Publications by authors named "Sijing Li"

40 Publications

Cancer cell-autonomous overactivation of PARP1 compromises immunosurveillance in non-small cell lung cancer.

J Immunother Cancer 2022 06;10(6)

Equipe 11 labellisée par la Ligue contre le Cancer, Université de Paris Cité, Sorbonne Université, Centre de Recherche des Cordeliers, INSERM UMR1138, Paris, France

Background: High activity of poly(ADP-ribose) polymerase-1 (PARP1) in non-small cell lung cancer (NSCLC) cells leads to an increase in immunohistochemically detectable PAR, correlating with poor prognosis in patients with NSCLC, as well as reduced tumor infiltration by cytotoxic T lymphocytes (CTLs). Intrigued by this observation, we decided to determine whether PARP1 activity in NSCLC cells may cause an alteration of anticancer immunosurveillance.

Methods: Continuous culture of mouse NSCLC cells in the presence of cisplatin led to the generation of cisplatin-resistant PAR clones. As compared with their parental controls, such PAR cells formed tumors that were less infiltrated by CTLs when they were injected into immunocompetent mice, suggesting a causative link between high PARP1 activity and compromised immunosurveillance. To confirm this cause-and-effect relationship, we used CRISPR/Cas9 technology to knock out PARP1 in two PAR NSCLC mouse cell lines (Lewis lung cancer [LLC] and tissue culture number one [TC1]), showing that the removal of PARP1 indeed restored cisplatin-induced cell death responses.

Results: PARP1 knockout (PARP1) cells became largely resistant to the PARP inhibitor niraparib, meaning that they exhibited less cell death induction, reduced DNA damage response, attenuated metabolic shifts and no induction of PD-L1 and MHC class-I molecules that may affect their immunogenicity. PAR tumors implanted in mice responded to niraparib irrespective of the presence or absence of T lymphocytes, suggesting that cancer cell-autonomous effects of niraparib dominate over its possible immunomodulatory action. While PAR NSCLC mouse cell lines proliferated similarly in immunocompetent and T cell-deficient mice, PARP1 cells were strongly affected by the presence of T cells. PARP1 LLC tumors grew more quickly in immunodeficient than in immunocompetent mice, and PARP1 TC1 cells could only form tumors in T cell-deficient mice, not in immunocompetent controls. Importantly, as compared with PAR controls, the PARP1 LLC tumors exhibited signs of T cell activation in the immune infiltrate such as higher inducible costimulator (ICOS) expression and lower PD-1 expression on CTLs.

Conclusions: These results prove at the genetic level that PARP1 activity within malignant cells modulates the tumor microenvironment.
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http://dx.doi.org/10.1136/jitc-2021-004280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247697PMC
June 2022

A Simplified Herbal Formula Improves Cardiac Function and Reduces Inflammation in Mice Through the TLR-Mediated NF-κB Signaling Pathway.

Front Pharmacol 2022 6;13:865614. Epub 2022 Jun 6.

Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Nuanxinkang tablet (NXK), a Chinese herbal formula, can improve heart function and quality of life in patients with chronic heart failure (CHF). However, the mechanisms of action of NXK are not fully understood. In this study, we investigated the effects of NXK on inflammation in the CHF mouse model. This model was established by transverse aortic constriction (TAC) and treated with NXK for 8 weeks. Then, the cardiac function and myocardial fibrosis were evaluated. The monocytes/macrophages were evaluated by immunofluorescence. The mRNA levels of β, , α, , and were measured by quantitative real-time polymerase chain reaction (qRT-PCR), while TLR4, MyD88, NF-κB p65, P-IκBα, TLR2, TLR7 and TLR9 protein levels were evaluated by Western blot. The results showed that NXK improved the left ventricular ejection fraction (LVEF) and left ventricular end-systolic dimension, reversed myocardial fibrosis, and inhibited pro-inflammatory (CD11b + Ly6C+) monocytes/macrophages in the TAC mouse model. NXK also reduced the mRNA and protein levels of the above markers. Taken together, NXK improved heart function and reduced inflammation through the TLR-mediated NF-κB signaling pathway, suggesting that it might be used as an innovative treatment strategy for CHF.
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http://dx.doi.org/10.3389/fphar.2022.865614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207450PMC
June 2022

bFGF-Loaded Mesoporous Silica Nanoparticles Promote Bone Regeneration Through the Wnt/β-Catenin Signalling Pathway.

Int J Nanomedicine 2022 7;17:2593-2608. Epub 2022 Jun 7.

School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, People's Republic of China.

Background: Bone defects remain an unsolved clinical problem due to the lack of effective osteogenic induction protocols. Nanomaterials play an important role in bone defect repair by stimulating osteogenesis. However, constructing an effective bioactive nanomaterial remains a substantial challenge.

Methods: In this study, mesoporous silica nanoparticles (MSNs) were prepared and used as nanocarriers for basic fibroblast growth factor (bFGF). The characteristics and biological properties of the synthetic [email protected] were tested. The osteogenic effects of the particles on the behavior of MC3T3-E1 cells were investigated in vitro. In addition, the differentially expressed genes during induction of osteogenesis were analyzed by transcriptomic sequencing. Radiological and histological observations were carried out to determine bone regeneration capability in a distal femur defect model.

Results: Achieving bFGF sustained release, [email protected] had uniform spherical morphology and good biocompatibility. In vitro osteogenesis induction experiments showed that [email protected] exhibited excellent osteogenesis performance, with upregulation of osteogenesis-related genes (RUNX2, OCN, Osterix, ALP). Transcriptomic sequencing revealed that the Wnt/β-catenin signalling pathway could be activated in regulation of biological processes. In vivo, bone defect repair experiments showed enhanced bone regeneration, as indicated by radiological and histological analysis, after the application of [email protected]

Conclusion: [email protected] can promote bone regeneration by activating the Wnt/β-catenin signalling pathway. These particles are expected to become a potential therapeutic bioactive material for clinical application in repairing bone defects in the future.
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http://dx.doi.org/10.2147/IJN.S366926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188412PMC
June 2022

An obesogenic feedforward loop involving PPARγ, acyl-CoA binding protein and GABA receptor.

Cell Death Dis 2022 Apr 18;13(4):356. Epub 2022 Apr 18.

Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France.

Acyl-coenzyme-A-binding protein (ACBP), also known as a diazepam-binding inhibitor (DBI), is a potent stimulator of appetite and lipogenesis. Bioinformatic analyses combined with systematic screens revealed that peroxisome proliferator-activated receptor gamma (PPARγ) is the transcription factor that best explains the ACBP/DBI upregulation in metabolically active organs including the liver and adipose tissue. The PPARγ agonist rosiglitazone-induced ACBP/DBI upregulation, as well as weight gain, that could be prevented by knockout of Acbp/Dbi in mice. Moreover, liver-specific knockdown of Pparg prevented the high-fat diet (HFD)-induced upregulation of circulating ACBP/DBI levels and reduced body weight gain. Conversely, knockout of Acbp/Dbi prevented the HFD-induced upregulation of PPARγ. Notably, a single amino acid substitution (F77I) in the γ2 subunit of gamma-aminobutyric acid A receptor (GABAR), which abolishes ACBP/DBI binding to this receptor, prevented the HFD-induced weight gain, as well as the HFD-induced upregulation of ACBP/DBI, GABAR γ2, and PPARγ. Based on these results, we postulate the existence of an obesogenic feedforward loop relying on ACBP/DBI, GABAR, and PPARγ. Interruption of this vicious cycle, at any level, indistinguishably mitigates HFD-induced weight gain, hepatosteatosis, and hyperglycemia.
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http://dx.doi.org/10.1038/s41419-022-04834-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016078PMC
April 2022

Inhibition of Myocardial Cell Apoptosis Is Important Mechanism for Ginsenoside in the Limitation of Myocardial Ischemia/Reperfusion Injury.

Front Pharmacol 2022 1;13:806216. Epub 2022 Mar 1.

School of Chinese Classics, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Ischemic heart disease has a high mortality, and the recommended therapy is reperfusion. Nevertheless, the restoration of blood flow to ischemic tissue leads to further damage, namely, myocardial ischemia/reperfusion injury (MIRI). Apoptosis is an essential pathogenic factor in MIRI, and ginsenosides are effective in inhibiting apoptosis and alleviating MIRI. Here, we reviewed published studies on the anti-apoptotic effects of ginsenosides and their mechanisms of action in improving MIRI. Each ginsenoside can regulate multiple pathways to protect the myocardium. Overall, the involved apoptotic pathways include the death receptor signaling pathway, mitochondria signaling pathway, PI3K/Akt signaling pathway, NF-κB signaling pathway, and MAPK signaling pathway. Ginsenosides, with diverse chemical structures, regulate different apoptotic pathways to relieve MIRI. Summarizing the effects and mechanisms of ginsenosides contributes to further mechanism research studies and structure-function relationship research studies, which can help the development of new drugs. Therefore, we expect that this review will highlight the importance of ginsenosides in improving MIRI anti-apoptosis and provide references and suggestions for further research in this field.
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http://dx.doi.org/10.3389/fphar.2022.806216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921549PMC
March 2022

Machine Learning-Driven Multiobjective Optimization: An Opportunity of Microfluidic Platforms Applied in Cancer Research.

Cells 2022 03 5;11(5). Epub 2022 Mar 5.

Department of Bioengineering, Lehigh University, Bethlehem, PA 18015, USA.

Cancer metastasis is one of the primary reasons for cancer-related fatalities. Despite the achievements of cancer research with microfluidic platforms, understanding the interplay of multiple factors when it comes to cancer cells is still a great challenge. Crosstalk and causality of different factors in pathogenesis are two important areas in need of further research. With the assistance of machine learning, microfluidic platforms can reach a higher level of detection and classification of cancer metastasis. This article reviews the development history of microfluidics used for cancer research and summarizes how the utilization of machine learning benefits cancer studies, particularly in biomarker detection, wherein causality analysis is useful. To optimize microfluidic platforms, researchers are encouraged to use causality analysis when detecting biomarkers, analyzing tumor microenvironments, choosing materials, and designing structures.
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http://dx.doi.org/10.3390/cells11050905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909684PMC
March 2022

Analysis of the Clinicopathologic Characteristics and Prognosis of Head and Neck Lymphoma.

Anal Cell Pathol (Amst) 2022 22;2022:4936099. Epub 2022 Feb 22.

Department of Pathology, The Tumor Hospital Affiliated to Xinjiang Medical University, No. 789 Suzhou Dongjie, Urumqi, The Xinjiang Uygur Autonomous Region of China, 830011, China.

Statistical reports on non-Hodgkin's lymphoma (NHL) of the head and neck combining clinical medicine with pathology are rare. To provide a basis for prognosis prediction and individualized treatment, we will investigate the clinicopathologic characteristics and prognosis of lymphoma in the head and neck region. Four hundred sixty-one patients with NHL in the head and neck region diagnosed through histological biopsy were retrospectively analyzed. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed in all cases to evaluate the genetic status and protein expression levels. Patients were followed up by telephone. The prevalence rate of primary extranodal NHL (PENHL) in the head and neck region was 44.62% (166/372). The incidence of extranodal lymphoma accounted for 36.66% (169/461) of all head and neck lymphomas. Among the cases of PENHL of the head and neck, diffuse large B-cell lymphoma (DLBCL) (60/76, 78.95%) and extranodal NK/T-cell lymphoma, nasal type (ENKTCL) (21/24, 87.5%) were the most common subtypes originating from B-cell lymphoma (BCL) and T-cell lymphoma (TCL), respectively. The most common sites of nodal and extranodal onset were neck lymph nodes and the gastrointestinal tract, respectively. The most common and primary locations of BCL and TCL were the tonsils and nasal cavity, respectively. The 3-year survival rates of PENHL, ENKTCL, and DLBCL of the head and neck were 42%, 28.57%, and 41.67%, respectively, and the 5-year survival rates were 24%, 19.05%, and 20%, respectively. Survival analysis showed that male sex was a risk factor (HR = 5.421; 95% CI, 1.164-25.267; < 0.05) and that comprehensive treatment was a protective factor (HR = 0.117; 95% CI, 0.025-0.545; < 0.05) against extranodal DLBCL in the head and neck region. Bone marrow involvement was a risk factor for PENHL of the head and neck (HR = 5.072; 95% CI, 1.17-21.991; < 0.05). The purpose of this review is to show that PENHL of the head and neck with high incidence deserves more attention, and a model of multidisciplinary diagnosis and treatment should be adopted.
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http://dx.doi.org/10.1155/2022/4936099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888118PMC
April 2022

Stereocomplexation Reinforced High Strength Poly(L-lactide)/Nanohydroxyapatite Composites for Potential Bone Repair Applications.

Polymers (Basel) 2022 Feb 8;14(3). Epub 2022 Feb 8.

School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China.

Composite materials composed of polylactide (PLA) and nano-hydroxyapatite (n-HA) have been recognized as excellent candidate material in bone repai The difference in hydrophilicity/hydrophobicity and poor interfacial compatibility between n-HA filler and PLA matrix leads to non-uniform dispersion of n-HA in PLA matrix and consequent poor reinforcement effect. In this study, an HA/PLA nanocomposite was designed based on the surface modification of n-HA with poly(D-lactide) (PDLA), which not only can improve the dispersion of n-HA in the poly(L-lactide) (PLLA) matrix but also could form a stereocomplex crystal with the matrix PLLA at the interface and ultimately lead to greatly enhanced mechanical performance The n-HA/PLA composites were characterized by means of scanning electron microscopy, Fourier transform infrared spectroscopy, X-Ray diffraction, thermal gravity analysis, differential scanning calorimetry, and a mechanical test; in vitro cytotoxicity of the composite material as well as its efficacy in inducing osteogenic differentiation of rat bone marrow stromal cells (rMSCs) were also evaluated. Compared with those of neat PLLA, the tensile strength, Young's modulus, interfacial shear strength, elongation at break and crystallinity of the composites increased by 34%, 53%, 26%, 70%, and 17%, respectively. The adhesion and proliferation as well as the osteogenic differentiation of rMSCs on HA/PLA composites were clearly evidenced. Therefore, the HA/PLA composites have great potential for bone repai.
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http://dx.doi.org/10.3390/polym14030645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8915188PMC
February 2022

Exploring cell-specific miRNA regulation with single-cell miRNA-mRNA co-sequencing data.

BMC Bioinformatics 2021 Dec 2;22(1):578. Epub 2021 Dec 2.

UniSA STEM, University of South Australia, Mawson Lakes, SA, 5095, Australia.

Background: Existing computational methods for studying miRNA regulation are mostly based on bulk miRNA and mRNA expression data. However, bulk data only allows the analysis of miRNA regulation regarding a group of cells, rather than the miRNA regulation unique to individual cells. Recent advance in single-cell miRNA-mRNA co-sequencing technology has opened a way for investigating miRNA regulation at single-cell level. However, as currently single-cell miRNA-mRNA co-sequencing data is just emerging and only available at small-scale, there is a strong need of novel methods to exploit existing single-cell data for the study of cell-specific miRNA regulation.

Results: In this work, we propose a new method, CSmiR (Cell-Specific miRNA regulation) to combine single-cell miRNA-mRNA co-sequencing data and putative miRNA-mRNA binding information to identify miRNA regulatory networks at the resolution of individual cells. We apply CSmiR to the miRNA-mRNA co-sequencing data in 19 K562 single-cells to identify cell-specific miRNA-mRNA regulatory networks for understanding miRNA regulation in each K562 single-cell. By analyzing the obtained cell-specific miRNA-mRNA regulatory networks, we observe that the miRNA regulation in each K562 single-cell is unique. Moreover, we conduct detailed analysis on the cell-specific miRNA regulation associated with the miR-17/92 family as a case study. The comparison results indicate that CSmiR is effective in predicting cell-specific miRNA targets. Finally, through exploring cell-cell similarity matrix characterized by cell-specific miRNA regulation, CSmiR provides a novel strategy for clustering single-cells and helps to understand cell-cell crosstalk.

Conclusions: To the best of our knowledge, CSmiR is the first method to explore miRNA regulation at a single-cell resolution level, and we believe that it can be a useful method to enhance the understanding of cell-specific miRNA regulation.
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http://dx.doi.org/10.1186/s12859-021-04498-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641245PMC
December 2021

Inappropriate use of antibiotics exacerbates inflammation through OMV-induced pyroptosis in MDR Klebsiella pneumoniae infection.

Cell Rep 2021 09;36(12):109750

Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan 650106, China. Electronic address:

The inappropriate use of antibiotics is a severe public health problem worldwide, contributing to the emergence of multidrug-resistant (MDR) bacteria. To explore the possible impacts of the inappropriate use of antibiotics on the immune system, we use Klebsiella pneumoniae (K. pneumoniae) infection as an example and show that imipenem increases the mortality of mice infected by MDR K. pneumoniae. Further studies demonstrate that imipenem enhances the secretion of outer membrane vesicles (OMVs) with significantly elevated presentation of GroEL, which promotes the phagocytosis of OMVs by macrophages that depends on the interaction between GroEL and its receptor, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). OMVs cause the pyroptosis of macrophages and the release of proinflammatory cytokines, which contribute to exacerbated inflammatory responses. We propose that the inappropriate use of antibiotics in the cases of infection by MDR bacteria such as K. pneumoniae might cause damaging inflammatory responses, which underlines the pernicious effects of inappropriate use of antibiotics.
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http://dx.doi.org/10.1016/j.celrep.2021.109750DOI Listing
September 2021

Elevated plasma levels of the appetite-stimulator ACBP/DBI in fasting and obese subjects.

Cell Stress 2021 Jul 28;5(7):89-98. Epub 2021 Jun 28.

Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Inserm U1138, Université de Paris, Sorbonne Université, Paris, France.

Eukaryotic cells release the phylogenetically ancient protein acyl coenzyme A binding protein (ACBP, which in humans is encoded by the gene DBI, diazepam binding inhibitor) upon nutrient deprivation. Accordingly, mice that are starved for one to two days and humans that undergo voluntary fasting for one to three weeks manifest an increase in the plasma concentration of ACBP/DBI. Paradoxically, ACBP/DBI levels also increase in obese mice and humans. Since ACBP/DBI stimulates appetite, this latter finding may explain why obesity constitutes a self-perpetuating state. Here, we present a theoretical framework to embed these findings in the mechanisms of weight control, as well as a bioinformatics analysis showing that, irrespective of the human cell or tissue type, one single isoform of ACBP/DBI (ACBP1) is preponderant (~90% of all DBI transcripts, with the sole exception of the testis, where it is ~70%). Based on our knowledge, we conclude that ACBP1 is subjected to a biphasic transcriptional and post-transcriptional regulation, explaining why obesity and fasting both are associated with increased circulating ACBP1 protein levels.
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http://dx.doi.org/10.15698/cst2021.07.252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283301PMC
July 2021

Prevalence and molecular characteristics of drug-resistant Mycobacterium tuberculosis in Hainan, China: from 2014 to 2019.

BMC Microbiol 2021 06 19;21(1):185. Epub 2021 Jun 19.

NHC Key Laboratory of Control of Tropical diseases, Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, 571199, China.

Background: The emergence of antimicrobial resistance against Mycobacterium tuberculosis (M. tuberculosis) has become the major concern in global tuberculosis control due to its limited therapy options and high mortality. However, the clinical and molecular characteristics of drug-resistant strains vary in different geographical areas. Hainan Island located in southern China, is a high drug-resistant tuberculosis burden area. This study aimed to determine the dynamic changes of drug-resistance patterns and drug-related gene mutation types of M. tuberculosis in Hainan from 2014 to 2019.

Results: A total of 1484 culture-confirmed M. tuberculosis were included in this study. It was found that the proportions of drug resistance to isoniazid and rifampin were 31.3 and 31.1% respectively. Overall the proportion of multidrug resistant M. tuberculosis was 24.9%. Multivariate logistic regression analysis showed that age and the treatment history were independent influencing factors of drug resistant tuberculosis. The proportions of drug-resistant tuberculosis in retreatment patients were considerably higher than those in new patients. The most common mutation types of isoniazid were Ser315 → Thr (66.3%), and the most common mutation types of rifampin were Ser531 → Leu (41.5%).

Conclusions: Our data suggests that the prevalence of drug resistant TB remains high in Hainan, and the risks for developing drug resistance with diversified mutation types increased significantly in retreatment patients. These results contribute to the knowledge of the prevalence of drug resistance in Hainan Province and expand the molecular characteristics of drug resistance in China simultaneously.
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http://dx.doi.org/10.1186/s12866-021-02246-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214299PMC
June 2021

The comprehensive landscape of miR-34a in cancer research.

Cancer Metastasis Rev 2021 09 6;40(3):925-948. Epub 2021 May 6.

New Drug Screening Center, China Pharmaceutical University, Nanjing, 210009, China.

MicroRNA-34 (miR-34) plays central roles in human diseases, especially cancers. Inactivation of miR-34 is detected in cancer cell lines and tumor tissues versus normal controls, implying its potential tumor-suppressive effect. Clinically, miR-34 has been identified as promising prognostic indicators for various cancers. In fact, members of the miR-34 family, especially miR-34a, have been convincingly proved to affect almost the whole cancer progression process. Here, a total of 512 (miR-34a, 10/21), 85 (miR-34b, 10/16), and 114 (miR-34c, 10/14) putative targets of miR-34a/b/c are predicted by at least ten miRNA databases, respectively. These targets are further analyzed in gene ontology (GO), KEGG pathway, and the Reactome pathway dataset. The results suggest their involvement in the regulation of signal transduction, macromolecule metabolism, and protein modification. Also, the targets are implicated in critical signaling pathways, such as MAPK, Notch, Wnt, PI3K/AKT, p53, and Ras, as well as apoptosis, cell cycle, and EMT-related pathways. Moreover, the upstream regulators of miR-34a, mainly including transcription factors (TFs), lncRNAs, and DNA methylation, will be summarized. Meanwhile, the potential TF upstream of miR-34a/b/c will be predicted by PROMO, JASPAR, Animal TFDB 3.0, and GeneCard databases. Notably, miR-34a is an attractive target for certain cancers. In fact, miR-34a-based systemic delivery combined with chemotherapy or radiotherapy can more effectively control tumor progression. Collectively, this review will provide a panorama for miR-34a in cancer research.
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http://dx.doi.org/10.1007/s10555-021-09973-3DOI Listing
September 2021

miRSM: an R package to infer and analyse miRNA sponge modules in heterogeneous data.

RNA Biol 2021 12 6;18(12):2308-2320. Epub 2021 Apr 6.

UniSA STEM, University of South Australia, Mawson Lakes, SA, Australia.

In molecular biology, microRNA (miRNA) sponges are RNA transcripts which compete with other RNA transcripts for binding with miRNAs. Research has shown that miRNA sponges have a fundamental impact on tissue development and disease progression. Generally, to achieve a specific biological function, miRNA sponges tend to form modules or communities in a biological system. Until now, however, there is still a lack of tools to aid researchers to infer and analyse miRNA sponge modules from heterogeneous data. To fill this gap, we develop an R/Bioconductor package, , for facilitating the procedure of inferring and analysing miRNA sponge modules. provides a collection of 50 co-expression analysis methods to identify gene co-expression modules (which are candidate miRNA sponge modules), four module discovery methods to infer miRNA sponge modules and seven modular analysis methods for investigating miRNA sponge modules. will enable researchers to quickly apply new datasets to infer and analyse miRNA sponge modules, and will consequently accelerate the research on miRNA sponges.
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http://dx.doi.org/10.1080/15476286.2021.1905341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632112PMC
December 2021

Synthesis of carboxymethyl chitosan-strontium complex and its therapeutic effects on relieving osteoarthritis.

Carbohydr Polym 2021 Jun 26;261:117869. Epub 2021 Feb 26.

Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China; Shenzhen Key Laboratory of Cell Microenvironment, PR China. Electronic address:

Osteoarthritis (OA) is an age-related joint disorder and one of the leading causes of physical disability. In this study, we designed and synthesized a new polysaccharide complex, carboxymethyl chitosan strontium (CMCS-Sr), which is believed to have positive effects on relieving OA. The synthesized CMCS-Sr was structurally verified by SEM, EDS, FTIR, etc. The therapeutic effects of CMCS-Sr were evaluated using various biological experiments. The cell viability and apoptosis results reveal that CMCS-Sr can significantly promote the proliferation and suppress OA chondrocytes apoptosis in vitro. The immunofluorescence staining results suggest that CMCS-Sr facilitates the promotion of the secretion of Type II collagen (Col-II). The transcriptomic results support the observed positive effects of CMCS-Sr on inhibiting chondrocytes apoptosis and alleviating inflammatory reactions. Moreover, animal study demonstrates that CMCS-Sr effectively reduced articular cartilage damage and subchondral bone degradation. Therefore, we propose the use of CMCS-Sr as a promising candidate for relieving OA.
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http://dx.doi.org/10.1016/j.carbpol.2021.117869DOI Listing
June 2021

Reduction of Autophagosome Overload Attenuates Neuronal Cell Death After Traumatic Brain Injury.

Neuroscience 2021 04 16;460:107-119. Epub 2021 Feb 16.

Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, China; Sichuan Clinical Research Center for Neurosurgery, China; Neurological Diseases and Brain Functions Laboratory, Clinical Medical Research Center of Southwest Medical University, China; Academician (Expert) Workstation of Sichuan Province, China. Electronic address:

Previous studies have shown that alterations in autophagy-related proteins exist extensively after traumatic brain injury (TBI). However, whether autophagy is enhanced or suppressed by TBI remains controversial. In our study, a controlled cortical impact was used to establish a model of moderate TBI in rats. We found that a significant increase in protein levels of LC3-II and SQSTM1 in the injured cortex group. However, there were no significant differences in protein levels of VPS34, Beclin-1, and phosphor-ULK1, which are the promoters of autophagy. Lysosome dysfunction after TBI might lead to autophagosome accumulation. In addition, the highly specific autophagy inhibitor SAR405 administration reduced TBI-induced apoptosis-related protein cleaved caspase-3 and cleaved caspase-9 levels in the ipsilateral cortex, as well as brain edema and neurological defects accessed by mNSS. Furthermore, chloroquine treatment reversed the beneficial effects of SAR405 by increasing the accumulation of autophagosomes. Finally, our data showed that autophagy inhibition by VPS34 gene knockout method attenuated cell death after TBI. Our findings indicate that impaired autophagosome degradation is involved in the pathological reaction after TBI, and the inhibition of autophagy contributes to attenuate neuronal cell death and functional defects.
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http://dx.doi.org/10.1016/j.neuroscience.2021.02.007DOI Listing
April 2021

Identification and Analysis of Three Hub Prognostic Genes Related to Osteosarcoma Metastasis.

J Oncol 2021 30;2021:6646459. Epub 2021 Jan 30.

Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Osteosarcoma (OS) often occurs in children and often undergoes metastasis, resulting in lower survival rates. Information on the complexity and pathogenic mechanism of OS is limited, and thus, the development of treatments involving alternative molecular and genetic targets is hampered. We categorized transcriptome data into metastasis and nonmetastasis groups, and 400 differential RNAs (230 messenger RNAs (mRNAs) and 170 long noncoding RNAs (lncRNAs)) were obtained by the edgeR package. Prognostic genes were identified by performing univariate Cox regression analysis and the Kaplan-Meier (KM) survival analysis. We then examined the correlation between the expression level of prognostic lncRNAs and mRNAs. Furthermore, microRNAs (miRNAs) corresponding to the coexpression of lncRNA-mRNA was predicted, which was used to construct a competitive endogenous RNA (ceRNA) regulatory network. Finally, multivariate Cox proportional risk regression analysis was used to identify hub prognostic genes. Three hub prognostic genes (ABCG8, LOXL4, and PDE1B) were identified as potential prognostic biomarkers and therapeutic targets for OS. Furthermore, transcriptions factors (TFs) (DBP, ESX1, FOS, FOXI1, MEF2C, NFE2, and OTX2) and lncRNAs (RP11-357H14.16, RP11-284N8.3, and RP11-629G13.1) that were able to affect the expression levels of genes before and after transcription were found to regulate the prognostic hub genes. In addition, we identified drugs related to the prognostic hub genes, which may have potential clinical applications. Immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR) confirmed that the expression levels of ABCG8, LOXL4, and PDE1B coincided with the results of bioinformatics analysis. Moreover, the relationship between the hub prognostic gene expression and patient prognosis was also validated. Our study elucidated the roles of three novel prognostic biomarkers in the pathogenesis of OS as well as presenting a potential clinical treatment for OS.
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http://dx.doi.org/10.1155/2021/6646459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867449PMC
January 2021

Sulfate transport mutants affect hydrogen sulfide and sulfite production during alcoholic fermentation.

Yeast 2021 06 1;38(6):367-381. Epub 2021 Mar 1.

Department of Wine and Food Science, University of Adelaide, Adelaide, South Australia, Australia.

Hydrogen sulfide is a common wine fault, with a rotten-egg odour, which is directly related to yeast metabolism in response to nitrogen and sulfur availability. In grape juice, sulfate is the most abundant inorganic sulfur compound, which is taken up by yeast through two high-affinity sulfate transporters, Sul1p and Sul2p, and a low affinity transporter, Soa1p. Sulfate contributes to H S production under nitrogen limitation, by being reduced via the Sulfur Assimilation Pathway (SAP). Therefore, yeast strains with limited H S are highly desirable. We report on the use of toxic analogues of sulfate following ethyl methane sulfate treatment, to isolate six wine yeast mutants that produce no or reduced H S and SO during fermentation in synthetic and natural juice. Four amino acid substitutions (A99V, G380R, N588K and E856K) in Sul1p were found in all strains except D25-1 which had heterozygous alleles. Two changes were also identified in Sul2p (L268S and A470T). The Sul1p (G380R) and Sul2p (A470T) mutations were chosen for further investigation as these residues are conserved amongst SLC26 membrane proteins (including sulfate permeases). The mutations were introduced into EC1118 using Crispr cas9 technology and shown to reduce accumulation of H S and do not result in increased SO production during fermentation of model medium (chemically defined grape juice) or Riesling juice. The Sul1p (G380R) and Sul2p (A470T) mutations are newly reported as causal mutations. Our findings contribute to knowledge of the genetic basis of H S production as well as the potential use of these strains for winemaking and in yeast breeding programmes.
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http://dx.doi.org/10.1002/yea.3553DOI Listing
June 2021

Retracted: Pleuromutilin Inhibits Proliferation and Migration of A2780 and Caov-3 Ovarian Carcinoma Cells and Growth of Mouse A2780 Tumor Xenografts by Down-Regulation of pFAK2.

Med Sci Monit 2021 Jan 21;27:e930778. Epub 2021 Jan 21.

Department of Minimally Invasive Gynecological Centre, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China (mainland).

Some cells or groups of cells in figures appear to be visible multiple times. Because the manuscript contains non-credible results this journal is retracting the above publication. Reference: Bo Zhang, Xiaoli Ma, Yuan Li, Sijing Li, Jiumei Cheng: Pleuromutilin Inhibits Proliferation and Migration of A2780 and Caov-3 Ovarian Carcinoma Cells and Growth of Mouse A2780 Tumor Xenografts by Down-Regulation of pFAK2. Med Sci Monit, 2020; 26: e920407. DOI: 10.12659/MSM.920704.
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http://dx.doi.org/10.12659/MSM.930778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837332PMC
January 2021

Effects of alginate/chondroitin sulfate-based hydrogels on bone defects healing.

Mater Sci Eng C Mater Biol Appl 2020 Nov 20;116:111217. Epub 2020 Jun 20.

Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, PR China; Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, PR China; Shenzhen Key Laboratory of Cell Microenvironment, PR China. Electronic address:

Repairing bone defects remains challenging in orthopedics. Here, strontium (Sr) alginate hydrogels containing chondroitin sulfate (CS) were fabricated for enhancing bone defects repair. The effects of CS incorporation ratio on the morphology, structure, thermal stability, water uptake and mechanical performance of Sr-CS/alginate hydrogels were also evaluated. Increasing CS incorporation ratio, Sr-CS/alginate hydrogels exhibit decreasing mechanical properties and lower water retention capacity. In vitro results suggest that Sr-CS/alginate hydrogels with higher CS ratio facilitate the proliferation of osteoblasts. Additionally, the osteogenic genes expressions were investigated by real-time quantitative polymerase chain reaction (RT-qPCR). The results reveal that Sr-CS/alginate hydrogels should have positive effects on modulating the osteogenic factors. Moreover, by employing repair femoral cylindrical defects rabbit model, the efficiency of as-fabricated Sr-CS/alginate hydrogels in bone regeneration was evaluated. The animal study suggests that Sr-CS/alginate hydrogel could significantly facilitate bone defects repair and therefore should potentially be useful for osteochondral tissue engineering.
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http://dx.doi.org/10.1016/j.msec.2020.111217DOI Listing
November 2020

Prognostic value of MYD88 L265P mutation in diffuse large B cell lymphoma via droplet digital PCR.

Mol Med Rep 2020 08 27;22(2):1243-1256. Epub 2020 May 27.

Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region 830054, P.R. China.

To assess the prevalence and prognostic value of myeloid differentiation factor 88 (MYD88) expression and mutational status in diffuse large B cell lymphoma (DLBCL), a total cohort of 100 patients with DLBCL were studied using immunohistochemistry (IHC) and droplet digital polymerase chain reaction (DDPCR), and the association between MYD88 expression and clinicopathological parameters was analyzed. Overall, the positive expression rate of MYD88 protein was 38% and the gene mutation rate was 29%. The positive expression and mutation rates were the highest in the primary central nervous system lymphomas (58.33 and 66.67%, respectively). The coincidence rate of the results of MYD88 expression between IHC and DDPCR results was 73% (73/100). Univariate survival analysis showed that age (≥60 years old), high neutrophil/lymphocyte count ratio, low lymphocyte count, c‑Myc ≥40%, positive MYD88 protein expression, and gene mutation were associated with poorer prognosis rates. Multivariate survival analysis revealed that MYD88 expression was an independent prognostic factor affecting overall survival. In conclusion, the results of this study demonstrated that MYD88 mutation was a valuable index to evaluate the prognosis of DLBCL. DDPCR can be used as a method for detecting MYD88 mutations, although it was not completely consistent with the results of IHC.
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http://dx.doi.org/10.3892/mmr.2020.11186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339516PMC
August 2020

LMSM: A modular approach for identifying lncRNA related miRNA sponge modules in breast cancer.

PLoS Comput Biol 2020 04 23;16(4):e1007851. Epub 2020 Apr 23.

School of Information Technology and Mathematical Sciences, University of South Australia, Mawson Lakes, SA, Australia.

Until now, existing methods for identifying lncRNA related miRNA sponge modules mainly rely on lncRNA related miRNA sponge interaction networks, which may not provide a full picture of miRNA sponging activities in biological conditions. Hence there is a strong need of new computational methods to identify lncRNA related miRNA sponge modules. In this work, we propose a framework, LMSM, to identify LncRNA related MiRNA Sponge Modules from heterogeneous data. To understand the miRNA sponging activities in biological conditions, LMSM uses gene expression data to evaluate the influence of the shared miRNAs on the clustered sponge lncRNAs and mRNAs. We have applied LMSM to the human breast cancer (BRCA) dataset from The Cancer Genome Atlas (TCGA). As a result, we have found that the majority of LMSM modules are significantly implicated in BRCA and most of them are BRCA subtype-specific. Most of the mediating miRNAs act as crosslinks across different LMSM modules, and all of LMSM modules are statistically significant. Multi-label classification analysis shows that the performance of LMSM modules is significantly higher than baseline's performance, indicating the biological meanings of LMSM modules in classifying BRCA subtypes. The consistent results suggest that LMSM is robust in identifying lncRNA related miRNA sponge modules. Moreover, LMSM can be used to predict miRNA targets. Finally, LMSM outperforms a graph clustering-based strategy in identifying BRCA-related modules. Altogether, our study shows that LMSM is a promising method to investigate modular regulatory mechanism of sponge lncRNAs from heterogeneous data.
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http://dx.doi.org/10.1371/journal.pcbi.1007851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200020PMC
April 2020

MiRNA: a potential target for gene diagnosis and treatment of atherosclerotic stroke.

Int J Neurosci 2021 Mar 31;131(3):283-288. Epub 2020 Mar 31.

Department of Neurology, Hubei University of Medicine, Shiyan City, Hubei Province, China.

Stroke is one of the major diseases that endanger the physical health life of middle-aged and old people. It has the characteristics of high incidence, mortality and disability rate. Atherosclerosis is the main intervention target for stroke prevention and treatment. MiRNAs are highly expressed in the cerebral vasculature and play an important regulatory role in the pathogenesis of neuronal damage and ischemic stroke. This article reviews the mechanism of action between miRNAs and atherosclerosis, stroke, ischemia-reperfusion injury, collateral circulation and circRNA molecular networks, providing theoretical support for miRNA in gene diagnosis and drug therapy of atherosclerotic stroke.
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http://dx.doi.org/10.1080/00207454.2020.1738428DOI Listing
March 2021

Pleuromutilin Inhibits Proliferation and Migration of A2780 and Caov-3 Ovarian Carcinoma Cells and Growth of Mouse A2780 Tumor Xenografts by Down-Regulation of pFAK2.

Med Sci Monit 2020 02 11;26:e920407. Epub 2020 Feb 11.

Department of Minimally Invasive Gynecological Centre, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China (mainland).

BACKGROUND Pleuromutilin is a natural tricyclic, derived from the fungus, Pleurotus mutilus. This study aimed to investigate the effects of pleuromutilin on migration and proliferation of A2780 and Caov-3 human ovarian carcinoma cells and the growth of A2780 tumor xenografts in mice and the molecular mechanisms involved. MATERIAL AND METHODS A2780 and Caov-3 human ovarian carcinoma cells were cultured with and without 40, 160, and 200 μM of pleuromutilin. The Edu fluorescence assay, the wound-healing assay, and Matrigel were used to measure A2780 and Caov-3 cell proliferation, migration, invasion, and adhesion in vitro, respectively. Western blot measured protein levels of FAK, p-FAK, MMP-2, and MMP-9. A2780 cells were injected subcutaneously into mice to determine the effects of pleuromutilin on the growth of tumor xenografts. RESULTS Pleuromutilin significantly reduced A2780 and Caov-3 cell proliferation at 48 h in a dose-dependent manner (P<0.05), and at 200 μM, pleuromutilin reduced cell proliferation by 21.43% and 23.65%, respectively. Treatment of A2780 cells with pleuromutilin significantly reduced cell migration, invasion, and adhesion and the expression of p-FAK, MMP-2, and MMP-9 compared with untreated controls. In the mouse tumor xenograft model, treatment with pleuromutilin significantly reduced tumor size compared with the untreated group and inhibited tumor metastasis to the intestine, spleen, and peritoneal cavity. CONCLUSIONS In A2780 and Caov-3 human ovarian carcinoma cells, pleuromutilin inhibited cell proliferation, migration, invasion, and adhesion in a dose-dependent manner, and reduced tumor growth and metastases in a mouse A2780 cell tumor xenograft model.
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http://dx.doi.org/10.12659/MSM.920407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034521PMC
February 2020

Pectolytic enzyme reduces the concentration of colloidal particles in wine due to changes in polysaccharide structure and aggregation properties.

Int J Biol Macromol 2019 Nov 9;140:546-555. Epub 2019 Aug 9.

The Australian Wine Research Institute, P.O. Box 197, Glen Osmond, SA 5064, Australia. Electronic address:

To explore the effect of pectolytic enzyme application on polysaccharide size and colloidal interactions, rosé wines were prepared from pressed Shiraz grape juice, and red wines were made from the same juice by the addition of skins and seeds from fresh pressings. A pectolytic enzyme preparation containing primarily polygalacturonase and side-activities of arabinase and pectin lyase was used. Enzyme treatment enhanced the contribution of high molecular weight (≈ 200 kDa) polysaccharides rich in mannose and glucose (mannoproteins) and removed arabinose-rich polysaccharides of intermediate (≈ 40 kDa) size. Enzyme application reduced the molecular weight average of a class of smaller polysaccharides of approximately 6 kDa (rhamnogalacturonan II). All wines had similar particle sizes, but enzyme treatment markedly reduced particle concentration in wines, particularly in rosé wines. Wine polysaccharides were purified and when reconstituted in model wine, showed reduced particle concentration in response to enzyme treatment. Aggregation of polysaccharide in the presence of seed tannin was also markedly reduced by enzyme treatment. The results indicated that changes in structure introduced by the enzyme affected wine colloidal properties, potentially increasing polysaccharide solubility.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.08.043DOI Listing
November 2019

Tumor-secreted PAI-1 promotes breast cancer metastasis via the induction of adipocyte-derived collagen remodeling.

Cell Commun Signal 2019 06 6;17(1):58. Epub 2019 Jun 6.

Jiangsu Key laboratory of Drug Screening, China Pharmaceutical University, No.24, Tongjiaxiang, Nanjing, China.

Background: Breast cancer cells recruit surrounding stromal cells, such as cancer-associated fibroblasts (CAFs), to remodel collagen and promote tumor metastasis. Adipocytes are the most abundant stromal partners in breast tissue, local invasion of breast cancer leads to the proximity of cancer cells and adipocytes, which respond to generate cancer-associated adipocytes (CAAs). These cells exhibit enhanced secretion of extracellular matrix related proteins, including collagens. However, the role of adipocyte-derived collagen on breast cancer progression still remains unclear.

Methods: Adipocytes were cocultured with breast cancer cells for 3D collagen invasion and collagen organization exploration. Breast cancer cells and adipose tissue co- implanted mouse model, clinical breast cancer samples analysis were used to study the crosstalk between adipose and breast cancer cells in vivo. A combination of proteomics, enzyme-linked immunosorbent assay, loss of function assay, qPCR, western blot, database analysis and chromatin immunoprecipitation assays were performed to study the mechanism mediated the activation of PLOD2 in adipocytes.

Results: It was found that CAAs remodeled collagen alignment during crosstalk with breast cancer cells in vitro and in vivo, which further promoted breast cancer metastasis. Tumor-derived PAI-1 was required to activate the expression of the intracellular enzyme procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) in CAAs. Pharmacologic blockade of PAI-1 or PLOD2 disrupted the collagen reorganization in CAAs. Mechanistically, it was observed that PI3K/AKT pathway was activated in adipocytes upon co-culturing with breast cancer cells or treatment with recombinant PAI-1, which could promote the translocation of transcription factor FOXP1 into the nucleus and further enhanced the promoter activity of PLOD2 in CAAs. In addition, collagen reorganization at the tumor-adipose periphery, as well as the positive relevance between PAI-1 and PLOD2 in invasive breast carcinoma were confirmed in clinical specimens of breast cancer.

Conclusion: In summary, our findings revealed a new stromal collagen network that favors tumor invasion and metastasis establish between breast cancer cells and surrounding adipocytes at the tumor invasive front, and identified PLOD2 as a therapeutic target for metastatic breast cancer treatment.
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http://dx.doi.org/10.1186/s12964-019-0373-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554964PMC
June 2019

Applying Nanoparticle Tracking Analysis to Characterize the Polydispersity of Aggregates Resulting from Tannin-Polysaccharide Interactions in Wine-Like Media.

Molecules 2019 Jun 3;24(11). Epub 2019 Jun 3.

The Australian Wine Research Institute, PO Box 197, Glen Osmond, SA 5064, Australia.

Interactions between grape seed tannin and either a mannoprotein or an arabinogalactan in model wine solutions of different ethanol concentrations were characterized with nanoparticle tracking analysis (NTA), UV-visible spectroscopy and dynamic light scattering (DLS). NTA results reflected a shift in particle size distribution due to aggregation. Furthermore, the light scattering intensity of each tracked particle measured by NTA demonstrated the presence of aggregates, even when a shift in particle size was not apparent. Mannoprotein and arabinogalactan behaved differently when combined with seed tannin. Mannoprotein formed large, highly light-scattering aggregates, while arabinogalactan exhibited only weak interactions with seed tannin. A 3% difference in alcohol concentration of the model solution (12 vs. 15% /) was sufficient to affect the interactions between mannoprotein and tannin when the tannin concentration was high. In summary, this study showed that NTA is a promising tool for measuring polydisperse samples of grape and wine macromolecules, and their aggregates under wine-like conditions. The implications for wine colloidal properties are discussed based on these results.
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http://dx.doi.org/10.3390/molecules24112100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600421PMC
June 2019

DT-13 suppresses breast cancer metastasis by modulating PLOD2 in the adipocytes microenvironment.

Phytomedicine 2019 Jun 2;59:152778. Epub 2018 Dec 2.

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China. Electronic address:

Background: Metastasis is the main cause of death in breast cancer and previous researches have indicated the pivotal role of adipocytes in breast cancer metastasis. DT-13, the saponin monomer 13 of the Dwarf lilyturf tuber, has been proved to exert potential anti-metastatic effect, the detailed mechanisms have not been well elucidated and the role of DT-13 in modulating adipocyte-breast cancer microenvironment has been given little attention.

Purpose: This study aims to explore the mechanisms of DT-13 in inhibiting breast cancer metastasis and whether DT-13 inhibit breast cancer metastasis via modulating the interactions between adipocytes and breast cancer cells.

Methods: The cytotoxic effect of DT-13 on breast cancer cell viability was detected by MTT assay. Migration assays was used to conduct the effect of DT-13 on breast cancer cells migration. Orthotopic xenograft tumor model was used to test the effect of DT-13 on breast cancer metastasis. qRT-PCR and Western blot were used to investigate the mechanisms of DT-13 inhibiting breast cancer metastasis.

Results: DT-13 inhibited breast cancer cells migration at the concentration without cytotoxicity. Furthermore, DT-13 decreased PLOD2 expression through modulating JAK/STAT3 and PI3K/AKT signaling pathways directly or indirectly in the adipocyte-breast cancer microenvironment. Orthotopic implantation mouse model of breast cancer further confirmed that DT-13 inhibited breast cancer metastasis via downregulating PLOD2 in vivo.

Conclusion: DT-13 suppressed breast cancer metastasis via reducing the expression of PLOD2.
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http://dx.doi.org/10.1016/j.phymed.2018.12.001DOI Listing
June 2019

Synthesis of chondroitin sulfate magnesium for osteoarthritis treatment.

Carbohydr Polym 2019 May 18;212:387-394. Epub 2019 Feb 18.

Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China. Electronic address:

Magnesium chondroitin sulfate (MgCS) has been fabricated and characterized in this study. We investigated its morphology, composition as well as structure. The results verify that the sodium of sodium chondroitin sulfate (CS) is successfully replaced by magnesium and formed a polysaccharide-metal ion complex. To evaluate the clinical potential of MgCS, cell proliferation and apoptosis test were conducted. The results reveal that MgCS could effectively increase the proliferation and decrease the apoptosis of osteoarthritis (OA) chondrocytes. Moreover, real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to evaluate the gene expression level. RT-qPCR analysis suggests that MgCS could significantly increase the expression of COLII and decrease the expression of IL-1β and iNOS in OA chondrocytes. Furthermore, significant upregulation of Bcl-2 mRNA expression and downregulation of the expression of apoptosis related gene p53 were observed. Thus, it is indicated that MgCS should have great potentials in OA treatment.
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http://dx.doi.org/10.1016/j.carbpol.2019.02.061DOI Listing
May 2019
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