Impact of parental smoking on adipokine profiles and cardiometabolic risk factors in Chinese children

Acknowledgments We thank Prof. Jie Miandall, the BCAMS study members,and all participants for their continuing support with this research effort. Financial support This work was supported by National Key Research program of China (2016YFC1304801),key program of Beijing Municipal Science & Technology Commission (D111100000611001, D111100000611002), Beijing Natural Science Foundation (7172169), Beijing Science & Technology Star Program (2004A027), Novo Nordisk Union Diabetes Research Talent Fund (2011A002), National Key Program of Clinical Science (WBYZ2011-873), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2017PT32020, 2018PT32001) and Jingxi Scientific Program of Beijing Chaoyang Hospital (JXPY201606).Peer reviewedPublisher PD

Brown adipocytes can display a mammary basal myoepithelial cell phenotype in vivo

This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13030000) and the CAS-Novonordisk Foundation, as well as grants from the ‘1000 talents’ recruitment program, and a ‘Great-wall professorship’ from the CAS-Novonordisk Foundation all to JRS. We are grateful to all the members of Molecular Energetics Group for their support and discussion of the results. We would like to thank the Center for Biological Imaging from Institute of Biophysics Chinese Academy of Sciences and Professor Zhaohui Wang's Lab from Institute of Genetics and Developmental Biology Chinese Academy of Sciences for confocal microscopy and the Center for Developmental Biology from Institute of Genetics and Developmental Biology Chinese Academy of Sciences and Dr. Jai from Core Facility for Protein Research from Institute of Biophysics Chinese Academy of Sciences for flow cytometry. We are grateful to Dr. Kuang from Purdue University and Dr. Zhu from Chinese Academy of Medical Sciences Peking Union Medical College for the kind donation of Myf5-Cre mice and Dr. Wolfrum from the Institute of Food Nutrition and Health at the ETH Zurich for the kind donation of the Ucp1-DTR mice. Xun Huang provided valuable comments on previous versions of the manuscript.Peer reviewedPublisher PD

Small interfering RNA for cancer treatment: overcoming hurdles in delivery

© 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies

Early Prediction of Gestational Diabetes Mellitus in the Chinese Population via Advanced Machine Learning

Acknowledgments We thank all those who helped to collect the data and the graduate students who took part in the statistical analysis. Financial Support: This work was supported by the National Key Research and Development Program of China (grant Nos.2018YFC1002804 and 2016YFC1000203), the National Natural Science Foundation of China (grant Nos. 81671412 and 81661128010), Program of Shanghai Academic Research Leader (grant No. 20XD1424100), the Outstanding Youth Medical Talents of Shanghai Rising Stars of Medical Talent Youth Development Program, Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (grant No. 2019-12M-5-064), the Foundation of Shanghai Municipal Commission of Health and Family Planning (grant No. 20144Y0110), the Natural Science Foundation of Shanghai (grant Nos. 20511101900 and 20ZR1427200), the Shanghai Shenkang Hospital Development Center, the Clinical Technology Innovation Project (grant Nos. SHDC12019107), and the Clinical Skills Improvement Foundation of Shanghai Jiaotong University School of Medicine (grant No. JQ201717).Peer reviewedPublisher PD

Hypericin enhances β-lactam antibiotics activity by inhibiting sarA expression in methicillin-resistant Staphylococcus aureus.

Bacteremia is a life-threating syndrome often caused by methicillin-resistant Staphylococcus aureus (MRSA). Thus, there is an urgent need to develop novel approaches to successfully treat this infection. Staphylococcal accessory regulator A (SarA), a global virulence regulator, plays a critical role in pathogenesis and β-lactam antibiotic resistance in Staphylococcus aureus. Hypericin is believed to act as an antibiotic, antidepressant, antiviral and non-specific kinase inhibitor. In the current study, we investigated the impact of hypericin on β-lactam antibiotics susceptibility and mechanism(s) of its activity. We demonstrated that hypericin significantly decreased the minimum inhibitory concentrations of β-lactam antibiotics (e.g., oxacillin, cefazolin and nafcillin), biofilm formation and fibronectin binding in MRSA strain JE2. In addition, hypericin significantly reduced sarA expression, and subsequently decreased mecA, and virulence-related regulators (e.g., agr RNAⅢ) and genes (e.g., fnbA and hla) expression in the studied MRSA strain. Importantly, the in vitro synergistic effect of hypericin with β-lactam antibiotic (e.g., oxacillin) translated into in vivo therapeutic outcome in a murine MRSA bacteremia model. These findings suggest that hypericin plays an important role in abrogation of β-lactam resistance against MRSA through sarA inhibition, and may allow us to repurpose the use of β-lactam antibiotics, which are normally ineffective in the treatment of MRSA infections (e.g., oxacillin)

Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates.

Tumor metastasis into the central nervous system (CNS) and lymph nodes (LNs) is a major obstacle for effective therapies. Therapeutic monoclonal antibodies (mAb) have revolutionized tumor treatment; however, their efficacy for treating metastatic tumors-particularly, CNS and LN metastases-is poor due to inefficient penetration into the CNS and LNs following intravenous injection. We recently reported an effective delivery of mAb to the CNS by encapsulating the anti-CD20 mAb rituximab (RTX) within a thin shell of polymer that contains the analogs of choline and acetylcholine receptors. This encapsulated RTX, denoted as n-RTX, eliminated lymphoma cells systemically in a xenografted humanized mouse model using an immunodeficient mouse as a recipient of human hematopoietic stem/progenitor cells and fetal thymus more effectively than native RTX; importantly, n-RTX showed notable anti-tumor effect on CNS metastases which is unable to show by native RTX. As an important step toward future clinical translation of this technology, we further analyzed the properties of n-RTX in immunocompetent animals, rats, and non-human primates (NHPs). Our results show that a single intravenous injection of n-RTX resulted in 10-fold greater levels in the CNS and 2-3-fold greater levels in the LNs of RTX, respectively, than the injection of native RTX in both rats and NHPs. In addition, we demonstrate the enhanced delivery and efficient B-cell depletion in lymphoid organs of NHPs with n-RTX. Moreover, detailed hematological analysis and liver enzyme activity tests indicate n-RTX treatment is safe in NHPs. As this nanocapsule platform can be universally applied to other therapeutic mAbs, it holds great promise for extending mAb therapy to poorly accessible body compartments

Targeted next-generation sequencing of dedifferentiated chondrosarcoma in the skull base reveals combined TP53 and PTEN mutations with increased proliferation index, an implication for pathogenesis

Dedifferentiated chondrosarcoma (DDCS) is a rare disease with a dismal prognosis. DDCS consists of two morphologically distinct components: the cartilaginous and noncartilaginous components. Whether the two components originate from the same progenitor cells has been controversial. Recurrent DDCS commonly displays increased proliferation compared with the primary tumor. However, there is no conclusive explanation for this mechanism. In this paper, we present two DDCSs in the sellar region. Patient 1 exclusively exhibited a noncartilaginous component with a TP53 frameshift mutation in the pathological specimens from the first surgery. The tumor recurred after radiation therapy with an exceedingly increased proliferation index. Targeted next-generation sequencing (NGS) revealed the presence of both a TP53 mutation and a PTEN deletion in the cartilaginous and the noncartilaginous components of the recurrent tumor. Fluorescence in situ hybridization and immunostaining confirmed reduced DNA copy number and protein levels of the PTEN gene as a result of the PTEN deletion. Patient 2 exhibited both cartilaginous and noncartilaginous components in the surgical specimens. Targeted NGS of cells from both components showed neither TP53 nor PTEN mutations, making Patient 2 a naïve TP53 and PTEN control for comparison. In conclusion, additional PTEN loss in the background of the TP53 mutation could be the cause of increased proliferation capacity in the recurrent tumor

An animal model of SARS produced by infection of Macaca mulatta with SARS coronavirus.

A new SARS animal model was established by inoculating SARS coronavirus (SARS-CoV) into rhesus macaques (Macaca mulatta) through the nasal cavity. Pathological pulmonary changes were successively detected on days 5-60 after virus inoculation. All eight animals showed a transient fever 2-3 days after inoculation. Immunological, molecular biological, and pathological studies support the establishment of this SARS animal model. Firstly, SARS-CoV-specific IgGs were detected in the sera of macaques from 11 to 60 days after inoculation. Secondly, SARS-CoV RNA could be detected in pharyngeal swab samples using nested RT-PCR in all infected animals from 5 days after virus inoculation. Finally, histopathological changes of interstitial pneumonia were found in the lungs during the 60 days after viral inoculation: these changes were less marked at later time points, indicating that an active healing process together with resolution of an acute inflammatory response was taking place in these animals. This animal model should provide insight into the mechanisms of SARS-CoV-related pulmonary disease and greatly facilitate the development of vaccines and therapeutics against SARS