Publications by authors named "Wenjia Li"

71 Publications

Recent Developments About the Pathogenesis of Dry Eye Disease: Based on Immune Inflammatory Mechanisms.

Front Pharmacol 2021 5;12:732887. Epub 2021 Aug 5.

Department of Ophthalmology, The Third People's Hospital of Dalian, Non-Directly Affiliated Hospital of Dalian Medical University, Dalian, China.

Dry eye disease is a common and frequently occurring ophthalmology with complex and diverse causes, and its incidence is on the upward trend. The pathogenesis of DED is still completely clear. However, the immune response based on inflammation has been recognized as the core basis of this disease. In this review, we will systematically review the previous research on the treatment of DED in immune inflammation, analyze the latest views and research hotspots, and provide reference for the prevention and treatment of DED.
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http://dx.doi.org/10.3389/fphar.2021.732887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375318PMC
August 2021

Participatory Action Research on the Impact of Community Gardening in the Context of the COVID-19 Pandemic: Investigating the Seeding Plan in Shanghai, China.

Int J Environ Res Public Health 2021 06 9;18(12). Epub 2021 Jun 9.

College of Architecture and Urban Planning, Key Laboratory of Ecology and Energy-Saving Study of Dense Habitat of Ministry of Education, Tongji University, Shanghai 200092, China.

This study aims to examine the impacts of community gardening on the daily life of residents and the management organisation of pandemic prevention in the context of the COVID-19 pandemic, a major public health scourge in 2020. The research team applied a participatory action research approach to work with residents to design and implement the Seeding Plan, a contactless community gardening program. The authors carried out a study to compare the everyday conditions reflecting residents' mental health of the three subject groups during the pandemic: the participants of the Seeding Plan (Group A), the non-participants living in the same communities that had implemented the Seeding Plan (Group B), and the non-participants in other communities (Group C). According to the results, group A showed the best mental health among the three; Group B, positively influenced by seeding activities, was better than Group C. The interview results also confirmed that the community connections established through gardening activities have a significant impact on maintaining a positive social mentality under extraordinary circumstances. From this, the study concluded that gardening activities can improve people's mental health, effectively resist negative impacts, and it is a convenient tool with spreading influence on the entire community, so as to support the collective response to public health emergencies in a bottom-up direction by the community.
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http://dx.doi.org/10.3390/ijerph18126243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295992PMC
June 2021

A General LC-MS-Based Method for Direct and De Novo Sequencing of RNA Mixtures Containing both Canonical and Modified Nucleotides.

Methods Mol Biol 2021 ;2298:261-277

Department of Biological and Chemical Sciences, New York Institute of Technology, New York, NY, USA.

Mass spectrometry (MS)-based sequencing has advantages in direct sequencing of RNA, compared to cDNA-based RNA sequencing methods, as it is completely independent of enzymes and base complementarity errors in sample preparation. In addition, it allows for sequencing of different RNA modifications in a single study, rather than just one specific modification type per study. However, many technical challenges remain in de novo MS sequencing of RNA, making it difficult to MS sequence mixed RNAs or to differentiate isomeric modifications such as pseudouridine (Ψ) from uridine (U). Our recent study incorporates a two-dimensional hydrophobic end labeling strategy into MS-based sequencing (2D-HELS MS Seq) to systematically address the current challenges in MS sequencing of RNA, making it possible to directly and de novo sequence purified single RNA and mixed RNA containing both canonical and modified nucleotides. Here, we describe the method to sequence representative single-RNA and mixed-RNA oligonucleotides, each with a different sequence and/or containing modified nucleotides such as Ψ and 5-methylcytosine (mC), using 2D-HELS MS Seq.
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http://dx.doi.org/10.1007/978-1-0716-1374-0_17DOI Listing
June 2021

CO activation and dissociation on InO(110) supported PdPt ( = 0-4) catalysts: a density functional theory study.

Phys Chem Chem Phys 2021 May;23(19):11557-11567

State Key Laboratory of Engines, Tianjin University, China.

Converting CO2 into valuable chemicals via catalytic reactions can mitigate both the greenhouse effect and energy shortage problems, thus designing efficient catalysts have attracted considerable attention over the past decades. In this work, a density functional theory (DFT) calculation was carried out to investigate the CO2 activation and dissociation processes on various PdnPt(4-n)/In2O3 (n = 0-4) catalysts. The PdnPt(4-n)/In2O3 models were initially built, and the interface sites of PdnPt(4-n)/In2O3 for CO2 adsorption were confirmed among cluster sites and substrate sites. The CO2 adsorption geometries, charger transfer, and projected density of states (PDOS) were analyzed to study the CO2-PdnPt(4-n)/In2O3 interactions. From the adsorbed *CO2, the transition states (TSs) for CO2 dissociation to form *CO and *O were gained to reveal the characteristics of the activated CO2δ-. Overall, according to the adsorption energy Eads results, the bimetallic PdPt3/In2O3 and Pd3Pt/In2O3 catalysts showed the strongest and weakest CO2 adsorption stabilities, respectively, while the Pd element addition decreases the barriers for CO2 dissociation with the priority order of Pd4 > Pd3Pt > Pd2Pt2 > PdPt3 > Pt4. The Brønsted-Evans-Polanyi (BEP) relation between activation barriers (Eb) and reaction energies E was obtained for the CO2 dissociation mechanism on PdnPt(4-n)/In2O3 catalysts with the equation of E = 0.20Eb + 0.40. Finally, the optimal Pd2Pt2/In2O3 catalyst for CO2 activation and dissociation was proposed. This study provides useful information for CO2 activation and conversation procedures on bimetal-oxide catalysts, and helps to take the optimal design of PdPt/In2O3 catalysts for the CO2 reaction.
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http://dx.doi.org/10.1039/d1cp01015hDOI Listing
May 2021

Relationship of epicardial fat volume with coronary plaque characteristics, coronary artery calcification score, coronary stenosis, and CT-FFR for lesion-specific ischemia in patients with known or suspected coronary artery disease.

Int J Cardiol 2021 06 26;332:8-14. Epub 2021 Mar 26.

Department of Radiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610041, China. Electronic address:

Background: We explored the association of epicardial fat volume (EFV) with coronary plaque characteristics, coronary artery calcification (CAC) score, coronary stenosis, lesion-specific ischemia in patients with known or suspected coronary artery disease (CAD).

Methods: 88 controls and 221 patients were analyzed in the study. High-risk plaque was defined as existing≥2 features, including positive remodeling, low attenuation, napkin-ring sign and spotty calcification. EFV, CAC score was measured. The severity of coronary stenosis was quantified using Gensini score. CT-FFR was performed in three major coronary arteries, with a threshold of ≤0.8 considered the presence of ischemia. Univariate and multivariate regression was used to evaluate the association of EFV with CAD, palque characteristics, CAC score, Gensini score, and lesion-specific ischemia derived from CT-FFR.

Results: Median EFV was 104.97 cm (85.47-136.09) in controls and 129.28cm (101.19-159.44) in patients (P < 0.001). Logistic regression analysis revealed a significant association of EFV with CAD even after adjusting for confounding factors (P < 0.05). At linear regression analysis, EFV was significantly correlated with high-risk plaque and lesion-specific ischemia, but not with non-calcified plaque, mixed plaque, calcified plaque, CAC score and Gensini score (P ≥ 0.05).

Conclusion: We found that EFV was associated with CAD, suggesting that it may be a promising marker of CAD. EFV was also correlated with high-risk plaque and lesion-specific ischemia, indicating that EAT was likely to be involved in myocardial ischemia and had the potential to definite patients' risk profile.
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http://dx.doi.org/10.1016/j.ijcard.2021.03.052DOI Listing
June 2021

The first complete mitochondrial genome of eggplant ().

Mitochondrial DNA B Resour 2021 Mar 1;6(2):650-652. Epub 2021 Mar 1.

Institute of Vegetable Research, Guangxi Academy of Agricultural Sciences, Nanning, China.

Eggplant is an important vegetable crop because of its rich nutrition, but to date no mitochondrial genome has been reported. In this study, the complete mitochondrial genome of the eggplant was sequenced. The complete mitochondrial genome was 498,136bp, linear structure, containing 54 protein-coding genes, four rRNAs, and 32 tRNAs. The phylogenetic tree supported the hypothesis that the eggplant is most closely related to and .
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http://dx.doi.org/10.1080/23802359.2021.1878948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928190PMC
March 2021

Effects of metformin, insulin on COVID-19 patients with pre-existed type 2 diabetes: A multicentral retrospective study.

Life Sci 2021 Jun 19;275:119371. Epub 2021 Mar 19.

Department of Endocrinology, Xiangyang No. 1 People's Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei Province 441000, China. Electronic address:

Aims: Type 2 diabetes is considered to be one of the essential risks of adverse outcomes in coronavirus disease 2019 (COVID-19). Metformin and insulin were suggested to affect the outcomes. However, divergent views are still expressed. We aim to gain further insight into metformin and insulin in both pre-admission and in-hospital usage in COVID-19 patients with pre-existed type 2 diabetes.

Main Methods: This is a multicentral retrospective study of the hospital confirmed COVID-19 patients between January 19 to April 09, 2020, who admitted to 3 main hospitals in Xiangyang city, China. The effect of type 2 diabetes, metformin, and insulin on COVID-19 were analyzed, respectively. Clinical characteristics, blood laboratory indices, clinical observational indices, and outcomes of these cases were collected.

Key Findings: A total of 407 confirmed COVID-19 patients (including 50 pre-existed type 2 diabetes) were eligible in our study. COVID-19 patients with type 2 diabetes had more adverse outcomes than non-diabetes (OR: mortality: 1.46 [95% CI 1.11, 1.93]; P < 0.001). Pre-admission metformin usage showed a declined intensive care unit admission rate in a dose-dependent fashion (OR 0.04 [95% CI 0.00, 0.99]; adjust P = 0.049). While in-hospital insulin usage attempted to increase the invasive ventilation (8 [34.8%] vs. 1 [3.7%], adjust P = 0.043), independent of age and blood glucose.

Significance: Our study indicated that pre-admitted metformin usage may have beneficial effects on COVID-19 with pre-existed type 2 diabetes, insulin should be used sparingly in the hospital stay.
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http://dx.doi.org/10.1016/j.lfs.2021.119371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972834PMC
June 2021

Switchable dual-band to broadband terahertz metamaterial absorber incorporating a VO phase transition.

Opt Express 2021 Feb;29(4):5437-5447

We design and demonstrate a thermally switchable terahertz metamaterial absorber consisting of an array of orthogonal coupled split-ring metal resonators involving a VO phase transition. Numerical results indicate that the active metamaterial always absorbs the TE wave in dual-band regardless of insulating and metallic VO, while the insulator-to-metal phase transition enables a switchable effect between dual-band and broadband absorption of the TM wave with the resonant frequency tunability of 33%. Especially under the metallic VO state, the absorption properties are polarization-dependent and exhibit a switching effect between dual-band and broadband absorption with the increase of the polarization angle. The tunable absorption mechanism can be explained by effective impedance theory and electric energy density distributions. The proposed dual-band to broadband metamaterial switching absorber may have broad applications in sensors, imaging and emitters.
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http://dx.doi.org/10.1364/OE.418020DOI Listing
February 2021

Microwave-assisted synthesis of fluorescent silicon quantum dots for ratiometric sensing of Hg (II) based on the regulation of energy transfer.

Talanta 2021 May 11;226:122093. Epub 2021 Jan 11.

Key Laboratory of Modern Agricultural Equipment and Technology, Ministry of Education, School of Agricultural Engineering, Jiangsu University, Zhenjiang, 212013, China. Electronic address:

The rapid and sensitive detection of Hg is highly required to protect the environmental safety and human healthy. In the present work, a ratiometric fluorescent sensing platform, consisting of silicon quantum dots (SiQDs), Rox-labelled DNA (Rox-DNA), and Exonuclease III (Exo III), is developed for the accurate detection of Hg. As for fluorescent probe, we report the first use of glutathione as reduction reagent for the microwave synthesis of SiQDs, achieving the facile (using a house-hold microwave oven) and rapid (within 8 min) synthesis. Such SiQDs show pH-independent spectra and reversible fluorescent behavior with temperature. Moreover, experimental results revealed that the electrostatic interaction-induced aggregation of Rox-DNA and SiQDs facilitated the occurring of energy transfer (ET). And detection principle based on the regulation of ET between Rox and SiQDs with Exo III was designed for analysis. ET effect resulted in the fluorescent fading of Rox while that of SiQDs kept stable. For analysis, the addition of Hg led to the formation of double-stranded Rox-DNA via T-Hg-T. Exo III would cut these double-stranded DNA to release Rox and Hg, thereby impeding the ET effect and recovering the fluorescent of Rox. Such SiQDs/Rox-DNA/Exo III ratiometric fluorescent sensing platform exhibited a linear response concentration range of 0.02 nM-10 nM with a detection limit of 0.01 nM. It was successfully used to analyze the water and soil samples. The reliability was validated by ICP-MS. Our work should promote the practical application of ratiometric fluorescent assay.
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http://dx.doi.org/10.1016/j.talanta.2021.122093DOI Listing
May 2021

Inheritance of chloroplast genomic DNA in interspecific hybrids.

Mitochondrial DNA B Resour 2021 Feb 8;6(2):351-357. Epub 2021 Feb 8.

Institute of Vegetable Research, Guangxi Academy of Agricultural Sciences, Nanning, China.

The chloroplast genomic information was obtained from three wild and four hybrids by chloroplast genome sequencing. The chloroplast genomes of the seven samples comprise of a circular structure and sizes from 155,581 to 155,612 bp and composed of 130 genes. The genome structures of the two hybrids were identical, while the other two hybrids showed 2 bp differences in the LSC when compared with their maternal parent. The total sites of SNP and InDel were 39-344 and 54-90, respectively. With the exception of one hybrid with two additional sites, the other hybrids were identical to their maternal.
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http://dx.doi.org/10.1080/23802359.2020.1866450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872556PMC
February 2021

Alda-1 treatment promotes the therapeutic effect of mitochondrial transplantation for myocardial ischemia-reperfusion injury.

Bioact Mater 2021 Jul 8;6(7):2058-2069. Epub 2021 Jan 8.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Mitochondrial damage is a critical driver in myocardial ischemia-reperfusion (I/R) injury and can be alleviated via the mitochondrial transplantation. The efficiency of mitochondrial transplantation is determined by mitochondrial vitality. Because aldehyde dehydrogenase 2 (ALDH2) has a key role in regulating mitochondrial homeostasis, we aimed to investigate its potential therapeutic effects on mitochondrial transplantation via the use of ALDH2 activator, Alda-1. Our present study demonstrated that time-dependent internalization of exogenous mitochondria by cardiomyocytes along with ATP production were significantly increased in response to mitochondrial transplantation. Furthermore, Alda-1 treatment remarkably promoted the oxygen consumption rate and baseline mechanical function of cardiomyocytes caused by mitochondrial transplantation. Mitochondrial transplantation inhibited cardiomyocyte apoptosis induced by the hypoxia-reoxygenation exposure, independent of Alda-1 treatment. However, promotion of the mechanical function of cardiomyocytes exposed to hypoxia-reoxygenation treatment was only observed after mitochondrial Alda-1 treatment and transplantation. By using a myocardial I/R mouse model, our results revealed that transplantation of Alda-1-treated mitochondria into mouse myocardial tissues limited the infarction size after I/R injury, which was at least in part due to increased mitochondrial potential-mediated fusion. In conclusion, ALDH2 activation in mitochondrial transplantation shows great potential for the treatment of myocardial I/R injury.
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http://dx.doi.org/10.1016/j.bioactmat.2020.12.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809100PMC
July 2021

A high-quality genome assembly of the eggplant provides insights into the molecular basis of disease resistance and chlorogenic acid synthesis.

Mol Ecol Resour 2021 May 3;21(4):1274-1286. Epub 2021 Feb 3.

Institute of Vegetable Research, Guangxi Academy of Agricultural Sciences, Nanning, China.

The eggplant (Solanum melongena L.) is one of the most important Solanaceae crops, ranking third for total production and economic value in its genus. Herein, we report a high-quality, chromosome-scale eggplant reference genome sequence of 1155.8 Mb, with an N50 of 93.9 Mb, which was assembled by combining PacBio long reads and Hi-C sequencing data. Repetitive sequences occupied 70.1% of the assembly length, and 35,018 high-confidence protein-coding genes were annotated based on multiple sources. Comparative analysis revealed 646 species-specific families and 364 positive selection genes, conferring distinguishing traits on the eggplant. We performed genome-wide comparative identification of disease resistance genes and discovered an expanded gene family of bacterial spot resistance in eggplant and pepper, but not in tomato and potato. The genes involved in chlorogenic acid synthesis were comprehensively characterized. Highly similar chromosomal distribution patterns of polyphenol oxidase genes were observed in the eggplant, tomato, and potato genomes. The eggplant reference genome sequence will not only facilitate evolutionary studies of the Solanaceae but also facilitate their breeding and improvement.
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http://dx.doi.org/10.1111/1755-0998.13321DOI Listing
May 2021

A novel GLP-1 and FGF21 dual agonist has therapeutic potential for diabetes and non-alcoholic steatohepatitis.

EBioMedicine 2021 Jan 7;63:103202. Epub 2021 Jan 7.

Department of Endocrinology, National Center of Gerontology, Beijing Hospital, Beijing, China. Electronic address:

Background: Fibroblast growth factor 21 (FGF21) has become a promising therapeutic target for metabolic diseases such as type 2 diabetes (T2D), obesity and non-alcoholic steatohepatitis. However, the clinical application of natural FGF21 molecule is limited because of its instability in vitro and short half-life in vivo. To improve FGF21's therapeutic property, we screened high receptor binding FGF21 analogs and made FGF21-Fc-GLP-1 dual-targeted constructs to investigate their activity in a number of experiments .

Methods: Utilizing phage display high-throughput screening we identified mutations that could improve β-Klotho binding property of FGF21. IgG4 Fc was fused to FGF21 variants to extend the in vivo half-life. We further explored the potential synergistic actions of FGF21 with the incretin glucagon-like peptide-1 (GLP-1) by generating GLP-1-Fc-FGF21 dual agonists.

Findings: Two Fc-FGF21 variants showed enhanced β-Klotho binding affinity in vitro as well as improved glucose lowering effect in vivo. One of the dual agonists, GLP-1-Fc-FGF21 D1, provided potent and sustained glucose lowering effect in diabetic mice models. It also demonstrated superior weight loss effect to GLP-1 or FGF21 alone. Moreover, GLP-1-Fc-FGF21 D1 exhibited strong anti-NASH effect in the high-fat diet-induced ob/ob model as it improved liver function, serum and hepatic lipid profile and reduced NAFLD activity score with an efficacy superior to either FGF21 or GLP-1 analogs alone.

Interpretation: This novel GLP-1/FGF21 dual agonist is worth clinical development for the treatment of T2D, obesity and NASH.

Funding: HEC Pharm R&D Co., Ltd, National natural science fund of China.
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http://dx.doi.org/10.1016/j.ebiom.2020.103202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806870PMC
January 2021

Epidermolysis bullosa acquisita as an adverse effect from rituximab therapy: A case report.

Medicine (Baltimore) 2020 Dec;99(49):e23496

The People's Hospital of Huantai County, Zibo, Shandong, China.

Rationale: Rituximab is a monoclonal antibody directed against B cells and is a first-line agent for the treatment of B cell lymphoma and a second-line agent for the treatment of idiopathic thrombocytopenic purpura (ITP). It has also been used for the treatment of several other autoimmune diseases. Epidermolysis bullosa acquisita (EBA) has never been reported as an adverse effect resulted from rituximab therapy.

Patient Concerns: A 54-year-old female presented with relapse of the ITP for around eight months. She was treated with rituximab. Intramuscular chlorpheniramine and intravenous methylprednisolone and cimetidine were used as premedication before rituximab infusion. The infusion was initially started at 50 mg/h for 1 h followed by 100 mg/h till the end of infusion. The day after rituximab infusion, the patient noticed pruritic blisters on both arms and chest skin. The next day, the lesions increased in severity and extent.

Diagnosis: The skin biopsy established the diagnosis of EBA. H&E staining revealed subepidermal blisters infiltrated by inflammatory cells, including eosinophils and lymphocytes. Direct immunofluorescence (DIF) showed linear deposition of IgG and C3 at the dermoepidermal junction. Indirect immunofluorescence with the patient's serum on salt-split skin revealed exclusive dermal binding of circulating IgG antibasement membrane antibodies at a titer of 1:160.

Interventions: She was treated with intravenous methylprednisolone and was continued on oral prednisolone.

Outcomes: The lesions regressed. Six weeks later, she had a recurrence of similar lesions but in milder form. This episode subsided in 4 to 5 days with topical steroid application.

Lessons: Physicians should consider this diagnosis when a patient develops bullous skin eruptions while undergoing Rituximab therapy.
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http://dx.doi.org/10.1097/MD.0000000000023496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717850PMC
December 2020

Zero-Dimensional MXene-Based Optical Devices for Ultrafast and Ultranarrow Photonics Applications.

Adv Sci (Weinh) 2020 Nov 27;7(22):2002209. Epub 2020 Sep 27.

Shenzhen Engineering Laboratory of Phosphorene and Optoelectronics Collaborative Innovation Center for Optoelectronic Science and Technology Shenzhen University Shenzhen 518060 China.

In recent years, MXene has become a hotspot because of its good conductivity, strong broadband absorption, and tunable band gap. In this contribution, 0D MXene TiCT quantum dots are synthesized by a liquid exfoliation method and a wideband nonlinear optical response from 800 to 1550 nm is studied, which have a larger nonlinear absorption coefficient of -(11.24 ± 0.14) × 10 cm GW. The carrier dynamic processes of 0D MXene are explored with ultrahigh time resolution nondegenerate transient absorption (TA) spectroscopy, which indicates that the TA signal reaches its maximum in 1.28 ps. Furthermore, 0D MXene is used to generate ultrashort pulses in erbium or ytterbium-doped fiber laser cavity. High signal-to-noise (72 dB) femtosecond lasers with pulse durations as short as 170 fs with spectrum bandwidth of 14.8 nm are obtained. Finally, an ultranarrow fiber laser based on 0D MXene is also investigated and has a full width at half maximum of only 5 kHz, and the power fluctuation is less than 0.75% of the average power. The experimental works prove that 0D MXene is an excellent SA and has a promising application in ultrafast and ultranarrow photonics.
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http://dx.doi.org/10.1002/advs.202002209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675195PMC
November 2020

Inhibition of Yes-Associated Protein by Verteporfin Ameliorates Unilateral Ureteral Obstruction-Induced Renal Tubulointerstitial Inflammation and Fibrosis.

Int J Mol Sci 2020 Oct 31;21(21). Epub 2020 Oct 31.

Department of Internal Medicine, Research Institute of Clinical Medicine, Jeonbuk National University Medical School, Jeonju 54907, Korea.

Yes-associated protein (YAP) activation after acute ischemic kidney injury might be related to interstitial fibrosis and impaired renal tubular regeneration. Verteporfin (VP) is a photosensitizer used in photodynamic therapy to treat age-related macular degeneration. In cancer cells, VP inhibits TEA domain family member (TEAD)-YAP interactions without light stimulation. The protective role of VP in unilateral ureteral obstruction (UUO)-induced renal fibrosis and related mechanisms remains unclear. In this study, we investigate the protective effects of VP on UUO-induced renal tubulointerstitial inflammation and fibrosis and its regulation of the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. We find that VP decreased the UUO-induced increase in tubular injury, inflammation, and extracellular matrix deposition in mice. VP also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells by modulating Smad2 and Smad3 phosphorylation. Therefore, YAP inhibition might have beneficial effects on UUO-induced tubulointerstitial inflammation and fibrosis by regulating the TGF-β1/Smad signaling pathway.
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http://dx.doi.org/10.3390/ijms21218184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662854PMC
October 2020

SIRT5 deficiency enhances the proliferative and therapeutic capacities of adipose-derived mesenchymal stem cells via metabolic switching.

Clin Transl Med 2020 Sep;10(5):e172

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China.

Background: Mesenchymal stem cells (MSCs) have therapeutic potential for multiple ischemic diseases. However, in vitro expansion of MSCs before clinical application leads to metabolic reprogramming from glycolysis to oxidative phosphorylation, drastically impairing their proliferative and therapeutic capacities. This study aimed to define the regulatory effects of Sirtuin 5 (SIRT5) on the proliferative and therapeutic functions of adipose-derived MSCs (ADMSCs) during in vitro expansion.

Methods: ADMSCs were isolated from wild-type (WT) and Sirt5-knockout (Sirt5 ) mice. Cell counting assay was used to investigate the proliferative capacities of the ADMSCs. Dihydroethidium and senescence-associated β-galactosidase stainings were used to measure intracellular ROS and senescence levels. Mass spectrometry was used to analyze protein succinylation. Oxygen consumption rates and extra cellular acidification rates were measured as indicators of mitochondrial respiration and glycolysis. Metabolic-related genes expression were verified by quantitative PCR and western blot. Hind limb ischemia mouse model was used to evaluate the therapeutic potentials of WT and Sirt5 ADSMCs.

Results: SIRT5 protein levels were upregulated in ADMCs during in vitro expansion. Sirt5 ADMSCs exhibited a higher proliferation rate, delayed senescence, and reduced ROS accumulation. Furthermore, elevated protein succinylation levels were observed in Sirt5 ADMSCs, leading to the reduced activity of tricarboxylic acid cycle-related enzymes and attenuated mitochondrial respiration. Glucose uptake, glycolysis, and pentose phosphate pathway were elevated in Sirt5 ADMSCs. Inhibition of succinylation by glycine or re-expression of Sirt5 reversed the metabolic alterations in Sirt5 ADMSCs, thus abolishing their enhanced proliferative capacities. In the hind limb ischemia mouse model, SIRT5 ADMSCs transplantation enhanced blood flow recovery and angiogenesis compared with WT ADMSCs.

Conclusions: Our results indicate that SIRT5 deficiency during ADMSC culture expansion leads to reversed metabolic pattern, enhanced proliferative capacities, and improved therapeutic outcomes. These data suggest SIRT5 as a potential target to enhance the functional properties of MSCs for clinical application.
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http://dx.doi.org/10.1002/ctm2.172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510333PMC
September 2020

Effects of alpha-lipoic acid on the behavior, serum indicators, and bone quality of broilers under stocking density stress.

Poult Sci 2020 Oct 16;99(10):4653-4661. Epub 2020 Jun 16.

Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China. Electronic address:

The objective of present study was to investigate the effects of alpha-lipoic acid (ALA) dietary supplementation on the behavior, physiological and oxidant stress indicators, and bone quality in broilers under high stocking density (HSD) stress. A total of one thousand eight hundred 22-day-old Arbor Acres male broiler chicks were randomly allocated to 18 pens (2.97 × 2.03 m) in 3 groups: 14 birds/m (NSD, normal stocking density) or 18 birds/m (HSD) or 18 birds/m plus 300 mg/kg ALA dietary supplement (HSD + ALA, high stocking density + alpha-lipoic acid). Each treatment had 6 replicates, and the experiment lasted 3 wk. The HSD group was significantly lower than the NSD group (P < 0.05) in the frequency of eating, walking, and preening behavior. The alkaline phosphatase activity and serum calcium content were significantly higher, and the parathyroid hormone (PTH) level was significantly lower in the HSD group than in the NSD group (P < 0.05). When compared with the NSD group, the HSD group showed an increase (P < 0.05) in serum heterophil/lymphocyte ratio (H/L ratio), corticosterone (CORT), malondialdehyde (MDA) content, and catalase (CAT) activity, whereas a decrease (P < 0.05) in total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) concentrations. The HSD group was also significantly lower (P < 0.05) than the NSD group in the tibia and femur breaking strength, bone mineral density, and BMC. Importantly, the addition of ALA into the diets of the HSD group enabled the HSD + ALA group to recover to the levels of NSD group (P > 0.05) in the standing and preening behavior, alkaline phosphatase activity, PTH concentration, H/L ratio, CAT, T-AOC, MDA, SOD, and GSH-Px. These results indicate that the increase of stocking density lowered the bone quality, increased the physiological and oxidative stress indicators, and modified the behavior of broilers, whereas ALA dietary supplementation could counteract the reduction in the performance and physiological responses of broilers under high-density environmental stress.
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http://dx.doi.org/10.1016/j.psj.2020.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598135PMC
October 2020

A green liquid chromatography method for rapid determination of ergosterol in edible fungi based on matrix solid-phase dispersion extraction and a core-shell column.

Anal Methods 2020 07;12(26):3337-3343

Key Laboratory of State Administration of Traditional Chinese Medicine, Sunshine Lake Pharma Co., Ltd., Dongguan, Guangdong 523850, China.

Developing a green analytical method for the analysis of components in food samples is an important research aspect of liquid chromatography (LC). The traditional LC method usually consumes a lot of toxic solvent for sample extraction and LC separation. In the current study, a green analytical method for the rapid determination of ergosterol in edible fungi was established. The sample was extracted and purified by matrix solid-phase dispersion (MSPD) with a green solution (ethanol and water). The LC separation was performed using a Poroshell 120 SB-C18 (4.6 × 30 mm, 2.7 μm) column with a green mobile phase (94% ethanol) at a flow rate of 1.0 mL min-1. The detection wavelength was set at 283 nm. The calibration curve of ergosterol showed good linearity (R = 0.9999) within the test range (4.21-25.27 μg mL-1). The RSD of precision was less than 2.0% and the recovery was 100.4% (RSD = 3.23%). The developed method was successfully applied to quantitative analysis of ergosterol in six edible fungi and the contents of ergosterol were in the range of 1.68-4.02 mg g-1. Only 11.5 mL ethanol water solution was used in the sample extraction and LC separation in the newly developed method, and no toxic organic solvents were used. The total analysis time was less than 15.5 min, about 12-14 min for sample extraction and 1.5 min for LC analysis. This method was environmentally friendly and time-saving, which is helpful to improve the quality evaluation of edible fungi.
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http://dx.doi.org/10.1039/d0ay00714eDOI Listing
July 2020

PARK2 promotes mitochondrial pathway of apoptosis and antimicrotubule drugs chemosensitivity degradation of phospho-BCL-2.

Theranostics 2020 8;10(22):9984-10000. Epub 2020 Aug 8.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

Neoadjuvant chemotherapy has become the standard treatment of locally advanced breast cancer. Antimicrotubule drugs and DNA-damaging drugs are the most popular medicines used for neoadjuvant chemotherapy. However, we are unable to predict which chemotherapeutic drug will benefit to an individual patient. PARK2 as a tumor suppressor in breast cancer has been reported. While the role of PARK2 in chemotherapy response remains unknown. In this study, we explore the impact of PARK2 on chemosensitivity in breast cancer. PARK2 expression in breast cancer patients with different neoadjuvant chemotherapeutic regimens was studied using immunohistochemistry. Data was correlated to disease-free survival (DFS), overall survival and pathologic complete response (pCR). The functional roles of PARK2 were demonstrated by a series of and experiments. Including mass spectrometry, Co-immunoprecipitation, isolation of subcellular fractionation, fluorescence microscopy, ubiquitination assay and luciferase analyses. Highly expressed PARK2 predicted better response to antimicrotubule drugs-containing regimen associated with higher rate of pathologic complete response (pCR). In contrast, PARK2 expression did not predict response to the DNA-damaging drugs regimen. Following antimicrotubule drugs treatment, levels of PARK2 was upregulated due to the repression of STAT3-mediated transcriptional inhibition of PARK2. Moreover, overexpression of PARK2 specifically rendered cells more sensitive to antimicrotubule drugs, but not to DNA-damaging drugs. Depletion of PARK2 enhanced resistance to antimicrotubule drugs. Mechanistically, PARK2 markedly activated the mitochondrial pathway of apoptosis after exposure to antimicrotubule drugs. This occurred through downregulating the antiapoptotic protein, phospho-BCL-2. BCL-2 phosphorylation can be specifically induced by antimicrotubule drugs, whereas DNA-damaging drugs do not. Notably, PARK2 interacted with phospho-BCL-2 (Ser70) and promoted ubiquitination of BCL-2 in an E3 ligase-dependent manner. Hence, PARK2 significantly enhanced the chemosensitivity of antimicrotubule drugs both , while loss-of-function PARK2 mutants did not. Our findings explained why PARK2 selectively confers chemosensitivity to antimicrotubule drugs, but not to DNA-damaging drugs. In addition, we identified PARK2 as a novel mediator of antimicrotubule drugs sensitivity, which can predict response of breast cancer patients to antimicrotubule drugs-containing regime.
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http://dx.doi.org/10.7150/thno.47044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481404PMC
May 2021

Comparative transcriptome analysis provides insights into the molecular mechanism underlying double fertilization between self-crossed Solanum melongena and that hybridized with Solanum aethiopicum.

PLoS One 2020 6;15(8):e0235962. Epub 2020 Aug 6.

Institute of Vegetable Research, Guangxi Academy of Agricultural Sciences, Nanning, China.

Wild relatives represent a source of variation for many traits of interest for eggplant (Solanum melongena) breeding, as well as for broadening its genetic base. However, interspecific hybridization with wild relatives has been barely used in eggplant breeding programs, and reproductive barriers have resulted in reduced seed numbers in interspecific combinations. The mechanism underlying this phenomenon remains unclear. We hybridized females of cultivated eggplant 177 (Solanum melongena) with males of wild relatives 53 and Y11 (Solanum aethiopicum). Self-crossed 177 was the control. The seed number per control fruit was significantly higher than that of the hybrids. Paraffin sections showed no significant difference between control and 177×53 and 177×Y11. Double fertilization began 4 days post-pollination. Sperm cells were fused with egg cells 6 days post-pollination. To understand the differences in molecular mechanisms underlying this process, transcriptomes of ovaries at 0, 4, and 6 days after self-crossing and hybridization were analyzed. We screened 22,311 differentially expressed genes (DEGs) between the control and hybrids 4 and 6 days post-pollination. A total of 497 DEGs were shared among all pollination combinations. These DEGs were enriched in plant hormone transduction, cell senescence, metabolism, and biosynthesis pathways. DEG clustering analysis indicated distinct expression patterns between the control and hybrids but not between the hybrids. The DEGs in hybrids involved secondary metabolic process, phenylpropanoid metabolic process, and carboxypeptidase activity, while those in the control involved xyloglucan metabolic process, auxin-activated signaling pathway, cell wall polysaccharide metabolic process, and xyloglucosyl transferase activity. Additionally, 1683 transcription factors, including members of the AP2-ERF, MYB, bHLH, and B3 families may play important roles in self-crossing and hybridization. Our results provide insights into the regulatory mechanisms underlying variations between ovaries of self-crossed and hybrid eggplants and a basis for future studies on crossbreeding Solanum and genetic mechanisms underlying double fertilization.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235962PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410197PMC
October 2020

Alpha-lipoic acid protects against pressure overload-induced heart failure via ALDH2-dependent Nrf1-FUNDC1 signaling.

Cell Death Dis 2020 07 30;11(7):599. Epub 2020 Jul 30.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.

Alpha-lipoic acid (α-LA), a well-known antioxidant, was proved to active ALDH2 in nitrate tolerance and diabetic animal model. However, the therapeutic advantage of α-LA for heart failure and related signaling pathway have not been explored. This study was designed to examine the role of α-LA-ALDH2 in heart failure injury and mitochondrial damage. ALDH2 knockout (ALDH2) mice and primary neonatal rat cardiomyocytes (NRCMs) were subjected to assessment of myocardial function and mitochondrial autophagy. Our data demonstrated α-LA significantly reduced the degree of TAC-induced LV hypertrophy and dysfunction in wild-type mice, not in ALDH2 mice. In molecular level, α-LA significantly restored ALDH2 activity and expression as well as increased the expression of a novel mitophagy receptor protein FUNDC1 in wild-type TAC mice. Besides, we confirmed that ALDH2 which was activated by α-LA governed the activation of Nrf1-FUNDC1 cascade. Our data suggest that α-LA played a positive role in protecting the heart against adverse effects of chronic pressure overload.
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http://dx.doi.org/10.1038/s41419-020-02805-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393127PMC
July 2020

2D-HELS MS Seq: A General LC-MS-Based Method for Direct and de novo Sequencing of RNA Mixtures with Different Nucleotide Modifications.

J Vis Exp 2020 07 10(161). Epub 2020 Jul 10.

Department of Biological and Chemical Sciences, New York Institute of Technology;

Mass spectrometry (MS)-based sequencing approaches have been shown to be useful in direct sequencing RNA without the need for a complementary DNA (cDNA) intermediate. However, such approaches are rarely applied as a de novo RNA sequencing method, but used mainly as a tool that can assist in quality assurance for confirming known sequences of purified single-stranded RNA samples. Recently, we developed a direct RNA sequencing method by integrating a 2-dimensional mass-retention time hydrophobic end-labeling strategy into MS-based sequencing (2D-HELS MS Seq). This method is capable of accurately sequencing single RNA sequences as well as mixtures containing up to 12 distinct RNA sequences. In addition to the four canonical ribonucleotides (A, C, G, and U), the method has the capacity to sequence RNA oligonucleotides containing modified nucleotides. This is possible because the modified nucleobase either has an intrinsically unique mass that can help in its identification and its location in the RNA sequence, or can be converted into a product with a unique mass. In this study, we have used RNA, incorporating two representative modified nucleotides (pseudouridine (Ψ) and 5-methylcytosine (mC)), to illustrate the application of the method for the de novo sequencing of a single RNA oligonucleotide as well as a mixture of RNA oligonucleotides, each with a different sequence and/or modified nucleotides. The procedures and protocols described here to sequence these model RNAs will be applicable to other short RNA samples (<35 nt) when using a standard high-resolution LC-MS system, and can also be used for sequence verification of modified therapeutic RNA oligonucleotides. In the future, with the development of more robust algorithms and with better instruments, this method could allow sequencing of more complex biological samples.
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http://dx.doi.org/10.3791/61281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398574PMC
July 2020

Joint Reconstituted Signaling of the IL-6 Receptor via Extracellular Vesicles.

Cells 2020 05 24;9(5). Epub 2020 May 24.

Biochemical Institute, Christian-Albrechts-University Kiel, Otto-Hahn Platz 9, 24118 Kiel, Germany.

Interleukin-6 (IL-6) signaling is a crucial regulatory event important for many biological functions, such as inflammation and tissue regeneration. Accordingly, several pathological conditions are associated with dysregulated IL-6 activity, making it an attractive therapeutic target. For instance, blockade of IL-6 or its α-receptor (IL-6R) by monoclonal antibodies has been successfully used to treat rheumatoid arthritis. However, based on different signaling modes, IL-6 function varies between pro- and anti-inflammatory activity, which is critical for therapeutic intervention. So far, three modes of IL-6 signaling have been described, the classic anti-inflammatory signaling, as well as pro-inflammatory trans-signaling, and trans-presentation. The IL-6/IL-6R complex requires an additional β-receptor (gp130), which is expressed on almost all cells of the human body, to induce STAT3 (signal transducer and activator of signal transcription 3) phosphorylation and subsequent transcriptional regulation. In contrast, the IL-6R is expressed on a limited number of cells, including hepatocytes and immune cells. However, the proteolytic release of the IL-6R enables trans-signaling on cells expressing gp130 only. Here, we demonstrate a fourth possibility of IL-6 signaling that we termed (JRS). We show that IL-6R on extracellular vesicles (EVs) can also be transported to and fused with other cells that lack the IL-6R on their surface. Importantly, JRS via EVs induces delayed STAT3 phosphorylation compared to the well-established trans-signaling mode. EVs isolated from human serum were already shown to carry the IL-6R, and thus this new signaling mode should be considered with regard to signal intervention.
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http://dx.doi.org/10.3390/cells9051307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291149PMC
May 2020

Extracts of Cordyceps sinensis inhibit breast cancer growth through promoting M1 macrophage polarization via NF-κB pathway activation.

J Ethnopharmacol 2020 Oct 15;260:112969. Epub 2020 May 15.

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

Ethnopharmacological Relevance: Cordyceps sinensis is a traditional Chinese medicine. It is widely reported that Cordyceps sinensis has inhibitory effect on tumor growth and immunoregulation effect on macrophages. However, the exact mechanism of Cordyceps sinensis on macrophage polarization in tumor progression is not known.

Aim Of Study: We aimed to investigate the role of extracts of Cordyceps sinensis on macrophage polarization and its underlying mechanism in antitumor activity.

Materials And Methods: The 4T1 orthotopic xenograft mouse model and immunohistochemical staining were used to investigate the effect of Cordyceps sinensis on breast tumor and the change of the macrophages phenotype in the tumor, respectively. A 3D co-culture assay was used to confirm the activity in vitro. Measurement of cytokines and NO, quantitative real-time PCR and flow cytometry assays were used to investigate the effect of Cordyceps sinensis on the macrophage polarization in vitro. The mechanism of the effect of Cordyceps sinensis on macrophages was investigated by using western blot assays.

Results: In the orthotopic mouse tumor model, Cordyceps sinensis inhibited the 4T1 tumor growth in a dose dependent manner, and the immunohistochemical staining analysis showed that there is a positive correlation between tumor growth inhibition and macrophage M1-like polarized phenotype. The cytokines and NO measurement, quantitative real-time PCR assay and flow cytometry assays confirmed that Cordyceps sinensis could promote macrophage differentiation toward the M1 phenotype. The 3D co-culture assay and western blot assay showed that Cordyceps sinensis could inhibit tumor growth by promoting macrophage polarization and enhance its activity by activating the NF-κB signaling pathway.

Conclusion: These findings suggest that Cordyceps sinensis could potently suppress TNBC progression by promoting M1 phenotypic differentiation of macrophages via activation NF-κB signaling pathway in tumor microenvironment.
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http://dx.doi.org/10.1016/j.jep.2020.112969DOI Listing
October 2020

Direct Sequencing of tRNA by 2D-HELS-AA MS Seq Reveals Its Different Isoforms and Dynamic Base Modifications.

ACS Chem Biol 2020 06 19;15(6):1464-1472. Epub 2020 May 19.

Department of Biological and Chemical Sciences, New York Institute of Technology, New York, New York 10023, United States.

Post-transcriptional modifications are intrinsic to RNA structure and function. However, methods to sequence RNA typically require a cDNA intermediate and are either not able to sequence these modifications or are tailored to sequence one specific nucleotide modification only. Interestingly, some of these modifications occur with <100% frequency at their particular sites, and site-specific quantification of their stoichiometries is another challenge. Here, we report a direct method for sequencing tRNA without cDNA by integrating a two-dimensional hydrophobic RNA end-labeling strategy with an anchor-based algorithm in mass spectrometry-based sequencing (2D-HELS-AA MS Seq). The entire tRNA was sequenced and the identity, location, and stoichiometry of all eleven different RNA modifications was determined, five of which were not 100% modified, including a 2'-O-methylated G (Gm) in the wobble anticodon position as well as an -dimethylguanosine (mG), a 7-methylguanosine (mG), a 1-methyladenosine (mA), and a wybutosine (Y), suggesting numerous post-transcriptional regulations in tRNA. Two truncated isoforms at the 3'-CCA tail of the tRNA (75 nt with a 3'-CC tail (80% abundance) and 74 nt with a 3'-C tail (3% abundance)) were identified in addition to the full-length 3'-CCA-tailed tRNA (76 nt, 17% abundance). We discovered a new isoform with A-G transitions/editing at the 44 and 45 positions in the tRNA variable loop, and discuss possible mechanisms related to the emergence and functions of the isoforms with these base transitions or editing. Our method revealed new isoforms, base modifications, and RNA editing as well as their stoichiometries in the tRNA that cannot be determined by current cDNA-based methods, opening new opportunities in the field of epitranscriptomics.
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http://dx.doi.org/10.1021/acschembio.0c00119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902080PMC
June 2020

Developmental recording of the ghost-moth larvae after ex situ infection by Ophiocordyceps sinensis.

Sci China Life Sci 2020 Jul 30;63(7):1093-1095. Epub 2020 Apr 30.

State Key laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.

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http://dx.doi.org/10.1007/s11427-020-1686-7DOI Listing
July 2020

miR-129-5p attenuates hypoxia-induced apoptosis in rat H9c2 cardiomyocytes by activating autophagy.

J Gene Med 2020 08 29;22(8):e3200. Epub 2020 Apr 29.

Department of Geriatric Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Background: Autophagy is closely associated with apoptosis in H9c2 cardiomyocytes as a result of hypoxia. The present study aimed to determine whether microRNAs (miRs) mediated apoptosis and autophagy in hypoxia-stimulated H9c2 cardiomyocytes.

Methods: miR microarrays and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays were used to detect differentially expressed miRs in H9c2 cardiomyocytes following hypoxia stimulation. Annexin V-fluorescein isothiocyanate double staining was performed to evaluate hypoxia-induced cell apoptosis, and the protein expression levels of autophagy-associated genes were detected using western blotting.

Results: miR microarrays and qRT-PCR assays showed that the expression of miR-129-5p is significantly decreased in hypoxia-exposed H9c2 cardiomyocytes. Under hypoxic stimulation, miR-129-5p mimics alleviated hypoxia-induced cell apoptosis and also restored autophagy in H9c2 cardiomyocytes. However, transfection with miR-129-5p inhibitors accelerated hypoxia-induced cell apoptosis and autophagy deficiency in H9c2 cardiomyocytes. Furthermore, overexpression of miR-129-5p enhanced cell viability and reduced the release of lactate dehydrogenase in hypoxia-stimulated H9c2 cardiomyocytes.

Conclusions: These findings highlight the protective effect of miR-129-5p against hypoxia-induced apoptosis in H9c2 cardiomyocytes through the activation of autophagy.
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http://dx.doi.org/10.1002/jgm.3200DOI Listing
August 2020

Effect of verapamil on the pharmacokinetics of hydroxycamptothecin and its potential mechanism.

Pharm Biol 2020 Dec;58(1):152-156

Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.

Hydroxycamptothecin (HCPT) has antitumor activity in various cancers, but its poor bioavailability and efflux limit its clinical application. Verapamil has been demonstrated to improve the bioavailability of many drugs. However, the effect of verapamil on the pharmacokinetics of HCPT was not clear. The effect of verapamil on the pharmacokinetics of HCPT was investigated to clarify the drug-drug interaction between HCPT and verapamil. The pharmacokinetic profiles of oral administration of HCPT (50 mg/kg) in two group of Sprague-Dawley rats (six rats each), with pre-treatment of verapamil (10 mg/kg/day) for 7 days were investigated, with the group without verapamil pre-treatment as control. Additionally, the metabolic stability and transport of HCPT in the presence or absence of verapamil were also investigated with the employment of the rat liver microsomes and Caco-2 cell transwell model. Verapamil significantly increased the peak plasma concentration (from 91.97 ± 11.30 to 125.30 ± 13.50 ng/mL), and decrease the oral clearance (from 63.85 ± 10.79 to 32.95 ± 6.17 L/h/kg). The intrinsic clearance rate was also significantly decreased (from 39.49 ± 0.42 to 28.64 ± 0.30 μL/min/mg protein) by the preincubation of verapamil. The results of Caco-2 cell transwell experiments showed the efflux of HCPT was inhibited by verapamil, as the efflux ratio decreased from 1.82 to 1.21. The system exposure of HCPT was increased by verapamil. Verapamil may exert this effect through inhibiting the activity of CYP3A4 or , which are related to the metabolism and transport of HCPT.
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http://dx.doi.org/10.1080/13880209.2020.1717550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034088PMC
December 2020

Tumor-suppressor microRNA-151-5p regulates the growth, migration and invasion of human breast cancer cells by inhibiting SCOS5.

Am J Transl Res 2019 15;11(12):7376-7384. Epub 2019 Dec 15.

Department of Breast Surgery, China-Japan Union Hospital of Jilin University Changchun 130033, Jinlin, China.

Breast cancer is a prevalent malignancy in women and its incidence is increasing at an alarming rate. Breast cancer treatment is mainly obstructed by late diagnosis due to lack of biomarkers, dearth of therapeutic targets, constant relapses, drug resistance, and adverse effects of the chemotherapy. MicroRNAs (miRs) have shown exceptional potential to act as therapeutic agents for treatment of cancer. This study was designed to investigate the role and therapeutic implications of miR-151-5p in breast cancer. The results of the present study revealed that miR-151-5p is significantly downregulated in breast cancer tissues and cell lines. Overexpression of miR-151-5p in SK-BR-3 and CAMA-1 cells inhibits their proliferation and colony formation. Wound heal and transwell assays showed that miR-151-5p inhibits the migration and invasion of the SK-BR-3 and CAMA-1 breast cancer cells. TargetScan analysis followed by the dual luciferase assay confirmed SOCS5 to be the target of miR-151-5p in breast cancer. The expression of SOCS5 was upregulated in all the breast cancer tissues and cell lines. Silencing of SOC5 caused significant inhibition in the proliferation, migration and invasion of the SK-BR-3 cells. Nonetheless, overexpression of SCOS5 could avoid the growth inhibitory effects of miR-151-5p on the breast cancer cells. To conclude, miR-151-5p acts as a tumor suppressor in breast cancer and may exhibit therapeutic implications.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943465PMC
December 2019
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