival crevicular fluid of the Sg group were lower in comparison with the Dg group. In addition, lower levels of IL-4 and higher levels of IL-7 in GCF were identified in the Dg group than those in the Cg group, while in the Sg group, lower levels of IL-4, MIP-1αand MIP-3αwere observed than those in the Cg group (p<0.05). Lower levels of IFN-γ, IL-6, IL-10, IL-13 and I-TAC were found in the Sp group compared with those in the Cp group. The IFN-γ, IL-6 and IL-10 levels were lower in the Dp group than those in the Cp group (p<0.05). Meanwhile, in the Sp group, lower levels of pro-inflammatory factors IFN-γ, IL-1β, IL-2, IL-6, IL-7, IL-21 and TNF-α, in addition to higher levels of anti-inflammatory factors IL-4 and IL-5 in gingival crevicular fluid, were identified than those in the Dp group. Higher levels of IFN-γ,IL-1β,IL-2,IL-7,IL-21 and TNF-α and a lower level of IL-5 in the Dp group were identified than those in the Cp group (p<0.05). Moreover, statins were able to substantially reduce PD in T2DM patients with periodontitis, indicating an obvious influence on the levels of cytokines secreted by Th1 cells, Th2 cells and Th17 cells, as revealed by PCA (principal component analysis).

Conclusion: Statins are associated with reduced PD and cytokines levels in the GCF and saliva of T2DM patients with periodontitis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244806PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793287PMC
May 2021

HTBPI, an active phenanthroindolizidine alkaloid, inhibits liver tumorigenesis by targeting Akt.

FASEB J 2020 09 24;34(9):12255-12268. Epub 2020 Jul 24.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Akt, a crucial protein involved in a variety of signaling pathways in cancer, acts as an important regulator of survival in hepatocellular carcinoma (HCC), and provides curative option for the related drugs development. We have found an active phenanthroindolizidine alkaloid, (13aR,14R)-9,11,12,13,13a,14-hexahydro-3,6,7-trimethoxydibenzo[f,h]pyrrolo[1,2-b]isoquinolin-14-ol (HTBPI), is a promising Akt inhibitor effective in the suppression of HCC cells proliferation through stimulating apoptotic and autophagic capability in vivo and in vitro. Treatment of HTBPI combined with a classical autophagy-lysosomal inhibitor (bafilomycin A1), could enhance stimulation effects of apoptosis on HCC cell lines. In addition, we confirmed HTBPI targeting Akt, occupied the kinase binding domain (Thr 308) of Akt to inactivate its function by CETSA and DARTS assay. In contrast, ectopic Akt-induced overexpression significantly abrogated inhibitory effects of HTBPI on cell viability and proliferation. Furthermore, high p-Akt (Thr 308) expression is collated with liver tumor formation and poor survival in HCC patients. In conclusions, HTBPI impeded HCC progress through regulation of apoptosis and autophagy machinery via interaction with p-Akt (Thr 308). This may provide potential molecular candidate by targeting Akt for the therapy of HCC patients.
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http://dx.doi.org/10.1096/fj.202000254RDOI Listing
September 2020

Anticancer activities of TCM and their active components against tumor metastasis.

Biomed Pharmacother 2021 Jan 11;133:111044. Epub 2020 Dec 11.

State Key Laboratory of Component-based Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. Electronic address:

Traditional Chinese Medicine (TCM) has the characteristics of multiple targets, slight side effects and good therapeutic effects. Good anti-tumor effects are shown by Traditional Chinese Medicine prescription, Chinese patent medicine, single Traditional Chinese Medicine and Traditional Chinese medicine monomer compound. Clinically, TCM prolonged the survival time of patients and improved the life quality of patients, due to less side effects. Cancer metastasis is a complex process involving numerous steps, multiple genes and their products. During the process of tumor metastasis, firstly, cancer cell increases its proliferative capacity by reducing autophagy and apoptosis, and then the cancer cell capacity is stimulated by increasing the ability of tumors to absorb nutrients from the outside through angiogenesis. Both of the two steps can increase tumor migration and invasion. Finally, the purpose of tumor metastasis is achieved. By inhibiting autophagy and apoptosis of tumor cells, angiogenesis and EMT outside the tumor can inhibit the invasion and migration of cancer, and consequently achieve the purpose of inhibiting tumor metastasis. This review explores the research achievements of Traditional Chinese Medicine on breast cancer, lung cancer, hepatic carcinoma, colorectal cancer, gastric cancer and other cancer metastasis in the past five years, summarizes the development direction of TCM on cancer metastasis research in the past five years and makes a prospect for the future.
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http://dx.doi.org/10.1016/j.biopha.2020.111044DOI Listing
January 2021

Complications and Pathophysiology of COVID-19 in the Nervous System.

Front Neurol 2020 4;11:573421. Epub 2020 Dec 4.

Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China.

The coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global public health threat. Majority of the patients with COVID-19 have fever, cough, and fatigue. Critically ill patients can develop dyspnea and acute respiratory distress syndrome. In addition to respiratory symptoms, neurological damage also occurs in some patients. However, the mechanisms by which SARS-CoV-2 invades the nervous system have not been elucidated yet. In order to provide some reference for designing optimal therapeutic strategies, we have discussed the complications and potential mechanisms of COVID-19 in the nervous system in this review.
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http://dx.doi.org/10.3389/fneur.2020.573421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746805PMC
December 2020

HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells.

Science 2021 02 17;371(6529). Epub 2020 Dec 17.

Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA, USA.

The RNA binding protein TDP-43 forms intranuclear or cytoplasmic aggregates in age-related neurodegenerative diseases. In this study, we found that RNA binding-deficient TDP-43 (produced by neurodegeneration-causing mutations or posttranslational acetylation in its RNA recognition motifs) drove TDP-43 demixing into intranuclear liquid spherical shells with liquid cores. These droplets, which we named "anisosomes", have shells that exhibit birefringence, thus indicating liquid crystal formation. Guided by mathematical modeling, we identified the primary components of the liquid core to be HSP70 family chaperones, whose adenosine triphosphate (ATP)-dependent activity maintained the liquidity of shells and cores. In vivo proteasome inhibition within neurons, to mimic aging-related reduction of proteasome activity, induced TDP-43-containing anisosomes. These structures converted to aggregates when ATP levels were reduced. Thus, acetylation, HSP70, and proteasome activities regulate TDP-43 phase separation and conversion into a gel or solid phase.
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http://dx.doi.org/10.1126/science.abb4309DOI Listing
February 2021

Comparative study of two poly(amino acid)-based photosensitizer-delivery systems for photodynamic therapy.

Int J Biol Macromol 2021 Feb 20;169:153-160. Epub 2020 Dec 20.

Department of Chemistry, Northeast Normal University, Changchun 130024, PR China. Electronic address:

The photosensitizers (PS) play a vital role in photodynamic therapy (PDT), but the clinical therapeutic effect is limited by its low solubility, easy aggregation and lack of selective tumor uptake. Hence, some biocompatible materials such as poly(amino acid) have been chosen to deliver PS to solve these problems. In this study, we fabricated two kind of poly(amino acid)-based PS delivery systems by using poly (-glutamic acid) (PLG) as the backbone material to physically encapsulate (P(T)) and chemically conjugate PS (PT), respectively. Moreover, the anticancer effect of these two PS delivery systems had been comparatively investigated. In vitro experiments verified that the delivery system of PT exhibited more effective treatment effect than that of P(T) because PS was chemically conjugated with PLG in PT which could obviously avoid the π-π stacking effect of PS and induced the aggregation. The less aggregation avoiding the quenching effect could result in an enhanced generation ability of reactive oxygen species to improve PDT treatment effect. Contrarily, the treatment effect of P(T) was lower due to the rigid structure and hydrophobic π-π stacking effect, in which the physically encapsulated PS was easier to aggregate and quench. Hence, the way how to combine carrier with drug is significant for satisfied treatment effect.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.12.019DOI Listing
February 2021