Publications by authors named "Lu Wan"

94 Publications

Stable Organic Passivated Carbon Nanotube-Silicon Solar Cells with an Efficiency of 22.

Adv Sci (Weinh) 2021 Sep 2:e2102027. Epub 2021 Sep 2.

Hebei Key Lab of Optic-Electronic Information and Materials, College of Physics Science and Technology, Hebei University, Baoding, 071002, China.

The organic passivated carbon nanotube (CNT)/silicon (Si) solar cell is a new type of low-cost, high-efficiency solar cell, with challenges concerning the stability of the organic layer used for passivation. In this work, the stability of the organic layer is studied with respect to the internal and external (humidity) water content and additionally long-term stability for low moisture environments. It is found that the organic passivated CNT/Si complex interface is not stable, despite both the organic passivation layer and CNTs being stable on their own and is due to the CNTs providing an additional path for water molecules to the interface. With the use of a simple encapsulation, a record power conversion efficiency of 22% is achieved and a stable photovoltaic performance is demonstrated. This work provides a new direction for the development of high-performance/low-cost photovoltaics in the future and will stimulate the use of nanotubes materials for solar cells applications.
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http://dx.doi.org/10.1002/advs.202102027DOI Listing
September 2021

A Comparative Analysis of Coronavirus Nucleocapsid (N) Proteins Reveals the SADS-CoV N Protein Antagonizes IFN-β Production by Inducing Ubiquitination of RIG-I.

Front Immunol 2021 16;12:688758. Epub 2021 Jun 16.

Department of Veterinary Medicine, Institute of Preventive Veterinary Medicine and Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou, China.

Coronaviruses (CoVs) are a known global threat, and most recently the ongoing COVID-19 pandemic has claimed more than 2 million human lives. Delays and interference with IFN responses are closely associated with the severity of disease caused by CoV infection. As the most abundant viral protein in infected cells just after the entry step, the CoV nucleocapsid (N) protein likely plays a key role in IFN interruption. We have conducted a comprehensive comparative analysis and report herein that the N proteins of representative human and animal CoVs from four different genera [swine acute diarrhea syndrome CoV (SADS-CoV), porcine epidemic diarrhea virus (PEDV), severe acute respiratory syndrome CoV (SARS-CoV), SARS-CoV-2, Middle East respiratory syndrome CoV (MERS-CoV), infectious bronchitis virus (IBV) and porcine deltacoronavirus (PDCoV)] suppress IFN responses by multiple strategies. In particular, we found that the N protein of SADS-CoV interacted with RIG-I independent of its RNA binding activity, mediating K27-, K48- and K63-linked ubiquitination of RIG-I and its subsequent proteasome-dependent degradation, thus inhibiting the host IFN response. These data provide insight into the interaction between CoVs and host, and offer new clues for the development of therapies against these important viruses.
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http://dx.doi.org/10.3389/fimmu.2021.688758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242249PMC
July 2021

Solution processable passivated silicon nanowires.

Nanoscale 2021 Jul;13(26):11439-11445

Hebei Key Lab of Optic-Electronic Information and Materials, College of Physics Science and Technology, Hebei University, Baoding 071002, China. and Institute of Nanotechnology, Karlsruhe Institute of Technology, Karlsruhe 76021, Germany.

The 1D confinement of silicon in the form of a nanowire revives its newness with the emergence of new optical and electronic properties. However, the development of a production process for silicon nanowires (SiNWs) having a high quality crystalline core and exhibiting good stability in solution with effective outer-shell defect passivation is still a challenge. In this work, SiNWs are prepared from a silicon wafer using solution processing steps, and importantly outer-shell-defect passivation is achieved by in situ grafting of organic molecules based on thin films. Defect passivation and the high quality of the SiNWs are confirmed with thin films on glass and flexible plastic substrates. A dramatic enhancement in both the fluorescence lifetime and infrared photoluminescence is observed. The in situ organic passivation of SiNWs has potential application in all low-dimensional silicon devices including infrared detectors, solar cells and lithium-ion battery anodes.
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http://dx.doi.org/10.1039/d1nr02131aDOI Listing
July 2021

Functional interplay between long non-coding RNAs and the Wnt signaling cascade in osteosarcoma.

Cancer Cell Int 2021 Jun 15;21(1):313. Epub 2021 Jun 15.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, No 139 Middle Renmin Road, Changsha, 410011, Hunan, China.

Osteosarcoma is a common and highly malignant bone tumor among children, adolescents and young adults. However, the underlying molecular mechanisms remain largely unexplored. LncRNAs are transcripts with no or limited protein-coding capacity in human genomes, and have been demonstrated to play crucial functions in initiation, progression, therapeutic resistance, recurrence and metastasis of tumor. Considerable studies revealed a dysregulated lncRNA expression pattern in osteosarcoma, which may act as oncogenes or suppressors to regulate osteosarcoma progression. Wnt signaling pathway is an important cascade in tumorigenesis by modulation of pleiotropic biological functions including cell proliferation, apoptosis, differentiation, stemness, genetic stability and chemoresistance. Hyperactivation or deficiency of key effectors in Wnt cascade is a common event in many osteosarcoma patients. Recently, increasing evidences have suggested that lncRNAs could interplay with component of Wnt pathway, and thereby contribute to osteosarcoma onset, progression and dissemination. In this review, we briefly summarize Wnt signaling-related lncRNAs in osteosarcoma progression, aiming to gain insights into their underlying crosstalk as well as clinical application in osteosarcoma therapeutic modalities.
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http://dx.doi.org/10.1186/s12935-021-02013-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207720PMC
June 2021

Phylogenetic Distribution of Polysaccharide-Degrading Enzymes in Marine Bacteria.

Front Microbiol 2021 18;12:658620. Epub 2021 Mar 18.

Microbial Technology Institute and State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China.

Deconstruction is an essential step of conversion of polysaccharides, and polysaccharide-degrading enzymes play a key role in this process. Although there is recent progress in the identification of these enzymes, the diversity and phylogenetic distribution of these enzymes in marine microorganisms remain largely unknown, hindering our understanding of the ecological roles of marine microorganisms in the ocean carbon cycle. Here, we studied the phylogenetic distribution of nine types of polysaccharide-degrading enzymes in marine bacterial genomes. First, we manually compiled a reference sequence database containing 961 experimentally verified enzymes. With this reference database, we annotated 9,335 enzyme sequences from 2,182 high-quality marine bacterial genomes, revealing extended distribution for six enzymes at the phylum level and for all nine enzymes at lower taxonomic levels. Next, phylogenetic analyses revealed intra-clade diversity in the encoding potentials and phylogenetic conservation of a few enzymes at the genus level. Lastly, our analyses revealed correlations between enzymes, with alginate lyases demonstrating the most extensive correlations with others. Intriguingly, chitinases showed negative correlations with cellulases, alginate lyases, and agarases in a few genera. This result suggested that intra-genus lifestyle differentiation occurred many times in marine bacteria and that the utilization of polysaccharides may act as an important driver in the recent ecological differentiation of a few lineages. This study expanded our knowledge of the phylogenetic distribution of polysaccharide enzymes and provided insights into the ecological differentiation of marine bacteria.
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http://dx.doi.org/10.3389/fmicb.2021.658620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012555PMC
March 2021

Correction to: Survivorship and prognostic factors for pleomorphic liposarcoma: a population-based study.

J Orthop Surg Res 2021 Mar 29;16(1):228. Epub 2021 Mar 29.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, 139 Renming Road, Changsha, 410011, Hunan, People's Republic of China.

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http://dx.doi.org/10.1186/s13018-021-02369-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006338PMC
March 2021

Survivorship and prognostic factors for pleomorphic liposarcoma: a population-based study.

J Orthop Surg Res 2021 Mar 4;16(1):175. Epub 2021 Mar 4.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, 139 Renming Road, Changsha, 410011, Hunan, People's Republic of China.

Background: Pleomorphic liposarcoma is the least common but most aggressive subtype of liposarcoma. Very few studies have presented data on pleomorphic liposarcoma specifically, often including a limited number of cases and short-term follow-up. As a result, the survivorship and prognostic characteristics of this tumor remain incompletely identified.

Study Design And Setting: Cross-sectional analysis of the Surveillance Epidemiology and End Results database (1996-2015).

Results: Overall survival for the entire series was 54% (95% confidence interval [CI], 49-58%) and 40% (95% CI, 35-45%) at 5 and 10 years, respectively. Disease-specific survival for the entire series was 60% (95% CI, 56-65%) and 53% (95% CI, 48-58%) at 5 and 10 years, respectively. Patients who survived 10 years or more were more likely to die of events unrelated to pleomorphic liposarcoma. Univariate and multivariate analysis demonstrated that not receiving cancer-directed surgery was an independent poor prognostic factor. Older age (≥ 65 years old) was associated with worse overall survival but not disease-specific survival. Tumor stage and radiotherapy showed different impact on survival depending on tumor size. In comparison to localized staged tumors, regional stage only predicts poor survival in patients with tumor size less than 5 cm, while distant stage is an independent worse prognosis factor. Radiotherapy only benefits patients with tumor size larger than 10 cm. These results were confirmed in competing risk analysis.

Conclusion: Survival rates of patients with pleomorphic liposarcoma has not changed over the past 20 years. Patients with distant stage have poor prognosis; regional stage indicates worse survival in patients with tumor size less than 5 cm. Receiving surgery could prolong the survival, while radiotherapy only benefits patients with large tumor size (> 10 cm). Older age is associated with poor overall survival but not disease-specific survival. Routine patient surveillance following initial diagnosis should at least be 10 years for pleomorphic liposarcoma.
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http://dx.doi.org/10.1186/s13018-021-02327-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931523PMC
March 2021

Metformin restores hippocampal neurogenesis and learning and memory via regulating gut microbiota in the obese mouse model.

Brain Behav Immun 2021 07 18;95:68-83. Epub 2021 Feb 18.

Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology (HUST), Wuhan 430074, China; Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

Numerous studies have shown that over-nutritional obesity may lead to pre-diabetes, type 2 diabetes and cognitive decline. As the degree of metabolic disorders increases, the cognitive decline is getting worse. However, the cellular events that cause this cognitive dysfunction is yet to be clarified. We used a high-fat diet (HFD) consumption-induced obesity mouse model to test the effects of metformin on the hippocampal neurogenesis and learning and memory abilities of obese mice. 5-Bromo-2'-deoxyuridine (BrdU) labelling and retrovirus labeling were applied to detect hippocampal newborn neurons. Behavioral experiments were used to detect learning and memory abilities of mice. 16S rRNA gene sequencing was performed to detect the composition of gut microbiota. The positron emission tomography (PET) was conducted to detect the energy metabolism activity of different mouse brain regions. Our results reveal that metformin restores the impairment of neurogenesis in the dentate gyrus and finally prevents the cognitive decline of the obese mice. Moreover, the therapeutic effects of metformin are achieved by regulating the composition of gut microbiota of mice, which may inhibit microglia activation and neuroinflammation in the brain of obese mice. This study suggests that metformin may be taken as a promising candidate for the intervention of cognitive decline related to imbalance of gut microbiota caused by obesity.
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http://dx.doi.org/10.1016/j.bbi.2021.02.011DOI Listing
July 2021

Effect of Increased IL-1β on Expression of HK in Alzheimer's Disease.

Int J Mol Sci 2021 Jan 28;22(3). Epub 2021 Jan 28.

College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by decreased glucose metabolism and increased neuroinflammation. Hexokinase (HK) is the key enzyme of glucose metabolism and is associated with mitochondria to exert its function. Recent studies have demonstrated that the dissociation of HK from mitochondria is enough to activate the NOD-like receptor protein 3 (NLRP3) inflammasome and leads to the release of interleukin-1β (IL-1β). However, the effect of increased IL-1β on the expression of HK is still unclear in AD. In this paper, we used positron emission tomography (PET), Western blotting and immunofluorescence to study the glucose metabolism, and the expression and distribution of HK in AD. Furthermore, we used lipopolysaccharide (LPS), nigericin (Nig), CY-09 and lonidamine (LND) to treat N2a and N2a-sw cells to investigate the link between IL-1β and HK in AD. The results show decreased expression of HK and the dissociation of HK from mitochondria in AD. Furthermore, a reduction of the expression of IL-1β could increase the expression of HK in AD. These results suggest that inhibiting inflammation may help to restore glucose metabolism in AD.
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http://dx.doi.org/10.3390/ijms22031306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865721PMC
January 2021

Diagnostic and Prognostic Significance of Dysregulated Expression of Circular RNAs in Osteosarcoma.

Expert Rev Mol Diagn 2021 Feb 22;21(2):235-244. Epub 2021 Jan 22.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Objective: This study aimed to perform an updated meta-analysis to explore the clinical, diagnostic, and prognostic values of circRNAs in osteosarcoma.

Methods: : PubMed, Web of Science, EMBASE, Scopus, and Cochrane Library were systematically searched up to December 15, 2020. Eligible studies regarding the relationship between circRNAs levels and clinicopathological, diagnostic, and prognostic values in osteosarcoma were included for study.

Results: 31 studies involving 1979 osteosarcoma patients were enrolled, with 22 studies on clinicopathological parameters, eleven on diagnosis, and 23 on prognosis. For clinical parameters, overexpression of oncogenic circRNAs was intimately correlated with larger tumor size, advanced Enneking stage, poor differentiation, and distant metastasis (DM). In contrast, the downregulated circRNAs showed negative correlation with Enneking stage and DM. For the diagnostic values, the summary area under the curve of circRNA for the discriminative efficacy between osteosarcoma patients and non-cancer counterparts was estimated to be 0.87, with a weighted sensitivity of 0.79, specificity of 0.81, respectively. For the prognostic significance, oncogenic circRNAs had poor overall survival (OS) and disease-free survival, while elevated expression of tumor-suppressor circRNAs were closely related to longer OS.

Conclusion: This study showed that aberrantly expressed circRNA signatures could serve as potential biomarkers in diagnosis and prognosis in osteosarcoma.
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http://dx.doi.org/10.1080/14737159.2021.1874922DOI Listing
February 2021

Dynamic characteristics of chlorine dispersion process and quantitative risk assessment of pollution hazard.

Environ Sci Pollut Res Int 2021 Sep 7;28(34):46161-46175. Epub 2021 Jan 7.

SINOPEC Qingdao Research Institute of Safety Engineering, Qingdao, 266101, Shandong, China.

The aim of this study was to analyze dispersion behavior characteristics and pollution hazard risk after a release of liquid chlorine. A full-scale model of liquid chlorine tanks in an area with a radius range of 3 km was established using FLACS (Flame Acceleration Simulator) code, and the chlorine dispersion characteristics of six leakage scenarios were calculated according to the POOL model, and the individual risk and social risk under different conditions as calculated quantitatively. The results show that leakage occurs in three stages: dynamic dispersion, gravity dispersion, and atmospheric dispersion. Variations in dispersion processes were expressed as "outward expansion" and "inward contraction." At the same time, dispersion was accompanied by the phenomenon of "cloud separation." In the six leakage scenarios, the total distance of chlorine dispersion was 84-1000 m for a concentration of 225 ppm, and 27.5-401.3 m for a concentration of 900 ppm. The corresponding times (duration) to the farthest dispersion distance were 235-1345 s and 185-680 s, respectively. Chlorine concentration and dispersion distance are consistent in trend; however, the farthest dispersion distance shows a "delay effect" in time. At 225 ppm and 900 ppm, the delay time was 125-1145 s and 75-480 s indifferent leakage scenarios. The installation of a safety instrument system (SIS) can effectively reduce the risk of chlorine dispersion.
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http://dx.doi.org/10.1007/s11356-020-11864-zDOI Listing
September 2021

Bnip3 interacts with vimentin, an intermediate filament protein, and regulates autophagy of hepatic stellate cells.

Aging (Albany NY) 2020 12 3;13(1):957-972. Epub 2020 Dec 3.

Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.

Bnip3, which is regulated by Hif-1 in cells under oxygen deprivation, is a death related protein associated with autophagy and apoptosis. Hif-1 was reported to regulate autophagy to activate hepatic stellate cells (HSCs), while the specific molecular mechanism is vague. The possible mechanism of Hif-1 regulating autophagy of HSCs via Bnip3 was explored in this study. Bnip3 was detected in fibrotic liver tissues from humans and mice. Hif-1 was inhibited by chemical inhibitor and Bnip3 was detected in activated HSCs. The co-localization of Bnip3 and LC3B was captured by confocal microscopy and autophagic flow was assessed in siRNA transfected cells. Bnip3 interacted proteins were screened with mass spectrometry. The interaction of Bnip3 and vimentin was detected with co-immunoprecipitation and confocal microscopy. The results showed that Bnip3 was increased in fibrotic liver tissues and activated HSCs. Hif-1 inhibition suppressed Bnip3 expression in activated HSCs. Bnip3 was partially co-localized with autophagosomes and Bnip3 inhibition suppessed autophagy in activated HSCs. Bnip3 interacted with vimentin and Bnip3 expression was inhibited as vimentin was inhibited in activated HSCs. Conclusively, this study indicated that Bnip3 promoted autophagy and activation of HSCs, via interacting with vimentin, an intermediate filament protein with highly abundant expression in HSCs.
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http://dx.doi.org/10.18632/aging.202211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834981PMC
December 2020

Next-generation sequencing: a follow-up of 36,913 singleton pregnancies with noninvasive prenatal testing in central China.

J Assist Reprod Genet 2020 Dec 23;37(12):3143-3150. Epub 2020 Oct 23.

Prenatal Diagnosis Center, Jiangxi Maternal and Child Health Hospital, Nanchang, 330006, Jiangxi, China.

Purpose: To evaluate the noninvasive prenatal testing (NIPT) results of 36,913 cases in Jiangxi province of central China and explore its application value in prenatal screening and diagnosis.

Methods: This retrospective analysis included 36,913 singleton pregnant women who underwent NIPT because of moderate-/high-risk pregnancy or voluntary requirements between January 2017 and December 2019 in our hospital. Chromosomal abnormalities such as trisomies 21, 18, and 13 (T21, T18, T13) and sex chromosome aneuploidies (SCAs) were judged by standard Z-score analysis. Positive NIPT results were confirmed by amniocentesis and karyotyping. Pregnancy outcomes were followed up via telephone interview.

Results: A total of 1.01% (371/36,913) positive cases were detected by NIPT, comprising 137, 46, 31, and 157 cases of T21, T18, T13, and SCAs, respectively. A total of 116 of T21, 27 of T18, 13 of T13, and 51 of SCAs were confirmed to be true positive; all normal cases that had been followed up were verified to be true negative. The NIPT sensitivity in T21, T18, T13, and SCAs was 100.00% individually, whereas the specificity was 99.94% (36,488/36,509), 99.95% (36,579/36,598), 99.95% (36,594/36,612), and 99.72% (36,472/36,574), respectively. Furthermore, the negative predictive values of T21, T18, T13, and SCAs were all 100%, while the positive predictive values were 84.67%, 58.70%, 41.94%, and 33.33%, respectively.

Conclusion: NIPT is highly sensitive and has a low false positive rate in testing clinically significant fetal aneuploidies of general reproductive women. However, this technique cannot substitute for amniocentesis and karyotyping, and detailed genetic counseling is also essential for the high-risk group of NIPT.
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http://dx.doi.org/10.1007/s10815-020-01977-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714822PMC
December 2020

Differential enrichment and physiological impacts of ingested microplastics in scleractinian corals in situ.

J Hazard Mater 2021 02 8;404(Pt B):124205. Epub 2020 Oct 8.

Department of Marine Sciences, University of Connecticut, Groton, CT, United States.

Microplastics are emerging contaminants and widespread in the ocean, but their impacts on coral reef ecosystems are poorly understood, and in situ study is still lacking. In the present study, the distribution patterns of microplastics in the environment and inhabiting organisms were investigated along the east coast of Hainan Island, South China Sea, and the physiological impacts of the microplastics on scleractinian corals were analyzed. We documented average microplastic concentrations of 14.90 particlesL in seawater, 343.04 particleskg in sediment, 4.97 particlescm in corals, and 0.67-3.12 particlescm in Tridacnidae, Trochidae and fish intestines. Further analysis revealed that the characteristics of microplastics in the organisms were different from those in the environment, indicating preferential enrichment in the organisms. Furthermore, there was an obvious correlation between microplastic concentration and symbiotic density in corals. Furthermore, caspase3 activity was significantly positively correlated with the microplastic content in the small-polyp coral Pocillopora damicornis, but the large-polyp coral Galaxea fascicularis showed higher tolerance to microplastics. Taken together, our results suggest that microplastics are selectively enriched in corals and other reef-dwellers, in which they exact differential stress (apoptotic) effects, with the potential to impact the coral-Symbiodiniaceae symbiosis and alter the coral community structure.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124205DOI Listing
February 2021

Morning brain: real-world neural evidence that high school class times matter.

Soc Cogn Affect Neurosci 2020 12;15(11):1193-1202

Max Planck-NYU Center for Language, Music and Emotion, New York, NY, USA.

Researchers, parents and educators consistently observe a stark mismatch between biologically preferred and socially imposed sleep-wake hours in adolescents, fueling debate about high school start times. We contribute neural evidence to this debate with electroencephalogram data collected from high school students during their regular morning, mid-morning and afternoon classes. Overall, student alpha power was lower when class content was taught via videos than through lectures. Students' resting state alpha brain activity decreased as the day progressed, consistent with adolescents being least attentive early in the morning. During the lessons, students showed consistently worse performance and higher alpha power for early morning classes than for mid-morning classes, while afternoon quiz scores and alpha levels varied. Together, our findings demonstrate that both class activity and class time are reflected in adolescents' brain states in a real-world setting, and corroborate educational research suggesting that mid-morning may be the best time to learn.
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http://dx.doi.org/10.1093/scan/nsaa142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745151PMC
December 2020

Multifaceted Functions and Novel Insight Into the Regulatory Role of RNA N-Methyladenosine Modification in Musculoskeletal Disorders.

Front Cell Dev Biol 2020 2;8:870. Epub 2020 Sep 2.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, China.

RNA modifications have emerged as key regulators of transcript expression in diverse physiological and pathological processes. As one of the most prevalent types of RNA modifications, N-methyladenosine (mA) has become the highlight in modulation of various diseases through interfering RNA splicing, translation, nuclear export, and decay. In many cases, the detailed functions of mA in cellular processes and diseases remain unclear. Notably, recent studies have determined the relationship between mA modification and musculoskeletal disorders containing osteosarcoma, osteoarthritis, rheumatoid arthritis, osteoporosis, etc. Herein, this review comprehensively summarizes the recent advances of mA modification in pathogenesis and progression of musculoskeletal diseases. Specifically, the underlying molecular mechanisms, detection technologies, regulatory functions, clinical implications, and future perspectives of mA in musculoskeletal disorders are discussed, with the aim to provide a novel insight into their association.
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http://dx.doi.org/10.3389/fcell.2020.00870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493464PMC
September 2020

The Role of Chemotherapy in Extraskeletal Osteosarcoma: A Propensity Score Analysis of the Surveillance Epidemiology and End Results (SEER) Database.

Med Sci Monit 2020 Aug 14;26:e925107. Epub 2020 Aug 14.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China (mainland).

BACKGROUND Incidence of extraskeletal osteosarcoma (ESOS) is extremely low and the prognosis remains unclear. We conducted this study to explore prognostic factors and the role of chemotherapy in ESOS. MATERIAL AND METHODS We screened data from the Surveillance Epidemiology and End Results (SEER) database (1975-2016). Three hundred ten patients with ESOS were included and 49.4% (107/310) of them underwent chemotherapy. We performed logistic regression analysis to investigate potential factors determining selection of chemotherapy. An inverse probability of treatment weighting (IPTW) and propensity score matching (PSM)-adjusted Kaplan-Meier curve was created and log-rank test and Cox regression analysis were performed to compare overall survival (OS) and cancer-specific survival (CSS) in patients treated with and without chemotherapy. Subgroup analysis also was conducted based on age, tumor site, stage, size, and surgery. RESULTS Chemotherapy in ESOS was not associated with improved OS in the unmatched cohort (HR, 0.764; 95% CI, 0.555-1.051; p=0.098). The insignificant treatment effect of chemotherapy was also noted in IPTW-adjusted (HR, 0.737; 95% CI, 0.533-1.021; p=0.066) and PSM-adjusted (HR, 0.804; 95% CI, 0.552-1.172; p=0.257) Cox regression analysis. The insignificant treatment effect was consistent across all subgroups and there was no significant heterogeneity of chemotherapy effect (all p for interaction >0.05). CONCLUSIONS The study suggested that chemotherapy has no significant benefit on prognosis of patients with ESOS. These findings should be considered when making treatment decisions about patients with ESOS.
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http://dx.doi.org/10.12659/MSM.925107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446278PMC
August 2020

The crosstalk between lncRNAs and the Hippo signalling pathway in cancer progression.

Cell Prolif 2020 Sep 10;53(9):e12887. Epub 2020 Aug 10.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, China.

LncRNAs play a pivotal role in the regulation of epigenetic modification, cell cycle, differentiation, proliferation, migration and other physiological activities. In particular, considerable studies have shown that the aberrant expression and dysregulation of lncRNAs are widely implicated in cancer initiation and progression by acting as tumour promoters or suppressors. Hippo signalling pathway has attracted researchers' attention as one of the critical cancer-related pathways in recent years. Increasing evidences have demonstrated that lncRNAs could interact with Hippo cascade and thereby contribute to acquisition of multiple malignant hallmarks, including proliferation, metastasis, relapse and resistance to anti-cancer treatment. Specifically, Hippo signalling pathway is reported to modulate or be regulated by widespread lncRNAs. Intriguingly, certain lncRNAs could form a reciprocal feedback loop with Hippo signalling. More speculatively, lncRNAs related to Hippo pathway have been poised to become important putative biomarkers and therapeutic targets in human cancers. Herein, this review focuses on the crosstalk between lncRNAs and Hippo pathway in carcinogenesis, summarizes the comprehensive role of Hippo-related lncRNAs in tumour progression and depicts their clinical diagnostic, prognostic or therapeutic potentials in tumours.
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http://dx.doi.org/10.1111/cpr.12887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507458PMC
September 2020

polysaccharide attenuates Aβ toxicity and cognitive defects in APP/PS1 mice.

Aging (Albany NY) 2020 07 11;12(13):13422-13436. Epub 2020 Jul 11.

Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Polysaccharides (CPPs), a traditional Chinese medicine used for thousands of years, is a potential neuroprotective polysaccharide via a relatively poorly understood mechanism. We previously reported that CPPs attenuated tau pathology in hTau transfected mice and therefore in the current work investigated the effect of CPPs on Aβ toxicity and cognitive defects in APP/PS1 mice model. It was found that one-month intragastric administration of CPPs significantly ameliorated cognitive defects in APP/PS1 mice. In addition, CPPs treatment mitigated the loss of the synaptic plasticity and increased the synaptic proteins including synaptotagmin and PSD95. The expression of Aβ42 and Aβ40 was remarkably decreased in the hippocampus of APP/PS1 mice after CPPs treatment. We also found that CPPs coincubation significantly reduced the amount of APPβ and Aβ42 expression in cells. Intriguingly, the activity of BACE1 was decreased following CPPs treatment in both the hippocampus of APP/PS1 mice and in vitro experiments. Collectively, these results indicated that CPPs attenuated Aβ pathology in APP/PS1 mice, and down-regulating BACE1 might be the underlaying mechanism which could be a therapeutic target for alleviating cognitive defects in AD pathology.
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http://dx.doi.org/10.18632/aging.103445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377903PMC
July 2020

TIPE2 inhibits the migration and invasion of endometrial cells by targeting β-catenin to reverse epithelial-mesenchymal transition.

Hum Reprod 2020 06;35(6):1377-1390

Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, P. R. China.

Study Question: Do changes in tumor necrosis factor-α-induced protein 8 (TNFAIP8)-like 2 (TIPE2) levels in endometrium of patients with adenomyosis alter the proliferation, migration and invasion ability of endometrial cells?

Summary Answer: TIPE2 expression levels were low in eutopic and ectopic endometrium of adenomyosis patients, and TIPE2 inhibited the migration and invasion of endometrial cells, mainly by targeting β-catenin, to reverse the epithelial-mesenchymal transition (EMT).

What Is Known Already: Adenomyosis is a benign disease, but it has some pathophysiological characteristics similar to the malignant tumor. TIPE2 is a novel negative immune regulatory molecule, and it also participates in the development of malignant tumors.

Study Design, Size, Duration: Control endometrium (n = 48 women with non-endometrial diseases) and eutopic/ectopic endometrium from patients with adenomyosis (n = 50), human endometrial cancer cell lines, and primary endometrial cells from the eutopic endometrium of adenomyosis patients were used in the study.

Participants/materials, Setting, Methods: The expression level of TIPE2 mRNA and protein in the eutopic/ectopic endometrial tissues of adenomyosis patients and control endometrium was determined by quantitative RT-PCR (qRT-PCR), western blot and immunohistochemistry. The effects of TIPE2 overexpression and knockdown on the proliferation, migration and invasion of endometrial cell lines and primary adenomyotic endometrial cells were determined using a cell counting kit-8, 5-ethynyl-2'-deoxyuridine assay, colony-forming assay, transwell migration assay and matrigel invasion assay. The expression of EMT-related markers and signal molecules was detected by western blot. The interaction between TIPE2 and β-catenin was detected by co-immunoprecipitation and laser confocal microscopy.

Main Results And The Role Of Chance: The mRNA and protein expression levels of TIPE2 in the eutopic and ectopic endometrial tissues of adenomyosis patients were significantly downregulated compared with the control endometrium (P ˂ 0.01). TIPE2 could bind to β-catenin and inhibit the nuclear translocation of β-catenin, downregulate the expression of stromal cell markers, upregulate the expression of glandular epithelial cell markers, decrease the occurrence of epithelial-mesenchymal transition (EMT) and suppress the migration and invasion of endometrial cells (P ˂ 0.01).

Large Scale Data: N/A.

Limitations, Reasons For Caution: In this study, the experiments were performed only in eutopic and ectopic endometrial tissues, endometrial cancer cell lines and primary adenomyotic endometrial cells. A mouse model of adenomyosis will be constructed to detect the effects of TIPE2 in vivo.

Wider Implications Of The Findings: These results suggest that TIPE2 is involved in the development of adenomyosis, which provides a potential new diagnostic and therapeutic strategy for the treatment of adenomyosis.

Study Fundings/competing Interest(s): This present study was supported by grants from the National Natural Science Foundation of China (81471437, 81771554), Natural Science Foundation of Shandong (ZR2018MH013), Science and technology development plan provided by Health and Family Planning Committee in Shandong (2014-25). The authors declare that they have no conflicts of interest.
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http://dx.doi.org/10.1093/humrep/deaa062DOI Listing
June 2020

Factors associated with the duration of viral shedding in adults with COVID-19 outside of Wuhan, China: a retrospective cohort study.

Int J Infect Dis 2020 Jul 17;96:531-537. Epub 2020 May 17.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha 410011, China; Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Changsha 410011, China.

Objectives: To investigate factors associated with the duration of viral shedding in patients with COVID-19, outside of Wuhan.

Methods: In this retrospective cohort study, patients with laboratory-confirmed COVID-19 in Changsha, China were included. Clinical characteristics, laboratory findings, treatment, and outcome were retrieved. Univariate and multivariate analyses were performed to explore potential factors.

Results: Overall, 147 patients with COVID-19 were included. The median duration of viral shedding (the number of days from symptoms onset until the successive negative detection of SARS-CoV-2 RNA) was 17 days (interquartile range [IQR], 12-21). Multivariate Logistic regression analysis indicated that the highest temperature at admission (odds ratio [OR], 5.200; 95% confidence interval [CI]: 1.190-22.726; p = 0.028), time from symptom onset to admission (OR, 1.740; 95% CI: 1.296-2.337; p < 0.001) and hospital length of stay (OR, 1.604; 95% CI: 1.262-2.040; p < 0.001) were risk factors for prolonged duration of viral shedding.

Conclusions: This study, with a relatively large sample size, focused on the duration of viral shedding and related factors in patients with COVID-19, outside of Wuhan, China. Potential risk factors were identified and should be taken into consideration for the strategy of quarantining infected patients.
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http://dx.doi.org/10.1016/j.ijid.2020.05.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231495PMC
July 2020

Adipose-derived mesenchymal stem cells and extracellular vesicles confer antitumor activity in preclinical treatment of breast cancer.

Pharmacol Res 2020 07 30;157:104843. Epub 2020 Apr 30.

Vaccine and Immunotherapy Center, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Experimental Therapeutics and Molecular Imaging Laboratory, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address:

Both antitumor and protumor property of mesenchymal stem cells (MSCs) have been demonstrated. We hypothesize that this contradiction is due to the heterogeneity of MSC subsets and that extracellular vesicles (EVs) from distinct MSC subsets can transfer the corresponding antitumor activities. Here we evaluated the antitumor activities of two subsets of adipose-derived mesenchymal stem cells (ADSCs) and ADSC-derived EVs (ADSC-EVs) in immunocompetent syngeneic mouse models of breast cancer. We identified CD90 and CD90 ADSC subsets and demonstrated that CD90 ADSCs could be converted into CD90 ADSCs by stimulation with LPS. CD90 ADSCs and its derived EVs significantly inhibited tumor growth in tumor-bearing mice. Benefit of tumor control were associated with decreased tumor cell proliferation and migration, and enhanced tumor cell apoptosis mediated by ADSC-EVs. Antioncogenic miRNA-16-5p loaded CD90 ADSC-EVs further significantly enhanced antitumor activities. Taken together, this study represents the first attempt to apply our newly identified antitumor ADSCs and its derived EVs in preclinical treatment of breast cancer. This study also provides the evidence that EVs can serve as a novel and effective therapeutics or drug delivery vesicle. This new therapeutic approach could be potentially applicable to breast cancer and many other types of cancer.
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http://dx.doi.org/10.1016/j.phrs.2020.104843DOI Listing
July 2020

Heparanase Facilitates PMA-Induced Megakaryocytic Differentiation in K562 Cells via Interleukin 6/STAT3 Pathway.

Thromb Haemost 2020 Apr 14;120(4):647-657. Epub 2020 Apr 14.

Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Academy of Military Medical Sciences, Beijing, China.

Heparanase (HPSE) is an endo-β-D-glucuronidase that cleaves heparan sulfate and hence participates in remodeling of the extracellular matrix, leading to release of cytokines that are immobilized by binding to heparan sulfate proteoglycans (HSPGs), and consequently activating signaling pathways. This function of HPSE is correlated to its expression level that is normally very low in majority of the tissues. Exceptionally, human platelets express high level of HPSE, suggesting a unique physiological role in this cell. Using K562 cell line, we found a progressive increase of HPSE during the megakaryocytic differentiation. Analysis of a series of megakaryocytic differentiation-related heparin-binding proteins (HBPs) in the cell culture medium revealed an exclusive positive correlation between the level of interleukin 6 (IL-6) and HPSE expression. IL-6 modulated megakaryocytic differentiation through activation of STAT3. Further, we demonstrated that overexpression of HPSE potentiates megakaryocytic differentiation, whereas elimination of HPSE led to a delayed differentiation. This function of HPSE is associated with its activity, as overexpression of inactive HPSE had no effect on IL-6 production and megakaryocytic differentiation. The role of HPSE is further supported by the observation in an umbilical cord blood CD34+ cells megakaryocytic differentiation model. Our data propose a novel role for HPSE in platelets production by a HPSE/IL-6/STAT3 positive feedback loop that specifically regulates megakaryocytes maturation.
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http://dx.doi.org/10.1055/s-0040-1705117DOI Listing
April 2020

Correction: Bis(ethylmaltolato)oxidovanadium(iv) inhibited the pathogenesis of Alzheimer's disease in triple transgenic model mice.

Metallomics 2020 04;12(4):631

Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Sciences and Oceanography, Shenzhen University, 518060 Shenzhen, China.

Correction for 'Bis(ethylmaltolato)oxidovanadium(iv) inhibited the pathogenesis of Alzheimer's disease in triple transgenic model mice' by Zhijun He et al., Metallomics, 2020, DOI: 10.1039/c9mt00271e.
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http://dx.doi.org/10.1039/d0mt90008gDOI Listing
April 2020

Direct Activation of Protein Phosphatase 2A (PP2A) by Tricyclic Sulfonamides Ameliorates Alzheimer's Disease Pathogenesis in Cell and Animal Models.

Neurotherapeutics 2020 07;17(3):1087-1103

Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease for which there are limited therapeutic strategies. Protein phosphatase 2A (PP2A) activity is decreased in AD brains, which promotes the hyperphosphorylation of Tau and APP, thus participate in the formation of neurofibrillary tangles (NFTs) and β-amyloid (Aβ) overproduction. In this study, the effect of synthetic tricyclic sulfonamide PP2A activators (aka SMAPs) on reducing AD-like pathogenesis was evaluated in AD cell models and AD-like hyperhomocysteinemia (HHcy) rat models. SMAPs effectively increased PP2A activity, and decreased tau phosphorylation and Aβ levels in AD cell models. In HHcy-AD rat models, cognitive impairments induced by HHcy were rescued by SMAP administration. HHcy-induced tau hyperphosphorylation and Aβ overproduction were ameliorated through increasing PP2A activity on compound treatment. Importantly, SMAP therapy also prevented neuronal cell spine loss and neuronal synapse impairment in the hippocampus of HHcy-AD rats. In summary, our data reveal that pharmacological PP2A reactivation may be a novel therapeutic strategy for AD treatment, and that the tricyclic sulfonamides constitute a novel candidate class of AD therapeutic.
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http://dx.doi.org/10.1007/s13311-020-00841-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609734PMC
July 2020

A mini-panel PET scanner-based microfluidic radiobioassay system allowing high-throughput imaging of real-time cellular pharmacokinetics.

Lab Chip 2020 03;20(6):1110-1123

Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, Hubei Province 430022, China. and Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China.

On-chip radiometric detection of biological samples using radiotracers has become an emerging research field known as microfluidic radiobioassays. Performing parallel radiobioassays is highly desirable for saving time/effort, reducing experimental variation between assays, and minimizing the cost of the radioisotope. Continuously infused microfluidic radioassay (CIMR) is one of the useful tools for investigating cellular pharmacokinetics and assessing the binding and uptakes of radiopharmaceuticals. However, existing CIMR systems can only measure the dynamics of one sample at a time due to the limited field of view (FOV) of the positron detector. To increase the throughput, we propose a new CIMR system with a custom-built miniaturized panel-based positron-emission tomography (PET) scanner and a parallel infusion setup/method, capable of imaging the cellular pharmacokinetics of three samples in one measurement. With this system, the pharmacokinetics of parallel or comparison samples can be imaged simultaneously. The increased throughput is attributed to two innovations: 1) the large 3D FOV of the mini-panel PET scanner, enabling more samples to be imaged in the microfluidic chip; and 2) a parallel infusion method, in which only one reference chamber is needed for indicating the dynamic input of the infused radiotracer medium, thus saving the total reference chambers needed compared to the current sequential infusion method. Combining the CIMR technique and the mini-panel PET scanner, this study also firstly demonstrated the feasibility of using PET, as an imaging modality, for microfluidic radiobioassays. Besides the increased throughput, the 3D imaging of PET also provides possibilities for further applications such as organoid/3D culturing systems, non-planar microfluidics, and organs-on-chips. The system is more practical for a broader range of applications in nuclear medicine, molecular imaging, and lab-on-a-chip studies.
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http://dx.doi.org/10.1039/c9lc01066aDOI Listing
March 2020

Bis(ethylmaltolato)oxidovanadium(iv) inhibited the pathogenesis of Alzheimer's disease in triple transgenic model mice.

Metallomics 2020 04 23;12(4):474-490. Epub 2020 Jan 23.

Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Sciences and Oceanography, Shenzhen University, 518060 Shenzhen, China.

Vanadium compounds have been reported to mimic the anti-diabetes effects of insulin on rodent models, but their effects on Alzheimer's disease (AD) have rarely been explored. In this paper, 9-month-old triple transgenic AD model mice (3×Tg-AD) received bis(ethylmaltolato)oxidovanadium(iv) (BEOV) at doses of 0.2 mmol L (68.4 μg mL) and 1.0 mmol L (342 μg mL) for 3 months. BEOV at both doses was found to improve contextual memory and spatial learning in AD mice. It also improved glucose metabolism and protected neuronal synapses in the AD brain, as evidenced respectively by F-labeled fluoro-deoxyglucose positron emission tomography (F-FDG-PET) scanning and by transmission electron microscopy. Inhibitory effects of BEOV on β-amyloid (Aβ) plaques and neuronal impairment in the cortex and hippocampus of fluorescent AD mice were visualized three-dimensionally by applying optical clearing technology to brain slices before confocal laser scanning microscopy. Western blot analysis semi-quantitatively revealed the altered levels of Aβ in the brains of wildtype, AD, and AD treated with 0.2 and 1.0 mmol L BEOV mice (70.3%, 100%, 83.2% and 56.8% in the hippocampus; 82.4%, 100%, 66.9% and 42% in the cortex, respectively). The mechanism study showed that BEOV increased the expression of peroxisome proliferator-activated receptor γ (PPARγ) (140%, 100%, 142% and 160% in the hippocampus; 167%, 100%, 124% and 133% in the cortex) to inactivate the JAK2/STAT3/SOCS-1 pathway and to block the amyloidogenesis cascade, thus attenuating Aβ-induced insulin resistance in AD models. BEOV also reduced protein tyrosine phosphatase 1B (PTP1B) expression (74.8%, 100%, 76.5% and 53.8% in the hippocampus; 71.8%, 100%, 94.2% and 81.8% in cortex) to promote insulin sensitivity and to stimulate the PI3K/Akt/GSK3β pathway, subsequently reducing tau hyperphosphorylation (phosphorylated tau396 levels were 51.1%, 100%, 56.1% and 50.2% in the hippocampus; 22.2%, 100%, 36.1%, and 24% in the cortex). Our results suggested that BEOV reduced the pathological hallmarks of AD by targeting the pathways of PPARγ and PTP1B in 3×Tg AD mice.
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http://dx.doi.org/10.1039/c9mt00271eDOI Listing
April 2020

VAS2870 and VAS3947 attenuate platelet activation and thrombus formation via a NOX-independent pathway downstream of PKC.

Sci Rep 2019 12 11;9(1):18852. Epub 2019 Dec 11.

Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, 110, Taipei, Taiwan.

NADPH oxidase (NOX) enzymes are involved in a various physiological and pathological processes such as platelet activation and inflammation. Interestingly, we found that the pan-NOX inhibitors VAS compounds (VAS2870 and its analog VAS3947) exerted a highly potent antiplatelet effect. Unlike VAS compounds, concurrent inhibition of NOX1, 2, and 4 by treatment with ML171, GSK2795039, and GKT136901/GKT137831 did not affect thrombin and U46619-induced platelet aggregation. These findings suggest that VAS compounds may inhibit platelet aggregation via a NOX-independent manner. Thus, we aimed to investigate the detailed antiplatelet mechanisms of VAS compounds. The data revealed that VAS compounds blocked various agonist-induced platelet aggregation, possibly via blocking PKC downstream signaling, including IKKβ and p38 MAPK, eventually reducing platelet granule release, calcium mobilization, and GPIIbIIIa activation. In addition, VAS compounds inhibited mouse platelet aggregation-induced by collagen and thrombin. The in vivo study also showed that VAS compounds delayed thrombus formation without affecting normal hemostasis. This study is the first to demonstrate that, in addition to inhibiting NOX activity, VAS compounds reduced platelet activation and thrombus formation through a NOX-independent pathway downstream of PKC. These findings also indicate that VAS compounds may be safe and potentially therapeutic agents for treating patients with cardiovascular diseases.
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http://dx.doi.org/10.1038/s41598-019-55189-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906488PMC
December 2019

FGF-induced regulates the progression and metastasis of osteosarcoma via FRS2/TGF-β/β-catenin pathway.

Cell Div 2019 25;14:13. Epub 2019 Nov 25.

Orthopaedics, Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, No. 139 Renming Road, Changsha, 410010 Hunan People's Republic of China.

Background: Fibroblast growth factor (FGF) and tumor growth factor-β (TGFβ) have emerged as pivotal regulators during the progression of osteosarcoma (OS). LHX9 is one crucial transcription factor controlled by FGF, however, its function in OS has not been investigated yet.

Methods: The expression of , , , -, , - and metastasis-related proteins was measured by real-time quantitative PCR (RT-qPCR) and Western blot. CCK-8 assay and colony formation assay were employed to determine the proliferation of OS cells, while scratch wound healing assay and transwell assay were used to evaluate their migration and invasion, respectively. In vivo tumor growth and metastasis were determined by subcutaneous or intravenous injection of OS cells into nude mice.

Results: expression was evidently up-regulated in OS tumor tissues and cell lines. Knockdown of impaired the proliferation, migration, invasion and metastasis of OS cells. Mechanistically, silencing led to the down-regulation of BMP-4, β-catenin and metastasis-related proteins, which was also observed in - knockdown OS cells. By contrast, knockdown conduced to the up-regulation of , BMP4, β-catenin and TGF-βR1, while - inhibition repressed the expression of and metastasis-related proteins. Additionally, - modulates and metastasis-related proteins by suppressing TGF- R1 expression on transcriptional level.

Conclusions: This study revealed was essential for the proliferation, migration, invasion, and metastasis of OS cells via FGF and TGF-β/β-catenin signaling pathways.
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http://dx.doi.org/10.1186/s13008-019-0056-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876112PMC
November 2019
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