Publications by authors named "Yan Zhu"

1,537 Publications

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Impaired generation of mature neurons due to extended expression of Tlx by repressing Sox2 transcriptional activity.

Stem Cells 2021 Jul 16. Epub 2021 Jul 16.

Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, People's Republic of China.

As a master regulator of the dynamic process of adult neurogenesis, timely expression and regulation of the orphan nuclear receptor Tailless (Tlx) is essential. However, there is no study yet to directly investigate the essential role of precise spatiotemporal expressed Tlx. Here, we generated a conditional gain of Tlx expression transgenic mouse model, which allowed the extended Tlx expression in neural stem cells (NSCs) and their progeny by mating with a TlxCreER mouse line. We demonstrate that extended expression of Tlx induced the impaired generation of mature neurons in adult subventricular zone and subgranular zone. Furthermore, we elucidated for the first time that this mutation decreased the endogenous expression of Sox2 by directly binding to its promoter. Restoration experiments further confirmed that Sox2 partially rescued these neuron maturation defects. Together, these findings not only highlight the importance of shutting-off Tlx on time in controlling NSC behavior, but also provide insights for further understanding adult neurogenesis and developing treatment strategies for neurological disorders.
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http://dx.doi.org/10.1002/stem.3435DOI Listing
July 2021

CHK Methylation Is Elevated in Colon Cancer Cells and Contributes to the Oncogenic Properties.

Front Cell Dev Biol 2021 29;9:708038. Epub 2021 Jun 29.

Argus Pharmaceuticals, Changsha, China.

Src is an important oncogene that plays key roles in multiple signal transduction pathways. Csk-homologous kinase (CHK) is a kinase whose molecular roles are largely uncharacterized. We previously reported expression of CHK in normal human colon cells, and decreased levels of CHK protein in colon cancer cells leads to the activation of Src (Zhu et al., 2008). However, how CHK protein expression is downregulated in colon cancer cells has been unknown. We report herein that CHK mRNA was decreased in colon cancer cells as compared to normal colon cells, and similarly in human tissues of normal colon and colon cancer. Increased levels of DNA methylation at promotor CpG islands of CHK gene were observed in colon cancer cells and human colon cancer tissues as compared to their normal healthy counterparts. Increased levels of DNA methyltransferases (DNMTs) were also observed in colon cancer cells and tissues. DNA methylation and decreased expression of CHK mRNA were inhibited by DNMT inhibitor 5-Aza-CdR. Cell proliferation, colony growth, wound healing, and Matrigel invasion were all decreased in the presence of 5-Aza-CdR. These results suggest that increased levels of DNA methylation, possibly induced by enhanced levels of DNMT, leads to decreased expression of CHK mRNA and CHK protein, promoting increased oncogenic properties in colon cancer cells.
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http://dx.doi.org/10.3389/fcell.2021.708038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276677PMC
June 2021

Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor.

Emerg Microbes Infect 2021 Jul 15:1-27. Epub 2021 Jul 15.

CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China.

Severe respiratory disease coronavirus-2 (SARS-CoV-2) has been the most devastating disease COVID-19 in the century. One of the unsolved scientific questions of SARS-CoV-2 is the animal origin of this virus. Bats and pangolins are recognized as the most probable reservoir hosts that harbor highly similar SARS-CoV-2 related viruses (SARSr-CoV-2). This study identified a novel lineage of SARSr-CoVs, including RaTG15 and seven other viruses, from bats at the same location where we found RaTG13 in 2015. Although RaTG15 and the related viruses share 97.2% amino acid sequence identities with SARS-CoV-2 in the conserved ORF1b region, it only shows less than 77.6% nucleotide identity to all known SARSr-CoVs at the genome level, thus forming a distinct lineage in the phylogenetic tree. We found that the RaTG15 receptor-binding domain (RBD) can bind to ACE2 from , Malayan pangolin, and use it as an entry receptor, except for ACE2 from humans. However, it contains a short deletion and has different key residues responsible for ACE2 binding. In addition, we showed that none of the known viruses in bat SARSr-CoV-2 lineage discovered uses human ACE2 as efficiently as the pangolin-derived SARSr-CoV-2 or some viruses in the SARSr-CoV-1 lineage. Therefore, further systematic and longitudinal studies in bats are needed to prevent future spillover events caused by SARSr-CoVs or to understand the origin of SARS-CoV-2 better.
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http://dx.doi.org/10.1080/22221751.2021.1956373DOI Listing
July 2021

Chidamide-Induced Accumulation of Reactive Oxygen Species Increases Lenalidomide Sensitivity Against Multiple Myeloma Cells.

Onco Targets Ther 2021 6;14:4061-4075. Epub 2021 Jul 6.

Department of Hematology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.

Background: Lenalidomide, an immunomodulatory drug (IMiD), is an effective therapy for the treatment of multiple myeloma (MM). However, prolonged treatment may be accompanied by toxicity, second primary malignancies, and drug resistance. There is an inherent vulnerability in MM cells that high rates of immunoglobulin synthesis resulting in the high level of reactive oxygen species (ROS). This provides a therapeutic potential for MM.

Materials And Methods: The intracellular ROS levels, HO production and glutathione (GSH) levels were measured using detection kit. Cell viability was evaluated using cell-counting kit-8 (CCK-8) and soft agar colony formation assay. Apoptosis was determined in whole living cells using flow cytometry. Chidamide and its anti-myeloma efficacy in combination with lenalidomide were characterized in MM cell lines in vitro and in a mouse xenograft model. Moreover, Western blotting, immunofluorescence and immunohistochemical studies were performed.

Results: ROS levels increased in a time- and dose-dependent manner with chidamide treatment. Moreover, the GSH levels were decreased and the mRNA level of SLC7A11 downregulated after chidamide treatment. The co-treatment with chidamide and lenalidomide increased apoptosis and proliferation inhibition, with combination index (CI) in the synergistic range (0.2-0.5) using the Chou-Talalay method. The cooperative anti-myeloma efficacy was confirmed in the murine model, and immunohistochemical studies also supported this potentiation. Chidamide enhanced the effect of lenalidomide-induced degradation of IKZF1 and IKZF3 by elevating HO. In addition, co-treatment with chidamide and lenalidomide increased biomarkers of caspase and DNA damage.

Conclusion: Elevated ROS production may constitute a potential biochemical basis for anti-myeloma effects of chidamide plus lenalidomide. The results of this study confirm the synergistic effect of chidamide and lenalidomide against MM and provide a promising therapeutic strategy for MM.
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http://dx.doi.org/10.2147/OTT.S312249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274322PMC
July 2021

Survival outcomes of patients with brain metastasis of osteosarcoma can be improved by aggressive multi-disciplinary interventions including chemotherapy.

Br J Neurosurg 2021 Jul 15:1-6. Epub 2021 Jul 15.

Jinling Hospital Department of Orthopaedics, Nanjing Medical University, Nanjing, China.

Background/objective: Brain metastasis in osteosarcoma (BMO) is rare and its clinical characteristics are often buried among studies on brain metastasis of bone and soft tissue sarcomas. The aim of the present study was to summarize the incidence, clinical characteristics, treatment and outcomes of patients with BMO.

Methods: This retrospective study included 7 patients with BMO who received treatment in our center between 2005 and 2019. The clinical medical records of the 7 patients, together with data of 70 BMO patients published in 33 articles and retrieved by means of PubMed and Medline, were analyzed, retrospectively.

Results: Data analysis of the 97 BMO patients showed a high correlation between the interval from the primary diagnosis to BMO occurrence and the interval from the primary diagnosis to prior metastases. Multivariate analysis showed that chemotherapy, radiotherapy and surgery were three main factors affecting the overall survival of BMO patients (HR = 0.427; HR = 0.372; HR = 0.296). Surgery combined with chemotherapy or radiotherapy offered a better overall survival than surgery alone.

Conclusion: Patients with BMO may obtain survival benefits from regular neuroimaging and early aggressive multi-disciplinary interventions including surgical resection, postoperative radiotherapy and chemotherapy.

Synopsis: This is a retrospective study describing the characteristics of metastasic intervals, locations, clinical features and prognosis in 97 patients with brain metastasis of osteosarcoma (BMO). Multivariate analysis showed that chemotherapy was effective as surgery and radiotherapy for the treatment of BMO. Our findings emphasize the importance of regular neuroimaging and early aggressive multi-disciplinary interventions including surgical resection, postoperative radiotherapy and chemotherapy.
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http://dx.doi.org/10.1080/02688697.2021.1950624DOI Listing
July 2021

Tissue Type: A Crucial Factor Influencing the Fungal Diversity and Communities in Sichuan Pork Bacon.

Front Microbiol 2021 25;12:655500. Epub 2021 Jun 25.

College of Food Science and Engineering, Gansu Agricultural University, Lanzhou, China.

This study aimed to the variations of fungal diversity and community structure in different parts of traditional homemade Sichuan pork bacon. A total of seven phyla and 91 fungal genera were identified. Among them, Ascomycota and Basidiomycota were the first and second most abundant phyla in the bacon tissues. In addition, five dominant genera (, and ) were shared by all bacon tissues. The numbers of OTUs unique to individual groups were 14, 67, and 65 for the muscle tissue, the adipose tissue, and pork skin, respectively. Linear discriminant analysis showed that a total of 31 taxa significantly differed among the groups. Results of redundancy analysis indicated that fat content, protein content, aw, and pH of bacon tissue shaped the bacon fungal communities. Results of network analysis also indicated that tissue type was a crucial factor influencing the fungal interactions in different tissues. This study can lay a foundation for further isolation and identification of fungi in the product and provides a basis for further research of food health in homemade traditional pork bacon.
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http://dx.doi.org/10.3389/fmicb.2021.655500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268000PMC
June 2021

The effect of dehydroepiandrosterone (DHEA) supplementation on estradiol levels in women: A dose-response and meta-analysis of randomized clinical trials.

Steroids 2021 Jul 9;173:108889. Epub 2021 Jul 9.

Clinical Laboratory, Zhucheng Maternal and Child Health Hospital, Zhucheng, Shandong 262200, China. Electronic address:

Estradiol, an estrogen steroid hormone, serves as the dominant female hormone and its levels fluctuate during lifetime. In women, after the menopause, all estrogens and almost all androgens are locally developed in the peripheral tissues from dehydroepiandrosterone (DHEA). However, the effect of DHEA supplementation on estradiol levels in women is unclear as previously published data has resulted in conflicting findings. Thus, we conducted the present dose-response meta-analysis of randomized controlled trials (RCTs) evaluating the influence of DHEA on estradiol concentrations in women. The PubMed/Medline, Embase, Web of Science and Scopus databases were systematically searched for articles published on this topic until May 10, 2021. No time or language restrictions were applied. The data were expressed as weighted mean differences (WMDs) and 95% confidence intervals (CI), and a P-value of less than 0.05 was considered to be statistically significant. The pooled results were obtained using the generic inverse of variance method with a random effects model. A total of 21 arms, including 1223 participants (case = 610, and control = 613), reported estradiol concentrations as an outcome measure. The overall results demonstrated that estradiol significantly increased following the administration of DHEA (WMD: 7.02 pg/mL, 95% CI: 5.43, 8.62, P = 0.000). The stratified analyses revealed that the elevation of estradiol concentrations was more pronounced in subjects aged ≥60 years old (WMD: 8.56 pg/mL, 95% CI: 6.97, 10.16, I = 94%) and in those receiving DHEA supplements for ≥26 weeks (WMD: 7.30 pg/mL, 95% CI: 6.28, 8.32, I = 61%). Moreover, estradiol levels increased significantly with DHEA dosages of 50 mg/day (WMD: 7.75 pg/mL, 95% CI: 9.12, 9.39, I = 94%) and when DHEA was prescribed to postmenopausal women (WMD: 7.61 pg/mL, 95% CI: 5.97, 9.24, I = 93%). This meta-analysis has provided a comprehensive overview of the effects of DHEA administration on circulating estradiol levels, far beyond the available evidence from different RCTs. Subsequent subgroup analyses revealed that postmenopausal women, females aged 60 years and above, those on DHEA dosages of 50 mg/day and those receiving DHEA for ≥26 weeks registered a more pronounced elevation of the circulating estradiol levels.
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http://dx.doi.org/10.1016/j.steroids.2021.108889DOI Listing
July 2021

RNA landscape of the emerging cancer-associated microbe Fusobacterium nucleatum.

Nat Microbiol 2021 Jul 8. Epub 2021 Jul 8.

Helmholtz Institute for RNA-based Infection Research, Helmholtz Centre for Infection Research, Würzburg, Germany.

Fusobacterium nucleatum, long known as a constituent of the oral microflora, has recently garnered renewed attention for its association with several different human cancers. The growing interest in this emerging cancer-associated bacterium contrasts with a paucity of knowledge about its basic gene expression features and physiological responses. As fusobacteria lack all established small RNA-associated proteins, post-transcriptional networks in these bacteria are also unknown. In the present study, using differential RNA-sequencing, we generate high-resolution global RNA maps for five clinically relevant fusobacterial strains-F. nucleatum subspecies nucleatum, animalis, polymorphum and vincentii, as well as F. periodonticum-for early, mid-exponential growth and early stationary phase. These data are made available in an online browser, and we use these to uncover fundamental aspects of fusobacterial gene expression architecture and a suite of non-coding RNAs. Developing a vector for functional analysis of fusobacterial genes, we discover a conserved fusobacterial oxygen-induced small RNA, FoxI, which serves as a post-transcriptional repressor of the major outer membrane porin FomA. Our findings provide a crucial step towards delineating the regulatory networks enabling F. nucleatum adaptation to different environments, which may elucidate how these bacteria colonize different compartments of the human body.
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http://dx.doi.org/10.1038/s41564-021-00927-7DOI Listing
July 2021

Plasma exosomal caveolin-1 predicts Poor Prognosis in Ovarian Cancer.

J Cancer 2021 16;12(16):5005-5012. Epub 2021 Jun 16.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, P.R. China.

In this study, we aimed to evaluate the levels of plasma exosomal caveolin-1(CAV1) and determine its prognostic value in ovarian cancer patients. Exosome-rich fractions were isolated from the plasma of 155 patients with ovarian cancer. TEM, NTA and western blot analysis were used to confirm the exosome integrity and purification. Compared with healthy controls, plasma exosomal CAV1 levels in ovarian cancer patient were significantly down-regulated ( < 0.001). The low plasma levels of exosomal CAV1 in ovarian cancer patient plasma were related to FIGO stages, grades and lymph node metastasis (all < 0.01). Among all ovarian cancer patients, DFS was worse in patients who had low plasma exosomal CAV1 levels compared with that in patients with high plasma exosomal CAV1 levels ( < 0.001). The OS of patients with low plasma exosomal CAV1 levels was shorter than that in patients with high plasma exosomal CAV1 levels ( < 0.001). The AUROC of plasma exosomal CAV1 was 0.76 (95% CI: 0.68-0.82) for DFS prediction in ovarian cancer patients, with a sensitivity 52.9 (95% CI: 42.8-62.9) and a specificity 88.7 (95% CI: 77.0-95.7). For OS prediction in ovarian cancer patients, the AUROC of plasma exosomal CAV1 was 0.78 (95% CI: 0.70-0.84), with a sensitivity 65.1 (95% CI: 49.1-79.0) and a specificity 81.2 (95% CI: 72.8-88.0). Low exosomal CAV1 levels were closely related to the FIGO stages I/II, low grade, lymph node metastasis and prognosis of ovarian cancer patients. Plasma exosomal CAV1 may be a potential biomarker for the prognosis in ovarian cancer patients.
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http://dx.doi.org/10.7150/jca.58762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247381PMC
June 2021

[Environmental Background Values of Heavy Metals and Physicochemical Properties in Different Soils in Shenzhen].

Huan Jing Ke Xue 2021 Jul;42(7):3518-3526

State Environmental Protection Key Laboratory of Drinking Water Source Management and Technology, Shenzhen Academy of Environmental Science, Shenzhen 518001, China.

Research on the characteristics of environmental background values of soil can provide a scientific basis for setting regional standards for soils. To determine the characteristics of environmental background values and main influencing factors of heavy metals (Cr, Cu, Zn, Ni, Pb, Co, V, Cd, and Hg) in soils in Shenzhen, 500 topsoil samples (0-20 cm) were collected by decision unit multi increment sampling (DUMS) from 500 soil background sites in the whole city, including 405 latosolic red soil, 77 red soil, and 18 yellow soil samples. The results show that the concentrations of heavy metals in red soil are relatively low in general, and those of Cr, Ni, Co, and V in latosolic red soil and Cu, Zn, Hg, Pb, and Cd in yellow soil are higher. Compared with the environmental background values of soil in the Seventh Five-year Plan of China in 1980s, the concentrations of Cr, Cu, Zn, Ni, Co, and V in latosolic red soil, red soil, and yellow soil are lower, the concentrations of Cd and Hg are similar, and the concentration of Pb is higher. The spatial distribution patterns of the nine heavy metals are significantly different. Pb, Zn, and Co present an obvious zonal distribution pattern, while Cr, Cu, Ni, V, Cd, and Hg present a point-like distribution pattern. Moreover, the correlation analysis between heavy metal content and physicochemical properties of different soils showed that the correlation between heavy metal content and physicochemical properties of latosolic red soil was the most significant. Stepwise regression analysis was used to elucidate the relationship between heavy metal content in latosolic red soil, and physicochemical properties were quantified. The physicochemical properties affecting heavy metal content in latosolic red soil were found to be mechanical composition, pH, organic matter, and cation exchange capacity.
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http://dx.doi.org/10.13227/j.hjkx.202011082DOI Listing
July 2021

Methoxy terminated poly dimethylsiloxane bonded stationary phase for reversed-phase liquid chromatography.

J Chromatogr A 2021 Jun 15;1652:462348. Epub 2021 Jun 15.

Department of Chemistry, Xixi Campus, Zhejiang University, Hangzhou 310028, China.

In this work, a methoxy terminated poly dimethylsiloxane modified silica gel material was proposed as a novel stationary phase for reversed-phase liquid chromatography. With 5 μm silica gel as matrix, methoxy terminated poly dimethylsiloxane polymer was grafted by one step chemical bonding reaction. The obtained stationary phase was characterized by scanning electron microscopy, fourier transform infrared spectroscopy and element analysis. To our knowledge, this is the novel methoxy terminated poly dimethylsiloxane bonded stationary phase with good separation efficiency (42107-46988 plates/m for benzene homologues) and high stability (RSD is 0.08-5.09%). Comparing to other traditional columns of the same type, the proposed stationary phase has a wider polarity separation scale and shorter analysis time. In addition to the rapid separation of hydrophobic compound, such column also exhibited great potential in the separation of hydrophilic analytes.
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http://dx.doi.org/10.1016/j.chroma.2021.462348DOI Listing
June 2021

Cd-driven surface reconstruction and photodynamics in gold nanoclusters.

Chem Sci 2021 Jan 5;12(9):3290-3294. Epub 2021 Jan 5.

School of Chemistry and Chemical Engineering, Nanjing University Nanjing 210093 China

With atomically precise gold nanoclusters acting as a starting unit, substituting one or more gold atoms of the nanocluster with other metals has become an effective strategy to create metal synergy for improving catalytic performances and other properties. However, so far detailed insight into how to design the gold-based nanoclusters to optimize the synergy is still lacking, as atomic-level exchange between the surface-gold (or core-gold) and the incoming heteroatoms is quite challenging without changing other parts. Here we report a Cd-driven reconstruction of Au(DMBT) (DMBT = 3,5-dimethylbenzenethiol), in which four Au(DMBT) staples are precisely replaced by two AuCd(DMBT) staples to form AuCd(DMBT) with the face-centered cubic inner core retained. With the dual modifications of the surface and electronic structure, the AuCd(DMBT) nanocluster exhibits distinct excitonic behaviors and superior photocatalytic performances compared to the parent Au(DMBT) nanocluster.
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http://dx.doi.org/10.1039/d0sc05163bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179392PMC
January 2021

Recovery of post-stroke cognitive and motor deficiencies by Shuxuening injection via regulating hippocampal BDNF-mediated Neurotrophin/Trk Signaling.

Biomed Pharmacother 2021 Jun 17;141:111828. Epub 2021 Jun 17.

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin 300457, China. Electronic address:

A mild ischemic stroke may cause both debilitating locomotor and cognitive decline, for which the mechanism is not fully understood, and no therapies are currently available. In this study, a nonfatal stroke model was constructed in mice by a modified middle cerebral artery occlusion (MCAO) procedure, allowing an extended recovery period up to 28 days. The extended MCAO model successfully mimicked phenotypes of a recovery phase post-stroke, including locomotor motor and cognitive deficiencies, which were effectively improved after Shuxuening injection (SXNI) treatment. Tissue slices staining showed that SXNI repaired brain injury and reduced neuronal apoptosis, especially in the hippocampus CA3 region. Transcriptomics sequencing study revealed 565 differentially expressed genes (DEGs) in the ischemic brain after SXNI treatment. Integrated network pharmacological analysis identified Neurotrophin/Trk Signaling was the most relevant pathway, which involves 15 key genes. Related DEGs were further validated by RT-PCR. Western-blot analysis showed that SXNI reversed the abnormal expression of BDNF, TrkB, Mek3 and Jnk1after stroke. ELISA found that SXNI increased brain level of p-Erk and Creb. At sub-brain level, the expression of BDNF and TrkB was decreased and GFAP was increased on the hippocampal CA3 region in the post-stroke recovery phase and this abnormality was improved by SXNI. In vitro experiments also found that oxygen glucose deprivation reduced the expression of BDNF and TrkB, which was reversed by SXNI. In summary, we conclude that SXNI facilitates the recovery of cognitive and locomotor dysfunction by modulating Neurotrophin/Trk Signaling in a mouse model for the recovery phase of post-ischemic stroke.
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http://dx.doi.org/10.1016/j.biopha.2021.111828DOI Listing
June 2021

New nodules in oral cavity and forehead face: A decisive clinical clue to the diagnosis of epithelioid sarcoma.

Oral Oncol 2021 Jun 12:105376. Epub 2021 Jun 12.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China. Electronic address:

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http://dx.doi.org/10.1016/j.oraloncology.2021.105376DOI Listing
June 2021

Kaempferol inhibits benign prostatic hyperplasia by resisting the action of androgen.

Eur J Pharmacol 2021 Jun 12;907:174251. Epub 2021 Jun 12.

Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Poyang Lake Road 10, Tianjin, 301617, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Poyang Lake Road 10, Tianjin, 301617, China; Laboratory of Pharmacology of TCM Formulae Co-Constructed By the Province-Ministry, Tianjin University of TCM, Poyang Lake Road 10, Tianjin, 301617, China. Electronic address:

Kaempferol is a natural compound that inhibits tumor development in androgenic related prostate cancer. However, it is still not clear about its phyto-androgenic activity and whether it suppresses testosterone-induced benign prostatic hyperplasia (BPH) development. In this study, molecular docking, cellular immunofluorescence staining, chromatin immunoprecipitation and dual luciferase reporter assay were performed to investigate the androgenic activity of kaempferol. Dihydrotestosterone-induced gene expression and cell proliferation were further analyzed upon treatment with kaempferol. Testosterone-induced BPH was established in rats and the effect and mechanism of action of kaempferol on BPH development was then assessed. Docking data showed that kaempferol could bind to ASN705 and THR877 residues of androgen receptor which were also the binding sites of dihydrotestosterone. The nuclear translocation of androgen receptor was promoted directly by kaempferol in androgen-dependent prostate cancer LNCaP cells. In addition, the in vivo interaction of androgen receptor with PSA promoter region and the transcriptional activity of androgen receptor were both significantly enhanced after kaempferol stimulation. However, kaempferol pretreatment suppressed dihydrotestosterone-induced effects including the transcriptional activity of androgen receptor, the expressions of PSA and AR genes and cell proliferation of LNCaP, BPH-1 and WPMY-1 cells. Consistently, kaempferol declined the prostate index and improved the pathological properties in BPH rats, and the up-regulated T level in serum from BPH rats was highly decreased after kaempferol administration. Kaempferol exhibited its androgenic-like activity and served as a selective androgen receptor modulator that contributes to androgen-related BPH development.
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http://dx.doi.org/10.1016/j.ejphar.2021.174251DOI Listing
June 2021

Loss of ARID1A expression promotes lung adenocarcinoma metastasis and predicts a poor prognosis.

Cell Oncol (Dordr) 2021 Jun 9. Epub 2021 Jun 9.

Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, 59 Haier Road, Shandong, 266000, Qingdao, China.

Background: ARID1A is an essential subunit of SWI/SNF chromatin remodeling complexes. ARID1A gene mutations and loss of ARID1A expression have been observed in a variety of cancers, and to be correlated with invasion, immune escape and synthetic lethality. As yet, however, the biological effect of ARID1A expression and its role in the prognosis of lung adenocarcinoma (LUAD) patients have remained unclear. In this study we aimed to further elucidate the role of ARID1A expression in LUAD in vitro and in vivo and to assess its effect on the clinical prognosis of LUAD patients.

Methods: ARID1A expression was detected by IHC in tissue samples from LUAD patients. After regular culturing of LUAD cell lines and constructing stable ARID1A knockdown lines, wound healing and Transwell assays were used to assess the role of ARID1A in cell migration and invasion. The effect of ARID1A knockdown on metastasis was verified in vivo. Western blotting was used to examine the expression of target proteins. Univariate and multivariate analyses were performed to assess survival and to provide variables for nomogram construction. In addition, we used the "rms" package to construct a prognostic nomogram based on a Cox regression model.

Results: We found that ARID1A expression serves as an effective prognostic marker for LUAD patients. Loss of ARID1A expression correlated with a poor prognosis, as verified with a nomogram based on a Cox regression model. In addition, we found that ARID1A knockdown promoted LUAD cell proliferation, migration and invasion in vitro and enhanced LUAD metastasis in vivo by activating the Akt signaling pathway.

Conclusions: Our data indicate that loss of ARID1A expression promotes LUAD metastasis and predicts a poor prognosis in LUAD patients.
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http://dx.doi.org/10.1007/s13402-021-00616-xDOI Listing
June 2021

Contributions of Internal Atoms of Atomically Precise Metal Nanoclusters to Catalytic Performances.

Chemistry 2021 Jun 6. Epub 2021 Jun 6.

School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, P. R. China.

Every atom of a heterogeneous catalyst can play a direct or indirect role in its overall catalytic properties. However, it is extremely challenging to determine explicitly which atom(s) of a catalyst can contribute most to its catalytic performance because the observed performance usually reflects an average of all the atoms in the catalyst. The emergence of atomically precise metal nanoclusters brings unprecedented opportunities to address these central issues, as the crystal structures of such nanoclusters have been solved, and hence very fundamental understanding of nanocatalysis can be attained at an atomic level. This minireview focuses on recent efforts to reveal the contributions of the internal atoms or vacancies of nanocluster catalysts to the catalytic processes, including how the catalytic activity can be dramatically changed by the central doping of a foreign atom, how catalytic activation and inactivation can be reversibly switched by shuttling the central atom into and out of nanoclusters, and how evolution in catalytic activity can be driven by structural periodicity in the inner kernels of the nanoclusters. We anticipate that progress in this research area could represent a novel conceptual framework for understanding the crucial roles of internal atoms of the catalysts in tuning the catalytic properties.
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http://dx.doi.org/10.1002/chem.202101310DOI Listing
June 2021

The precise editing of surface sites on a molecular-like gold catalyst for modulating regioselectivity.

Chem Sci 2020 Jul 21;11(30):8000-8004. Epub 2020 Jul 21.

School of Chemistry and Chemical Engineering, Nanjing University Nanjing 210093 China

It is extremely difficult to precisely edit a surface site on a typical nanoparticle catalyst without changing other parts of the catalyst. This precludes a full understanding of which site primarily determines the catalytic properties. Here, we couple experimental data collection with theoretical analysis to correlate rich structural information relating to atomically precise gold clusters with the catalytic performance for the click reaction of phenylacetylene and benzyl azide. We also identify a specific surface site that is capable of achieving high regioselectivity. We further conduct site-specific editing on a thiolate-protected gold cluster by peeling off two monomeric RS-Au-SR motifs and replacing them with two PhP-CH-PPh staples. We demonstrate that the surface Au-PhP-CH-PPh-Au motifs enable extraordinary regioselectivity for the click reaction of alkyne and azide. The editing strategy for the surface motifs allows us to exploit previously inaccessible individual active sites and elucidate which site can explicitly govern the reaction outcome.
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http://dx.doi.org/10.1039/d0sc02207aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163066PMC
July 2020

Construction of direct Z-scheme photocatalyst by the interfacial interaction of WO and SiC to enhance the redox activity of electrons and holes.

Chemosphere 2021 May 25;282:130866. Epub 2021 May 25.

College of Chemistry and Chemical Engineering, Chongqing University, Chongqing, 401331, China; College of Physics, Chongqing University, Chongqing, 401331, China. Electronic address:

The direct Z-scheme heterojunction structure benefits separation and migration of photoinduced carriers while maintaining original redox ability of each component. Nowadays, most Z-scheme structures are fabricated by g-CN with other narrow band photocatalysts due to its low conduction band (CB). In this paper, SiC, another kind of photoelectric semiconductor with low CB, was employed to prepare direct Z-scheme photocatalyst with 2D WO by simple water oxidation precipitation method. The component and interface band structure of Z-scheme heterojunction WO/SiC (WS) were verified by XPS, KPFM, Mott-Schottky method. The photodegradation efficiency and rate constant values of WS-1 for degrading RhB enhanced 2.5 and 5.3 times respectively compared with pristine WO. Radical capture experiments and ESR tests affirmed that WS-1 photocatalyst produced •OH and •Oactive species, which further confirmed the photogenerated carriers were transmitted through the Z-scheme mode in principle. Band structure investigation showed that the direct Z-scheme structure assembled by WO with high valence band (VB) and SiC with low CB could maintain the high photocatalytic activity of active species. Therefore, this study offers a feasible method for construction of a novel and efficient direct Z-scheme photocatalyst.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130866DOI Listing
May 2021

Tengdan Capsule Prevents Hypertensive Kidney Damage in SHR by Inhibiting Periostin-Mediated Renal Fibrosis.

Front Pharmacol 2021 18;12:638298. Epub 2021 May 18.

Institute of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Hypertension-induced renal damage is a serious and complex condition that has not been effectively treated by conventional blood pressure-lowering drugs. Tengdan capsule (TDC) is a China FDA-approved compound herbal medicine for treating hypertension; however, its chemical basis and pharmacological efficacy have not been fully investigated in a preclinical setting. High-performance liquid chromatography (HPLC) was used to identify and quantify the major chemical components of TDC extracted from ultrapure water. Adult spontaneously hypertensive rats (SHR) and age/sex-matched Wistar Kyoto normotensive rats (WKY) were both treated with TDC, losartan, or saline for one month, and their blood pressure (BP) was monitored at the same time by tail-cuff BP system. Biochemical indexes such as urine creatinine (CRE) and blood urea nitrogen (BUN) were determined. Kidney tissue sections were examined with (H&E), and Masson staining to evaluate the pathological effect of TDC on SHR's kidneys. After TDC treatment, the differentially expressed proteins in the kidneys of SHR were identified by the TMT-based quantitative proteomics analysis, which may provide the targets and possible mechanisms of TDC action. In addition, Western blot analysis, RT-qPCR, and ELISA assays were carried out to further verify the proteomics findings. Finally, two different models involving renal injuries were established using human kidney HEK293 cells; and the molecular mechanism of TDC kidney protection was demonstrated. Seven chemical compounds, namely Notoginsenoside R1, Ginsenoside RG1, Ginsenoside Re, Ginsenoside Rb1, Sodium Danshensu, Protocatechualdehyde, and Salvianolic acid B, were identified and quantified from the water-soluble extracts of TDC by HPLC. study using rats showed that TDC effectively reduced BP, BUN, and CRE levels and attenuated renal fibrosis in SHR, and ameliorated damage to the kidneys. Proteomics and subsequent bioinformatics analyses indicated that periostin-mediated inflammatory response and TGFβ/Smad signaling pathway proteins were closely related to the therapeutic effect of TDC in rat kidneys. Western blot analysis and RT-qPCR showed that TDC markedly downregulated the mRNA and protein expression of periostin in renal tissues compared to the untreated SHR. In addition, TGF-β and COL1A1 mRNA levels also decreased in SHR renal tissues following TDC treatment. studies showed that low to medium doses of TDC down-regulated the expression of periostin in the injury model of HEK293 cell. In addition, medium to high doses of TDC significantly inhibited collagen deposition in TGFβ1-induced HEK293 cell fibrosis. Major components from the compound herbal medicine Tengdan Capsule are identified and quantified. TDC effectively lowers blood pressure and protects against renal damage caused by hypertension in SHR. Mechanistically, TDC blocks periostin by regulating the TGF-β/Smad signaling pathway in the kidney, both and . Preventing periostin-mediated renal fibrosis and inflammation might be a promising strategy for treating a hypertensive renal injury.
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http://dx.doi.org/10.3389/fphar.2021.638298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167194PMC
May 2021

Rescue of pulmonary artery intra-stent re-stenosis by unzipping an under-sized stent in an adult patient with fibrosing mediastinitis.

Chin Med J (Engl) 2021 Jun 2. Epub 2021 Jun 2.

Department of Cardiology, Xianyang Central Hospital, Xianyang, Shaanxi 712000, China Department of Cardiology, Gansu Provincial Hospital, Lanzhou, Gansu 730000, China Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200000, China Critical Care and Sleep Division, Tufts Medical Center, Boston, MA 02111, USA Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China.

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http://dx.doi.org/10.1097/CM9.0000000000001493DOI Listing
June 2021

Individual and Combined Effects of Booting and Flowering High-Temperature Stress on Rice Biomass Accumulation.

Plants (Basel) 2021 May 20;10(5). Epub 2021 May 20.

National Engineering and Technology Center for Information Agriculture, Nanjing Agricultural University, Nanjing 210095, China.

Extreme temperature events as a consequence of global climate change result in a significant decline in rice production. A two-year phytotron experiment was conducted using three temperature levels and two heating durations to compare the effects of heat stress at booting, flowering, and combined (booting + flowering) stages on the production of photosynthates and yield formation. The results showed that high temperature had a significant negative effect on mean net assimilation rate (MNAR), harvest index (HI), and grain yield per plant (YPP), and a significant positive effect under treatment T on mean leaf area index (MLAI) and duration of photosynthesis (DOP), and no significant effect on biomass per plant at maturity (BPP), except at the flowering stage. Negative linear relationships between heat degree days (HDD) and MNAR, HI, and YPP were observed. Conversely, HDD showed positive linear relationships with MLAI and DOP. In addition, BPP also showed a positive relationship with HDD, except at flowering, for both cultivars and Wuyunjing-24 at combined stages. The variation of YPP in both cultivars was mainly attributed to HI compared to BPP. However, for biomass, from the first day of high-temperature treatment to maturity (BPP), the main change was caused by MNAR followed by DOP and then MLAI. The projected alleviation effects of multiple heat stress at combined stages compared to single-stage heat stress would help to understand and evaluate rice yield formation and screening of heat-tolerant rice cultivars under current scenarios of high temperature during the rice-growing season.
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http://dx.doi.org/10.3390/plants10051021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160744PMC
May 2021

Automated Assessment of Thoracic-Abdominal Asynchrony in Patients with Morquio Syndrome.

Diagnostics (Basel) 2021 May 15;11(5). Epub 2021 May 15.

Nemours Biomedical Research, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA.

Morquio syndrome is a rare disease caused by a disorder in the storage of mucopolysaccharides that affects multiple organs, including musculoskeletal, respiratory, cardiovascular, and digestive systems. Respiratory failure is one of the leading causes of mortality in Morquio patients; thus, respiratory function testing is vital to the management of the disease. An automated respiratory assessment methodology using the RIP device and a machine-learning algorithm was developed. RIP is a noninvasive approach that uses differences between thoracic and abdominal movements (thoracic-abdominal asynchrony) during respiration to assess respiratory status. The technique was evaluated on 17 patients with Morquio (9 females and 8 males) between the ages of 2 and 57 years. The results of the automated technique agreed with the clinical assessment in 16 out of the 17 patients. It was found that the inverse cumulative percentage representation of the time delay between the thorax and abdomen was the most critical variable for accurate evaluation. It was demonstrated that the technique could be successfully used on patients with Morquio who have difficulty breathing with 100% compliance. This technique is highly accurate, portable, noninvasive, and easy to administer, making it suitable for a variety of settings, such as outpatient clinics, at home, and emergency rooms.
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http://dx.doi.org/10.3390/diagnostics11050880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156300PMC
May 2021

Proteomics analysis reveals the effect of 1α,25(OH)VD-glycosides on development of early testes in piglets.

Sci Rep 2021 May 31;11(1):11341. Epub 2021 May 31.

College of Animal Science and Technology, Huazhong Agricultural University, Hongshan District, No.1 Shizishan Road, Wuhan, 430070, China.

1α,25(OH)VD is the most active form of VD3 in animals. It plays an important role in regulating mineral metabolism but also in reproduction. Testes are the main reproductive organs of male mammals. Our research aims to reveal the effect of 1α,25(OH)VD-glycosides on development of early testes in piglets. 140 weaned 21-day old piglets were selected. The piglets were randomly divided into four groups and were fed a commercial diet supplemented with 0, 1, 2 and 4 μg/kg of 1α,25(OH)VD, provided as 1α,25(OH)VD-glycosides. Sixty days after the start of the experiment, at piglet age 82 days, testes were harvested. The morphology and histology of early testicular development were assessed. In addition, the proteomic TMT/iTRAQ labelling technique was used to analyse the protein profile of the testes in each group. Western blotting was applied to verify the target of differentially abundant proteins (DAPs). The analysis of morphology and histology of testes showed that a certain concentration of 1α,25(OH)VD-glycosides had a positive and significant effect on testicular development. And the results of proteomics analysis showed that of the identified 132,715 peptides, 122,755 were unique peptides. 7852 proteins, of which 6573 proteins contain quantitative information. Screening for DAPs focused on proteins closely related to the regulation of testicular development such as steroid hormone synthesis, steroid biosynthesis, peroxisome and fatty acid metabolism pathways. These results indicated that 1α,25(OH)VD is involved in the regulation of early testicular development in piglets. At the same time, these findings provide valuable information for the proteins involved in the regulation of testicular development, and help to better understand the mechanisms of 1α,25(OH)VD in regulating the development of piglets' testes.
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http://dx.doi.org/10.1038/s41598-021-90676-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167176PMC
May 2021

Long Non-coding RNA RUNDC3A-AS1 Promotes Lung Metastasis of Thyroid Cancer via Targeting the miR-182-5p/ADAM9.

Front Cell Dev Biol 2021 11;9:650004. Epub 2021 May 11.

Department of Head and Neck Surgery, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.

Long non-coding RNAs (lncRNAs) have been identified as influential indicators in variety of malignancies. Among which, LncRNA RUNDC3A-AS1 is reported to upregulate in thyroid cancer. However, the expression pattern and the pathological function of lncRNA RUNDC3A-AS1 in thyroid cancer is unclear. In this study, we examined the expression levels of lncRNA RUNDC3A-AS1 in the thyroid cancer tissues and cell lines via RT-qPCR analysis. The effects of RUNDC3A-AS1 on thyroid cancer cell metastasis were detected by transwell chamber assay, scratch assay and lung metastasis model . The results indicated that RUNDC3A-AS1 was highly expressed in the thyroid cancer tissues and cell lines. Functionally, knockdown of RUNDC3A-AS1 could repress the migration and invasion of thyroid cancer cells , and inhibit thyroid cancer metastasis to lung . Mechanistically, RUNDC3A-AS1 served as an inhibitor of miR-182-5p in tumor tissues and cell lines. RUNDC3A-AS1 inhibited the expression of miR-182-5p to increase the expression level of ADAM9, thus further aggravating the malignancy of thyroid cancer. Therefore, the RUNDC3A-AS1/miR-182-5p/ADAM9 axis may be a potential therapeutic target for the treatment of thyroid cancer metastasis.
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http://dx.doi.org/10.3389/fcell.2021.650004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147562PMC
May 2021

Astragalus saponins improves stroke by promoting the proliferation of neural stem cells through phosphorylation of Akt.

J Ethnopharmacol 2021 Sep 24;277:114224. Epub 2021 May 24.

Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China. Electronic address:

Ethnopharmacological Relevance: As one of major components of Buyang Huanwu decoction, Astragali Radix is broadly used for stroke treatment. Astragalus saponins (AST), the main active compound from Astragali Radix has the potentials for neuroprotection and improving spatial memory without clear pharmacological mechanism.

Aim Of The Study: The aim of this study was to investigate that pretreatment of AST is beneficial to protect against focal ischemic stroke in mouse model and its related underlying mechanism.

Materials And Methods: The neurological and motor function of MCAO mice were assessed by TTC staining and CatWalk gait analysis. The effect of AST on proliferation of NSCs was showed by the expression of Ki67 of MCAO mice and the number and size of primary neurospheres cultured from adult SVZ. The intersection of stroke-related targets, neurogenesis targets and drug-related targets were identified by the online website (https://www.omicstudio.cn/index). Then GO functional annotation and KEGG pathway enrichment analysis were performed. Candidate target Akt was confirmed to increase proliferation of cultured NSCs from adult SVZ by CCK8 assay and Western blot.

Results: We found that with the prolongation of administration time, AST improved neurological and motor function of MCAO mice, by promoting the proliferation of NSCs both in vivo and in vitro. Then, the primary network among drug, genes and biological pathway was established by using compound-target-disease & function-pathway analysis of astragalus membranaceus. PI3K/Akt which plays a key role in cell proliferation was among the top 10 most significant GO terms from above three aspects. Further analysis using cultured NSCs from adult SVZ confirmed that AST, astragaloside I (A1) and astragaloside III (A3) increased the proliferation of NSCs through targeting Akt.

Conclusion: The present study elucidated that Astragalus saponins pretreatment could provide a protective effect on experimental stroke mainly by enhancing proliferation of NSCs through targeting Akt. The findings provided a basis for the development of novel strategies for the treatment of stroke.
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http://dx.doi.org/10.1016/j.jep.2021.114224DOI Listing
September 2021

[Clinical effect and mechanism of moxibustion combined with western medication for rheumatoid arthritis of liver-kidney deficiency].

Zhongguo Zhen Jiu 2021 May;41(5):489-92

First Department of Geriatrics, Second Affiliated Hospital of Anhui University of CM, Hefei 230061.

Objective: To observe the clinical effect of moxibustion combined with western medication for rheumatoid arthritis (RA) of liver-kidney deficiency, and explore the mechanism of moxibustion for RA.

Methods: A total of 60 patients with RA of liver-kidney deficiency were randomly divided into an observation group and a control group, 30 cases in each group. In the control group,leflunomide tablets were taken orally, once a day. On the base of the treatment as the control group, moxibustion was applied at Sanyinjiao (SP 6), Shenshu (BL 23), Zusanli (ST 36) and points in the observation group, once every other day, three times a week. Totally 8 weeks were required in both groups. Before and after treatment, the TCM syndrome score, health assessment questionnaire (HAQ) score, 28-joint disease activity score (DAS-28) and serum levels of calcium ion (Ca), erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP) and rheumatoid factors (RF) were compared, and the clinicial efficacy was evaluated in the two groups.

Results: After treatment, the TCM syndrome scores, HAQ scores and DAS-28 scores were decreased in the two groups (<0.01), and those in the observation group were lower than the control group (<0.01). After treatment, the serum levels of Ca were increased (<0.01), ESR and hs-CRP were decreased in the two groups (<0.01), and the serum level of RF was decreased in the observation group (<0.01). The serum level of Ca in the observation group was higher than the control group (<0.01), ESR and RF were lower than the control group (<0.01). The total effective rate was 83.3% (25/30) in the observation group,higher than 60.0% (18/30) in the control group (<0.05).

Conclusion: Moxibustion combined with western medication can effectively relieve clinical symptoms, improve quality of life in RA patients, the curative effect is better than simple western medication. And its mechanism may be related to the regulation of serum level of Ca and immune inflammatory response to inhibit bone destruction.
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http://dx.doi.org/10.13703/j.0255-2930.20200519-k0005DOI Listing
May 2021

Paeoniflorin and Hydroxysafflor Yellow A in Xuebijing Injection Attenuate Sepsis-Induced Cardiac Dysfunction and Inhibit Proinflammatory Cytokine Production.

Front Pharmacol 2020 13;11:614024. Epub 2021 Apr 13.

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Sepsis-induced myocardial dysfunction is a major contributor to the poor outcomes of septic shock. As an add-on with conventional sepsis management for over 15 years, the effect of Xuebijing injection (XBJ) on the sepsis-induced myocardial dysfunction was not well understood. The material basis of Xuebijing injection (XBJ) in managing infections and infection-related complications remains to be defined. A murine cecal ligation and puncture (CLP) model and cardiomyocytes culture were adopted to study the influence of XBJ on infection-induced cardiac dysfunction. XBJ significantly improved the survival of septic-mice and rescued cardiac dysfunction . RNA-seq revealed XBJ attenuated the expression of proinflammatory cytokines and related signalings in the heart which was further confirmed on the mRNA and protein levels. Xuebijing also protected cardiomyocytes from LPS-induced mitochondrial calcium ion overload and reduced the LPS-induced ROS production in cardiomyocytes. The therapeutic effect of XBJ was mediated by the combination of paeoniflorin and hydroxysafflor yellow A (HSYA) (C0127-2). C0127-2 improved the survival of septic mice, protected their cardiac function and cardiomyocytes while balancing gene expression in cytokine-storm-related signalings, such as TNF-α and NF-κB. In summary, Paeoniflorin and HSYA are key active compounds in XBJ for managing sepsis, protecting cardiac function, and controlling inflammation in the cardiac tissue partially by limiting the production of IL-6, IL-1β, and CXCL2.
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http://dx.doi.org/10.3389/fphar.2020.614024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112230PMC
April 2021

Large-scale analysis of 2,152 Ig-seq datasets reveals key features of B cell biology and the antibody repertoire.

Cell Rep 2021 May;35(6):109110

Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai 200433, China. Electronic address:

Antibody repertoire sequencing enables researchers to acquire millions of B cell receptors and investigate these molecules at the single-nucleotide level. This power and resolution in studying humoral responses have led to its wide applications. However, most of these studies were conducted with a limited number of samples. Given the extraordinary diversity, assessment of these key features with a large sample set is demanded. Thus, we collect and systematically analyze 2,152 high-quality heavy-chain antibody repertoires. Our study reveals that 52 core variable genes universally contribute to more than 99% of each individual's repertoire; a distal interspersed preferences characterize V gene recombination; the number of public clones between two repertoires follows a linear model, and the positive selection dominates at RGYW motif in somatic hypermutations. Thus, this population-level analysis resolves some critical features of the antibody repertoire and may have significant value to the large cadre of scientists.
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http://dx.doi.org/10.1016/j.celrep.2021.109110DOI Listing
May 2021