Publications by authors named "Shengnan Liu"

112 Publications

Evaluation indicators of nutritional quality.

J Food Sci Technol 2021 Aug 30;58(8):2943-2951. Epub 2020 Sep 30.

College of Food Science and Engineering, Ocean University of China, Qingdao, 266003 Shandong People's Republic of China.

To access the nutritional quality of the , a comprehensive quality evaluation procedure is always important to be established. In this study, fifteen nutritional quality evaluation indicators of from 7 months were analyzed, and the most important indicators were determined using a combination of multiple chemometric methods such as correlation analysis (CA), principal component analysis (PCA), and system cluster analysis (SCA). Significant differences in nutritional quality were observed across the 7 months, as per the ANOVA results ( < 0.05). The coefficient of variation values for the fifteen evaluation indicators for across 7 months was 1.67-43.47%. The CA results revealed that some indicators were correlated to each other within a certain range. Four principal components with eigen-values > 1 were obtained with PCA, and a cumulative contribution of 92.11% was achieved. In addition, four essential quality indicators were extracted using SCA. Using these four indicators, a simple and efficient procedure can be applied for quality control in aquaculture.
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http://dx.doi.org/10.1007/s13197-020-04796-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249540PMC
August 2021

Facile Surface Functionalization Strategy for Two-Photon Lithography Microstructures.

Small 2021 Jul 16:e2101048. Epub 2021 Jul 16.

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.

Two-photon lithography (TPL) is a powerful tool to construct small-scale objects with complex and precise 3D architectures. While the limited selection of chemical functionalities on the printed structures has restricted the application of this method in fabricating functional objects and devices, this study presents a facile, efficient, and extensively applicable method to functionalize the surfaces of the objects printed by TPL. TPL-printed objects, regardless of their compositions, can be efficiently functionalized by combining trichlorovinylsilane treatment and thiol-ene chemistry. Various functionalities can be introduced on the printed objects, without affecting their micro-nano topographies. Hence, microstructures with diverse functions can be generated using non-functional photoresists. Compared to existed strategies, this method is fast, highly efficient, and non photoresist-dependent. In addition, this method can be applied to various materials, such as metals, metal oxides, and plastics that can be potentially utilized in TPL or other 3D printing technologies. The applications of this method on the biofunctionalization of microrobots and cell scaffolds are also demonstrated.
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http://dx.doi.org/10.1002/smll.202101048DOI Listing
July 2021

Dissolvable microneedles based on Panax notoginseng polysaccharide for transdermal drug delivery and skin dendritic cell activation.

Carbohydr Polym 2021 Sep 18;268:118211. Epub 2021 May 18.

School of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; Key Laboratory of Sustainable Utilization of Panax Notoginseng Resources of Yunnan Province, Kunming 650500, China. Electronic address:

This work explored the feasibility of using biological polysaccharide to fabricate dissolvable microneedles (MNs) for the purpose of transdermal drug delivery and skin dendritic cell (DC) activation. Panax notoginseng polysaccharide (PNPS), a naturally derived immunoactive macromolecule, was used to fabricate dissolvable MNs. The prepared PNPS MNs showed a satisfactory mechanical strength and a skin penetration depth. By Franz diffusion cell assay, the PNPS MNs demonstrated a high transdermal delivery amount of model drugs. Furthermore, with the assistance of MNs, PNPS easily penetrated across the stratum corneum and target ear skin DCs, activating the maturation and migration of immunocytes by increasing the expressions of CD40, CD80, CD86, and MHC II of skin DCs. Consequently, the matured DCs migrated to the auricular draining lymph nodes and increased the proportions of CD4+ T and CD8+ T cells. Thus, PNPS might be a promising biomaterial for transdermal drug delivery, with adjuvant potential.
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http://dx.doi.org/10.1016/j.carbpol.2021.118211DOI Listing
September 2021

Physiological and pathological functions of βB2-crystallins in multiple organs: a systematic review.

Aging (Albany NY) 2021 06 11;13(11):15674-15687. Epub 2021 Jun 11.

Department of Obstetrics and Gynecology, Changhai Hospital, Naval Military Medical University, Yangpu, Shanghai 200433, China.

Crystallins, the major constituent proteins of mammalian lenses, are significant not only for the maintenance of eye lens stability, transparency, and refraction, but also fulfill various physiopathological functions in extraocular tissues. βB2-crystallin, for example, is a multifunctional protein expressed in the human retina, brain, testis, ovary, and multiple tumors. Mutations in the βB2 crystallin gene or denaturation of βB2-crystallin protein are associated with cataracts, ocular pathologies, and psychiatric disorders. A prominent role for βB2-crystallins in axonal growth and regeneration, as well as in dendritic outgrowth, has been demonstrated after optic nerve injury. Studies in βB2-crystallin-null mice revealed morphological and functional abnormalities in testis and ovaries, indicating βB2-crystallin contributes to male and female fertility in mice. Interestingly, although pathogenic significance remains obscure, several studies identified a clear correlation between βB2 crystallin expression and the prognosis of patients with breast cancer, colorectal cancer, prostate cancer, renal cell carcinoma, and glioblastoma in the African American population. This review summarizes the physiological and pathological functions of βB2-crystallin in the eye and other organs and tissues and discusses findings related to the expression and potential role of βB2-crystallin in tumors.
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http://dx.doi.org/10.18632/aging.203147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221336PMC
June 2021

Perceptions of patients with chronic obstructive pulmonary disease towards telemedicine: A qualitative systematic review.

Heart Lung 2021 Sep-Oct;50(5):675-684. Epub 2021 Jun 6.

School of Nursing, Jilin University, China.

Background: There are some qualitative studies on the views of patients with chronic obstructive pulmonary disease (COPD) on telemedicine, however, there are few related qualitative systematic reviews.

Objectives: To systematically review and synthesize qualitative studies involving the perceptions of patients with COPD about telemedicine to understand patients' attitudes and expectations for telemedicine and determine the obstacles and stimulus in the use of telemedicine.

Methods: We searched PubMed, Web of Science, MEDLINE, Embase and CINAHL for articles published from January 2000 to December 2020. The data were analysed using thematic synthesis.

Results: We included 20 articles involving 19 studies and 301 patients, and we identified four themes: perceived ease of use, perceived usefulness, perceived difficulty of use, and perceived uselessness. We found that although patients have different views on telemedicine, most of them have a positive attitude towards it.

Conclusions: The synthesis of views will help us determine the factors that promote or hinder the application of telemedicine and guide the design and implementation of telemedicine in the future.
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http://dx.doi.org/10.1016/j.hrtlng.2021.03.081DOI Listing
June 2021

A GLUT1 inhibitor-based fluorogenic probe for Warburg effect-targeted drug screening and diagnostic imaging of hyperglycolytic cancers.

Anal Chim Acta 2021 Jul 30;1167:338593. Epub 2021 Apr 30.

Institute of Molecular Plus, Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin, 300072, PR China. Electronic address:

Increased expression of glucose transporters, especially GLUT1 has been proven to be involved in the Warburg effect. Therefore, GLUT1-targeted oncological approaches are being successfully employed for clinical tumor diagnostic imaging (e.g. the F-FDG/PET), drug delivery and novel anticancer drug development. Despite the long history of the Warburg effect-targeted cancer diagnosis, other than antibody labeling, there have been no imaging tools developed for direct detection of the GLUT1 expression. Herein, we report the new strategy of using a non-antibody GLUT1 binding probe for Warburg effect-based tumor detection and diagnostic imaging. By specifically inhibits the transport function of GLUT1, the newly designed fluorescent probe, CUM-5, was found to be a useful tool not only for sensitive GLUT1-mediated cancer cell detection, but also for cell-based high-throughput GLUT inhibitor screening. In in vivo studies, CUM-5 shows clear advantages including desirable tumor-to-normal tissue contrast and excellent tumor selectivity (Tm/Bkg and Tm/Torg), as well as high fluorescence stability (long response time) and ideal physiological biocompatibility. In particular, the GLUT1 inhibitor probe offers the potential use for glycolysis-based diagnostic imaging in triple-negative breast cancer which is claimed to have unsatisfactory results with FDG/PET diagnosis, thus remaining a highly metastatic and lethal disease with a need for sensitive and precise identification.
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http://dx.doi.org/10.1016/j.aca.2021.338593DOI Listing
July 2021

A GLUT1 inhibitor-based probe significantly ameliorates the sensitivity of tumor detection and diagnostic imaging.

Chem Commun (Camb) 2021 Jun;57(45):5530-5533

Institute of Molecular Plus, Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Rd, Nankai, Tianjin 300072, P. R. China.

We report a non-antibody GLUT1 inhibitor probe NBDQ that is 30 times more sensitive than the traditional GLUT1 transportable tracer for cancer cell imaging and Warburg effect-based tumor detection. NBDQ reveals significant advantages in terms of tumor selectivity, fluorescence stability and in vivo biocompatibility in xenograft tumor imaging, including triple-negative breast cancer.
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http://dx.doi.org/10.1039/d1cc00343gDOI Listing
June 2021

Tunable Dual-Color Emission Perovskites via Post-Synthetic Modification Strategy for Near-Unity Photoluminescence Quantum Yield.

ACS Appl Mater Interfaces 2021 May 30;13(18):21645-21652. Epub 2021 Apr 30.

Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province, Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin 130024, P. R. China.

Lead halide perovskites (LHPs) with excellent performance have become promising materials for optoelectrical devices. However, as for the dual-color emission LHPs (DELHPs), the low photoluminescence quantum yield (PLQY) hinders their applications. Herein, a simple low-cost room-temperature post-synthetic modification strategy is used to achieve a near-unity PLQY of DELHPs. It is proven that ZnBr plays an important role as an inorganic ligand in reducing surface defects to induce a 95.4% increase in the radiative decay rate and a 99.5% decrease in the nonradiative decay rate in the treated DELHPs compared with the pristine DELHPs. The performance of the blue emission from the surface lattice is greatly improved via the modification of ZnBr. DELHPs with different ratios of blue and green emissions are obtained by changing the specific surface area and ZnBr concentration. The distribution and mechanism of Zn are discussed using the research model based on these DELHPs. The first example of the single-layer dual-color perovskite electroluminescence device is realized from DELHPs. This work provides a new perspective for improving the performance of DELHPs, which will greatly accelerate the development of emission materials of LHPs.
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http://dx.doi.org/10.1021/acsami.1c03768DOI Listing
May 2021

Management of early-stage breast cancer patients during the coronavirus disease 2019 (COVID-19) pandemic: The experience in China from a surgical standpoint.

J Cancer 2021 22;12(8):2190-2198. Epub 2021 Feb 22.

Department of Breast Surgery, China-Japan Union Hospital of Jilin University, 126 Xiantai Blvd, Changchun 130033, China.

Breast cancer is the most common malignant tumor in women globally. Currently, due to limited data, there are no international guidelines for addressing the management of a large group of patients during infectious disease pandemics. Coronavirus disease 2019 (COVID-19), declared as a pandemic by the World Health Organization (WHO), has rapidly spread globally. The COVID-19 pandemic changed our daily routines and forced us to rethink the management of breast cancer patients. Clinicians need to take into account multiple factors such as the timing and delivery of cancer care, epidemic prevention and control, and the allocation of medical resources. Determining ways to reasonably adjust the treatment strategy is a real challenge. In this review, we aim to discuss particular challenges associated with managing breast cancer patients during the COVID-19 pandemic, share experience from Chinese oncologists and surgeons and propose some practical approaches to the management of early-stage breast cancer patients from a surgical standpoint.
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http://dx.doi.org/10.7150/jca.50501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974893PMC
February 2021

Hepatic miR-378 modulates serum cholesterol levels by regulating hepatic bile acid synthesis.

Theranostics 2021 25;11(9):4363-4380. Epub 2021 Feb 25.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

An improved understanding of thyroid hormone (TH) action on cholesterol metabolism will facilitate the identification of novel therapeutic targets for hypercholesterolemia. TH-regulated microRNAs (miRNAs) have been implicated in TH-controlled biological processes; however, whether and how TH-regulated miRNAs mediate the cholesterol-lowering effect of TH remains unclear. Our aim was to identify TH-regulated microRNAs that have cholesterol-lowering effects and explore the underlying mechanism. Microarray and RNA-seq were performed to identify TH-regulated microRNAs and the genes regulated by mmu-miR-378-3p (miR-378) in the liver of mice, respectively. Recombinant adenoviruses encoding miR-378, , and shRNA for , antagomiR-378, liver-specific miR-378 transgenic mice, and miR-378 knockout mice were employed to investigate the roles of hepatic miR-378 and MAFG in cholesterol and bile acid homeostasis. The levels of bile salt species were determined by using UFLC-Triple-time of flight/MS. Here, we show that hepatic miR-378 is positively regulated by TH. Transient overexpression of miR-378 in the liver of mice reduces serum cholesterol levels, accompanied with an increase in the expression of key enzymes in primary bile acid synthetic pathways and corresponding increases in biliary and fecal bile acid levels. Consistently, liver-specific miR-378 transgenic mice with moderate overexpression of hepatic miR-378 display decreased serum cholesterol levels and resistance to diet-induced hypercholesterolemia, while mice lacking miR-378 exhibit defects in bile acid and cholesterol homeostasis. Mechanistically, hepatic miR-378 regulates the expression of key enzymes in both classic and alternative bile acid synthetic pathways through MAFG, a transcriptional repressor, thereby modulating bile acid and cholesterol metabolism. TH-responsive hepatic miR-378 is capable of modulating serum cholesterol levels by regulating both the classic and alternative BA synthetic pathways. Our study not only identifies a previously undescribed role of hepatic miR-378 but also provides new cholesterol-lowering approaches.
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http://dx.doi.org/10.7150/thno.53624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977473PMC
July 2021

miR-130b inhibits proliferation and promotes differentiation in myocytes via targeting Sp1.

J Mol Cell Biol 2021 Mar 5. Epub 2021 Mar 5.

CAS Key laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai 200031, China.

Muscle regeneration after damage or during myopathies requires a fine cooperation between myoblast proliferation and myogenic differentiation. A growing body of evidence suggests that microRNAs play critical roles in myocyte proliferation and differentiation transcriptionally. However, the molecular mechanisms underlying the orchestration are not fully understood. Here, we showed that miR-130b is able to repress myoblast proliferation and promote myogenic differentiation via targeting Sp1 transcription factor. Importantly, overexpression of miR-130b is capable of improving the recovery of damaged muscle in a freeze injury model. Moreover, miR-130b expression is declined in the muscle of muscular dystrophy patients. Thus, these results indicated that miR-130b may play a role in skeletal muscle regeneration and myopathy progression. Together, our findings suggest that the miR-130b/Sp1 axis may serve as a potential therapeutic target for the treatment of patients with muscle damage or severe myopathies.
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http://dx.doi.org/10.1093/jmcb/mjab012DOI Listing
March 2021

The Prognostic Value of a Validated and Automated Intravascular Ultrasound-Derived Calcium Score.

J Cardiovasc Transl Res 2021 Feb 23. Epub 2021 Feb 23.

Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands.

Background: Coronary calcification has been linked to cardiovascular events. We developed and validated an algorithm to automatically quantify coronary calcifications on intravascular ultrasound (IVUS). We aimed to assess the prognostic value of an IVUS-calcium score (ICS) on patient-oriented composite endpoint (POCE).

Methods: We included patients that underwent coronary angiography plus pre-procedural IVUS imaging. The ICS was calculated per patient. The primary endpoint was a composite of all-cause mortality, stroke, myocardial infarction, and revascularization (POCE).

Results: In a cohort of 408 patients, median ICS was 85. Both an ICS ≥ 85 and a 100 unit increase in ICS increased the risk of POCE at 6-year follow-up (adjusted hazard ratio (aHR) 1.51, 95%CI 1.05-2.17, p value = 0.026, and aHR 1.21, 95%CI 1.04-1.41, p value = 0.014, respectively).

Conclusions: The ICS, calculated by a validated automated algorithm derived from routine IVUS pullbacks, was strongly associated with the long-term risk of POCE.
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http://dx.doi.org/10.1007/s12265-021-10103-1DOI Listing
February 2021

Geniposide protects depression through BTK/JAK2/STAT1 signaling pathway in lipopolysaccharide-induced depressive mice.

Brain Res Bull 2021 May 6;170:65-73. Epub 2021 Feb 6.

Department of Pharmacology, China Pharmaceutical University, 639, Longmian Avenue, Nanjing, 211198, China. Electronic address:

The purpose of this study was to investigate the antidepressant mechanism of GEN (geniposide) on depression mice induced by LPS. The mice were intragastrically treated with GEN (10 mg/kg/d or 40 mg/kg/d) or ibrutinib for continuous 7 days prior to LPS injection. The anxiety- and depression-like behaviors of mice were assessed via behavioral tests (sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and open-field test (OFT)). Microglial BV2 cells were treated with GEN or/and ibrutinib and stimulated with LPS. The productions of pro-inflammatory cytokines IL-6 and TNF-α in hippocampus, serum, and supernatant were detected by ELISA. The correlative proteins BTK, p-BTK, JAK2, p-JAK2, STAT1, p-STAT1, BDNF, TrkB, and p-TrkB were assessed through western blot. As a result, GEN ameliorated the anxiety- and depression-like behaviors of mice in behavioral tests. GEN treatment also regulated microglia polarization towards anti-inflammatory phenotype M2 and inhibited the production of pro-inflammatory cytokines IL-6 and TNF-α. In addition, with the application of ibrutinib, the selective inhibitor of BTK, it was proclaimed that the administration of GEN restrained the activation of JAK2/STAT1 pathway via attenuating the hyperphosphorylation of BTK both in mice and BV2 cells. Furthermore, it was also found that GEN activated BDNF/TrkB neuroprotective signaling pathway through the reduction of BTK phosphorylation. From the overall results, we suggested that GEN exerted a beneficial effect on LPS-induced depression in mice possibly through the modulation of BTK/JAK2/STAT1 signaling.
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http://dx.doi.org/10.1016/j.brainresbull.2021.02.008DOI Listing
May 2021

L-Arabinose suppresses gluconeogenesis through modulating AMP-activated protein kinase in metabolic disorder mice.

Food Funct 2021 Mar;12(4):1745-1756

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

l-Arabinose is a kind of plant-specific five-carbon aldose with benefits in type 2 diabetes mellitus. It has been shown to have good properties in improving glucose homeostasis, but the underlying molecular mechanisms are still not clear. Hepatic gluconeogenesis is critical for regulating glucose homeostasis. Here, this study aimed to investigate whether l-arabinose could improve glucose metabolism via suppressing hepatic gluconeogenesis. High-fat-high-sucrose diet (HFHSD) or high-sucrose diet (HSD)-fed mice were supplemented with or without l-arabinose for 12 weeks. Fasting blood glucose levels were measured and glucose tolerance test and the histological analysis were performed after l-arabinose administration. AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), peroxisome proliferator activated receptor-γ coactivator-1α (PGC1α), Forkhead box O1 (FoxO1), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) expression levels were determined by RT-PCR and western blotting. As expected, l-arabinose apparently decreased body weight and attenuated hyperglycemia and glucose intolerance caused by HFHSD or HSD. l-Arabinose also had beneficial effects on glycogen synthesis by inactivating GSK3β. The expression levels of gluconeogenic genes were all decreased by l-arabinose administration in vivo and in vitro. In addition, our work revealed that AMPK is required for the inhibitory effects of l-arabinose on hepatic gluconeogenesis. l-Arabinose significantly up-regulated the phosphorylated levels of AMPK and its downstream protein ACC. Furthermore, blocking AMPK signaling through an inhibitor (compound C) or siAMPK significantly attenuated the inhibition of hepatic gluconeogenesis and the promotion of glycogen synthesis with l-arabinose, indicating that the inhibitory effect of l-arabinose on hepatic gluconeogenesis was AMPK dependent. Our work revealed that l-arabinose is a promising natural product for the regulation of hyperglycemia through inhibition of hepatic gluconeogenesis by activating AMPK.
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http://dx.doi.org/10.1039/d0fo02163fDOI Listing
March 2021

Oxaliplatin derived monofunctional triazole-containing platinum(II) complex counteracts oxaliplatin-induced drug resistance in colorectal cancer.

Bioorg Chem 2021 02 8;107:104636. Epub 2021 Jan 8.

School of Pharmaceutical Science and Technology and Institute of Molecular Plus, Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, PR China; Department of Biology, Gudui BioPharma Technology Inc, 5 Lanyuan Road, Huayuan Industrial Park, Tianjin 300384, PR China. Electronic address:

Oxaliplatin-based chemotherapy is the current standard of care in adjuvant therapy for advanced colorectal cancer (CRC). But acquired resistance to oxaliplatin eventually occurs and becoming a major cause of treatment failure. Thus, there is an unmet need for developing new chemical entities (NCE) as new therapeutic candidates to target chemotherapy-resistant CRC. Novel Pt(II) complexes were designed and synthesized as cationic monofunctional oxaliplatin derivatives for DNA platination-mediated tumor targeting. The complex Ph-glu-Oxa sharing the same chelating ligand of diaminocyclohexane (DACH) with oxaliplatin but is equally potent in inhibiting the proliferation of HT29 colon cancer cells and its oxaliplatin-resistant phenotype of HT29/Oxa. The in vivo therapeutic potential of Ph-glu-Oxa was confirmed in oxaliplatin-resistant xenograft model demonstrating the reversibility of the drug resistance by the new complex and the efficacy was associated with the unimpaired high intracellular drug accumulation in HT29/Oxa. Guanosine-5'-monophosphate (5'-GMP) reactivity, double-strand plasmid DNA cleavage, DNA-intercalated ethidium bromide (EB) fluorescence quenching and atomic force microscopy (AFM)-mediated DNA denaturing studies revealed that Ph-glu-Oxa was intrinsically active as DNA-targeting agent. The diminished susceptibility of the complex to glutathione (GSH)-mediated detoxification, which confers high intracellular accumulation of the drug molecule may play a key role in maintaining cytotoxicity and counteracting oxaliplatin drug resistance.
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http://dx.doi.org/10.1016/j.bioorg.2021.104636DOI Listing
February 2021

The effect of geniposide on chronic unpredictable mild stress-induced depressive mice through BTK/TLR4/NF-κB and BDNF/TrkB signaling pathways.

Phytother Res 2021 Feb 8;35(2):932-945. Epub 2020 Nov 8.

Department of Pharmacology, China Pharmaceutical University, Nanjing, China.

The purpose of this study was to estimate the pharmacological effect of geniposide (GEN) on depression, caused by chronic unpredictable mild stress (CUMS), and explore its potential mechanism. During the 6 week CUMS procedure, the mice were treated with GEN (10, 40 mg/kg) by gavage once daily for 3 weeks. As a result, the GEN treatment remarkably improved the behavioral manifestations and suppressed the generations of inflammatory cytokines both in vivo and in vitro. The MDA level was significantly increased, while the activities of SOD, GSH-PX were decreased in CUMS-challenged mice and corticosterone-stimulated PC12 cells. GEN administration significantly inhibited those changes. Moreover, GEN treatment could downregulate the expressions of p-BTK, TLR4, MyD88, p-NF-κB proteins, and upregulate BDNF, p-TrkB generations in CUMS-induced mice. Moreover, GEN administration inhibited the protein levels of p-BTK, TLR4, MyD88, p-NF-κB in corticosterone-induced PC12 cell. In summary, the results suggested that GEN exerted a therapeutic effect on CUMS-induced depressive mice possibly through the regulation of BTK/TLR4/NF-κB and BDNF/TrkB signaling pathways.
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http://dx.doi.org/10.1002/ptr.6846DOI Listing
February 2021

The Cost-Effectiveness of Pulmonary Rehabilitation for COPD in Different Settings: A Systematic Review.

Appl Health Econ Health Policy 2021 05 20;19(3):313-324. Epub 2020 Oct 20.

School of Nursing, Jilin University, No. 965 Xinjiang Street, Changchun, 130021, China.

Background: Chronic obstructive pulmonary disease (COPD) has high morbidity and mortality rates. COPD impairs body functioning, reduces quality of life, and creates a great economic burden for society. Pulmonary rehabilitation (PR) has become an important nonpharmacological treatment for COPD. This paper systematically reviews economic evaluations of PR in COPD patients in different settings.

Objectives: We aimed to understand the cost-effectiveness of PR in different settings for COPD to provide economic evidence for decision-makers.

Methods: We searched eight databases from their inception to 23 November 2019. The results were presented in terms of an incremental cost-effectiveness ratio (ICER), and the decision uncertainty was expressed by cost-effectiveness acceptability curves (CEACs). We used the Consensus on Health Economic Criteria to assess study quality.

Results: This review included ten studies that matched the selection criteria. Five studies compared PR with usual care in primary healthcare or outpatient departments. Two studies compared community-based PR with hospital PR or usual care. In the other studies, PR was mainly carried out at home. Compared with usual care, PR was cost-effective in primary healthcare institutions or outpatient departments. According to CEACs, community-based PR had a 50% probability of cost-effectiveness at £30,000/quality-adjusted life year (QALY) compared with hospital PR in the UK. Based on the ICER, community-based PR was "moderately" cost-effective, with a ratio of €32,425/QALY compared with usual care in the Netherlands. Home-based PR was dominant compared with usual care, and tele-rehabilitation was dominant compared with traditional home PR.

Conclusions: PR conducted in different settings can potentially be cost-effective, as measured using QALY or the Chronic Respiratory Questionnaire (CRQ).
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http://dx.doi.org/10.1007/s40258-020-00613-5DOI Listing
May 2021

The role of CCR5 in the protective effect of Esculin on lipopolysaccharide-induced depressive symptom in mice.

J Affect Disord 2020 12 1;277:755-764. Epub 2020 Sep 1.

Department of Pharmacology, China Pharmaceutical University, Longmian Avenue, Nanjing 211198, China. Electronic address:

Background: The purpose of this study was to evaluate whether Esculin could improve the depressive symptom induced by LPS in mice and explore the role of CCR5 in its potential mechanism.

Methods: Mice were stimulated with LPS to establish depression model and treated with Esculin. The emotional alteration was assessed via behavior tests. The ELISA assay and western blot analysis were applied to detect the expressions of inflammatory cytokines and correlative proteins.

Results: As a result, Esculin played a protective role in LPS-induced depressive dysfunction, which was possible through the reduction of M1 microglia, and elevation of M2 microglia by inhibiting TLR4/NF-κB signaling pathway regulated by CCR5. Besides, Esculin led to up-regulation of the CREB/BDNF neuroprotective pathway, and suppression of inflammatory cytokines both in the central and peripheral system. BV2 cells were stimulated with LPS to further elucidate the accordant mechanism in vitro. Molecular docking results suggested that Esc bound to CCR5 at amino acid residues TYR187 and THR105 through hydrogen-bonding.

Limitations: Transgenic animals might be useful for the further investigation.

Conclusions: From the overall results, we concluded that Esculin might exert a beneficial effect on LPS-induced depression in mice and represent an effective treatment for depression.
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http://dx.doi.org/10.1016/j.jad.2020.08.065DOI Listing
December 2020

Consecutive dephosphorylation by alkaline phosphatase-directed formation of porous hydrogels of SF with nanocrystalline calcium phosphate ceramics for bone regeneration.

J Mater Chem B 2020 Sep 21. Epub 2020 Sep 21.

College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, China.

Alkaline phosphatase, as an enzyme involved in the process of bone mineralization and regeneration, was incorporated into a solution of SF to induce its gelation and mineralization through consecutive dephosphorylation actions on different substrates. In these processes, alkaline phosphatase firstly worked on a small peptide of NapGFFYp by removing its hydrophilic phosphate group. The resulted NapGFFY performed supramolecular assembly in the solution of SF and synergistically induced the conformation transition of SF from random coil to β-sheet structures, leading to the formation of a stable SF hydrogel under physiological conditions. And then, the entrapped ALP within the SF-NY gel network retained its catalytic activity, released phosphate ions from glycerophosphate, and catalysed the formation of calcium phosphate minerals within the porous gel. Because of the mild conditions of these processes and good biocompatibility of the scaffold, the mineralized SF gel can work as a biomimetic scaffold to promote the osteogenic differentiation of rBMSCs and stimulate femoral defect regeneration in a rat model.
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http://dx.doi.org/10.1039/d0tb01777aDOI Listing
September 2020

A mechanochromic cyclemetalated cationic Ir(iii) complex with AIE activity by strategic modification of ligands.

Dalton Trans 2020 Oct 14;49(37):13066-13071. Epub 2020 Sep 14.

Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province, Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin Province 130024, P. R. China.

Two new aggregation-induced emission (AIE)-active cyclemetalated cationic Ir(iii) complexes have been rationally designed and synthesized by introducing O-H substituents into Schiff base ligands. π-Hydrogen bonding is successfully exploited for the first time to realize the mechanochromic luminescence (MCL) property by the synergistic effect of O-H and F substituents in complex 1. An X-ray crystal structure analysis of the two complexes suggests that the intramolecular hydrogen bonding effectively restricted the molecular motions, thus causing typical AIE characteristics. More importantly, a loosely packed structure constructed from intermolecular hydrogen bonding interactions (O-Hπ and C-HF) is obtained, and it is susceptible to mechanical stimulation. Powder X-ray diffraction (PXRD) studies also prove that the MCL behavior of complex 1 is caused by the reversible phase transition from crystalline to amorphous state under grinding and solvent recrystallization, leading to a change in emission colors. A re-writable phosphorescence data recording device was fabricated using complex 1 as the active material. Our molecular design strategies provide a new avenue for achieving efficient phosphorescence materials with AIE and MCL properties.
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http://dx.doi.org/10.1039/d0dt02526gDOI Listing
October 2020

Tryptophan-Based Self-Assembling Peptides with Bacterial Flocculation and Antimicrobial Properties.

Langmuir 2020 09 16;36(38):11316-11323. Epub 2020 Sep 16.

College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China.

Tryptophan as an aromatic amino acid with a hydrophobic indole group plays important roles in stabilizing protein structures and enhancing molecular bindings in nature, but was rarely used in the molecular design of self-assembling peptides or gelators. Therefore, we prepared a series of short peptides from Trp amino acids and examined the potential roles of Trp residues for regulating peptide self-assembly and gelation. The introduced Trp amino acids not only diversify the molecular structures of peptide gelators, but also promote aromatic and hydrogen-bonding interactions for supramolecular self-assembling and gelation, which generates self-assembled nanostructures with twisted helical morphologies and supramolecular hydrogels with low minimal gelation concentrations. More importantly, the self-assembling peptides with Trp residues displayed strong preference for interacting with the lipidic membranes of bacteria, which resulted in bacterial flocculation and the death of and .
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http://dx.doi.org/10.1021/acs.langmuir.0c01957DOI Listing
September 2020

Brain Network Analysis by Stable and Unstable EEG Components.

IEEE J Biomed Health Inform 2021 04 6;25(4):1080-1092. Epub 2021 Apr 6.

Objective: Previous studies have already shown that electroencephalography (EEG) brain network (BN) can reflect the health status of individuals. However, novel methods are still needed for BN analysis. Therefore, in this study, BNs were constructed based on stable and unstable EEG components, and these may be implemented for disease diagnosis.

Methods: Parkinson's disease (PD) was used as an example to illustrate this method. First, EEG signals were decomposed into dynamic modes (DMs). Each DM contains one eigenvalue that can determine not only the stability of that mode, but also its corresponding oscillatory frequency. Second, the stable and unstable components of EEG signals in each frequency band (delta, theta, alpha and beta) were calculated, which are based on the stable and unstable DMs within each respective frequency band. Third, newly developed BNs were constructed, including stable brain network (SBN), unstable brain network (UBN) and inter-connected brain network (IBN). Finally, their topological attributes were extracted in order to differentiate between PD patients and healthy controls (HC). Furthermore, topological attributes were also derived from traditional brain network (TBN) for comparison.

Results: Most topological attributes of SBN, UBN and IBN can significantly differentiate between PD patients and HC ( p value 0.05). Furthermore, the area under the curve (AUC), precision and recall values of SBN analysis are all significantly higher than TBN.

Conclusion: We proposed a new perspective on EEG BN analysis.

Significance: These newly developed BNs not only have biological significance, but also could be widely applied in most medical and engineering fields.
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http://dx.doi.org/10.1109/JBHI.2020.3015471DOI Listing
April 2021

Automated Quantitative Assessment of Coronary Calcification Using Intravascular Ultrasound.

Ultrasound Med Biol 2020 10 4;46(10):2801-2809. Epub 2020 Jul 4.

Department of Cardiology, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address:

Coronary calcification represents a challenge in the treatment of coronary artery disease by stent placement. It negatively affects stent expansion and has been related to future adverse cardiac events. Intravascular ultrasound (IVUS) is known for its high sensitivity in detecting coronary calcification. At present, automated quantification of calcium as detected by IVUS is not available. For this reason, we developed and validated an optimized framework for accurate automated detection and quantification of calcified plaque in coronary atherosclerosis as seen by IVUS. Calcified lesions were detected by training a supported vector classifier per IVUS A-line on manually annotated IVUS images, followed by post-processing using regional information. We applied our framework to 35 IVUS pullbacks from each of the three commonly used IVUS systems. Cross-validation accuracy for each system was >0.9, and the testing accuracy was 0.87, 0.89 and 0.89 for the three systems. Using the detection result, we propose an IVUS calcium score, based on the fraction of calcium-positive A-lines in a pullback segment, to quantify the extent of calcified plaque. The high accuracy of the proposed classifier suggests that it may provide a robust and accurate tool to assess the presence and amount of coronary calcification and, thus, may play a role in image-guided coronary interventions.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2020.04.032DOI Listing
October 2020

A flexible and physically transient electrochemical sensor for real-time wireless nitric oxide monitoring.

Nat Commun 2020 06 25;11(1):3207. Epub 2020 Jun 25.

School of Materials Science and Engineering, The Key Laboratory of Advanced Materials of Ministry of Education, State Key Laboratory of New Ceramics and Fine Processing, Center for Flexible Electronics Technology, Tsinghua University, Beijing, 100084, China.

Real-time sensing of nitric oxide (NO) in physiological environments is critically important in monitoring neurotransmission, inflammatory responses, cardiovascular systems, etc. Conventional approaches for NO detection relying on indirect colorimetric measurement or built with rigid and permanent materials cannot provide continuous monitoring and/or require additional surgical retrieval of the implants, which comes with increased risks and hospital cost. Herein, we report a flexible, biologically degradable and wirelessly operated electrochemical sensor for real-time NO detection with a low detection limit (3.97 nmol), a wide sensing range (0.01-100 μM), and desirable anti-interference characteristics. The device successfully captures NO evolution in cultured cells and organs, with results comparable to those obtained from the standard Griess assay. Incorporated with a wireless circuit, the sensor platform achieves continuous sensing of NO levels in living mammals for several days. The work may provide essential diagnostic and therapeutic information for health assessment, treatment optimization and postsurgical monitoring.
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http://dx.doi.org/10.1038/s41467-020-17008-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316789PMC
June 2020

Flanker Task-Elicited Event-Related Potential Sources Reflect Human Recombinant Erythropoietin Differential Effects on Parkinson's Patients.

Parkinsons Dis 2020 22;2020:8625794. Epub 2020 May 22.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China.

We used EEG source analysis to identify which cortical areas were involved in the automatic and controlled processes of inhibitory control on a flanker task and compared the potential efficacy of recombinant-human erythropoietin (rHuEPO) on the performance of Parkinson's Disease patients. The samples were 18 medicated PD patients (nine of them received rHuEPO in addition to their usual anti-PD medication through random allocation and the other nine patients were on their regular anti-PD medication only) and 9 age and education-matched healthy controls (HCs) who completed the flanker task with simultaneous EEG recordings. N1 and N2 event-related potential (ERP) components were identified and a low resolution tomography (LORETA) inverse solution was employed to localize the neural generators. Reaction times and errors were increased for the incongruent flankers for PD patients compared to controls. EEG source analysis identified an effect of rHuEPO on the lingual gyri for the early N1 component. N2-related sources in middle cingulate and precuneus were associated with the inhibition of automatic responses evoked by incongruent stimuli differentiated PD and HCs. From our results rHuEPO seems to mediate an effect on N1 sources in lingual gyri but not on behavioural performance. N2-related sources in middle cingulate and precuneus were evoked by incongruent stimuli differentiated PD and HCs.
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http://dx.doi.org/10.1155/2020/8625794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261337PMC
May 2020

Structural characterization of a novel polysaccharide from Panax notoginseng residue and its immunomodulatory activity on bone marrow dendritic cells.

Int J Biol Macromol 2020 Oct 15;161:797-809. Epub 2020 Jun 15.

School of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; Key Laboratory of Sustainable Utilization of Panax Notoginseng Resources of Yunnan, Province, Kunming 650500, China. Electronic address:

This study isolated and characterized a novel polysaccharide (PNPS-0.3) from the residue of Panax notoginseng by gradient elution. PNPS-0.3 mainly consisted of a backbone of →4)- α-D-GalAp-(1 → 4-β-L-Rhap-1 → 4)-β-D-Galp-(1 → residues, with an α-L-Araf-1 → 5)-α-L-Araf-(1 → branch connecting to the backbone at O-3 of →4-β-L-Rhap-1 → and a molecular weight of 76,655 Da. Furthermore, the adjuvant potential of PNPS-0.3 with bone marrow dendritic cells (BMDCs) was investigated. The results suggested that PNPS-0.3 could induce maturation of BMDCs by reshaping the morphology, upregulating the CD40, CD80, CD86 and MHC II membrane phenotypic markers, and by promoting the secretion of TNF-α and IL-12 proinflammatory cytokines. Moreover, PNPS-0.3 can trigger the DC-induced T-cell immune response, as indicated by the higher expressions of CD4, CD8, CD69, and MHC II in T cells with increased secretion of INF-β. Furthermore, PNPS-0.3 can bind to the pattern recognition receptors (PRR) of Toll-like receptor 4 (TLR 4), Toll-like receptor 2 (TLR 2), and mannose receptor (MR) on BMDCs. PNPS-0.3 also upregulated the expressions of Myd88, IKKβ, PP65, T-P65, and NF-κB, suggesting that the TLR4/TLR2-NF-κB signaling pathway was involved in the immunomodulatory mechanism. In conclusion, the immunoadjuvant potential of novel PNPS-0.3 was characterized, which is beneficial for the future utilization and development of P. notoginseng.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.06.117DOI Listing
October 2020

Superclean Growth of Graphene Using a Cold-Wall Chemical Vapor Deposition Approach.

Angew Chem Int Ed Engl 2020 Sep 29;59(39):17214-17218. Epub 2020 Jul 29.

Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, P. R. China.

Chemical vapor deposition (CVD) has become a promising approach for the industrial production of graphene films with appealing controllability and uniformity. However, in the conventional hot-wall CVD system, CVD-derived graphene films suffer from surface contamination originating from the gas-phase reaction during the high-temperature growth. Shown here is that the cold-wall CVD system is capable of suppressing the gas-phase reaction, and achieves the superclean growth of graphene films in a controllable manner. The as-received superclean graphene film, exhibiting improved optical and electrical properties, was proven to be an ideal candidate material used as transparent electrodes and substrate for epitaxial growth. This study provides a new promising choice for industrial production of high-quality graphene films, and the finding about the engineering of the gas-phase reaction, which is usually overlooked, will be instructive for future research on CVD growth of graphene.
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http://dx.doi.org/10.1002/anie.202005406DOI Listing
September 2020

Preliminary study on the electromagnetic field treatment of osteoporosis in rats.

Technol Health Care 2020 ;28(S1):47-55

Study Center, The First Hospital of Harbin City, Harbin, Heilongjiang, 150010, China.

Objective: In our study, the influence of PEMF on skeleton morphology and bone metabolism on rats with disuse osteoporosis was investigated, and the possibility of using it for the treatment of disuse osteoporosis was explored.

Methods: The rats in the ALN group were treated with alendronate, and the rats in the PEMF group were exposed to pulsed electromagnetic fields (3.82 mT, 10 Hz) for 40 mind-1. Rats were sacrificed by the end of 2, 4, 8 and 12 weeks, and serum and right leg bones were collected. Serum BMP-2, BGP concentrations and bone metabolism and biomechanical parameters were measured.

Results: The bone structural mechanical indices and material mechanical indices of the right femur in all groups of mice during weeks 2 and 4 were decreased. At week 8 the bone structural mechanical index and maximum stress of the right femur in the ALN group were markedly raised compared with the CON group (P< 0.01). Only maximum stress and strain were improved in the ALN group and had a significant difference (P< 0.05) at week 12. The serum BGP and BMP-2 concentration in the PEMF and ALN groups was increased (P< 0.05) at week 2, but this increase was not synchronized. After 8 weeks, BGP and BMP-2 level in the PEMF group was observably elevated (P<0.01) in contrast to the ALN group.

Conclusion: From the experimental time interval analysis, PEMF can improve the mechanical stability of bone structure more gently and permanently than alendronate.
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http://dx.doi.org/10.3233/THC-209006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369098PMC
April 2021

Ryanodine receptor-targeting small molecule fluorescent probes enables non-isotopic labeling and efficient drug screening for green insecticides.

Anal Chim Acta 2020 Apr 26;1108:108-117. Epub 2020 Feb 26.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, Institute of Molecular Plus, School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin, 300072, China; Department of Biology, Gudui BioPharma Technology Inc., 5 Lanyuan Road, Huayuan Industrial Park, Tianjin, 300384, China. Electronic address:

Ryanodine receptors (RyRs) are calcium release channels located on endoplasmic reticulum (ER) membrane, which play important role in excitation-contraction coupling in muscular response. Flubendiamide represents a novel chemical family of green insecticides which selectively activate invertebrate RyR by interacting with the receptor distinct from the ryanodine binding site and has almost no effect on mammalian ryanodine receptors. Traditional methods to screen RyR modulators involve either radio-labeled RyR substrates or calcium signal-based indirect approaches. However, there is lack of RyR-directed non-isotope molecular tools for RyR agonists/antagonists screening and bioimaging. Here we developed a series of fluorescent probes based on the pharmacophore of flubendiamide with the aims to elucidate the mechanism of diamide insecticides and screen novel RyR-targeting insecticides. These probes revealed the specific RyR staining and in vivo RyR targeting properties in diamondback moth RyR transfected Sf9 cells (Sf9-RyR) and RyR enriched insect tissues. The designed fluorescent probes could induce an effective calcium release from ER membrane of Sf9-RyR cells and also showed competitive RyR binding effect with flubendiamide in cell-based fluorometric assay. Having the non-isotope RyR recognition probes will not only accelerate the screening process of new green agrochemicals but also enables deciphering molecular mechanisms of the high selectivity and the drug resistance associated with the diamides.
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http://dx.doi.org/10.1016/j.aca.2020.02.047DOI Listing
April 2020

Effect of miR-26b-5p on cis-diamine dichloroplatinum-induced ovarian granulosa cell injury by targeting MAP3K9.

In Vitro Cell Dev Biol Anim 2020 Mar 17;56(3):213-221. Epub 2020 Mar 17.

Department of Obstetrics and Gynecology, Changhai Hospital, Naval Military Medical University, No.168, Changhai Road, Yangpu District, Shanghai, 200433, China.

The proliferation and differentiation of granulosa cells are very important for follicular development. The dysfunction of granulosa cells leading to follicular development is an important cause of ovarian endocrine abnormalities. More and more evidence shows that microRNAs are involved in the regulation of ovarian granulosa cell function. It has been found that MiR-26b may be involved in CDDP resistance. Studies have shown that miR-26b can promote apoptosis of ovarian granulosa cells, but there are few studies on its mechanism, and no studies have been found on the damage of miR-26b-5p to rat ovarian granulosa cells induced by CDDP. Identification of ovarian granulosa cells was conducted by immunochemical staining. Cell counting kit 8 (CCK-8) was used to detect cell viability, flow cytometry was used to detect cell apoptosis, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot (WB) were used to analyze the expression of miR-26b-5p, MAP3K9, cleaved Caspase-3, Bax, and Bcl-2; dual-luciferase reporter assay results further verify the targeting relation between miR-26b-5p and MAP3K9. CDDP remarkably inhibited ovarian granulosa cell viability and induced ovarian granulosa cell apoptosis; miR-26b-5p inhibitor enhanced viability and inhibited apoptosis of ovarian granulosa cells, which treated with CDDP, but had little effect on normal cells. MAP3K9 partially reversed the effect of miR-26b-5p on ovarian granulosa cells induced by CDDP. miR-26b-5p has a protective effect on CDDP-induced ovarian granulosa cells via targeting MAP3K9.
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http://dx.doi.org/10.1007/s11626-020-00439-4DOI Listing
March 2020
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