Publications by authors named "Wenjing Wang"

545 Publications

Capture and selective release of multiple types of circulating tumor cells using smart DNAzyme probes.

Chem Sci 2020 Jan 9;11(7):1948-1956. Epub 2020 Jan 9.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University Nanjing 210023 China

The effective capture, release and reanalysis of circulating tumor cells (CTCs) are of great significance to acquire tumor information and promote the progress of tumor therapy. Particularly, the selective release of multiple types of CTCs is critical to further study; however, it is still a great challenge. To meet this challenge, we designed a smart DNAzyme probe-based platform. By combining multiple targeting aptamers and multiple metal ion responsive DNAzymes, efficient capture and selective release of multiple types CTCs were realized. Sgc8c aptamer integrated Cu-dependent DNAzyme and TD05 aptamer integrated Mg-dependent DNAzyme can capture CCRF-CEM cells and Ramos cells respectively on the substrate. With the addition of Cu or Mg, CCRF-CEM cells or Ramos cells will be released from the substrate with specific selectivity. Furthermore, our platform has been successfully demonstrated in the whole blood sample. Therefore, our capture/release platform will benefit research on the molecular analysis of CTCs after release and has great potential for cancer diagnosis and individualized treatment.
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http://dx.doi.org/10.1039/c9sc04309hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148068PMC
January 2020

Place cells and geometry lead to a flexible grid pattern.

J Comput Neurosci 2021 Jun 14. Epub 2021 Jun 14.

School of Systems Science, Beijing Normal University, Beijing, 100875, China.

Place cells and grid cells are important neurons involved in spatial navigation in the mammalian brain. Grid cells are believed to play an important role in forming a cognitive map of the environment. Experimental observations in recent years showed that the grid pattern is not invariant but is influenced by the shape of the spatial environment. However, the cause of this deformation remains elusive. Here, we focused on the functional interactions between place cells and grid cells, utilizing the information of location relationships between the firing fields of place cells to optimize the previous grid cell feedforward generation model and expand its application to more complex environmental scenarios. Not only was the regular equilateral triangle periodic firing field structure of the grid cells reproduced, but the expected results were consistent with the experiment for the environment with various complex boundary shapes and environmental deformation. Even in the field of three-dimensional spatial grid patterns, forward-looking predictions have been made. This provides a possible model explanation for how the coupling of grid cells and place cells adapt to the diversity of the external environment to deepen our understanding of the neural basis for constructing cognitive maps.
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http://dx.doi.org/10.1007/s10827-021-00794-5DOI Listing
June 2021

Neuroprotective effects of microRNA-211-5p on chronic stress-induced neuronal apoptosis and depression-like behaviours.

J Cell Mol Med 2021 Jun 13. Epub 2021 Jun 13.

Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.

Findings from recent studies have revealed that microRNAs (miRNAs) are related to numerous neurological disorders. However, whether miRNAs regulate neuronal anomalies involved in the pathogenesis of depression remain unclear. In the present study, we screened miRNA expression profiles in the CA1 hippocampus of a rat model of depression and found that a specific miRNA, microRNA-211-5p, was significantly down-regulated in depressed rats. When miR-211-5p was up-regulated in these rats, neuronal apoptosis within the CA1 area was suppressed, effects which were accompanied with an amelioration of depression-like behaviours in these rats. These neuroprotective effects of miR-211-5p in depressed rats appear to result through suppression of the Dyrk1A/ASK1/JNK signalling pathway within the CA1 area. In further support of this proposal are the findings that knock-down of miR-211-5p within the CA1 area of normal rats activated the Dyrk1A/ASK1/JNK pathway, resulting in the promotion of neuronal apoptosis and display of depression-like behaviours in these rats. Taken together, these results demonstrate that deficits in miR-211-5p contribute to neuronal apoptosis and thus depression-like behaviours in rats. Therefore, the miR-211-5p/Dyrk1A pathway may be critically involved in the pathogenesis of depression and serve as a potential therapeutic target for the treatment of depression.
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http://dx.doi.org/10.1111/jcmm.16716DOI Listing
June 2021

A prediction score model and survival analysis of acute kidney injury following orthotopic liver transplantation in adults.

Ann Palliat Med 2021 May 24. Epub 2021 May 24.

Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Acute kidney injury (AKI) is one of the postoperative complications following orthotopic liver transplantation (OLT), and is related to the high morbidity and mortality. Although there were numerous propensity factors for AKI, their cumulative influence remains unclear. Our aims were to develop a score model to predict postoperative AKI and to evaluate the impact of AKI on the recipients' long-term survival.

Methods: We retrospectively analyzed 99 adult patients underwent OLT in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between October 2014 and July 2020. The patients were dichotomized into the non-AKI and the AKI groups according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. We defined stage-1 AKI as mild AKI, stage-2 AKI and stage-3 AKI as severe AKI.

Results: Overall, 29 (29.29%) patients developed AKI after OLT, of these, stage-1, stage-2, stage-3 account for 20.20% (20 of 99 patients), 2.02% (2 of 99 patients), 7.07% (7 of 99 patients), respectively; and 13.79% of postoperative AKI patients (4 of 29 patients) accepted renal replacement therapy (RRT). Operative time and MELD-Na score predicted the postoperative AKI, with odds ratio of 1.006, 1.061, respectively. The generated AKI prediction model is as follows: -5.594+0.007×Operative time+0.060×MELD-Na. The area under the receiver operating characteristic curve (AUC) for the AKI prediction model was 0.762, and the sensitivity and specificity were 79.3%, 61.4%, respectively. There was no difference in long-term survival among the mild AKI group and the non-AKI group (P=0.751). However, the impact of severe AKI on longterm survival of patients was statistically significant when comparing the non-AKI group and the mild AKI group (P=0.001, P=0.011).

Conclusions: AKI occurs frequently in adult patients after OLT, and it poses a threat to patients' longterm survival. The severe AKI has negative impact on long-term survival, while the mild AKI has limited impact on long-term survival, compared with non-AKI group. The novel AKI prediction model has prognostic value in identifying patients at high risk for postoperative AKI.
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http://dx.doi.org/10.21037/apm-21-842DOI Listing
May 2021

Comparative analysis of alfalfa (Medicago sativa L.) seedling transcriptomes reveals genotype-specific drought tolerance mechanisms.

Plant Physiol Biochem 2021 May 29;166:203-214. Epub 2021 May 29.

Agricultural College, Ningxia University, Yinchuan, 750021, China. Electronic address:

Drought is one of the main abiotic factors that affect alfalfa yield. The identification of genes that control this complex trait can provide important insights for alfalfa breeding. However, little is known about how alfalfa responds and adapts to drought stress, particularly in cultivars of differing drought tolerance. In this study, the drought-tolerant cultivar Dryland 'DT' and the drought-sensitive cultivar WL343HQ 'DS' were used to characterize leaf and root physiological responses and transcriptional changes in response to water deficit. Under drought stress, Dryland roots (DTR) showed more differentially expressed genes than WL343HQ roots (DSR), whereas WL343HQ leaves (DSL) showed more differentially expressed genes than Dryland leaves (DTL). Many of these genes were involved in stress-related pathways, carbohydrate metabolism, and lignin and wax biosynthesis, which may have improved the drought tolerance of alfalfa. We also observed that several genes related to ABA metabolism, root elongation, peroxidase activity, cell membrane stability, ubiquitination, and genetic processing responded to drought stress in alfalfa. We highlighted several candidate genes, including sucrose synthase, xylan 1,4-beta-xylosidase, primary-amine oxidase, and alcohol-forming fatty acyl-CoA reductase, for future studies on drought stress resistance in alfalfa and other plant species. In summary, our results reveal the unique drought adaptation and resistance characteristics of two alfalfa genotypes. These findings, which may be valuable for drought resistance breeding, warrant further gene functional analysis to augment currently available information and to clarify the drought stress regulatory mechanisms of alfalfa and other plants.
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http://dx.doi.org/10.1016/j.plaphy.2021.05.008DOI Listing
May 2021

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

Heart Lung 2021 Jun 6;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

Deep biopsy via endoscopic submucosal dissection for primary gastric amyloidosis.

Endoscopy 2021 Jun 8. Epub 2021 Jun 8.

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

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http://dx.doi.org/10.1055/a-1493-2081DOI Listing
June 2021

Three-dimensional folding dynamics of the Xenopus tropicalis genome.

Nat Genet 2021 Jun 7. Epub 2021 Jun 7.

Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.

Animal interphase chromosomes are organized into topologically associating domains (TADs). How TADs are formed is not fully understood. Here, we combined high-throughput chromosome conformation capture and gene silencing to obtain insights into TAD dynamics in Xenopus tropicalis embryos. First, TAD establishment in X. tropicalis is similar to that in mice and flies and does not depend on zygotic genome transcriptional activation. This process is followed by further refinements in active and repressive chromatin compartments and the appearance of loops and stripes. Second, within TADs, higher self-interaction frequencies at one end of the boundary are associated with higher DNA occupancy of the architectural proteins CTCF and Rad21. Third, the chromatin remodeling factor ISWI is required for de novo TAD formation. Finally, TAD structures are variable in different tissues. Our work shows that X. tropicalis is a powerful model for chromosome architecture analysis and suggests that chromatin remodeling plays an essential role in de novo TAD establishment.
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http://dx.doi.org/10.1038/s41588-021-00878-zDOI Listing
June 2021

Snapshot polarized light scattering spectroscopy using spectrally-modulated polarimetry for early gastric cancer detection.

J Biophotonics 2021 Jun 5:e202100140. Epub 2021 Jun 5.

Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Polarized light scattering spectroscopy (PLSS) is a promising optical technique developed for the detection of cancer, which extracts the single scattering light to infer morphological information of epithelial cells. However, traditional PLSS uses either a rotatable polarizer or two orthogonal polarizers to purify the single scattering light, which makes it complicated and challenged to build a PLSS endoscope. Herein, we propose a snapshot PLSS with a single optical path to directly get the single scattering light for the first time. The single scattering light is encoded using the spectrally-modulated polarimetry and decoded using the continuous slide iterative method. Both the polystyrene microsphere solutions and the ex vivo gastric cancer samples are used to verify the method. The experimental results of the snapshot PLSS are consistent well with that of the traditional PLSS. The proposed method has a potential for the building of snapshot PLSS endoscope systems in future.
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http://dx.doi.org/10.1002/jbio.202100140DOI Listing
June 2021

The different replication between nonenveloped and quasi-enveloped hepatitis E virus.

J Med Virol 2021 Jun 2. Epub 2021 Jun 2.

Medical Faculty, Kunming University of Science and Technology, Kunming, PR China.

Hepatitis E virus (HEV) is the major pathogen of viral hepatitis. However, the understanding of the HEV life cycle is limited. In the present study, cells were separately infected with nonenveloped HEV (derived from feces or bile) or quasi-enveloped HEV (derived from the cell culture after serial passages, eHEV) and observed by confocal fluorescence microscopy to investigate the life cycle of HEV. HEV finished its binding and entry into host cells at first 6 h postinoculation (hpi). Cells inoculated with eHEV showed less infectivity than cells inoculated with nonenveloped HEV. Newly synthesized progeny virions were released into the supernatant of cell cultures from 48 hpi. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis results showed that the supernatant's progeny viruses were infectious even after five serial passages. These results show the significant difference between nonenveloped HEV and eHEV, which will provide novel insights into the HEV replication cycle. The efficient cell culture of HEV will promote the development of anti-HEV drugs and vaccines.
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http://dx.doi.org/10.1002/jmv.27121DOI Listing
June 2021

Hippocampal miR-211-5p regulates neurogenesis and depression-like behaviors in the rat.

Neuropharmacology 2021 Aug 29;194:108618. Epub 2021 May 29.

Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; Shandong Key Laboratory of Mental Disorders, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China. Electronic address:

Emerging evidence has shown that microRNAs (miRNAs) contribute to the pathogenesis of depression, a potentially life-threatening and disabling mental disorder caused by the interaction of genetic and environmental factors. However, the specific miRNAs and their underlying molecular mechanisms as involved in the pathogenesis and development of depression remain largely unknown. In the present study, we screened miRNA expression profiles and found that miR-211-5p was significantly down-regulated within the dentate gyrus (DG) hippocampus in the chronic unpredictable mild stress (CUMS) induced rat model of depression. Deficits in miR-211-5p were accompanied with reductions in neurogenesis and increased apoptosis in these CUMS rats. In contrast, an up-regulation of miR-211-5p within the DG area in CUMS rats promoted neuronal neurogenesis, reduced neuronal apoptosis via suppression of the Dyrk1A/STAT3 signaling pathway and relieved depression-like behaviors in these CUMS rats. In rats subjected to a knock-down of miR-211-5p in the DG there was an increase in neuronal apoptosis and a decrease in neuronal regeneration, effects which were accompanied with an induction of depression-like behaviors. Taken together, the results of our study reveal that altered levels of miR-211-5p in the hippocampal DG area exert a significant impact on neurogenesis, apoptosis and thus depression-like behaviors in rats. These findings suggest that the miR-211-5p/Dyrk1A pathway plays an important role in the pathogenesis of depression and may serve as a potential therapeutic target for the treatment of depression.
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http://dx.doi.org/10.1016/j.neuropharm.2021.108618DOI Listing
August 2021

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.

Signal Transduct Target Ther 2021 May 31;6(1):201. Epub 2021 May 31.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-molecule targeted anti-cancer drugs still face many challenges, such as a low response rate and drug resistance. To better promote the development of targeted anti-cancer drugs, we conducted a comprehensive review of small-molecule targeted anti-cancer drugs according to the target classification. We present all the approved drugs as well as important drug candidates in clinical trials for each target, discuss the current challenges, and provide insights and perspectives for the research and development of anti-cancer drugs.
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http://dx.doi.org/10.1038/s41392-021-00572-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165101PMC
May 2021

FBXO43 variants in patients with female infertility characterized by early embryonic arrest.

Hum Reprod 2021 May 30. Epub 2021 May 30.

Institute of Pediatrics, Children's Hospital of Fudan University, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China.

Study Question: Can any new genetic factors responsible for early embryonic arrest in infertile patients be identified, together with the mechanism of pathogenic variants?

Summary Answer: We identified three homozygous variants in the F-box protein 43 gene (FBXO43) in infertile patients and studies on the effects of the variants in HEK293T cells and mouse oocytes provided evidence for a causal relation between FBXO43 and female infertility.

What Is Known Already: FBXO43, an inhibitor of the anaphase-promoting complex/cyclosome, mediates Metaphase II arrest as a component of the cytostatic factor in oocytes. Both male and female Fbxo43 knockout mice are viable but sterile. FBXO43, therefore, appears to be an essential component of the mammalian cell-cycle machinery that regulates both male and female meiosis. Until now, only one article has reported a homozygous FBXO43 variant associated with teratozoospermia, but the causal relationship was not established with functional evidence.

Study Design, Size, Duration: Whole-exome sequencing (WES) and homozygosity mapping were performed in 24 probands from consanguineous families who suffered from early embryonic arrest, and two different homozygous variants in FBXO43 were identified in two independent families. WES data from a further 950 infertile women with early embryonic arrest were screened for homozygous and compound heterozygous variants in FBXO43, and a third individual with an additional homozygous variant in FBXO43 was identified. The infertile patients presenting with early embryonic arrest were recruited from August 2016 to May 2020.

Participants/materials, Setting, Methods: The women diagnosed with primary infertility were recruited from the reproduction centers of local hospitals. Genomic DNA samples from the affected individuals, their family members, and healthy controls were extracted from peripheral blood. The FBXO43 variants were identified using WES, homozygosity mapping, in silico analysis, and variant screening. All of the variants were confirmed by Sanger sequencing, and the effects of the variants were investigated in human embryonic kidney (HEK) 293T cells by western blotting and in mouse oocytes by complementary RNA injection.

Main Results And The Role Of Chance: We identified three homozygous variants in FBXO43 (NM_001029860.4)-namely, c.1490_1497dup (p.(Glu500Serfs*2)), c.1747C>T (p.(Gln583*)), and c.154delG (p.(Asp52Thrfs*30))-in three independent families. All of the homozygous variants reduced the protein level of FBXO43 and reduced the level of its downstream target Cyclin B1 in HEK293T cells. In addition, the variants reduced the ability of exogenous human FBXO43 to rescue the parthenogenetic activation phenotype in Fbxo43 knockdown mouse oocytes.

Limitations, Reasons For Caution: Owing to the lack of in vivo data from the oocytes of patients, the exact molecular mechanism remains unknown and should be further investigated using knock out or knock in mice.

Wider Implications Of The Findings: Our study has identified three pathogenic variants in FBXO43 that are involved in human early embryonic arrest. These findings contribute to our understanding of the role of FBXO43 in human early embryonic development and provide a new genetic marker for female infertility.

Study Funding/competing Interest(s): This work was supported by the National Key Research and Development Program of China (2018YFC1003800, 2017YFC1001500, and 2016YFC1000600), the National Natural Science Foundation of China (81725006, 81822019, 81771581, 81971450, 81971382, and 82001552), the project supported by the Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), the Project of the Shanghai Municipal Science and Technology Commission (19JC1411001), the Natural Science Foundation of Shanghai (19ZR1444500), the Shuguang Program of the Shanghai Education Development Foundation and the Shanghai Municipal Education Commission (18SG03), the Foundation of the Shanghai Health and Family Planning Commission (20154Y0162), the Capacity Building Planning Program for Shanghai Women and Children's Health Service, and the collaborative innovation center project construction for Shanghai Women and Children's Health. None of the authors have any competing interests.

Trial Registration Number: N/A.
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http://dx.doi.org/10.1093/humrep/deab131DOI Listing
May 2021

Novel biallelic mutations in MEI1: expanding the phenotypic spectrum to human embryonic arrest and recurrent implantation failure.

Hum Reprod 2021 May 25. Epub 2021 May 25.

Institute of Pediatrics, Children's Hospital of Fudan University and Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China.

Study Question: Are any novel mutations and corresponding new phenotypes, other than recurrent hydatidiform moles, seen in patients with MEI1 mutations?

Summary Answer: We identified several novel mutations in MEI1 causing new phenotypes of early embryonic arrest and recurrent implantation failure.

What Is Known Already: It has been reported that biallelic mutations in MEI1, encoding meiotic double-stranded break formation protein 1, cause azoospermia in men and recurrent hydatidiform moles in women.

Study Design, Size, Duration: We first focused on a pedigree in which two sisters were diagnosed with recurrent hydatidiform moles in December 2018. After genetic analysis, two novel mutations in MEI1 were identified. We then expanded the mutational screening to patients with the phenotype of embryonic arrest, recurrent implantation failure, and recurrent pregnancy loss, and found another three novel MEI1 mutations in seven new patients from six families recruited from December 2018 to May 2020.

Participants/materials, Setting, Methods: Nine primary infertility patients were recruited from the reproduction centers in local hospitals. Genomic DNA from the affected individuals, their family members, and healthy controls was extracted from peripheral blood. The MEI1 mutations were screened using whole-exome sequencing and were confirmed by the Sanger sequencing. In silico analysis of mutations was performed with Sorting Intolerant From Tolerant (SIFT) and Protein Variation Effect Analyzer (PROVEAN). The influence of the MEI1 mutations was determined by western blotting and minigene analysis in vitro.

Main Results And The Role Of Chance: In this study, we identified five novel mutations in MEI1 in nine patients from seven independent families. Apart from recurrent hydatidiform moles, biallelic mutations in MEI1 were also associated with early embryonic arrest and recurrent implantation failure. In addition, we demonstrated that protein-truncating and missense mutations reduced the protein level of MEI1, while the splicing mutations caused abnormal alternative splicing of MEI1.

Limitations, Reasons For Caution: Owing to the lack of in vivo data from the oocytes of the patients, the exact molecular mechanism(s) involved in the phenotypes remains unknown and should be further investigated using knock-out or knock-in mice.

Wider Implications Of The Findings: Our results not only reveal the important role of MEI1 in human oocyte meiosis and early embryonic development, but also extend the phenotypic and mutational spectrum of MEI1 and provide new diagnostic markers for genetic counseling of clinical patients.

Study Funding/competing Interest(s): This work was supported by the National Key Research and Development Program of China (2018YFC1003800, 2017YFC1001500, and 2016YFC1000600), the National Natural Science Foundation of China (81725006, 81822019, 81771581, 81971450, and 81971382), the project supported by the Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), the Project of the Shanghai Municipal Science and Technology Commission (19JC1411001), the Natural Science Foundation of Shanghai (19ZR1444500), the Shuguang Program of the Shanghai Education Development Foundation and the Shanghai Municipal Education Commission (18SG03), the Shanghai Health and Family Planning Commission Foundation (20154Y0162), the Strategic Collaborative Research Program of the Ferring Institute of Reproductive Medicine, Ferring Pharmaceuticals and the Chinese Academy of Sciences (FIRMC200507) and the Chongqing Key Laboratory of Human Embryo Engineering (2020KFKT008). No competing interests are declared.

Trial Registration Number: N/A.
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http://dx.doi.org/10.1093/humrep/deab118DOI Listing
May 2021

The mRNA-destabilizing protein Tristetraprolin targets "meiosis arrester" mRNA in mammalian preovulatory follicles.

Proc Natl Acad Sci U S A 2021 Jun;118(22)

Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, 100193 Beijing, P. R. China

C-natriuretic peptide (CNP) and its receptor guanylyl cyclase, natriuretic peptide receptor 2 (NPR2), are key regulators of cyclic guanosine monophosphate (cGMP) homeostasis. The CNP-NPR2-cGMP signaling cascade plays an important role in the progression of oocyte meiosis, which is essential for fertility in female mammals. In preovulatory ovarian follicles, the luteinizing hormone (LH)-induced decrease in CNP and its encoding messenger RNA (mRNA) natriuretic peptide precursor C () are a prerequisite for oocyte meiotic resumption. However, it has never been determined how LH decreases CNP/ In the present study, we identified that tristetraprolin (TTP), also known as zinc finger protein 36 (ZFP36), a ubiquitously expressed mRNA-destabilizing protein, is the critical mechanism that underlies the LH-induced decrease in mRNA. mRNA was transiently up-regulated in mural granulosa cells (MGCs) in response to the LH surge. Loss- and gain-of-function analyses indicated that TTP is required for mRNA degradation in preovulatory MGCs by targeting the rare noncanonical AU-rich element harbored in the 3' UTR. Moreover, MGC-specific knockout of , as well as lentivirus-mediated knockdown in vivo, impaired the LH/hCG-induced mRNA decline and oocyte meiotic resumption. Furthermore, we found that LH/hCG activates /TTP expression through the EGFR-ERK1/2-dependent pathway. Our findings reveal a functional role of TTP-induced mRNA degradation, a global posttranscriptional regulation mechanism, in orchestrating the progression of oocyte meiosis. We also provided a mechanism for understanding CNP-dependent cGMP homeostasis in diverse cellular processes.
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http://dx.doi.org/10.1073/pnas.2018345118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179146PMC
June 2021

How hydrophilic group affects drug-protein binding modes: Differences in interaction between sirtuins inhibitors Tenovin-1/Tenovin-6 and human serum albumin.

J Pharm Biomed Anal 2021 Jul 7;201:114121. Epub 2021 May 7.

School of Chemical Engineering, Sichuan University, Chengdu, 610065, Sichuan, China. Electronic address:

Introduction of hydrophilic groups can improve the solubility of leading drugs but inevitably affect their interaction with proteins. This study selected sirtuin inhibitors Tenovin-1 (T1) and Tenovin-6 (T6) as drug models to determine differences in binding mode to human serum albumin (HSA). T1 and T6 quenched the endogenous fluorescence of HSA via static quenching mechanism. Introduction of hydrophilic groups greatly reduced the binding constant, i.e., from 1.302 × 10 L mol for the HSA-T6 system to 0.128 × 10 L mol for the HSA-T1 system. HSA-T1 system was mainly driven by electrostatic interactions while that of HSA-T6 system was hydrophobic interaction and both systems were spontaneous reactions. Site marker experiments and molecular docking indicated that both systems mainly bound to the hydrophobic site I of HSA. Molecular dynamics (MD) simulation analysis further revealed that Tyr148, Tyr150 and Arg257 residues played a key role in this recognition process for both systems. In particular, T6 maintained additional several hydrogen bonds with the surrounding residues. T1 had almost no effect on the esterase-like activity of HSA, but T6 inhibited the hydrolysis of p-NPA. Furthermore, differential scanning calorimetry (VP-DSC), circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy confirmed that HSA in the T6 system undergone a more significant conformational transition than that in the T1 system.
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http://dx.doi.org/10.1016/j.jpba.2021.114121DOI Listing
July 2021

Brucella Outer Membrane Lipoproteins 19 and 16 Differentially Induce IL-18 Response or Pyroptosis in Human Monocytic Cells.

J Infect Dis 2021 May 20. Epub 2021 May 20.

Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China.

Background: Brucella species (B. spp.) are Gram-negative intracellular bacteria, causing severe inflammatory diseases in animals and humans. Two major lipoproteins (L19) and (L16) of Brucella outer membrane proteins (OMPs) were extensively explored in associating with inflammatory response of human monocytes (THP-1).

Methods: Activated THP-1 cells induced with recombinant L19 and L16 were analyzed in comparison with unlipidated forms (U19 and U16) and lipopolysaccharide (LPS) of B. melitensis, respectively.

Results: Secretion of inflammatory factors TNF-α, IL-6 and IL-1β was significantly increased from L19, L16 or both stimulated THP-1 cells. High secretion of IL-18 was detected only from L19-induced cells. Signaling of those cytokine responses was identified mainly through P38-MAPK pathway, and signaling of L19-induced IL-1β response was partly occurred via NF-κB. Exploration for different forms of IL-18 found that L19-induced production of active IL-18 (18 kD) was through up-regulating NLRP3 and activating caspase-1, while L16-induced production of inactive IL-18 fragments (15 kD and 16 kD) occurred through activating caspase-8/3. Additionally, L19 up-regulated phosphorylation of XIAP for inhibiting caspase-3 activity to cleave IL-18, while L16 activated caspase-3 for producing GSDME-N and leading to pyroptosis of THP-1 cells.

Conclusion: Brucella L19 and L16 differentially induce IL-18 response or pyroptosis in THP-1 cells, respectively.
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http://dx.doi.org/10.1093/infdis/jiab272DOI Listing
May 2021

Response to crizotinib in a patient with MET-amplified hepatocellular carcinoma.

Hepatol Res 2021 May 15. Epub 2021 May 15.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Aims: Molecular profiling of hepatocellular carcinoma (HCC) has helped identify actionable genomic alterations that could guide therapeutic decision-making and clinical trial enrollment. However, in clinical practice, next-generation sequencing (NGS) is not extensively used in routine clinical care to identify patients with HCC who are likely to benefit from genome-directed targeted therapies.

Methods: Here, we describe the case of a 66-year-old man with advanced HCC. After rapid progression on transarterial chemoembolization, the tissue sample obtained from biopsy was subjected to NGS to verify whether precision therapy was an option.

Results: Our analysis revealed high MET amplification. The patient received crizotinib (250 mg, bid) and showed a remarkable response.

Conclusions: Our case report suggests NGS could help identify patients with high MET amplification in HCC who were likely to benefit from MET inhibitors; moreover, this requires further investigation in clinical trials.
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http://dx.doi.org/10.1111/hepr.13664DOI Listing
May 2021

Inhibition of sphingosine kinase 2 down-regulates ERK/c-Myc pathway and reduces cell proliferation in human epithelial ovarian cancer.

Ann Transl Med 2021 Apr;9(8):645

Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Epithelial ovarian cancer (EOC) is the leading cause of death from female cancers. In our previous study, sphingosine kinase 2 (SphK2) inhibitor was shown to display anti-EOC activities. The purpose of this study was to evaluate further the expression characteristics and clinical significance of SphK2 in EOC and to explore the roles and underlying mechanisms of SphK2 in EOC cell survival.

Methods: The expression of SphK2 was examined by immunohistochemistry (IHC) and Western blot, and its clinical implications and prognostic significance were analyzed. We performed a cellular proliferation assay, and a mouse xenograft model was established to confirm the roles of SphK2 and . Cell cycle analysis, apoptosis assay, and Western blot were performed to examine cell cycle progression and apoptosis rate. Gene set enrichment analysis (GSEA), and Western blot were used to investigate the downstream signaling pathways related to SphK2 function.

Results: The expression level of SphK2 was shown to be associated with stage, histological grade, lymph node metastasis, and ascites status. More importantly, a high SphK2 expression level was a prognostic indicator of overall survival (OS) and relapse-free survival (RFS). Moreover, knockdown of SphK2 arrested cell cycle progression and inhibited EOC cell proliferation both in vitro and in vivo. Furthermore, ERK/c-Myc, the key pathway in EOC progression, was important for SphK2-mediated mitogenic action in EOC cells.

Conclusions: Our findings provided the first evidence that SphK2 played a crucial role in EOC proliferation by regulating the ERK/c-Myc pathway. This indicated that SphK2 might serve as a prognostic marker and potential therapeutic target in EOC.
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http://dx.doi.org/10.21037/atm-20-6742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106111PMC
April 2021

Solvatomorphism Influence of Porous Organic Cage on CH/CO Separation.

ACS Appl Mater Interfaces 2021 May 12;13(20):24042-24050. Epub 2021 May 12.

State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, China.

Porous organic molecular (POM) materials can exhibit solvatomorphs via altering their crystallographic packing in the solid state, but investigating real gas mixture separation by porous materials with such a behavior is still very rare. Herein, we report that a lantern-shaped calix[4]resorcinarene-based porous organic cage (POC, namely, ) can exhibit eight distinct solid-state solvatomorphs via crystallization in different solvents. This POC solvatomorphism has a significant influence on their gas sorption capacities as well as separation abilities. Specifically, the apparent Brunauer-Emmett-Teller (BET) surface area determined by nitrogen gas sorption at 77 K for crystallized from toluene/chloroform is up to 406 m g, which is much higher than the rest of solvatomorphs with BET values less than 40 m g. More interestingly, CH and CO adsorbed capacities, in addition to the CH/CO separation ability at room temperature for , are superior to those of crystalized from nitrobenzene, the representative of POC solvatomorphs with low BET surface areas. These results indicate the possibility of adjusting gas sorption and separation properties of POC materials by controlling their solvatomorphs.
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http://dx.doi.org/10.1021/acsami.1c04573DOI Listing
May 2021

Synthesis of a Boron-Imidazolate Framework Nanosheet with Dimer Copper Units for CO Electroreduction to Ethylene.

Angew Chem Int Ed Engl 2021 May 12. Epub 2021 May 12.

State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, 350002, P. R. China.

Fundamental understanding of the dependence between the structure and composition on the electrochemical CO reduction reaction (CO RR) would guide the rational design of highly efficient and selective electrocatalysts. A major impediment to the deep reduction CO to multi-carbon products is the complexity of carbon-carbon bond coupling. The chemically well-defined catalysts with atomically dispersed dual-metal sites are required for these C-C coupling involved processes. Here, we developed a catalyst (BIF-102NSs) that features Cl bridged dimer copper (Cu ) units, which delivers high catalytic activity and selectivity for C H . Mechanistic investigation verifies that neighboring Cu monomers not only perform as regulator for varying the reaction barrier, but also afford distinct reaction paths compared with isolated monomers, resulting in greatly improved electroreduction performance for CO .
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http://dx.doi.org/10.1002/anie.202106004DOI Listing
May 2021

A window-space-directed assembly strategy for the construction of supertetrahedron-based zeolitic mesoporous metal-organic frameworks with ultramicroporous apertures for selective gas adsorption.

Chem Sci 2021 Mar 5;12(16):5767-5773. Epub 2021 Mar 5.

Department of Chemistry, University of North Texas Denton 76201 USA

Despite their scarcity due to synthetic challenges, supertetrahedron-based metal-organic frameworks (MOFs) possess intriguing architectures, diverse functionalities, and superb properties that make them in-demand materials. Employing a new window-space-directed assembly strategy, a family of mesoporous zeolitic MOFs have been constructed herein from corner-shared supertetrahedra based on homometallic or heterometallic trimers [M(OH/O)(COO)] (M = Co, Ni or CoTi). These MOFs consisted of close-packed truncated octahedral cages possessing a sodalite topology and large β-cavity mesoporous cages (∼22 Å diameter) connected by ultramicroporous apertures (∼5.6 Å diameter). Notably, the supertetrahedron-based sodalite topology MOF combined with the CoTi trimer exhibited high thermal and chemical stability as well as the ability to efficiently separate acetylene (CH) from carbon dioxide (CO).
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http://dx.doi.org/10.1039/d0sc06841aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083976PMC
March 2021

Equivalent effect of extracellular proteins and polysaccharides on biofilm formation by clinical isolates of .

Biofouling 2021 Mar 3;37(3):327-340. Epub 2021 May 3.

Department of Clinical Laboratory Medicine, The First Medical Center, Chinese Peoples' Liberation Army General Hospital, Beijing, P.R. China.

Biofilm formation by involves formation of an extracellular matrix; however, the identity of the constituents responsible for the structure of biofilms fabricated by different clinical strains is largely unclear. Here, biofilms produced by 24 clinical isolates of were characterized. The optimal medium for was selected, and the biofilm-forming capacity was assessed. Extracelullar polymeric substances (EPS) contributing to biofilm robustness were determined by evaluating the susceptibility of biofilms to EPS-degrading agents using field emission scanning electron microscopy and confocal laser scanning microscopy. Biofilm formation by the clinical isolates of was augmented by glucose supplementation. Further, extracellular DNA (eDNA), proteins, and polysaccharides were present in the 24 clinical isolates. Proteins and polysaccharides were the most common components within the biofilms, whereas the eDNA content was marginal in biofilm formation. Therefore, proteins and polysaccharides within biofilms may be used as the primary targets for developing eradication strategies to prevent biofilm formation.
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http://dx.doi.org/10.1080/08927014.2021.1914021DOI Listing
March 2021

Complete genome sequence of Streptomyces sp. HSG2 from rhizosphere soil of mangrove in Qingmei Gang, Sanya.

Arch Microbiol 2021 May 1. Epub 2021 May 1.

Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen, 361005, Fujian, People's Republic of China.

Streptomyces sp. HSG2 was isolated from rhizosphere soil of a mangrove forest sample at Qingmei Gang, Sanya. The complete genome sequence of the strain HSG2 was obtained using PacBio Sequel HGAP.4 and comprised of 5,282,528 base pairs with a 71.9 mol% G + C content, 4504 protein-coding genes, and 71 RNAs. An in-silico analysis confirmed that genes associated with polysaccharide hydrolyzation, hydrocarbon degradation, and aerobic denitrification were presented in the genome. We also identified 24 natural product biosynthetic gene clusters for secondary metabolites, including those for streptobactin and nystatin A1. The complete genome sequence indicated that Streptomyces sp. HSG2 will provide insight into the biosynthesis and regulatory mechanisms for its secondary metabolites, and propose a potential use in biotechnological and novel bioactive natural product biosynthetic applications.
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http://dx.doi.org/10.1007/s00203-021-02339-xDOI Listing
May 2021

Activation of SphK1 by adipocytes mediates epithelial ovarian cancer cell proliferation.

J Ovarian Res 2021 May 1;14(1):62. Epub 2021 May 1.

Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.

Background: Adipocytes, active facilitators of epithelial ovarian cancer (EOC) growth, have been implicated in the link between obesity and EOC. However, the current understanding of the mechanisms underlying adipocyte-induced EOC cell proliferation remains incomplete.

Results: We provide the first evidence showing that sphingosine kinase (SphK) 1 is critical for adipocyte-induced EOC cell proliferation. Adipocytes are capable of activating SphK1, which then leads to extracellular signal-regulated kinase (ERK) phosphorylation. Moreover, adipocyte-induced SphK1 activation is ERK dependent. Furthermore, sphingosine 1-phosphate receptor (S1PR) 1 and S1PR3, key components of the SphK1 signalling pathway, participate in adipocyte-mediated growth-promoting action in EOC cells.

Conclusions: Our study reveals a previously unrecognized role of SphK1 in adipocyte-induced growth-promoting action in EOC, suggesting a new target for EOC therapy.
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http://dx.doi.org/10.1186/s13048-021-00815-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088075PMC
May 2021

Molecular recognition patterns between vitamin B12 and human serum albumin explored through STD-NMR and spectroscopic methods.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Sep 20;258:119828. Epub 2021 Apr 20.

School of Chemical Engineering, Sichuan University, Chengdu 610065, China. Electronic address:

Ligand-receptor molecular recognitionis the basis of biological process. The Saturation Transfer Difference-NMR (STD-NMR) technique has been recently used to gain qualitative and quantitative information about physiological interactions at atomic-resolution. The molecular recognition patterns between Vitamin B12 (VB12) and human serum albumin (HSA) were investigated by STD-NMR supplemented by other spectroscopies and molecular docking. STD-NMR delivered a complete picture that the substituent groups on the tetrapyrrole ring of VB12 interacted with site III of HSA through binding epitope mapping and competitive probe experiments. STD-NMR and fluorescence results proved the moderate binding capability of VB12 and clarified a static, spontaneous, and temperature-sensitive binding mechanism. 3D-fluorencence, FT-IR and circular dichroism spectra showed a compact protein structure by interacting with VB12. Size distribution and surface hydrophobicity showed the surface properties changes of HSA caused by the binding of VB12. Computer simulation confirmed the recognition mode in theory and was compared with experiments. This work is beneficial for understanding the safety and biological action of VB12, and will attract researchers interested in NMR technology.
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http://dx.doi.org/10.1016/j.saa.2021.119828DOI Listing
September 2021

The Protective A673T Mutation of Amyloid Precursor Protein (APP) in Alzheimer's Disease.

Mol Neurobiol 2021 Apr 29. Epub 2021 Apr 29.

Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.

Alzheimer's disease is a progressive neurodegenerative disorder characterized by extracellular amyloid beta peptides and neurofibrillary tangles consisted of intracellular hyperphosphorylated Tau in the hippocampus and cerebral cortex. Most of the mutations in key genes that code for amyloid precursor protein can lead to significant accumulation of these peptides in the brain and cause Alzheimer's disease. Moreover, some point mutations in amyloid precursor protein can cause familial Alzheimer's disease, such as Swedish mutation (KM670/671NL) and A673V mutation. However, recent studies have found that the A673T mutation in amyloid precursor protein gene can protect against Alzheimer's disease, even if it is located next to the Swedish mutation (KM670/671NL) and at the same site as A673V mutation, which are pathogenic. It makes us curious about the protective A673T mutation. Here, we summarize the most recent insights of A673T mutation, focus on their roles in protective mechanisms against Alzheimer's disease, and discuss their involvement in future treatment.
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http://dx.doi.org/10.1007/s12035-021-02385-yDOI Listing
April 2021

Two case reports of rare diseases occurring in rare parts: splenic vein solitary fibrous tumor and liver solitary fibrous tumor.

AME Case Rep 2021 25;5:17. Epub 2021 Apr 25.

Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Solitary fibrous tumor (SFT) is a rare soft tissue tumor originating from mesenchymal cells. Here we report two new cases of SFT. One case was a 37-year-old female patient whose primary tumor site was located in the splenic vein and the primary tumor resulted in splenomegaly and hypersplenism; its recurred for many times after surgical resection and eventually transferred to the liver, 4 operations were performed during 10 years of follow-up, and the patient is in a good condition right now. The second case was a 54-year-old male patient whose primary tumor site was located in the liver, spleen and left side of the chest wall. We performed two operations to remove these tumors, totally. Six years later, SFT recurred in the liver, given that the tumor was too large to be surgical resected completely, we chose orthotopic liver transplantation (OLT), and no tumor recurred during 6 years' follow-up, he is also in a good condition right now. The reports of these two cases of SFT are exceedingly rare, especially the splenic vein SFT is the first report case, which helps expand the understanding of SFT. Although the current mainstream treatment of SFT is surgical resection, liver transplantation may be a new option treatment for the huge liver SFT.
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http://dx.doi.org/10.21037/acr-20-142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060157PMC
April 2021

Identification of Novel Mutations in : Expanding the Mutational Spectrum for Female Infertility.

Front Cell Dev Biol 2021 9;9:647130. Epub 2021 Apr 9.

Institute of Pediatrics, Children's Hospital of Fudan University and Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China.

Oocyte maturation and fertilization are fundamental processes for successful human reproduction, and abnormalities in these processes will cause infertility. Recently, we identified biallelic mutations in that are responsible for human oocyte maturation arrest, fertilization failure, and early embryonic development arrest. In this study, we screened for further mutations in a new cohort of patients with abnormalities in oocyte maturation, fertilization, and early embryonic development. Through whole-exome sequencing, we identified the four novel mutations c.887G > A (p. Arg296Gln), c.964C > T (p.Arg322), c.1155G > C (p.Trp385Cys), and c.330 + 1G > A (p. Glu111Ilefs36) and one previously reported mutation c.965G > A (p.Arg322Gln) in in four infertile individuals from three independent families. The patients had different phenotypes of oocyte maturation arrest and fertilization failure resulting from the different mutations. This study confirms our previous research and expands the spectrum of known mutations in , providing new evidence supporting the function of in the genetic etiology of female infertility characterized by oocyte maturation arrest and fertilization failure.
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http://dx.doi.org/10.3389/fcell.2021.647130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063106PMC
April 2021

A dual-targeting ruthenium nanodrug that inhibits primary tumor growth and lung metastasis via the PARP/ATM pathway.

J Nanobiotechnology 2021 Apr 23;19(1):115. Epub 2021 Apr 23.

Department of Medicinal Chemistry, College of Pharmaceutical Sciences of Capital Medical University, 10 Xi Tou Tiao, You An Men, Beijing, 100069, People's Republic of China.

Background: Many studies have found that ruthenium complexes possess unique biochemical characteristics and inhibit tumor growth or metastasis.

Results: Here, we report the novel dual-targeting ruthenium candidate 2b, which has both antitumor and antimetastatic properties and targets tumor sites through the enhanced permeability and retention (EPR) effect and transferrin/transferrin receptor (TF/TFR) interaction. The candidate 2b is composed of ruthenium-complexed carboline acid and four chloride ions. In vitro, 2b triggered DNA cleavage and thus blocked cell cycle progression and induced apoptosis via the PARP/ATM pathway. In vivo, 2b inhibited not only Lewis lung cancer (LLC) tumor growth but also lung metastasis. We detected apoptosis and decreased CD31 expression in tumor tissues, and ruthenium accumulated in the primary tumor tissue of C57BL/6 mice implanted with LLC cells.

Conclusions: Thus, we conclude that 2b targets tumors, inhibits tumor growth and prevents lung metastasis.
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http://dx.doi.org/10.1186/s12951-021-00799-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063440PMC
April 2021